Commentary

On March 11, 2020, the World Health Organization declared that coronavirus disease 2019 (COVID-19) was a pandemic.¹ As of mid-May 2020, the illness had claimed more than 316,000 lives worldwide.² The main symptoms of the respiratory illness caused by COVID-19 are fever, dry cough, and shortness of breath. However, disorders of consciousness also have been reported, especially in patients who succumb to the illness.³ In fact, approximately one-third of hospitalized COVID-19 patients experience neurologic symptoms.⁴ Although the most common of these symptoms are dizziness, headache, and loss of smell and taste, patients with more severe cases can experience acute cerebrovascular diseases and impaired consciousness.⁴ As such, psychiatrists assessing confusion should include COVID-19 in their differential diagnosis as a potential cause of altered mental status.

How COVID-19 might affect the CNS

Although primarily considered a respiratory illness, COVID-19 also may have neurotropic potential. The virus that causes COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is a beta-coronavirus. Two other highly pathogenic coronaviruses—SARS-CoV-1 and Middle East respiratory syndrome–related coronavirus (MERS-CoV)—are also beta-coronaviruses, and both have been reported to invade the CNS in some patients.⁵ These viruses are thought to invade cells via angiotensin-converting enzyme 2 (ACE2) receptors.⁶ These receptors are located on the epithelial cells of the respiratory and gastrointestinal (GI) tracts, but also are expressed in certain areas of the brain.⁷ Transmission to the brain could occur through various routes. However, the clinical symptom of loss of smell and taste hints to possible transmission of the virus from nasal cells to the olfactory bulb via trans-synaptic transmission in olfactory neurons.^5,8,9

Immune injury via systemic inflammation is another proposed mechanism for nervous system damage.^8,9 This has been described as “cytokine storm syndrome” and provides support to the role of immuno­therapy in COVID-19 patients.¹⁰ Such inflammation has been long hypothesized as a contributor to psychiatric illnesses, especially neurocognitive disorders.^11,12

Neuropsychiatric complications of COVID-19

Disorders of consciousness were identified early as a symptom of COVID-19.³ Subsequent studies and case reports have confirmed impaired consciousness as a possible symptom of COVID-19.⁴ The first case of encephalitis secondary to COVID-19 was reported by Chinese media on March 5, 2020 in Beijing, China.¹³ Subsequently, cases of encephalopathy secondary to COVID-19 have been reported in the United States. A 74-year-old man in Boca Raton, Florida who had recently returned from the Netherlands presented with altered mental status and was confirmed positive for COVID-19.¹⁴ A female airline worker in her late 50s who presented with altered mental status and tested positive for COVID-19 was found on imaging to have acute hemorrhagic necrotizing encephalopathy.¹⁵ There also have been cases of patients with confirmed COVID-19 who initially presented with complaints of seizures¹⁶ and Guillain-Barré syndrome.¹⁷ As such, neuro­psychiatric complications of COVID-19 are being increasingly recognized and are important to consider during psychiatric assessments.

Consider COVID-19 when assessing altered mental status

Psychiatrists are often consulted to assess patients with impaired consciousness, mental status changes, or confusion. Acute changes to mentation raise concern for delirium. In fact, delirium should always be ruled out when assessing new psychiatric symptoms. The astute psychiatrist is aware of the myriad of medical contributors to delirium. However, because knowledge of COVID-19 is in its infancy, it can be easy to overlook this virus as a potential contributor to delirium. Even patients whose confusion seems to be more in line with a major neurocognitive disorder should be evaluated for COVID-19, because the sudden onset of cognitive impairment may be due to hypoxia, inflammatory damage, or cerebrovascular changes secondary to infection with the virus or its respiratory complications, such as acute respiratory distress syndrome (ARDS).¹⁸

The most obvious clues to the possible presence of COVID-19 in a patient who is confused would be fever, dry cough, and shortness of breath. Because ACE2 receptors are also located in the GI tract, nausea, vomiting, and diarrhea also are possible. However, patients who are confused may be poor historians, demonstrating behavioral symptoms that might make physical assessments challenging, or simply may be pre- or asymptomatic carriers of the virus. Hence, a thorough review of the patient’s history and collateral information is invaluable. A recent history of travel or contact with COVID-19–positive individuals should raise suspicion for viral infection. A patient who mentions a loss of taste or smell would also alert the psychiatrist to the possibility of COVID-19. A patient might not directly state this information, but may mention that he/she has been eating less or has not been disturbed by odors. Neuroimaging can be useful because patients with severe cases are at increased risk for acute cerebrovascular diseases.⁴ Also, ordering a chest CT may prove helpful because this testing is highly sensitive for COVID-19.¹⁹ If there is sufficient clinical evidence to suspect viral infection, testing for COVID-19 should be performed immediately.

It is important to be vigilant for the possibility of COVID-19 infection in patients who present with confusion. Because the virus is highly contagious, the threshold for COVID-19 testing should be low. Viral infection in patients can manifest in ways other than classic respiratory symptoms. Psychiatrists should be aware of COVID-19’s potential to invade the CNS and cause neuropsychiatric symptoms. When assessing confusion in any setting, the clinical and historical clues for COVID-19 should be kept in mind. This will allow patients with COVID-19 to be quickly diagnosed to initiate appropriate management and minimize progression of the illness. Additionally, this will allow for efficient quarantine of the patient to prevent the spread of the virus to others. As such, psychiatrists can play an important role in containing this virus and resolving the COVID-19 pandemic.

Continue to: Bottom Line

Although primarily considered a respiratory illness, coronavirus disease 2019 (COVID-19) also may have the potential to invade the CNS and cause neuropsychiatric symptoms, such as impaired consciousness, encephalitis, or a loss of taste or smell. When assessing a patient who presents with confusion, be vigilant for the possibility of COVID-19.

Related Resources

• American Psychiatry Association. APA coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-coronavirus#psych.
• Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun. 2020;S0889-1591(20)30489-X. doi: 10.1016/j.bbi.2020.04.027.

On March 11, 2020, the World Health Organization declared that coronavirus disease 2019 (COVID-19) was a pandemic.¹ As of mid-May 2020, the illness had claimed more than 316,000 lives worldwide.² The main symptoms of the respiratory illness caused by COVID-19 are fever, dry cough, and shortness of breath. However, disorders of consciousness also have been reported, especially in patients who succumb to the illness.³ In fact, approximately one-third of hospitalized COVID-19 patients experience neurologic symptoms.⁴ Although the most common of these symptoms are dizziness, headache, and loss of smell and taste, patients with more severe cases can experience acute cerebrovascular diseases and impaired consciousness.⁴ As such, psychiatrists assessing confusion should include COVID-19 in their differential diagnosis as a potential cause of altered mental status.

How COVID-19 might affect the CNS

Although primarily considered a respiratory illness, COVID-19 also may have neurotropic potential. The virus that causes COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is a beta-coronavirus. Two other highly pathogenic coronaviruses—SARS-CoV-1 and Middle East respiratory syndrome–related coronavirus (MERS-CoV)—are also beta-coronaviruses, and both have been reported to invade the CNS in some patients.⁵ These viruses are thought to invade cells via angiotensin-converting enzyme 2 (ACE2) receptors.⁶ These receptors are located on the epithelial cells of the respiratory and gastrointestinal (GI) tracts, but also are expressed in certain areas of the brain.⁷ Transmission to the brain could occur through various routes. However, the clinical symptom of loss of smell and taste hints to possible transmission of the virus from nasal cells to the olfactory bulb via trans-synaptic transmission in olfactory neurons.^5,8,9

Immune injury via systemic inflammation is another proposed mechanism for nervous system damage.^8,9 This has been described as “cytokine storm syndrome” and provides support to the role of immuno­therapy in COVID-19 patients.¹⁰ Such inflammation has been long hypothesized as a contributor to psychiatric illnesses, especially neurocognitive disorders.^11,12

Neuropsychiatric complications of COVID-19

Disorders of consciousness were identified early as a symptom of COVID-19.³ Subsequent studies and case reports have confirmed impaired consciousness as a possible symptom of COVID-19.⁴ The first case of encephalitis secondary to COVID-19 was reported by Chinese media on March 5, 2020 in Beijing, China.¹³ Subsequently, cases of encephalopathy secondary to COVID-19 have been reported in the United States. A 74-year-old man in Boca Raton, Florida who had recently returned from the Netherlands presented with altered mental status and was confirmed positive for COVID-19.¹⁴ A female airline worker in her late 50s who presented with altered mental status and tested positive for COVID-19 was found on imaging to have acute hemorrhagic necrotizing encephalopathy.¹⁵ There also have been cases of patients with confirmed COVID-19 who initially presented with complaints of seizures¹⁶ and Guillain-Barré syndrome.¹⁷ As such, neuro­psychiatric complications of COVID-19 are being increasingly recognized and are important to consider during psychiatric assessments.

Consider COVID-19 when assessing altered mental status

Psychiatrists are often consulted to assess patients with impaired consciousness, mental status changes, or confusion. Acute changes to mentation raise concern for delirium. In fact, delirium should always be ruled out when assessing new psychiatric symptoms. The astute psychiatrist is aware of the myriad of medical contributors to delirium. However, because knowledge of COVID-19 is in its infancy, it can be easy to overlook this virus as a potential contributor to delirium. Even patients whose confusion seems to be more in line with a major neurocognitive disorder should be evaluated for COVID-19, because the sudden onset of cognitive impairment may be due to hypoxia, inflammatory damage, or cerebrovascular changes secondary to infection with the virus or its respiratory complications, such as acute respiratory distress syndrome (ARDS).¹⁸

The most obvious clues to the possible presence of COVID-19 in a patient who is confused would be fever, dry cough, and shortness of breath. Because ACE2 receptors are also located in the GI tract, nausea, vomiting, and diarrhea also are possible. However, patients who are confused may be poor historians, demonstrating behavioral symptoms that might make physical assessments challenging, or simply may be pre- or asymptomatic carriers of the virus. Hence, a thorough review of the patient’s history and collateral information is invaluable. A recent history of travel or contact with COVID-19–positive individuals should raise suspicion for viral infection. A patient who mentions a loss of taste or smell would also alert the psychiatrist to the possibility of COVID-19. A patient might not directly state this information, but may mention that he/she has been eating less or has not been disturbed by odors. Neuroimaging can be useful because patients with severe cases are at increased risk for acute cerebrovascular diseases.⁴ Also, ordering a chest CT may prove helpful because this testing is highly sensitive for COVID-19.¹⁹ If there is sufficient clinical evidence to suspect viral infection, testing for COVID-19 should be performed immediately.

It is important to be vigilant for the possibility of COVID-19 infection in patients who present with confusion. Because the virus is highly contagious, the threshold for COVID-19 testing should be low. Viral infection in patients can manifest in ways other than classic respiratory symptoms. Psychiatrists should be aware of COVID-19’s potential to invade the CNS and cause neuropsychiatric symptoms. When assessing confusion in any setting, the clinical and historical clues for COVID-19 should be kept in mind. This will allow patients with COVID-19 to be quickly diagnosed to initiate appropriate management and minimize progression of the illness. Additionally, this will allow for efficient quarantine of the patient to prevent the spread of the virus to others. As such, psychiatrists can play an important role in containing this virus and resolving the COVID-19 pandemic.

Continue to: Bottom Line

Although primarily considered a respiratory illness, coronavirus disease 2019 (COVID-19) also may have the potential to invade the CNS and cause neuropsychiatric symptoms, such as impaired consciousness, encephalitis, or a loss of taste or smell. When assessing a patient who presents with confusion, be vigilant for the possibility of COVID-19.

Related Resources

• American Psychiatry Association. APA coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-coronavirus#psych.
• Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun. 2020;S0889-1591(20)30489-X. doi: 10.1016/j.bbi.2020.04.027.

On March 11, 2020, the World Health Organization declared that coronavirus disease 2019 (COVID-19) was a pandemic.¹ As of mid-May 2020, the illness had claimed more than 316,000 lives worldwide.² The main symptoms of the respiratory illness caused by COVID-19 are fever, dry cough, and shortness of breath. However, disorders of consciousness also have been reported, especially in patients who succumb to the illness.³ In fact, approximately one-third of hospitalized COVID-19 patients experience neurologic symptoms.⁴ Although the most common of these symptoms are dizziness, headache, and loss of smell and taste, patients with more severe cases can experience acute cerebrovascular diseases and impaired consciousness.⁴ As such, psychiatrists assessing confusion should include COVID-19 in their differential diagnosis as a potential cause of altered mental status.

How COVID-19 might affect the CNS

Although primarily considered a respiratory illness, COVID-19 also may have neurotropic potential. The virus that causes COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is a beta-coronavirus. Two other highly pathogenic coronaviruses—SARS-CoV-1 and Middle East respiratory syndrome–related coronavirus (MERS-CoV)—are also beta-coronaviruses, and both have been reported to invade the CNS in some patients.⁵ These viruses are thought to invade cells via angiotensin-converting enzyme 2 (ACE2) receptors.⁶ These receptors are located on the epithelial cells of the respiratory and gastrointestinal (GI) tracts, but also are expressed in certain areas of the brain.⁷ Transmission to the brain could occur through various routes. However, the clinical symptom of loss of smell and taste hints to possible transmission of the virus from nasal cells to the olfactory bulb via trans-synaptic transmission in olfactory neurons.^5,8,9

Immune injury via systemic inflammation is another proposed mechanism for nervous system damage.^8,9 This has been described as “cytokine storm syndrome” and provides support to the role of immuno­therapy in COVID-19 patients.¹⁰ Such inflammation has been long hypothesized as a contributor to psychiatric illnesses, especially neurocognitive disorders.^11,12

Neuropsychiatric complications of COVID-19

Disorders of consciousness were identified early as a symptom of COVID-19.³ Subsequent studies and case reports have confirmed impaired consciousness as a possible symptom of COVID-19.⁴ The first case of encephalitis secondary to COVID-19 was reported by Chinese media on March 5, 2020 in Beijing, China.¹³ Subsequently, cases of encephalopathy secondary to COVID-19 have been reported in the United States. A 74-year-old man in Boca Raton, Florida who had recently returned from the Netherlands presented with altered mental status and was confirmed positive for COVID-19.¹⁴ A female airline worker in her late 50s who presented with altered mental status and tested positive for COVID-19 was found on imaging to have acute hemorrhagic necrotizing encephalopathy.¹⁵ There also have been cases of patients with confirmed COVID-19 who initially presented with complaints of seizures¹⁶ and Guillain-Barré syndrome.¹⁷ As such, neuro­psychiatric complications of COVID-19 are being increasingly recognized and are important to consider during psychiatric assessments.

Consider COVID-19 when assessing altered mental status

Psychiatrists are often consulted to assess patients with impaired consciousness, mental status changes, or confusion. Acute changes to mentation raise concern for delirium. In fact, delirium should always be ruled out when assessing new psychiatric symptoms. The astute psychiatrist is aware of the myriad of medical contributors to delirium. However, because knowledge of COVID-19 is in its infancy, it can be easy to overlook this virus as a potential contributor to delirium. Even patients whose confusion seems to be more in line with a major neurocognitive disorder should be evaluated for COVID-19, because the sudden onset of cognitive impairment may be due to hypoxia, inflammatory damage, or cerebrovascular changes secondary to infection with the virus or its respiratory complications, such as acute respiratory distress syndrome (ARDS).¹⁸

The most obvious clues to the possible presence of COVID-19 in a patient who is confused would be fever, dry cough, and shortness of breath. Because ACE2 receptors are also located in the GI tract, nausea, vomiting, and diarrhea also are possible. However, patients who are confused may be poor historians, demonstrating behavioral symptoms that might make physical assessments challenging, or simply may be pre- or asymptomatic carriers of the virus. Hence, a thorough review of the patient’s history and collateral information is invaluable. A recent history of travel or contact with COVID-19–positive individuals should raise suspicion for viral infection. A patient who mentions a loss of taste or smell would also alert the psychiatrist to the possibility of COVID-19. A patient might not directly state this information, but may mention that he/she has been eating less or has not been disturbed by odors. Neuroimaging can be useful because patients with severe cases are at increased risk for acute cerebrovascular diseases.⁴ Also, ordering a chest CT may prove helpful because this testing is highly sensitive for COVID-19.¹⁹ If there is sufficient clinical evidence to suspect viral infection, testing for COVID-19 should be performed immediately.

It is important to be vigilant for the possibility of COVID-19 infection in patients who present with confusion. Because the virus is highly contagious, the threshold for COVID-19 testing should be low. Viral infection in patients can manifest in ways other than classic respiratory symptoms. Psychiatrists should be aware of COVID-19’s potential to invade the CNS and cause neuropsychiatric symptoms. When assessing confusion in any setting, the clinical and historical clues for COVID-19 should be kept in mind. This will allow patients with COVID-19 to be quickly diagnosed to initiate appropriate management and minimize progression of the illness. Additionally, this will allow for efficient quarantine of the patient to prevent the spread of the virus to others. As such, psychiatrists can play an important role in containing this virus and resolving the COVID-19 pandemic.

Continue to: Bottom Line

Although primarily considered a respiratory illness, coronavirus disease 2019 (COVID-19) also may have the potential to invade the CNS and cause neuropsychiatric symptoms, such as impaired consciousness, encephalitis, or a loss of taste or smell. When assessing a patient who presents with confusion, be vigilant for the possibility of COVID-19.

Related Resources

• American Psychiatry Association. APA coronavirus resources. https://www.psychiatry.org/psychiatrists/covid-19-coronavirus#psych.
• Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun. 2020;S0889-1591(20)30489-X. doi: 10.1016/j.bbi.2020.04.027.

A 46-year-old man who lives in Tacoma, Wash., is seen for fatigue. He has a no significant past medical history. He is not taking any medications. His physical exam is unremarkable. His hemoglobin is 12 gm/dL, hematocrit is 37 gm/dL, mean corpuscular volume (MCV) is 103 fL, and thyroid-stimulating hormone level is 1.2 mU/L.

What workup do you recommend?

A) B₁₂, folate testing

B) Alcohol history, B₁₂, folate testing

C) Alcohol history, B₁₂ testing

I would choose doing a careful alcohol history and vitamin B₁₂ testing.

Dr. Seppä and colleagues looked at all outpatients who had a blood count done over an 8-month period.¹ A total of 9,527 blood counts were ordered, and 287 (3%) had macrocytosis.¹ Further workup was done for 113 of the patients. The most common cause found for macrocytosis was alcohol abuse, in 74 (65%) of the patients (80% of the men and 36% of the women). In several studies, vitamin B₁₂ deficiency was the cause of macrocytosis in 5%-7% of patients.^2,3

In 1978, a study by Davidson and Hamilton looked at 200 consecutive patients with MCVs over 100, and were able to find a cause in 80%.⁴ Sixteen of these patients had a low B₁₂ level and 10 had a low folate level.

In recent years, folate has become an extremely unlikely cause of macrocytic anemias. In 1998, the Food and Drug Administration required folic acid fortification of enriched grain products in the United States to help decrease the risk of neural tube defects. Similar fortification efforts were undertaken in Canada. Since 1998, anemia due to folate deficiency has essentially disappeared in individuals who have access to fortified grain products.

Joelson and colleagues looked at data on folate testing from the year prior to fortification of the grain supply (1997) and after (2004).⁵ They found that, in 1997, 4.8% of tests had a folate level less than 160 ng/mL compared with only 0.6% of tests in 2004.

When a more stringent cutoff for deficiency was used (94 ng/mL) 0.98% of tests were below that level in 1997, and 0.09% in 2004. The mean RBC folate level in 1997 was 420 ng/mL and rose to 697 ng/mL in 2004. Of the patients who did have low folate levels, only a minority had elevated MCVs.

Shojania et al. looked at folate testing in Canada after widespread fortification had started.⁶ They found that 0.5% of 2,154 serum folate levels were low and 0.7% of 560 red blood cell folate levels were low. Folate deficiency was not the cause of anemia in any of the patients with low folate levels.

Theisen-Toupal and colleagues did a retrospective study looking at folate testing over an 11-year period after fortification.⁷ The researchers examined the results of 84,187 assessments of folate levels. Forty-seven (0.056%) of the tests found patients with folate deficiency, 166 (0.197%), found patients with low-normal folate levels, 57,411 (68.195%) of tests yielded normal results, and 26,563 (31.552%) of tests found high folate levels. The opinion of the authors was that folate testing should be severely reduced or eliminated. Furthermore, the American Society for Clinical Pathology, as part of the Choosing Wisely campaign, states: “Do not order red blood cell folate levels at all.”⁸

So what does this all mean? We have been taught to have a reflex response to the evaluation of macrocytosis to test for B₁₂ and folate. Neither of these are particularly common causes of macrocytosis, and in countries where there is grain fortification, folate deficiency is exceedingly uncommon, and should not be tested for early in any diagnostic process.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Seppä K et al. Evaluation of macrocytosis by general practitioners. J Stud Alcohol. 1996 Jan;57(1):97-100.

2. Seppä K et al. Blood count and hematologic morphology in nonanemic macrocytosis: Differences between alcohol abuse and pernicious anemia. Alcohol. 1993 Sep-Oct;10(5):343-7.

3. Wymer A, Becker DM. Recognition and evaluation of red blood cell macrocytosis in the primary care setting. J Gen Intern Med. 1990 May-Jun;5(3):192-7.

4. Davidson RJ, Hamilton PJ. High mean red cell volume: Its incidence and significance in routine haematology. J Clin Pathol. 1978 May;31[5]:493-8.

5. Joelson DW, Fiebig EW. Diminished need for folate measurements among indigent populations in the post folic acid supplementation era. Arch Pathol Lab Med. 2007 Mar;131(3):477-80.

6. Shojania AM, von Kuster K. Ordering folate assays is no longer justified for investigation of anemias, in folic acid fortified countries. BMC Res Notes. 2010 Jan 25;3:22. doi: 10.1186/1756-0500-3-22.

7. Theisen-Toupal et al. Low yield of outpatient serum folate testing. JAMA Intern Med. 2014 Oct. doi: 10.1001/jamainternmed.2014.3593.

8. Choosing Wisely: American Society for Clinical Pathology, Oct. 19, 2017. Recommendation.

A 46-year-old man who lives in Tacoma, Wash., is seen for fatigue. He has a no significant past medical history. He is not taking any medications. His physical exam is unremarkable. His hemoglobin is 12 gm/dL, hematocrit is 37 gm/dL, mean corpuscular volume (MCV) is 103 fL, and thyroid-stimulating hormone level is 1.2 mU/L.

What workup do you recommend?

A) B₁₂, folate testing

B) Alcohol history, B₁₂, folate testing

C) Alcohol history, B₁₂ testing

I would choose doing a careful alcohol history and vitamin B₁₂ testing.

Dr. Seppä and colleagues looked at all outpatients who had a blood count done over an 8-month period.¹ A total of 9,527 blood counts were ordered, and 287 (3%) had macrocytosis.¹ Further workup was done for 113 of the patients. The most common cause found for macrocytosis was alcohol abuse, in 74 (65%) of the patients (80% of the men and 36% of the women). In several studies, vitamin B₁₂ deficiency was the cause of macrocytosis in 5%-7% of patients.^2,3

In 1978, a study by Davidson and Hamilton looked at 200 consecutive patients with MCVs over 100, and were able to find a cause in 80%.⁴ Sixteen of these patients had a low B₁₂ level and 10 had a low folate level.

In recent years, folate has become an extremely unlikely cause of macrocytic anemias. In 1998, the Food and Drug Administration required folic acid fortification of enriched grain products in the United States to help decrease the risk of neural tube defects. Similar fortification efforts were undertaken in Canada. Since 1998, anemia due to folate deficiency has essentially disappeared in individuals who have access to fortified grain products.

Joelson and colleagues looked at data on folate testing from the year prior to fortification of the grain supply (1997) and after (2004).⁵ They found that, in 1997, 4.8% of tests had a folate level less than 160 ng/mL compared with only 0.6% of tests in 2004.

When a more stringent cutoff for deficiency was used (94 ng/mL) 0.98% of tests were below that level in 1997, and 0.09% in 2004. The mean RBC folate level in 1997 was 420 ng/mL and rose to 697 ng/mL in 2004. Of the patients who did have low folate levels, only a minority had elevated MCVs.

Shojania et al. looked at folate testing in Canada after widespread fortification had started.⁶ They found that 0.5% of 2,154 serum folate levels were low and 0.7% of 560 red blood cell folate levels were low. Folate deficiency was not the cause of anemia in any of the patients with low folate levels.

Theisen-Toupal and colleagues did a retrospective study looking at folate testing over an 11-year period after fortification.⁷ The researchers examined the results of 84,187 assessments of folate levels. Forty-seven (0.056%) of the tests found patients with folate deficiency, 166 (0.197%), found patients with low-normal folate levels, 57,411 (68.195%) of tests yielded normal results, and 26,563 (31.552%) of tests found high folate levels. The opinion of the authors was that folate testing should be severely reduced or eliminated. Furthermore, the American Society for Clinical Pathology, as part of the Choosing Wisely campaign, states: “Do not order red blood cell folate levels at all.”⁸

So what does this all mean? We have been taught to have a reflex response to the evaluation of macrocytosis to test for B₁₂ and folate. Neither of these are particularly common causes of macrocytosis, and in countries where there is grain fortification, folate deficiency is exceedingly uncommon, and should not be tested for early in any diagnostic process.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Seppä K et al. Evaluation of macrocytosis by general practitioners. J Stud Alcohol. 1996 Jan;57(1):97-100.

2. Seppä K et al. Blood count and hematologic morphology in nonanemic macrocytosis: Differences between alcohol abuse and pernicious anemia. Alcohol. 1993 Sep-Oct;10(5):343-7.

3. Wymer A, Becker DM. Recognition and evaluation of red blood cell macrocytosis in the primary care setting. J Gen Intern Med. 1990 May-Jun;5(3):192-7.

4. Davidson RJ, Hamilton PJ. High mean red cell volume: Its incidence and significance in routine haematology. J Clin Pathol. 1978 May;31[5]:493-8.

5. Joelson DW, Fiebig EW. Diminished need for folate measurements among indigent populations in the post folic acid supplementation era. Arch Pathol Lab Med. 2007 Mar;131(3):477-80.

6. Shojania AM, von Kuster K. Ordering folate assays is no longer justified for investigation of anemias, in folic acid fortified countries. BMC Res Notes. 2010 Jan 25;3:22. doi: 10.1186/1756-0500-3-22.

7. Theisen-Toupal et al. Low yield of outpatient serum folate testing. JAMA Intern Med. 2014 Oct. doi: 10.1001/jamainternmed.2014.3593.

8. Choosing Wisely: American Society for Clinical Pathology, Oct. 19, 2017. Recommendation.

A 46-year-old man who lives in Tacoma, Wash., is seen for fatigue. He has a no significant past medical history. He is not taking any medications. His physical exam is unremarkable. His hemoglobin is 12 gm/dL, hematocrit is 37 gm/dL, mean corpuscular volume (MCV) is 103 fL, and thyroid-stimulating hormone level is 1.2 mU/L.

What workup do you recommend?

A) B₁₂, folate testing

B) Alcohol history, B₁₂, folate testing

C) Alcohol history, B₁₂ testing

I would choose doing a careful alcohol history and vitamin B₁₂ testing.

Dr. Seppä and colleagues looked at all outpatients who had a blood count done over an 8-month period.¹ A total of 9,527 blood counts were ordered, and 287 (3%) had macrocytosis.¹ Further workup was done for 113 of the patients. The most common cause found for macrocytosis was alcohol abuse, in 74 (65%) of the patients (80% of the men and 36% of the women). In several studies, vitamin B₁₂ deficiency was the cause of macrocytosis in 5%-7% of patients.^2,3

In 1978, a study by Davidson and Hamilton looked at 200 consecutive patients with MCVs over 100, and were able to find a cause in 80%.⁴ Sixteen of these patients had a low B₁₂ level and 10 had a low folate level.

In recent years, folate has become an extremely unlikely cause of macrocytic anemias. In 1998, the Food and Drug Administration required folic acid fortification of enriched grain products in the United States to help decrease the risk of neural tube defects. Similar fortification efforts were undertaken in Canada. Since 1998, anemia due to folate deficiency has essentially disappeared in individuals who have access to fortified grain products.

Joelson and colleagues looked at data on folate testing from the year prior to fortification of the grain supply (1997) and after (2004).⁵ They found that, in 1997, 4.8% of tests had a folate level less than 160 ng/mL compared with only 0.6% of tests in 2004.

When a more stringent cutoff for deficiency was used (94 ng/mL) 0.98% of tests were below that level in 1997, and 0.09% in 2004. The mean RBC folate level in 1997 was 420 ng/mL and rose to 697 ng/mL in 2004. Of the patients who did have low folate levels, only a minority had elevated MCVs.

Shojania et al. looked at folate testing in Canada after widespread fortification had started.⁶ They found that 0.5% of 2,154 serum folate levels were low and 0.7% of 560 red blood cell folate levels were low. Folate deficiency was not the cause of anemia in any of the patients with low folate levels.

Theisen-Toupal and colleagues did a retrospective study looking at folate testing over an 11-year period after fortification.⁷ The researchers examined the results of 84,187 assessments of folate levels. Forty-seven (0.056%) of the tests found patients with folate deficiency, 166 (0.197%), found patients with low-normal folate levels, 57,411 (68.195%) of tests yielded normal results, and 26,563 (31.552%) of tests found high folate levels. The opinion of the authors was that folate testing should be severely reduced or eliminated. Furthermore, the American Society for Clinical Pathology, as part of the Choosing Wisely campaign, states: “Do not order red blood cell folate levels at all.”⁸

So what does this all mean? We have been taught to have a reflex response to the evaluation of macrocytosis to test for B₁₂ and folate. Neither of these are particularly common causes of macrocytosis, and in countries where there is grain fortification, folate deficiency is exceedingly uncommon, and should not be tested for early in any diagnostic process.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Seppä K et al. Evaluation of macrocytosis by general practitioners. J Stud Alcohol. 1996 Jan;57(1):97-100.

2. Seppä K et al. Blood count and hematologic morphology in nonanemic macrocytosis: Differences between alcohol abuse and pernicious anemia. Alcohol. 1993 Sep-Oct;10(5):343-7.

3. Wymer A, Becker DM. Recognition and evaluation of red blood cell macrocytosis in the primary care setting. J Gen Intern Med. 1990 May-Jun;5(3):192-7.

4. Davidson RJ, Hamilton PJ. High mean red cell volume: Its incidence and significance in routine haematology. J Clin Pathol. 1978 May;31[5]:493-8.

5. Joelson DW, Fiebig EW. Diminished need for folate measurements among indigent populations in the post folic acid supplementation era. Arch Pathol Lab Med. 2007 Mar;131(3):477-80.

6. Shojania AM, von Kuster K. Ordering folate assays is no longer justified for investigation of anemias, in folic acid fortified countries. BMC Res Notes. 2010 Jan 25;3:22. doi: 10.1186/1756-0500-3-22.

7. Theisen-Toupal et al. Low yield of outpatient serum folate testing. JAMA Intern Med. 2014 Oct. doi: 10.1001/jamainternmed.2014.3593.

8. Choosing Wisely: American Society for Clinical Pathology, Oct. 19, 2017. Recommendation.

We are months into the COVID-19 crisis, and mental health issues are proving to be rampant. In every crisis, there is opportunity, and this one is no different. The opportunity is clear. For Mental Health Awareness Month and beyond, we must convey a powerful message that mental health is key to our well-being and must be actively addressed. Because almost everyone has felt excess anxiety these last months, we have a unique chance to engage a wider audience.

To address the urgent need, the Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. Spearheaded by social activist and fashion designer, Kenneth Cole, it is a coalition of leading mental health organizations, brands, celebrities, and advocates who have joined forces to end the stigma surrounding mental health and to change the way people talk about, and care for, mental illness. The group’s mission listed on its website states: “We must increase the conversation around mental health. We must act to end silence, reduce stigma, and engage our community to inspire hope at this essential moment.”

As most of the United States has been under stay-at-home orders, our traditional relationships have been radically disrupted. New types of relationships are forming as we are relying even more on technology to connect us. Social media seems to be on the only “social” we can now safely engage in.

The coalition’s campaign, “#howareyoureally?” is harnessing the power of social media and creating a storytelling platform to allow users to more genuinely share their feelings in these unprecedented times. Celebrities include Whoopi Goldberg, Kendall Jenner, Chris Cuomo, Deepak Chopra, Kesha, and many more have already shared their stories.

“How Are You, Really?” challenges people to answer this question using social media in an open and honest fashion while still providing hope.

The second component of the initiative is to increase access to care, and they have a long list of collaborators, including leading mental health organizations such as the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, Child Mind Institute, Depression and Bipolar Support Alliance, Didi Hirsch Mental Health Services, National Alliance on Mental Illness, and many more.

We have a unique opportunity this Mental Health Awareness Month, and I hope we will see more and more people sharing their stories and reaching out for help. As a community, we must be prepared to meet the escalating needs of our population.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018) and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

We are months into the COVID-19 crisis, and mental health issues are proving to be rampant. In every crisis, there is opportunity, and this one is no different. The opportunity is clear. For Mental Health Awareness Month and beyond, we must convey a powerful message that mental health is key to our well-being and must be actively addressed. Because almost everyone has felt excess anxiety these last months, we have a unique chance to engage a wider audience.

To address the urgent need, the Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. Spearheaded by social activist and fashion designer, Kenneth Cole, it is a coalition of leading mental health organizations, brands, celebrities, and advocates who have joined forces to end the stigma surrounding mental health and to change the way people talk about, and care for, mental illness. The group’s mission listed on its website states: “We must increase the conversation around mental health. We must act to end silence, reduce stigma, and engage our community to inspire hope at this essential moment.”

As most of the United States has been under stay-at-home orders, our traditional relationships have been radically disrupted. New types of relationships are forming as we are relying even more on technology to connect us. Social media seems to be on the only “social” we can now safely engage in.

The coalition’s campaign, “#howareyoureally?” is harnessing the power of social media and creating a storytelling platform to allow users to more genuinely share their feelings in these unprecedented times. Celebrities include Whoopi Goldberg, Kendall Jenner, Chris Cuomo, Deepak Chopra, Kesha, and many more have already shared their stories.

“How Are You, Really?” challenges people to answer this question using social media in an open and honest fashion while still providing hope.

The second component of the initiative is to increase access to care, and they have a long list of collaborators, including leading mental health organizations such as the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, Child Mind Institute, Depression and Bipolar Support Alliance, Didi Hirsch Mental Health Services, National Alliance on Mental Illness, and many more.

We have a unique opportunity this Mental Health Awareness Month, and I hope we will see more and more people sharing their stories and reaching out for help. As a community, we must be prepared to meet the escalating needs of our population.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018) and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

We are months into the COVID-19 crisis, and mental health issues are proving to be rampant. In every crisis, there is opportunity, and this one is no different. The opportunity is clear. For Mental Health Awareness Month and beyond, we must convey a powerful message that mental health is key to our well-being and must be actively addressed. Because almost everyone has felt excess anxiety these last months, we have a unique chance to engage a wider audience.

To address the urgent need, the Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. Spearheaded by social activist and fashion designer, Kenneth Cole, it is a coalition of leading mental health organizations, brands, celebrities, and advocates who have joined forces to end the stigma surrounding mental health and to change the way people talk about, and care for, mental illness. The group’s mission listed on its website states: “We must increase the conversation around mental health. We must act to end silence, reduce stigma, and engage our community to inspire hope at this essential moment.”

As most of the United States has been under stay-at-home orders, our traditional relationships have been radically disrupted. New types of relationships are forming as we are relying even more on technology to connect us. Social media seems to be on the only “social” we can now safely engage in.

The coalition’s campaign, “#howareyoureally?” is harnessing the power of social media and creating a storytelling platform to allow users to more genuinely share their feelings in these unprecedented times. Celebrities include Whoopi Goldberg, Kendall Jenner, Chris Cuomo, Deepak Chopra, Kesha, and many more have already shared their stories.

“How Are You, Really?” challenges people to answer this question using social media in an open and honest fashion while still providing hope.

The second component of the initiative is to increase access to care, and they have a long list of collaborators, including leading mental health organizations such as the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, Child Mind Institute, Depression and Bipolar Support Alliance, Didi Hirsch Mental Health Services, National Alliance on Mental Illness, and many more.

We have a unique opportunity this Mental Health Awareness Month, and I hope we will see more and more people sharing their stories and reaching out for help. As a community, we must be prepared to meet the escalating needs of our population.
 

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach, Fla. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018) and is the founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world. Dr. Ritvo also is the cofounder of the Bold Beauty Project, a nonprofit group that pairs women with disabilities with photographers who create art exhibitions to raise awareness.

On April 3, the Centers for Disease Control and Prevention issued an advisory that the general public wear cloth face masks when outside, particularly those residing in areas with significant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) community transmission.¹ Recent research reveals several factors related to the nature of the virus as well as the epidemiologic spread of the illness that may have led to this decision.

However, controversy still prevails whether this recommendation will alleviate or aggravate disease progression. With many hospitals across America lacking sufficient personal protective equipment (PPE) and scrambling for supplies, universal masking may create more chaos, especially with certain states imposing monetary fines on individuals spotted outdoors without a mask. With new information being discovered each day about COVID-19, it is more imperative than ever to update existing strategies and formulate more effective methods to flatten the curve.
 

Airborne vs. droplet transmission

According to a scientific brief released by the World Health Organization, there have been studies with mixed evidence and opinions regarding the presence of COVID-19 ribonucleic acid (RNA) in air samples.² In medRxiv, Santarpia et al., from the University of Nebraska Medical Center, Omaha, detected viral RNA in samples taken from beneath a patient’s bed and from a window ledge, both areas in which neither the patient nor health care personnel had any direct contact. They also found that 66.7% of air samples taken from a hospital hallway carried virus-containing particles.³ It is worth noting that certain aerosol-generating procedures (AGP) may increase the likelihood of airborne dissemination. Whether airborne transmission is a major mode of COVID-19 spread in the community and routine clinical settings (with no aerosol-generating procedures) is still a debatable question without a definitive answer.

We should consider the epidemiology of COVID-19 thus far in the pandemic to determine if transmission patterns are more consistent with that of other common respiratory viral pathogens or more consistent with that of the agents we classically consider to be transmitted by the airborne route (measles, varicella zoster virus, and Mycobacterium tuberculosis). The attack rates in various settings (household, health care, and the public) as well as the expected number of secondary cases from a single infected individual in a susceptible population (R0) are more consistent with those of a droplet spread pathogen.

For measles, the R0 is 12-18, and the secondary household attack rates are ≥ 90%. In case of the varicella zoster virus, the R0 is ~10, and the secondary household attack rate is 85%. The R0 for pulmonary tuberculosis is up to 10 (per year) and the secondary household attack rate has been reported to be >50%. With COVID-19, the R0 appears to be around 2.5-3 and secondary household attack rates are ~ 10% from data available so far, similar to that of influenza viruses. This discrepancy suggests that droplet transmission may be more likely. The dichotomy of airborne versus droplet mode of spread may be better described as a continuum, as pointed out in a recent article in the JAMA. Infectious droplets form turbulent gas clouds allowing the virus particles to travel further and remain in the air longer.⁴ The necessary precautions for an airborne illness should be chosen over droplet precautions, especially when there is concern for an AGP.
 

Universal masking: Risks and benefits

The idea of universal masking has been debated extensively since the initial stages of the COVID-19 pandemic. According to public health authorities, significant exposure is defined as “face-to-face contact within 6 feet with a patient with symptomatic COVID-19” in the range of a few minutes up to 30 minutes.⁵ The researchers wrote in the New England Journal of Medicine that the chance of catching COVID-19 from a passing interaction in a public space is therefore minimal, and it may seem unnecessary to wear a mask at all times in public.

As reported in Science, randomized clinical studies performed on other viruses in the past have shown no added protection conferred by wearing a mask, though small sample sizes and noncompliance are limiting factors to their validity.⁶ On the contrary, mask wearing has been enforced in many parts of Asia, including Hong Kong and Singapore with promising results.⁵ Leung et al. stated in The Lancet that the lack of proof that masks are effective should not rule them as ineffective. Also, universal masking would reduce the stigma around symptomatic individuals covering their faces. It has become a cultural phenomenon in many southeast Asian countries and has been cited as one of the reasons for relatively successful containment in Singapore, South Korea, and Taiwan. The most important benefit of universal masking is protection attained by preventing spread from asymptomatic, mildly symptomatic, and presymptomatic carriers.⁷

In a study in the New England Journal of Medicine that estimated viral loads during various stages of COVID-19, researchers found that asymptomatic patients had similar viral loads to symptomatic patients, thereby suggesting high potential for transmission.⁸ Furthermore, numerous cases are being reported concerning the spread of illness from asymptomatic carriers.^9-12 In an outbreak at a skilled nursing facility in Washington outlined in MMWR, 13 of 23 residents with positive test results were asymptomatic at the time of testing, and of those, 3 never developed any symptoms.¹²

Many hospitals are now embracing the policy of universal masking. A mask is a critical component of the personal protective equipment (PPE) clinicians need when caring for symptomatic patients with respiratory viral infections, in conjunction with a gown, gloves, and eye protection. Masking in this context is already part of routine operations in most hospitals. There are two scenarios in which there may be possible benefits. One scenario is the lower likelihood of transmission from asymptomatic and minimally symptomatic health care workers with COVID-19 to other providers and patients. The other less plausible benefit of universal masking among health care workers is that it may provide some protection in the possibility of caring for an unrecognized COVID-19 patient. However, universal masking should be coupled with other favorable practices like temperature checks and symptom screening on a daily basis to avail the maximum benefit from masking. Despite varied opinions on the outcomes of universal masking, this measure helps improve health care workers’ safety, psychological well-being, trust in their hospital, and decreases anxiety of acquiring the illness.
 

Efficacy of various types of masks

With the possibility of airborne transmission of the virus, are cloth masks as recommended by the CDC truly helpful in preventing infection? A study in the Journal of Medical Virology demonstrates 99.98%, 97.14%, and 95.15% efficacy for N95, surgical, and homemade masks, respectively, in blocking the avian influenza virus (comparable to coronavirus in size and physical characteristics). The homemade mask was created using one layer of polyester cloth and a four-layered kitchen filter paper.¹³

N95 masks (equivalent to FFP/P2 in European countries) are made of electrostatically charged polypropylene microfibers designed to filter particles measuring 100-300nm in diameter with 95% efficacy. A single SARS-CoV-2 molecule measures 125 nm approximately. N99 (FFP3) and N100 (P3) masks are also available, though not as widely used, with 99% and 99.7% efficacy respectively for the same size range. Though cloth masks are the clear-cut last resort for medical professionals, a few studies state no clinically proven difference in protection between surgical masks and N95 respirators.^14,15 Even aerosolized droplets (< 5 mcm) were found to be blocked by surgical masks in a Nature Medicine study in which 4/10 subjects tested positive for coronavirus in exhaled breath samples without masks and 0/10 subjects with masks.¹⁶

On the contrary, an Annals of Internal Medicine study of four COVID-19 positive subjects that “neither surgical masks nor cloth masks effectively filtered SARS-CoV-2 during coughs of infected patients.” In fact, more contamination was found on the outer surface of the masks when compared to the inner surface, probably owing to the masks’ aerodynamic properties.¹⁷ Because of limitations present in the above-mentioned studies, further research is necessary to conclusively determine which types of masks are efficacious in preventing infection by the virus. In a scarcity of surgical masks and respirators for health care personnel, suboptimal masks can be of some use provided there is adherent use, minimal donning and doffing, and it is to be accompanied by adequate hand washing practices.¹⁴

In case of severe infections with high viral loads or patients undergoing aerosol-generating procedures, powered air-purifying respirators (PAPRs) also are advisable as they confer greater protection than N95 respirators, according to a study in the Annals of Work Exposures and Health. Despite being more comfortable for long-term use and accommodative of facial hair, their use is limited because of high cost and difficult maintenance.¹⁸ 3-D printing also is being used to combat the current shortage of masks worldwide. However, a study from the International Journal of Oral & Maxillofacial Surgery reported that virologic testing for leakage between the two reusable components and contamination of the components themselves after one or multiple disinfection cycles is essential before application in real-life situations.¹⁹

Ongoing issues

WHO estimates a monthly requirement of nearly 90 million masks exclusively for health care workers to protect themselves against COVID-19.²⁰ In spite of increasing the production rate by 40%, if the general public hoards masks and respirators, the results could be disastrous. Personal protective equipment is currently at 100 times the usual demand and 20 times the usual cost, with stocks backlogged by 4-6 months. The appropriate order of priority in distribution to health care professionals first, followed by those caring for infected patients is critical.²⁰ In a survey conducted by the Association for Professionals in Infection Control and Epidemiology, results revealed that 48% of the U.S. health care facilities that responded were either out or nearly out of respirators as of March 25. ²¹

The gravest risk behind the universal masking policy is the likely depletion of medical resources.²² A possible solution to this issue could be to modify the policy to stagger the requirement based on the severity of community transmission in that area of residence. In the article appropriately titled “Rational use of face masks in the COVID-19 pandemic” published in The Lancet Respiratory Medicine, researchers described how the Chinese population was classified into moderate, low, and very-low risk of infection categories and advised to wear a surgical or disposable mask, disposable mask, and no mask respectively.²³ This curbs widespread panic and eagerness by the general public to stock up on essential medical equipment when it may not even be necessary.
 

Reuse, extended use, and sterilization

Several studies have been conducted to identify the viability of the COVID-19 on various surfaces.^24-25 The CDC and National Institute for Occupational Safety and Health (NIOSH) guidelines state that an N95 respirator can be used up to 8 hours with intermittent or continuous use, though this number is not fixed and heavily depends upon the extent of exposure, risk of contamination, and frequency of donning and doffing^26,27. Though traditionally meant for single-time usage, after 8 hours, the mask can be decontaminated and reused. The CDC defines extended use as the “practice of wearing the same N95 respirator for repeated close-contact encounters with several patients, without removing the respirator between patient encounters.” Reuse is defined as “using the same N95 respirator for multiple encounters with patients but removing it (‘doffing’) after each encounter. The respirator is stored in between encounters to be put on again (‘donned’) prior to the next encounter with a patient.”

It has been established that extended use is more advisable than reuse given the lower risk of self-inoculation. Furthermore, health care professionals are urged to wear a cleanable face shield or disposable mask over the respirator to minimize contamination and practice diligent hand hygiene before and after handling the respirator. N95 respirators are to be discarded following aerosol-generating procedures or if they come in contact with blood, respiratory secretions, or bodily fluids. They should also be discarded in case of close contact with an infected patient or if they cause breathing difficulties to the wearer.²⁷ This may not always be possible given the unprecedented shortage of PPE, hence decontamination techniques and repurposing are the need of the hour.

In Anesthesia & Analgesia, Naveen Nathan, MD, of Northwestern University, Chicago, recommends recycling four masks in a series, using one per day, keeping the mask in a dry, clean environment, and then repeating use of the first mask on the 5th day, the second on the 6th day, and so forth. This ensures clearance of the virus particles by the next use. Alternatively, respirators can be sterilized between uses by heating to 70º C (158º F) for 30 minutes. Liquid disinfectants such as alcohol and bleach as well as ultraviolet rays in sunlight tend to damage masks.²⁸ Steam sterilization is the most commonly utilized technique in hospitals. Other methods, described by the N95/PPE Working Group, report include gamma irradiation at 20kGy (2MRad) for large-scale sterilization (though the facilities may not be widely available), vaporized hydrogen peroxide, ozone decontamination, ultraviolet germicidal irradiation, and ethylene oxide.²⁹ Though a discussion on various considerations of decontamination techniques is out of the scope of this article, detailed guidelines have been published by the CDC30 and the COVID-19 Healthcare Coalition.³⁰

Conclusion

A recent startling discovery reported on in Emerging Infectious Diseases suggests that the basic COVID-19 reproductive number (R0) is actually much higher than previously thought. Using expanded data, updated epidemiologic parameters, and the current outbreak dynamics in Wuhan, the team came to the conclusion that the R0 for the novel coronavirus is actually 5.7 (95% CI 3.8-8.9), compared with an initial estimate of 2.2-2.7.³¹ Concern for transmissibility demands heightened prevention strategies until more data evolves. The latest recommendation by the CDC regarding cloth masking in the public may help slow the progression of the pandemic. However, it is of paramount importance to keep in mind that masks alone are not enough to control the disease and must be coupled with other nonpharmacologic interventions such as social distancing, quarantining/isolation, and diligent hand hygiene.

Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Bharathidasan is a recent medical graduate from India with an interest in public health and community research; she plans to pursue residency training in the United States. Ms. Freshman is currently the regional director of infection prevention for WellSpan Health and has 35 years of experience in nursing. Dr. Palabindala is the medical director, utilization management and physician advisory services, at the University of Mississippi Medical Center, Jackson. He is an associate professor of medicine and academic hospitalist in the UMMC School of Medicine.

References

1. Centers for Disease Control and Prevention. Recommendation regarding the use of cloth face coverings.

2. World Health Organization. Modes of transmission of virus causing COVID-19 : implications for IPC precaution recommendations. Sci Br. 2020 Mar 29:1-3.

3. Santarpia JL et al. Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center. 2020 Mar 26. medRxiv. 2020;2020.03.23.20039446.

4. Bourouiba L. Turbulent gas clouds and respiratory pathogen emissions: Potential implications for reducing transmission of COVID-19. JAMA. 2020 Mar 26. doi: 10.1001/jama.2020.4756.

5. Klompas M et al. Universal masking in hospitals in the Covid-19 era. N Engl J Med. 2020 Apr 1. doi: 10.1056/NEJMp2006372.

6. Servick K. Would everyone wearing face masks help us slow the pandemic? Science 2020 Mar 28. doi: 10.1126/science.abb9371.

7. Leung CC et al. Mass masking in the COVID-19 epidemic: People need guidance. Lancet 2020 Mar 21;395(10228):945. doi: 10.1016/S0140-6736(20)30520-1.

8. Zou L et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020 Mar 19;382(12):1177-9.

9. Pan X et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection. Lancet Infect Dis. 2020 Apr;20(4):410-1.

10. Bai Y et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020 Feb 21;323(14):1406-7.

11. Wei WE et al. Presymptomatic transmission of SARS-CoV-2 – Singapore, Jan. 23–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020;69:411-5.

12. Kimball A et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility – King County, Washington, March 2020. 2020 Apr 3. MMWR Morb Mortal Wkly Rep 2020;69:377-81.

13. Ma Q-X et al. Potential utilities of mask wearing and instant hand hygiene for fighting SARS-CoV-2. J Med Virol. 2020 Mar 31;10.1002/jmv.25805. doi: 10.1002/jmv.25805.

14. Abd-Elsayed A et al. Utility of substandard face mask options for health care workers during the COVID-19 pandemic. Anesth Analg. 2020 Mar 31;10.1213/ANE.0000000000004841. doi: 10.1213/ANE.0000000000004841.

15. Long Y et al. Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis. J Evid Based Med. 2020 Mar 13;10.1111/jebm.12381. doi: 10.1111/jebm.12381.

16. Leung NHL et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med. 2020 May;26(5):676-80.

17. Bae S et al. Effectiveness of surgical and cotton masks in blocking SARS-CoV-2: A controlled comparison in 4 patients. Ann Intern Med. 2020 Apr 6;M20-1342. doi: 10.7326/M20-1342.

18. Brosseau LM. Are powered air purifying respirators a solution for protecting healthcare workers from emerging aerosol-transmissible diseases? Ann Work Expo Health. 2020 Apr 30;64(4):339-41.

19. Swennen GRJ et al. Custom-made 3D-printed face masks in case of pandemic crisis situations with a lack of commercially available FFP2/3 masks. Int J Oral Maxillofac Surg. 2020 May;49(5):673-7.

20. Mahase E. Coronavirus: Global stocks of protective gear are depleted, with demand at “100 times” normal level, WHO warns. BMJ. 2020 Feb 10;368:m543. doi: 10.1136/bmj.m543.

21. National survey shows dire shortages of PPE, hand sanitizer across the U.S. 2020 Mar 27. Association for Professionals in Infection Control and Epidemiology (APIC) press briefing.

22. Wu HL et al. Facemask shortage and the novel coronavirus disease (COVID-19) outbreak: Reflections on public health measures. EClinicalMedicine. 2020 Apr 3:100329. doi: 10.1016/j.eclinm.2020.100329.

23. Feng S et al. Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med. 2020 May;8(5):434-6.

24. Chin AWH et al. Stability of SARS-CoV-2 in different environmental. The Lancet Microbe. 2020 May 1;5247(20):2004973. doi. org/10.1016/S2666-5247(20)30003-3.

25. van Doremalen N et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020 Apr 16;382(16):1564-7.

26. NIOSH – Workplace Safety and Health Topics: Recommended guidance for extended use and limited reuse of n95 filtering facepiece respirators in healthcare settings.

27. Centers for Disease Control and Prevention. COVID-19 decontamination and reuse of filtering facepiece respirators. 2020 Apr 15.

28. Nathan N. Waste not, want not: The re-usability of N95 masks. Anesth Analg. 2020 Mar 31.doi: 10.1213/ane.0000000000004843.

29. European Centre for Disease Prevention and Control technical report. Cloth masks and mask sterilisation as options in case of shortage of surgical masks and respirators. 2020 Mar. 

30. N95/PPE Working Group report. Evaluation of decontamination techniques for the reuse of N95 respirators. 2020 Apr 3;2:1-7.

31. Sanche Set al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020 Jul. doi. org/10.3201/eid2607.200282.

On April 3, the Centers for Disease Control and Prevention issued an advisory that the general public wear cloth face masks when outside, particularly those residing in areas with significant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) community transmission.¹ Recent research reveals several factors related to the nature of the virus as well as the epidemiologic spread of the illness that may have led to this decision.

However, controversy still prevails whether this recommendation will alleviate or aggravate disease progression. With many hospitals across America lacking sufficient personal protective equipment (PPE) and scrambling for supplies, universal masking may create more chaos, especially with certain states imposing monetary fines on individuals spotted outdoors without a mask. With new information being discovered each day about COVID-19, it is more imperative than ever to update existing strategies and formulate more effective methods to flatten the curve.
 

Airborne vs. droplet transmission

According to a scientific brief released by the World Health Organization, there have been studies with mixed evidence and opinions regarding the presence of COVID-19 ribonucleic acid (RNA) in air samples.² In medRxiv, Santarpia et al., from the University of Nebraska Medical Center, Omaha, detected viral RNA in samples taken from beneath a patient’s bed and from a window ledge, both areas in which neither the patient nor health care personnel had any direct contact. They also found that 66.7% of air samples taken from a hospital hallway carried virus-containing particles.³ It is worth noting that certain aerosol-generating procedures (AGP) may increase the likelihood of airborne dissemination. Whether airborne transmission is a major mode of COVID-19 spread in the community and routine clinical settings (with no aerosol-generating procedures) is still a debatable question without a definitive answer.

We should consider the epidemiology of COVID-19 thus far in the pandemic to determine if transmission patterns are more consistent with that of other common respiratory viral pathogens or more consistent with that of the agents we classically consider to be transmitted by the airborne route (measles, varicella zoster virus, and Mycobacterium tuberculosis). The attack rates in various settings (household, health care, and the public) as well as the expected number of secondary cases from a single infected individual in a susceptible population (R0) are more consistent with those of a droplet spread pathogen.

For measles, the R0 is 12-18, and the secondary household attack rates are ≥ 90%. In case of the varicella zoster virus, the R0 is ~10, and the secondary household attack rate is 85%. The R0 for pulmonary tuberculosis is up to 10 (per year) and the secondary household attack rate has been reported to be >50%. With COVID-19, the R0 appears to be around 2.5-3 and secondary household attack rates are ~ 10% from data available so far, similar to that of influenza viruses. This discrepancy suggests that droplet transmission may be more likely. The dichotomy of airborne versus droplet mode of spread may be better described as a continuum, as pointed out in a recent article in the JAMA. Infectious droplets form turbulent gas clouds allowing the virus particles to travel further and remain in the air longer.⁴ The necessary precautions for an airborne illness should be chosen over droplet precautions, especially when there is concern for an AGP.
 

Universal masking: Risks and benefits

The idea of universal masking has been debated extensively since the initial stages of the COVID-19 pandemic. According to public health authorities, significant exposure is defined as “face-to-face contact within 6 feet with a patient with symptomatic COVID-19” in the range of a few minutes up to 30 minutes.⁵ The researchers wrote in the New England Journal of Medicine that the chance of catching COVID-19 from a passing interaction in a public space is therefore minimal, and it may seem unnecessary to wear a mask at all times in public.

As reported in Science, randomized clinical studies performed on other viruses in the past have shown no added protection conferred by wearing a mask, though small sample sizes and noncompliance are limiting factors to their validity.⁶ On the contrary, mask wearing has been enforced in many parts of Asia, including Hong Kong and Singapore with promising results.⁵ Leung et al. stated in The Lancet that the lack of proof that masks are effective should not rule them as ineffective. Also, universal masking would reduce the stigma around symptomatic individuals covering their faces. It has become a cultural phenomenon in many southeast Asian countries and has been cited as one of the reasons for relatively successful containment in Singapore, South Korea, and Taiwan. The most important benefit of universal masking is protection attained by preventing spread from asymptomatic, mildly symptomatic, and presymptomatic carriers.⁷

In a study in the New England Journal of Medicine that estimated viral loads during various stages of COVID-19, researchers found that asymptomatic patients had similar viral loads to symptomatic patients, thereby suggesting high potential for transmission.⁸ Furthermore, numerous cases are being reported concerning the spread of illness from asymptomatic carriers.^9-12 In an outbreak at a skilled nursing facility in Washington outlined in MMWR, 13 of 23 residents with positive test results were asymptomatic at the time of testing, and of those, 3 never developed any symptoms.¹²

Many hospitals are now embracing the policy of universal masking. A mask is a critical component of the personal protective equipment (PPE) clinicians need when caring for symptomatic patients with respiratory viral infections, in conjunction with a gown, gloves, and eye protection. Masking in this context is already part of routine operations in most hospitals. There are two scenarios in which there may be possible benefits. One scenario is the lower likelihood of transmission from asymptomatic and minimally symptomatic health care workers with COVID-19 to other providers and patients. The other less plausible benefit of universal masking among health care workers is that it may provide some protection in the possibility of caring for an unrecognized COVID-19 patient. However, universal masking should be coupled with other favorable practices like temperature checks and symptom screening on a daily basis to avail the maximum benefit from masking. Despite varied opinions on the outcomes of universal masking, this measure helps improve health care workers’ safety, psychological well-being, trust in their hospital, and decreases anxiety of acquiring the illness.
 

Efficacy of various types of masks

With the possibility of airborne transmission of the virus, are cloth masks as recommended by the CDC truly helpful in preventing infection? A study in the Journal of Medical Virology demonstrates 99.98%, 97.14%, and 95.15% efficacy for N95, surgical, and homemade masks, respectively, in blocking the avian influenza virus (comparable to coronavirus in size and physical characteristics). The homemade mask was created using one layer of polyester cloth and a four-layered kitchen filter paper.¹³

N95 masks (equivalent to FFP/P2 in European countries) are made of electrostatically charged polypropylene microfibers designed to filter particles measuring 100-300nm in diameter with 95% efficacy. A single SARS-CoV-2 molecule measures 125 nm approximately. N99 (FFP3) and N100 (P3) masks are also available, though not as widely used, with 99% and 99.7% efficacy respectively for the same size range. Though cloth masks are the clear-cut last resort for medical professionals, a few studies state no clinically proven difference in protection between surgical masks and N95 respirators.^14,15 Even aerosolized droplets (< 5 mcm) were found to be blocked by surgical masks in a Nature Medicine study in which 4/10 subjects tested positive for coronavirus in exhaled breath samples without masks and 0/10 subjects with masks.¹⁶

On the contrary, an Annals of Internal Medicine study of four COVID-19 positive subjects that “neither surgical masks nor cloth masks effectively filtered SARS-CoV-2 during coughs of infected patients.” In fact, more contamination was found on the outer surface of the masks when compared to the inner surface, probably owing to the masks’ aerodynamic properties.¹⁷ Because of limitations present in the above-mentioned studies, further research is necessary to conclusively determine which types of masks are efficacious in preventing infection by the virus. In a scarcity of surgical masks and respirators for health care personnel, suboptimal masks can be of some use provided there is adherent use, minimal donning and doffing, and it is to be accompanied by adequate hand washing practices.¹⁴

In case of severe infections with high viral loads or patients undergoing aerosol-generating procedures, powered air-purifying respirators (PAPRs) also are advisable as they confer greater protection than N95 respirators, according to a study in the Annals of Work Exposures and Health. Despite being more comfortable for long-term use and accommodative of facial hair, their use is limited because of high cost and difficult maintenance.¹⁸ 3-D printing also is being used to combat the current shortage of masks worldwide. However, a study from the International Journal of Oral & Maxillofacial Surgery reported that virologic testing for leakage between the two reusable components and contamination of the components themselves after one or multiple disinfection cycles is essential before application in real-life situations.¹⁹

Ongoing issues

WHO estimates a monthly requirement of nearly 90 million masks exclusively for health care workers to protect themselves against COVID-19.²⁰ In spite of increasing the production rate by 40%, if the general public hoards masks and respirators, the results could be disastrous. Personal protective equipment is currently at 100 times the usual demand and 20 times the usual cost, with stocks backlogged by 4-6 months. The appropriate order of priority in distribution to health care professionals first, followed by those caring for infected patients is critical.²⁰ In a survey conducted by the Association for Professionals in Infection Control and Epidemiology, results revealed that 48% of the U.S. health care facilities that responded were either out or nearly out of respirators as of March 25. ²¹

The gravest risk behind the universal masking policy is the likely depletion of medical resources.²² A possible solution to this issue could be to modify the policy to stagger the requirement based on the severity of community transmission in that area of residence. In the article appropriately titled “Rational use of face masks in the COVID-19 pandemic” published in The Lancet Respiratory Medicine, researchers described how the Chinese population was classified into moderate, low, and very-low risk of infection categories and advised to wear a surgical or disposable mask, disposable mask, and no mask respectively.²³ This curbs widespread panic and eagerness by the general public to stock up on essential medical equipment when it may not even be necessary.
 

Reuse, extended use, and sterilization

Several studies have been conducted to identify the viability of the COVID-19 on various surfaces.^24-25 The CDC and National Institute for Occupational Safety and Health (NIOSH) guidelines state that an N95 respirator can be used up to 8 hours with intermittent or continuous use, though this number is not fixed and heavily depends upon the extent of exposure, risk of contamination, and frequency of donning and doffing^26,27. Though traditionally meant for single-time usage, after 8 hours, the mask can be decontaminated and reused. The CDC defines extended use as the “practice of wearing the same N95 respirator for repeated close-contact encounters with several patients, without removing the respirator between patient encounters.” Reuse is defined as “using the same N95 respirator for multiple encounters with patients but removing it (‘doffing’) after each encounter. The respirator is stored in between encounters to be put on again (‘donned’) prior to the next encounter with a patient.”

It has been established that extended use is more advisable than reuse given the lower risk of self-inoculation. Furthermore, health care professionals are urged to wear a cleanable face shield or disposable mask over the respirator to minimize contamination and practice diligent hand hygiene before and after handling the respirator. N95 respirators are to be discarded following aerosol-generating procedures or if they come in contact with blood, respiratory secretions, or bodily fluids. They should also be discarded in case of close contact with an infected patient or if they cause breathing difficulties to the wearer.²⁷ This may not always be possible given the unprecedented shortage of PPE, hence decontamination techniques and repurposing are the need of the hour.

In Anesthesia & Analgesia, Naveen Nathan, MD, of Northwestern University, Chicago, recommends recycling four masks in a series, using one per day, keeping the mask in a dry, clean environment, and then repeating use of the first mask on the 5th day, the second on the 6th day, and so forth. This ensures clearance of the virus particles by the next use. Alternatively, respirators can be sterilized between uses by heating to 70º C (158º F) for 30 minutes. Liquid disinfectants such as alcohol and bleach as well as ultraviolet rays in sunlight tend to damage masks.²⁸ Steam sterilization is the most commonly utilized technique in hospitals. Other methods, described by the N95/PPE Working Group, report include gamma irradiation at 20kGy (2MRad) for large-scale sterilization (though the facilities may not be widely available), vaporized hydrogen peroxide, ozone decontamination, ultraviolet germicidal irradiation, and ethylene oxide.²⁹ Though a discussion on various considerations of decontamination techniques is out of the scope of this article, detailed guidelines have been published by the CDC30 and the COVID-19 Healthcare Coalition.³⁰

Conclusion

A recent startling discovery reported on in Emerging Infectious Diseases suggests that the basic COVID-19 reproductive number (R0) is actually much higher than previously thought. Using expanded data, updated epidemiologic parameters, and the current outbreak dynamics in Wuhan, the team came to the conclusion that the R0 for the novel coronavirus is actually 5.7 (95% CI 3.8-8.9), compared with an initial estimate of 2.2-2.7.³¹ Concern for transmissibility demands heightened prevention strategies until more data evolves. The latest recommendation by the CDC regarding cloth masking in the public may help slow the progression of the pandemic. However, it is of paramount importance to keep in mind that masks alone are not enough to control the disease and must be coupled with other nonpharmacologic interventions such as social distancing, quarantining/isolation, and diligent hand hygiene.

Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Bharathidasan is a recent medical graduate from India with an interest in public health and community research; she plans to pursue residency training in the United States. Ms. Freshman is currently the regional director of infection prevention for WellSpan Health and has 35 years of experience in nursing. Dr. Palabindala is the medical director, utilization management and physician advisory services, at the University of Mississippi Medical Center, Jackson. He is an associate professor of medicine and academic hospitalist in the UMMC School of Medicine.

References

1. Centers for Disease Control and Prevention. Recommendation regarding the use of cloth face coverings.

2. World Health Organization. Modes of transmission of virus causing COVID-19 : implications for IPC precaution recommendations. Sci Br. 2020 Mar 29:1-3.

3. Santarpia JL et al. Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center. 2020 Mar 26. medRxiv. 2020;2020.03.23.20039446.

4. Bourouiba L. Turbulent gas clouds and respiratory pathogen emissions: Potential implications for reducing transmission of COVID-19. JAMA. 2020 Mar 26. doi: 10.1001/jama.2020.4756.

5. Klompas M et al. Universal masking in hospitals in the Covid-19 era. N Engl J Med. 2020 Apr 1. doi: 10.1056/NEJMp2006372.

6. Servick K. Would everyone wearing face masks help us slow the pandemic? Science 2020 Mar 28. doi: 10.1126/science.abb9371.

7. Leung CC et al. Mass masking in the COVID-19 epidemic: People need guidance. Lancet 2020 Mar 21;395(10228):945. doi: 10.1016/S0140-6736(20)30520-1.

8. Zou L et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020 Mar 19;382(12):1177-9.

9. Pan X et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection. Lancet Infect Dis. 2020 Apr;20(4):410-1.

10. Bai Y et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020 Feb 21;323(14):1406-7.

11. Wei WE et al. Presymptomatic transmission of SARS-CoV-2 – Singapore, Jan. 23–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020;69:411-5.

12. Kimball A et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility – King County, Washington, March 2020. 2020 Apr 3. MMWR Morb Mortal Wkly Rep 2020;69:377-81.

13. Ma Q-X et al. Potential utilities of mask wearing and instant hand hygiene for fighting SARS-CoV-2. J Med Virol. 2020 Mar 31;10.1002/jmv.25805. doi: 10.1002/jmv.25805.

14. Abd-Elsayed A et al. Utility of substandard face mask options for health care workers during the COVID-19 pandemic. Anesth Analg. 2020 Mar 31;10.1213/ANE.0000000000004841. doi: 10.1213/ANE.0000000000004841.

15. Long Y et al. Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis. J Evid Based Med. 2020 Mar 13;10.1111/jebm.12381. doi: 10.1111/jebm.12381.

16. Leung NHL et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med. 2020 May;26(5):676-80.

17. Bae S et al. Effectiveness of surgical and cotton masks in blocking SARS-CoV-2: A controlled comparison in 4 patients. Ann Intern Med. 2020 Apr 6;M20-1342. doi: 10.7326/M20-1342.

18. Brosseau LM. Are powered air purifying respirators a solution for protecting healthcare workers from emerging aerosol-transmissible diseases? Ann Work Expo Health. 2020 Apr 30;64(4):339-41.

19. Swennen GRJ et al. Custom-made 3D-printed face masks in case of pandemic crisis situations with a lack of commercially available FFP2/3 masks. Int J Oral Maxillofac Surg. 2020 May;49(5):673-7.

20. Mahase E. Coronavirus: Global stocks of protective gear are depleted, with demand at “100 times” normal level, WHO warns. BMJ. 2020 Feb 10;368:m543. doi: 10.1136/bmj.m543.

21. National survey shows dire shortages of PPE, hand sanitizer across the U.S. 2020 Mar 27. Association for Professionals in Infection Control and Epidemiology (APIC) press briefing.

22. Wu HL et al. Facemask shortage and the novel coronavirus disease (COVID-19) outbreak: Reflections on public health measures. EClinicalMedicine. 2020 Apr 3:100329. doi: 10.1016/j.eclinm.2020.100329.

23. Feng S et al. Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med. 2020 May;8(5):434-6.

24. Chin AWH et al. Stability of SARS-CoV-2 in different environmental. The Lancet Microbe. 2020 May 1;5247(20):2004973. doi. org/10.1016/S2666-5247(20)30003-3.

25. van Doremalen N et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020 Apr 16;382(16):1564-7.

26. NIOSH – Workplace Safety and Health Topics: Recommended guidance for extended use and limited reuse of n95 filtering facepiece respirators in healthcare settings.

27. Centers for Disease Control and Prevention. COVID-19 decontamination and reuse of filtering facepiece respirators. 2020 Apr 15.

28. Nathan N. Waste not, want not: The re-usability of N95 masks. Anesth Analg. 2020 Mar 31.doi: 10.1213/ane.0000000000004843.

29. European Centre for Disease Prevention and Control technical report. Cloth masks and mask sterilisation as options in case of shortage of surgical masks and respirators. 2020 Mar. 

30. N95/PPE Working Group report. Evaluation of decontamination techniques for the reuse of N95 respirators. 2020 Apr 3;2:1-7.

31. Sanche Set al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020 Jul. doi. org/10.3201/eid2607.200282.

On April 3, the Centers for Disease Control and Prevention issued an advisory that the general public wear cloth face masks when outside, particularly those residing in areas with significant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) community transmission.¹ Recent research reveals several factors related to the nature of the virus as well as the epidemiologic spread of the illness that may have led to this decision.

However, controversy still prevails whether this recommendation will alleviate or aggravate disease progression. With many hospitals across America lacking sufficient personal protective equipment (PPE) and scrambling for supplies, universal masking may create more chaos, especially with certain states imposing monetary fines on individuals spotted outdoors without a mask. With new information being discovered each day about COVID-19, it is more imperative than ever to update existing strategies and formulate more effective methods to flatten the curve.
 

Airborne vs. droplet transmission

According to a scientific brief released by the World Health Organization, there have been studies with mixed evidence and opinions regarding the presence of COVID-19 ribonucleic acid (RNA) in air samples.² In medRxiv, Santarpia et al., from the University of Nebraska Medical Center, Omaha, detected viral RNA in samples taken from beneath a patient’s bed and from a window ledge, both areas in which neither the patient nor health care personnel had any direct contact. They also found that 66.7% of air samples taken from a hospital hallway carried virus-containing particles.³ It is worth noting that certain aerosol-generating procedures (AGP) may increase the likelihood of airborne dissemination. Whether airborne transmission is a major mode of COVID-19 spread in the community and routine clinical settings (with no aerosol-generating procedures) is still a debatable question without a definitive answer.

We should consider the epidemiology of COVID-19 thus far in the pandemic to determine if transmission patterns are more consistent with that of other common respiratory viral pathogens or more consistent with that of the agents we classically consider to be transmitted by the airborne route (measles, varicella zoster virus, and Mycobacterium tuberculosis). The attack rates in various settings (household, health care, and the public) as well as the expected number of secondary cases from a single infected individual in a susceptible population (R0) are more consistent with those of a droplet spread pathogen.

For measles, the R0 is 12-18, and the secondary household attack rates are ≥ 90%. In case of the varicella zoster virus, the R0 is ~10, and the secondary household attack rate is 85%. The R0 for pulmonary tuberculosis is up to 10 (per year) and the secondary household attack rate has been reported to be >50%. With COVID-19, the R0 appears to be around 2.5-3 and secondary household attack rates are ~ 10% from data available so far, similar to that of influenza viruses. This discrepancy suggests that droplet transmission may be more likely. The dichotomy of airborne versus droplet mode of spread may be better described as a continuum, as pointed out in a recent article in the JAMA. Infectious droplets form turbulent gas clouds allowing the virus particles to travel further and remain in the air longer.⁴ The necessary precautions for an airborne illness should be chosen over droplet precautions, especially when there is concern for an AGP.
 

Universal masking: Risks and benefits

The idea of universal masking has been debated extensively since the initial stages of the COVID-19 pandemic. According to public health authorities, significant exposure is defined as “face-to-face contact within 6 feet with a patient with symptomatic COVID-19” in the range of a few minutes up to 30 minutes.⁵ The researchers wrote in the New England Journal of Medicine that the chance of catching COVID-19 from a passing interaction in a public space is therefore minimal, and it may seem unnecessary to wear a mask at all times in public.

As reported in Science, randomized clinical studies performed on other viruses in the past have shown no added protection conferred by wearing a mask, though small sample sizes and noncompliance are limiting factors to their validity.⁶ On the contrary, mask wearing has been enforced in many parts of Asia, including Hong Kong and Singapore with promising results.⁵ Leung et al. stated in The Lancet that the lack of proof that masks are effective should not rule them as ineffective. Also, universal masking would reduce the stigma around symptomatic individuals covering their faces. It has become a cultural phenomenon in many southeast Asian countries and has been cited as one of the reasons for relatively successful containment in Singapore, South Korea, and Taiwan. The most important benefit of universal masking is protection attained by preventing spread from asymptomatic, mildly symptomatic, and presymptomatic carriers.⁷

In a study in the New England Journal of Medicine that estimated viral loads during various stages of COVID-19, researchers found that asymptomatic patients had similar viral loads to symptomatic patients, thereby suggesting high potential for transmission.⁸ Furthermore, numerous cases are being reported concerning the spread of illness from asymptomatic carriers.^9-12 In an outbreak at a skilled nursing facility in Washington outlined in MMWR, 13 of 23 residents with positive test results were asymptomatic at the time of testing, and of those, 3 never developed any symptoms.¹²

Many hospitals are now embracing the policy of universal masking. A mask is a critical component of the personal protective equipment (PPE) clinicians need when caring for symptomatic patients with respiratory viral infections, in conjunction with a gown, gloves, and eye protection. Masking in this context is already part of routine operations in most hospitals. There are two scenarios in which there may be possible benefits. One scenario is the lower likelihood of transmission from asymptomatic and minimally symptomatic health care workers with COVID-19 to other providers and patients. The other less plausible benefit of universal masking among health care workers is that it may provide some protection in the possibility of caring for an unrecognized COVID-19 patient. However, universal masking should be coupled with other favorable practices like temperature checks and symptom screening on a daily basis to avail the maximum benefit from masking. Despite varied opinions on the outcomes of universal masking, this measure helps improve health care workers’ safety, psychological well-being, trust in their hospital, and decreases anxiety of acquiring the illness.
 

Efficacy of various types of masks

With the possibility of airborne transmission of the virus, are cloth masks as recommended by the CDC truly helpful in preventing infection? A study in the Journal of Medical Virology demonstrates 99.98%, 97.14%, and 95.15% efficacy for N95, surgical, and homemade masks, respectively, in blocking the avian influenza virus (comparable to coronavirus in size and physical characteristics). The homemade mask was created using one layer of polyester cloth and a four-layered kitchen filter paper.¹³

N95 masks (equivalent to FFP/P2 in European countries) are made of electrostatically charged polypropylene microfibers designed to filter particles measuring 100-300nm in diameter with 95% efficacy. A single SARS-CoV-2 molecule measures 125 nm approximately. N99 (FFP3) and N100 (P3) masks are also available, though not as widely used, with 99% and 99.7% efficacy respectively for the same size range. Though cloth masks are the clear-cut last resort for medical professionals, a few studies state no clinically proven difference in protection between surgical masks and N95 respirators.^14,15 Even aerosolized droplets (< 5 mcm) were found to be blocked by surgical masks in a Nature Medicine study in which 4/10 subjects tested positive for coronavirus in exhaled breath samples without masks and 0/10 subjects with masks.¹⁶

On the contrary, an Annals of Internal Medicine study of four COVID-19 positive subjects that “neither surgical masks nor cloth masks effectively filtered SARS-CoV-2 during coughs of infected patients.” In fact, more contamination was found on the outer surface of the masks when compared to the inner surface, probably owing to the masks’ aerodynamic properties.¹⁷ Because of limitations present in the above-mentioned studies, further research is necessary to conclusively determine which types of masks are efficacious in preventing infection by the virus. In a scarcity of surgical masks and respirators for health care personnel, suboptimal masks can be of some use provided there is adherent use, minimal donning and doffing, and it is to be accompanied by adequate hand washing practices.¹⁴

In case of severe infections with high viral loads or patients undergoing aerosol-generating procedures, powered air-purifying respirators (PAPRs) also are advisable as they confer greater protection than N95 respirators, according to a study in the Annals of Work Exposures and Health. Despite being more comfortable for long-term use and accommodative of facial hair, their use is limited because of high cost and difficult maintenance.¹⁸ 3-D printing also is being used to combat the current shortage of masks worldwide. However, a study from the International Journal of Oral & Maxillofacial Surgery reported that virologic testing for leakage between the two reusable components and contamination of the components themselves after one or multiple disinfection cycles is essential before application in real-life situations.¹⁹

Ongoing issues

WHO estimates a monthly requirement of nearly 90 million masks exclusively for health care workers to protect themselves against COVID-19.²⁰ In spite of increasing the production rate by 40%, if the general public hoards masks and respirators, the results could be disastrous. Personal protective equipment is currently at 100 times the usual demand and 20 times the usual cost, with stocks backlogged by 4-6 months. The appropriate order of priority in distribution to health care professionals first, followed by those caring for infected patients is critical.²⁰ In a survey conducted by the Association for Professionals in Infection Control and Epidemiology, results revealed that 48% of the U.S. health care facilities that responded were either out or nearly out of respirators as of March 25. ²¹

The gravest risk behind the universal masking policy is the likely depletion of medical resources.²² A possible solution to this issue could be to modify the policy to stagger the requirement based on the severity of community transmission in that area of residence. In the article appropriately titled “Rational use of face masks in the COVID-19 pandemic” published in The Lancet Respiratory Medicine, researchers described how the Chinese population was classified into moderate, low, and very-low risk of infection categories and advised to wear a surgical or disposable mask, disposable mask, and no mask respectively.²³ This curbs widespread panic and eagerness by the general public to stock up on essential medical equipment when it may not even be necessary.
 

Reuse, extended use, and sterilization

Several studies have been conducted to identify the viability of the COVID-19 on various surfaces.^24-25 The CDC and National Institute for Occupational Safety and Health (NIOSH) guidelines state that an N95 respirator can be used up to 8 hours with intermittent or continuous use, though this number is not fixed and heavily depends upon the extent of exposure, risk of contamination, and frequency of donning and doffing^26,27. Though traditionally meant for single-time usage, after 8 hours, the mask can be decontaminated and reused. The CDC defines extended use as the “practice of wearing the same N95 respirator for repeated close-contact encounters with several patients, without removing the respirator between patient encounters.” Reuse is defined as “using the same N95 respirator for multiple encounters with patients but removing it (‘doffing’) after each encounter. The respirator is stored in between encounters to be put on again (‘donned’) prior to the next encounter with a patient.”

It has been established that extended use is more advisable than reuse given the lower risk of self-inoculation. Furthermore, health care professionals are urged to wear a cleanable face shield or disposable mask over the respirator to minimize contamination and practice diligent hand hygiene before and after handling the respirator. N95 respirators are to be discarded following aerosol-generating procedures or if they come in contact with blood, respiratory secretions, or bodily fluids. They should also be discarded in case of close contact with an infected patient or if they cause breathing difficulties to the wearer.²⁷ This may not always be possible given the unprecedented shortage of PPE, hence decontamination techniques and repurposing are the need of the hour.

In Anesthesia & Analgesia, Naveen Nathan, MD, of Northwestern University, Chicago, recommends recycling four masks in a series, using one per day, keeping the mask in a dry, clean environment, and then repeating use of the first mask on the 5th day, the second on the 6th day, and so forth. This ensures clearance of the virus particles by the next use. Alternatively, respirators can be sterilized between uses by heating to 70º C (158º F) for 30 minutes. Liquid disinfectants such as alcohol and bleach as well as ultraviolet rays in sunlight tend to damage masks.²⁸ Steam sterilization is the most commonly utilized technique in hospitals. Other methods, described by the N95/PPE Working Group, report include gamma irradiation at 20kGy (2MRad) for large-scale sterilization (though the facilities may not be widely available), vaporized hydrogen peroxide, ozone decontamination, ultraviolet germicidal irradiation, and ethylene oxide.²⁹ Though a discussion on various considerations of decontamination techniques is out of the scope of this article, detailed guidelines have been published by the CDC30 and the COVID-19 Healthcare Coalition.³⁰

Conclusion

A recent startling discovery reported on in Emerging Infectious Diseases suggests that the basic COVID-19 reproductive number (R0) is actually much higher than previously thought. Using expanded data, updated epidemiologic parameters, and the current outbreak dynamics in Wuhan, the team came to the conclusion that the R0 for the novel coronavirus is actually 5.7 (95% CI 3.8-8.9), compared with an initial estimate of 2.2-2.7.³¹ Concern for transmissibility demands heightened prevention strategies until more data evolves. The latest recommendation by the CDC regarding cloth masking in the public may help slow the progression of the pandemic. However, it is of paramount importance to keep in mind that masks alone are not enough to control the disease and must be coupled with other nonpharmacologic interventions such as social distancing, quarantining/isolation, and diligent hand hygiene.

Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Bharathidasan is a recent medical graduate from India with an interest in public health and community research; she plans to pursue residency training in the United States. Ms. Freshman is currently the regional director of infection prevention for WellSpan Health and has 35 years of experience in nursing. Dr. Palabindala is the medical director, utilization management and physician advisory services, at the University of Mississippi Medical Center, Jackson. He is an associate professor of medicine and academic hospitalist in the UMMC School of Medicine.

References

1. Centers for Disease Control and Prevention. Recommendation regarding the use of cloth face coverings.

2. World Health Organization. Modes of transmission of virus causing COVID-19 : implications for IPC precaution recommendations. Sci Br. 2020 Mar 29:1-3.

3. Santarpia JL et al. Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center. 2020 Mar 26. medRxiv. 2020;2020.03.23.20039446.

4. Bourouiba L. Turbulent gas clouds and respiratory pathogen emissions: Potential implications for reducing transmission of COVID-19. JAMA. 2020 Mar 26. doi: 10.1001/jama.2020.4756.

5. Klompas M et al. Universal masking in hospitals in the Covid-19 era. N Engl J Med. 2020 Apr 1. doi: 10.1056/NEJMp2006372.

6. Servick K. Would everyone wearing face masks help us slow the pandemic? Science 2020 Mar 28. doi: 10.1126/science.abb9371.

7. Leung CC et al. Mass masking in the COVID-19 epidemic: People need guidance. Lancet 2020 Mar 21;395(10228):945. doi: 10.1016/S0140-6736(20)30520-1.

8. Zou L et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020 Mar 19;382(12):1177-9.

9. Pan X et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection. Lancet Infect Dis. 2020 Apr;20(4):410-1.

10. Bai Y et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020 Feb 21;323(14):1406-7.

11. Wei WE et al. Presymptomatic transmission of SARS-CoV-2 – Singapore, Jan. 23–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020;69:411-5.

12. Kimball A et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility – King County, Washington, March 2020. 2020 Apr 3. MMWR Morb Mortal Wkly Rep 2020;69:377-81.

13. Ma Q-X et al. Potential utilities of mask wearing and instant hand hygiene for fighting SARS-CoV-2. J Med Virol. 2020 Mar 31;10.1002/jmv.25805. doi: 10.1002/jmv.25805.

14. Abd-Elsayed A et al. Utility of substandard face mask options for health care workers during the COVID-19 pandemic. Anesth Analg. 2020 Mar 31;10.1213/ANE.0000000000004841. doi: 10.1213/ANE.0000000000004841.

15. Long Y et al. Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis. J Evid Based Med. 2020 Mar 13;10.1111/jebm.12381. doi: 10.1111/jebm.12381.

16. Leung NHL et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med. 2020 May;26(5):676-80.

17. Bae S et al. Effectiveness of surgical and cotton masks in blocking SARS-CoV-2: A controlled comparison in 4 patients. Ann Intern Med. 2020 Apr 6;M20-1342. doi: 10.7326/M20-1342.

18. Brosseau LM. Are powered air purifying respirators a solution for protecting healthcare workers from emerging aerosol-transmissible diseases? Ann Work Expo Health. 2020 Apr 30;64(4):339-41.

19. Swennen GRJ et al. Custom-made 3D-printed face masks in case of pandemic crisis situations with a lack of commercially available FFP2/3 masks. Int J Oral Maxillofac Surg. 2020 May;49(5):673-7.

20. Mahase E. Coronavirus: Global stocks of protective gear are depleted, with demand at “100 times” normal level, WHO warns. BMJ. 2020 Feb 10;368:m543. doi: 10.1136/bmj.m543.

21. National survey shows dire shortages of PPE, hand sanitizer across the U.S. 2020 Mar 27. Association for Professionals in Infection Control and Epidemiology (APIC) press briefing.

22. Wu HL et al. Facemask shortage and the novel coronavirus disease (COVID-19) outbreak: Reflections on public health measures. EClinicalMedicine. 2020 Apr 3:100329. doi: 10.1016/j.eclinm.2020.100329.

23. Feng S et al. Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med. 2020 May;8(5):434-6.

24. Chin AWH et al. Stability of SARS-CoV-2 in different environmental. The Lancet Microbe. 2020 May 1;5247(20):2004973. doi. org/10.1016/S2666-5247(20)30003-3.

25. van Doremalen N et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020 Apr 16;382(16):1564-7.

26. NIOSH – Workplace Safety and Health Topics: Recommended guidance for extended use and limited reuse of n95 filtering facepiece respirators in healthcare settings.

27. Centers for Disease Control and Prevention. COVID-19 decontamination and reuse of filtering facepiece respirators. 2020 Apr 15.

28. Nathan N. Waste not, want not: The re-usability of N95 masks. Anesth Analg. 2020 Mar 31.doi: 10.1213/ane.0000000000004843.

29. European Centre for Disease Prevention and Control technical report. Cloth masks and mask sterilisation as options in case of shortage of surgical masks and respirators. 2020 Mar. 

30. N95/PPE Working Group report. Evaluation of decontamination techniques for the reuse of N95 respirators. 2020 Apr 3;2:1-7.

31. Sanche Set al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020 Jul. doi. org/10.3201/eid2607.200282.

From the ash of our post “coron-apocalyptic” world, we emerge. It’s back to work, to life in a new normal. Patients are still scarce and scared, as are some doctors. Queues of patients wait to clear security and enter the sterile area at every medical office. Water bottles are allowed, fevers and visitors are not. Those who fail clearance or who are afraid to be seen in person must be treated virtually. In this context, virtually means by telephone or video, yet, aptly, it also means “nearly or almost,” as in we can nearly or almost treat them these ways. We’ve emerged safely, but we’ve lost sensibility. Because of this, what’s important in the doctor-patient relationships will drift a bit. Clinical acumen and technical skill won’t be enough. Successful practices will also have grace.

Hans Gerber/CC BY-SA 4.0

If your image of grace is Audrey Hepburn gliding along Fifth Avenue in a long black dress and elbow-length gloves, you’re in the right place. Ms. Hepburn embodied elegance and decorum and there are lessons to be drawn from her. Piling your hair high and donning oversized sunglasses along with your face mask would be to miss the point here though. Ms. Hepburn dressed exquisitely, yes, but her grace came from what wearing a difficult-to-walk-in dress meant to us, not to her. Appearance, self-control, and warmth are what made her charismatic.

To appear urbane requires effort; it’s the effort that we appreciate in someone who is graceful. When you’re thoughtful about how you look, you plan ahead, you work to look polished. In effect, you’re saying: “As my patient, you’re important enough for me to be well dressed.” It is a visible signal of all the unobservable work you’ve done to care for them. This is more critical now that our faces are covered and concern for infection means wearing shabby hospital scrubs rather than shirt and tie.

Effort is also required for telephone and video visits. In them, our doctor-patient connection is diminished – no matter how high definition, it’s a virtual affair. Ms. Hepburn would no doubt take the time to ensure she appeared professional, well lit, with a pleasing background. She’d plan for the call to be done in a quiet location and without distraction.

Whether in person or by phone, grace, as Ms. Hepburn demonstrated, is physical awareness and body control. She would often be completely still when someone is speaking, showing a countenance of warmth. She’d pause after the other person completed a thought and before replying. In doing so, she conveyed that she was present and engaged in what was being said. It is that confidence and ease of manner we perceived as grace.

I thought about this the other day during a mixed clinic of telephone and face-to-face visits. I had on my wrinkle-free scrubs (I could do better). I was listening to a patient describe all possible triggers for her hand dermatitis. My urge to interrupt grew with each paragraph of her storytelling. “Be patient,” I thought, “be at ease with her rambling. ... When she stops, thank her as if you were looking her in the eye acknowledging how interesting her observations were.” This is not just good manners, it’s the essence of grace: The art of showing how important others are to you.

Our world needs grace more than ever and what better place to start but with us. In pleasing, assisting, and honoring them, our patients can be reassured that we can and will care for them. Make Ms. Hepburn proud.

“For beautiful eyes, look for the good in others; for beautiful lips, speak only words of kindness; and for poise, walk with the knowledge that you are never alone.” – Audrey Hepburn

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. He has no disclosures related to this column. Write to him at [email protected] .

From the ash of our post “coron-apocalyptic” world, we emerge. It’s back to work, to life in a new normal. Patients are still scarce and scared, as are some doctors. Queues of patients wait to clear security and enter the sterile area at every medical office. Water bottles are allowed, fevers and visitors are not. Those who fail clearance or who are afraid to be seen in person must be treated virtually. In this context, virtually means by telephone or video, yet, aptly, it also means “nearly or almost,” as in we can nearly or almost treat them these ways. We’ve emerged safely, but we’ve lost sensibility. Because of this, what’s important in the doctor-patient relationships will drift a bit. Clinical acumen and technical skill won’t be enough. Successful practices will also have grace.

Hans Gerber/CC BY-SA 4.0

If your image of grace is Audrey Hepburn gliding along Fifth Avenue in a long black dress and elbow-length gloves, you’re in the right place. Ms. Hepburn embodied elegance and decorum and there are lessons to be drawn from her. Piling your hair high and donning oversized sunglasses along with your face mask would be to miss the point here though. Ms. Hepburn dressed exquisitely, yes, but her grace came from what wearing a difficult-to-walk-in dress meant to us, not to her. Appearance, self-control, and warmth are what made her charismatic.

To appear urbane requires effort; it’s the effort that we appreciate in someone who is graceful. When you’re thoughtful about how you look, you plan ahead, you work to look polished. In effect, you’re saying: “As my patient, you’re important enough for me to be well dressed.” It is a visible signal of all the unobservable work you’ve done to care for them. This is more critical now that our faces are covered and concern for infection means wearing shabby hospital scrubs rather than shirt and tie.

Effort is also required for telephone and video visits. In them, our doctor-patient connection is diminished – no matter how high definition, it’s a virtual affair. Ms. Hepburn would no doubt take the time to ensure she appeared professional, well lit, with a pleasing background. She’d plan for the call to be done in a quiet location and without distraction.

Whether in person or by phone, grace, as Ms. Hepburn demonstrated, is physical awareness and body control. She would often be completely still when someone is speaking, showing a countenance of warmth. She’d pause after the other person completed a thought and before replying. In doing so, she conveyed that she was present and engaged in what was being said. It is that confidence and ease of manner we perceived as grace.

I thought about this the other day during a mixed clinic of telephone and face-to-face visits. I had on my wrinkle-free scrubs (I could do better). I was listening to a patient describe all possible triggers for her hand dermatitis. My urge to interrupt grew with each paragraph of her storytelling. “Be patient,” I thought, “be at ease with her rambling. ... When she stops, thank her as if you were looking her in the eye acknowledging how interesting her observations were.” This is not just good manners, it’s the essence of grace: The art of showing how important others are to you.

Our world needs grace more than ever and what better place to start but with us. In pleasing, assisting, and honoring them, our patients can be reassured that we can and will care for them. Make Ms. Hepburn proud.

“For beautiful eyes, look for the good in others; for beautiful lips, speak only words of kindness; and for poise, walk with the knowledge that you are never alone.” – Audrey Hepburn

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. He has no disclosures related to this column. Write to him at [email protected] .

From the ash of our post “coron-apocalyptic” world, we emerge. It’s back to work, to life in a new normal. Patients are still scarce and scared, as are some doctors. Queues of patients wait to clear security and enter the sterile area at every medical office. Water bottles are allowed, fevers and visitors are not. Those who fail clearance or who are afraid to be seen in person must be treated virtually. In this context, virtually means by telephone or video, yet, aptly, it also means “nearly or almost,” as in we can nearly or almost treat them these ways. We’ve emerged safely, but we’ve lost sensibility. Because of this, what’s important in the doctor-patient relationships will drift a bit. Clinical acumen and technical skill won’t be enough. Successful practices will also have grace.

Hans Gerber/CC BY-SA 4.0

If your image of grace is Audrey Hepburn gliding along Fifth Avenue in a long black dress and elbow-length gloves, you’re in the right place. Ms. Hepburn embodied elegance and decorum and there are lessons to be drawn from her. Piling your hair high and donning oversized sunglasses along with your face mask would be to miss the point here though. Ms. Hepburn dressed exquisitely, yes, but her grace came from what wearing a difficult-to-walk-in dress meant to us, not to her. Appearance, self-control, and warmth are what made her charismatic.

To appear urbane requires effort; it’s the effort that we appreciate in someone who is graceful. When you’re thoughtful about how you look, you plan ahead, you work to look polished. In effect, you’re saying: “As my patient, you’re important enough for me to be well dressed.” It is a visible signal of all the unobservable work you’ve done to care for them. This is more critical now that our faces are covered and concern for infection means wearing shabby hospital scrubs rather than shirt and tie.

Effort is also required for telephone and video visits. In them, our doctor-patient connection is diminished – no matter how high definition, it’s a virtual affair. Ms. Hepburn would no doubt take the time to ensure she appeared professional, well lit, with a pleasing background. She’d plan for the call to be done in a quiet location and without distraction.

Whether in person or by phone, grace, as Ms. Hepburn demonstrated, is physical awareness and body control. She would often be completely still when someone is speaking, showing a countenance of warmth. She’d pause after the other person completed a thought and before replying. In doing so, she conveyed that she was present and engaged in what was being said. It is that confidence and ease of manner we perceived as grace.

I thought about this the other day during a mixed clinic of telephone and face-to-face visits. I had on my wrinkle-free scrubs (I could do better). I was listening to a patient describe all possible triggers for her hand dermatitis. My urge to interrupt grew with each paragraph of her storytelling. “Be patient,” I thought, “be at ease with her rambling. ... When she stops, thank her as if you were looking her in the eye acknowledging how interesting her observations were.” This is not just good manners, it’s the essence of grace: The art of showing how important others are to you.

Our world needs grace more than ever and what better place to start but with us. In pleasing, assisting, and honoring them, our patients can be reassured that we can and will care for them. Make Ms. Hepburn proud.

“For beautiful eyes, look for the good in others; for beautiful lips, speak only words of kindness; and for poise, walk with the knowledge that you are never alone.” – Audrey Hepburn

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. He has no disclosures related to this column. Write to him at [email protected] .

Reports have emerged about the unique vulnerability of psychiatric hospitals to the ravages of COVID-19.

In a South Korea psychiatric hospital, 101 of 103 patients contracted SARS-CoV-2 during an outbreak; 7 eventually died.^1,2 This report, among a few others, have led to the development of psychiatric COVID-19–positive units (PCU). However, it remains highly unclear how many are currently open, where they are located, or what their operations are like.

Early in the COVID-19 pandemic, it became clear to us that, as a public health measure, it would be necessary to test all patients for COVID-19 who were being considered for admission to our inpatient psychiatric units. We knew that we could not allow a medically asymptomatic “covertly” COVID-19–positive patient to be introduced to the social community of our inpatient units because of the risks of transmission to other patients and staff.

In coordination with our health system infection prevention experts, we have therefore required a confirmed negative COVID-19 polymerase chain reaction nasal swab performed no more than 48 hours prior to the time/date of acute psychiatric inpatient admission. Furthermore, as part of the broad health system response and surge planning, we were asked by our respective incident command centers to begin planning for a Psychiatric COVID-19–positive Unit (PCU) that might allow us to safely care for a cohort of patients needing such hospitalization.

It is worth emphasizing that the typical patient who is a candidate for a PCU is so acutely psychiatrically ill that they cannot be managed in a less restrictive environment than an inpatient psychiatric unit and, at the same time, is likely to not be medically ill enough to warrant admission to an internal medicine service in a general acute care hospital.

We have identified eight principles and critical decision points that can help inpatient units plan for the safe care of COVID-19–positive patients on a PCU.

1. Triage: Patients admitted to a PCU should be medically stable, particularly with regard to COVID-19 and respiratory symptomatology. PCUs should establish clear criteria for admission and discharge (or medical transfer). Examples of potential exclusionary criteria to a PCU include:

• Respiratory distress, shortness of breath, hypoxia, requirement for supplemental oxygen, or requirement for respiratory therapy breathing treatments.
• Fever, or signs of sepsis, or systemic inflammatory response syndrome.
• Medical frailty, significant medical comorbidities, delirium, or altered mental status;
• Requirements for continuous vital sign monitoring or of a monitoring frequency beyond the capacity of the PCU.

Discharge criteria may also include a symptom-based strategy because emerging evidence suggests that patients may be less infectious by day 10-14 of the disease course,³ and viral lab testing is very sensitive and will be positive for periods of time after individuals are no longer infectious. The symptom-based strategy allows for patients to not require retesting prior to discharge. However, some receiving facilities (for example residential or skilled nursing facilities) may necessitate testing, in which case a testing-based strategy can be used. The Centers for Disease Control and Prevention provides guidelines for both types of strategies.⁴

2. Infection control and personal protective equipment: PCUs require modifications or departures from the typical inpatient free-ranging environment in which common areas are provided for patients to engage in a community of care, including group therapy (such as occupational, recreational, Alcoholics Anonymous, and social work groups).

• Isolation: PCUs must consider whether they will require patients to isolate to their rooms or to allow modified or limited access to “public” or “community” areas. While there do not appear to be standard recommendations from the CDC or other public health entities regarding negative pressure or any specific room ventilation requirements, it is prudent to work with local infectious disease experts on protocols. Important considerations include spatial planning for infection control areas to don and doff appropriate personal protective equipment (PPE) and appropriate workspace to prevent contamination of non–COVID-19 work areas. Approaches can include establishing clearly identified and visually demarcated infection control “zones” (often referred to as “hot, warm, and cold zones”) that correspond to specific PPE requirements for staff. In addition, individuals should eat in their own rooms or designated areas because use of common areas for meals can potentially lead to aerosolized spread of the virus.
• Cohorting: Generally, PCUs should consider admitting only COVID-19–positive patients to a PCU to avoid exposure to other patients. Hospitals and health systems should determine protocols and locations for testing and managing “patients under investigation” for COVID-19, which should precede admission to the PCU.
• PPE: It is important to clearly establish and communicate PPE requirements and procedures for direct physical contact versus no physical contact (for example, visual safety checks). Identify clear supply chains for PPE and hand sanitizer.

3. Medical management and consultation: PCUs should establish clear pathways for accessing consultation from medical consultants. It may be ideal, in addition to standard daily psychiatric physician rounding, to have daily internal medicine rounding and/or medical nursing staff working on the unit. Given the potential of COVID-19–positive patients to rapidly devolve from asymptomatic to acutely ill, it is necessary to establish protocols for the provision of urgent medical care 24/7 and streamlined processes for transfer to a medical unit.

Clear protocols should be established to address any potential signs of decompensation in the respiratory status of a PCU unit, including administration of oxygen and restrictions (or appropriate precautions) related to aerosolizing treatment such as nebulizers or positive airway pressure.

4. Code blue protocol: Any emergent medical issues, including acute respiratory decompensation, should trigger a Code Blue response that has been specifically designed for COVID-19–positive patients, including considerations for proper PPE during resuscitation efforts.

• Telehealth: Clinicians (such as physicians, social workers, occupational therapists) should leverage and maximize the use of telemedicine to minimize direct or prolonged exposure to infectious disease risks.
• Nursing: It is important to establish appropriate ratios of nursing and support staff for a COVID-19–positive psychiatry unit given the unique work flows related to isolation precautions and to ensure patient and staff safety. These ratios may take into account patient-specific needs, including the need for additional staff to perform constant observation for high-risk patients, management of agitated patients, and sufficient staff to allow for relief and break-time from PPE. Admission and routine care processes should be adapted in order to limit equipment entering the room, such as computer workstations on wheels.
• Medication administration procedures: Develop work flows related to PPE and infection control when retrieving and administering medications.
• Workspace: Designate appropriate workspace for PCU clinicians to access computers and documents and to minimize use of non–COVID-19 unit work areas.

6. Restraints and management of agitated patients: PCUs should develop plans for addressing agitated patients, including contingency plans for whether seclusion or restraints should be administered in the patient’s individual room or in a dedicated restraint room in the PCU. Staff training should include protocols specifically designed for managing agitated patients in the PCU.

7. Discharge processes: If patients remain medically well and clear their COVID-19 PCR tests, it is conceivable that they might be transferred to a non–COVID-19 psychiatric unit if sufficient isolation time has passed and the infectious disease consultants deem it appropriate. It is also possible that patients would be discharged from a PCU to home or other residential setting. Such patients should be assessed for ability to comply with continued self-quarantine if necessary. Discharge planning must take into consideration follow-up plans for COVID-19 illness and primary care appointments, as well as needed psychiatric follow-up.

8. Patients’ rights: The apparently highly infectious and transmissible nature of SARS-CoV-2 creates novel tensions between a wide range of individual rights and the rights of others. In addition to manifesting in our general society, there are potentially unique tensions in acute inpatient psychiatric settings. Certain patients’ rights may require modification in a PCU (for example, access to outdoor space, personal belongings, visitors, and possibly civil commitment judicial hearings). These discussions may require input from hospital compliance officers, ethics committees, risk managers, and the local department of mental health and also may be partly solved by using video communication platforms.

References

1. Kim MJ. “ ‘It was a medical disaster’: The psychiatric ward that saw 100 patients with new coronavirus.” Independent. 2020 Mar 1.

2. Korean Society of Infectious Diseases et al. J Korean Med Sci. 2020 Mar 16;35(10):e112.

3. Centers for Disease Control and Prevention. Symptom-based strategy to discontinue isolation for persons with COVID-19. Decision Memo. 2020 May 3.

4. He X et al. Nature Medicine. 2020. 26:672-5.
 

Dr. Cheung is associate medical director and chief quality officer at the Stewart and Lynda Resnick Neuropsychiatric Hospital at the University of California, Los Angeles. He has no conflicts of interest. Dr. Strouse is medical director, UCLA Stewart and Lynda Resnick Neuropsychiatric Hospital and Maddie Katz Professor at the UCLA department of psychiatry/Semel Institute. He has no conflicts of interest. Dr. Li is associate medical director of quality improvement at Yale-New Haven Psychiatric Hospital in Connecticut. She also serves as medical director of clinical operations at the Yale-New Haven Health System. Dr. Li is a 2019-2020 Health and Aging Policy Fellow and receives funding support from the program.

Reports have emerged about the unique vulnerability of psychiatric hospitals to the ravages of COVID-19.

In a South Korea psychiatric hospital, 101 of 103 patients contracted SARS-CoV-2 during an outbreak; 7 eventually died.^1,2 This report, among a few others, have led to the development of psychiatric COVID-19–positive units (PCU). However, it remains highly unclear how many are currently open, where they are located, or what their operations are like.

Early in the COVID-19 pandemic, it became clear to us that, as a public health measure, it would be necessary to test all patients for COVID-19 who were being considered for admission to our inpatient psychiatric units. We knew that we could not allow a medically asymptomatic “covertly” COVID-19–positive patient to be introduced to the social community of our inpatient units because of the risks of transmission to other patients and staff.

In coordination with our health system infection prevention experts, we have therefore required a confirmed negative COVID-19 polymerase chain reaction nasal swab performed no more than 48 hours prior to the time/date of acute psychiatric inpatient admission. Furthermore, as part of the broad health system response and surge planning, we were asked by our respective incident command centers to begin planning for a Psychiatric COVID-19–positive Unit (PCU) that might allow us to safely care for a cohort of patients needing such hospitalization.

It is worth emphasizing that the typical patient who is a candidate for a PCU is so acutely psychiatrically ill that they cannot be managed in a less restrictive environment than an inpatient psychiatric unit and, at the same time, is likely to not be medically ill enough to warrant admission to an internal medicine service in a general acute care hospital.

We have identified eight principles and critical decision points that can help inpatient units plan for the safe care of COVID-19–positive patients on a PCU.

1. Triage: Patients admitted to a PCU should be medically stable, particularly with regard to COVID-19 and respiratory symptomatology. PCUs should establish clear criteria for admission and discharge (or medical transfer). Examples of potential exclusionary criteria to a PCU include:

• Respiratory distress, shortness of breath, hypoxia, requirement for supplemental oxygen, or requirement for respiratory therapy breathing treatments.
• Fever, or signs of sepsis, or systemic inflammatory response syndrome.
• Medical frailty, significant medical comorbidities, delirium, or altered mental status;
• Requirements for continuous vital sign monitoring or of a monitoring frequency beyond the capacity of the PCU.

Discharge criteria may also include a symptom-based strategy because emerging evidence suggests that patients may be less infectious by day 10-14 of the disease course,³ and viral lab testing is very sensitive and will be positive for periods of time after individuals are no longer infectious. The symptom-based strategy allows for patients to not require retesting prior to discharge. However, some receiving facilities (for example residential or skilled nursing facilities) may necessitate testing, in which case a testing-based strategy can be used. The Centers for Disease Control and Prevention provides guidelines for both types of strategies.⁴

2. Infection control and personal protective equipment: PCUs require modifications or departures from the typical inpatient free-ranging environment in which common areas are provided for patients to engage in a community of care, including group therapy (such as occupational, recreational, Alcoholics Anonymous, and social work groups).

• Isolation: PCUs must consider whether they will require patients to isolate to their rooms or to allow modified or limited access to “public” or “community” areas. While there do not appear to be standard recommendations from the CDC or other public health entities regarding negative pressure or any specific room ventilation requirements, it is prudent to work with local infectious disease experts on protocols. Important considerations include spatial planning for infection control areas to don and doff appropriate personal protective equipment (PPE) and appropriate workspace to prevent contamination of non–COVID-19 work areas. Approaches can include establishing clearly identified and visually demarcated infection control “zones” (often referred to as “hot, warm, and cold zones”) that correspond to specific PPE requirements for staff. In addition, individuals should eat in their own rooms or designated areas because use of common areas for meals can potentially lead to aerosolized spread of the virus.
• Cohorting: Generally, PCUs should consider admitting only COVID-19–positive patients to a PCU to avoid exposure to other patients. Hospitals and health systems should determine protocols and locations for testing and managing “patients under investigation” for COVID-19, which should precede admission to the PCU.
• PPE: It is important to clearly establish and communicate PPE requirements and procedures for direct physical contact versus no physical contact (for example, visual safety checks). Identify clear supply chains for PPE and hand sanitizer.

3. Medical management and consultation: PCUs should establish clear pathways for accessing consultation from medical consultants. It may be ideal, in addition to standard daily psychiatric physician rounding, to have daily internal medicine rounding and/or medical nursing staff working on the unit. Given the potential of COVID-19–positive patients to rapidly devolve from asymptomatic to acutely ill, it is necessary to establish protocols for the provision of urgent medical care 24/7 and streamlined processes for transfer to a medical unit.

Clear protocols should be established to address any potential signs of decompensation in the respiratory status of a PCU unit, including administration of oxygen and restrictions (or appropriate precautions) related to aerosolizing treatment such as nebulizers or positive airway pressure.

4. Code blue protocol: Any emergent medical issues, including acute respiratory decompensation, should trigger a Code Blue response that has been specifically designed for COVID-19–positive patients, including considerations for proper PPE during resuscitation efforts.

• Telehealth: Clinicians (such as physicians, social workers, occupational therapists) should leverage and maximize the use of telemedicine to minimize direct or prolonged exposure to infectious disease risks.
• Nursing: It is important to establish appropriate ratios of nursing and support staff for a COVID-19–positive psychiatry unit given the unique work flows related to isolation precautions and to ensure patient and staff safety. These ratios may take into account patient-specific needs, including the need for additional staff to perform constant observation for high-risk patients, management of agitated patients, and sufficient staff to allow for relief and break-time from PPE. Admission and routine care processes should be adapted in order to limit equipment entering the room, such as computer workstations on wheels.
• Medication administration procedures: Develop work flows related to PPE and infection control when retrieving and administering medications.
• Workspace: Designate appropriate workspace for PCU clinicians to access computers and documents and to minimize use of non–COVID-19 unit work areas.

6. Restraints and management of agitated patients: PCUs should develop plans for addressing agitated patients, including contingency plans for whether seclusion or restraints should be administered in the patient’s individual room or in a dedicated restraint room in the PCU. Staff training should include protocols specifically designed for managing agitated patients in the PCU.

7. Discharge processes: If patients remain medically well and clear their COVID-19 PCR tests, it is conceivable that they might be transferred to a non–COVID-19 psychiatric unit if sufficient isolation time has passed and the infectious disease consultants deem it appropriate. It is also possible that patients would be discharged from a PCU to home or other residential setting. Such patients should be assessed for ability to comply with continued self-quarantine if necessary. Discharge planning must take into consideration follow-up plans for COVID-19 illness and primary care appointments, as well as needed psychiatric follow-up.

8. Patients’ rights: The apparently highly infectious and transmissible nature of SARS-CoV-2 creates novel tensions between a wide range of individual rights and the rights of others. In addition to manifesting in our general society, there are potentially unique tensions in acute inpatient psychiatric settings. Certain patients’ rights may require modification in a PCU (for example, access to outdoor space, personal belongings, visitors, and possibly civil commitment judicial hearings). These discussions may require input from hospital compliance officers, ethics committees, risk managers, and the local department of mental health and also may be partly solved by using video communication platforms.

References

1. Kim MJ. “ ‘It was a medical disaster’: The psychiatric ward that saw 100 patients with new coronavirus.” Independent. 2020 Mar 1.

2. Korean Society of Infectious Diseases et al. J Korean Med Sci. 2020 Mar 16;35(10):e112.

3. Centers for Disease Control and Prevention. Symptom-based strategy to discontinue isolation for persons with COVID-19. Decision Memo. 2020 May 3.

4. He X et al. Nature Medicine. 2020. 26:672-5.
 

Dr. Cheung is associate medical director and chief quality officer at the Stewart and Lynda Resnick Neuropsychiatric Hospital at the University of California, Los Angeles. He has no conflicts of interest. Dr. Strouse is medical director, UCLA Stewart and Lynda Resnick Neuropsychiatric Hospital and Maddie Katz Professor at the UCLA department of psychiatry/Semel Institute. He has no conflicts of interest. Dr. Li is associate medical director of quality improvement at Yale-New Haven Psychiatric Hospital in Connecticut. She also serves as medical director of clinical operations at the Yale-New Haven Health System. Dr. Li is a 2019-2020 Health and Aging Policy Fellow and receives funding support from the program.

Reports have emerged about the unique vulnerability of psychiatric hospitals to the ravages of COVID-19.

In a South Korea psychiatric hospital, 101 of 103 patients contracted SARS-CoV-2 during an outbreak; 7 eventually died.^1,2 This report, among a few others, have led to the development of psychiatric COVID-19–positive units (PCU). However, it remains highly unclear how many are currently open, where they are located, or what their operations are like.

Early in the COVID-19 pandemic, it became clear to us that, as a public health measure, it would be necessary to test all patients for COVID-19 who were being considered for admission to our inpatient psychiatric units. We knew that we could not allow a medically asymptomatic “covertly” COVID-19–positive patient to be introduced to the social community of our inpatient units because of the risks of transmission to other patients and staff.

In coordination with our health system infection prevention experts, we have therefore required a confirmed negative COVID-19 polymerase chain reaction nasal swab performed no more than 48 hours prior to the time/date of acute psychiatric inpatient admission. Furthermore, as part of the broad health system response and surge planning, we were asked by our respective incident command centers to begin planning for a Psychiatric COVID-19–positive Unit (PCU) that might allow us to safely care for a cohort of patients needing such hospitalization.

It is worth emphasizing that the typical patient who is a candidate for a PCU is so acutely psychiatrically ill that they cannot be managed in a less restrictive environment than an inpatient psychiatric unit and, at the same time, is likely to not be medically ill enough to warrant admission to an internal medicine service in a general acute care hospital.

We have identified eight principles and critical decision points that can help inpatient units plan for the safe care of COVID-19–positive patients on a PCU.

1. Triage: Patients admitted to a PCU should be medically stable, particularly with regard to COVID-19 and respiratory symptomatology. PCUs should establish clear criteria for admission and discharge (or medical transfer). Examples of potential exclusionary criteria to a PCU include:

• Respiratory distress, shortness of breath, hypoxia, requirement for supplemental oxygen, or requirement for respiratory therapy breathing treatments.
• Fever, or signs of sepsis, or systemic inflammatory response syndrome.
• Medical frailty, significant medical comorbidities, delirium, or altered mental status;
• Requirements for continuous vital sign monitoring or of a monitoring frequency beyond the capacity of the PCU.

Discharge criteria may also include a symptom-based strategy because emerging evidence suggests that patients may be less infectious by day 10-14 of the disease course,³ and viral lab testing is very sensitive and will be positive for periods of time after individuals are no longer infectious. The symptom-based strategy allows for patients to not require retesting prior to discharge. However, some receiving facilities (for example residential or skilled nursing facilities) may necessitate testing, in which case a testing-based strategy can be used. The Centers for Disease Control and Prevention provides guidelines for both types of strategies.⁴

2. Infection control and personal protective equipment: PCUs require modifications or departures from the typical inpatient free-ranging environment in which common areas are provided for patients to engage in a community of care, including group therapy (such as occupational, recreational, Alcoholics Anonymous, and social work groups).

• Isolation: PCUs must consider whether they will require patients to isolate to their rooms or to allow modified or limited access to “public” or “community” areas. While there do not appear to be standard recommendations from the CDC or other public health entities regarding negative pressure or any specific room ventilation requirements, it is prudent to work with local infectious disease experts on protocols. Important considerations include spatial planning for infection control areas to don and doff appropriate personal protective equipment (PPE) and appropriate workspace to prevent contamination of non–COVID-19 work areas. Approaches can include establishing clearly identified and visually demarcated infection control “zones” (often referred to as “hot, warm, and cold zones”) that correspond to specific PPE requirements for staff. In addition, individuals should eat in their own rooms or designated areas because use of common areas for meals can potentially lead to aerosolized spread of the virus.
• Cohorting: Generally, PCUs should consider admitting only COVID-19–positive patients to a PCU to avoid exposure to other patients. Hospitals and health systems should determine protocols and locations for testing and managing “patients under investigation” for COVID-19, which should precede admission to the PCU.
• PPE: It is important to clearly establish and communicate PPE requirements and procedures for direct physical contact versus no physical contact (for example, visual safety checks). Identify clear supply chains for PPE and hand sanitizer.

3. Medical management and consultation: PCUs should establish clear pathways for accessing consultation from medical consultants. It may be ideal, in addition to standard daily psychiatric physician rounding, to have daily internal medicine rounding and/or medical nursing staff working on the unit. Given the potential of COVID-19–positive patients to rapidly devolve from asymptomatic to acutely ill, it is necessary to establish protocols for the provision of urgent medical care 24/7 and streamlined processes for transfer to a medical unit.

Clear protocols should be established to address any potential signs of decompensation in the respiratory status of a PCU unit, including administration of oxygen and restrictions (or appropriate precautions) related to aerosolizing treatment such as nebulizers or positive airway pressure.

4. Code blue protocol: Any emergent medical issues, including acute respiratory decompensation, should trigger a Code Blue response that has been specifically designed for COVID-19–positive patients, including considerations for proper PPE during resuscitation efforts.

• Telehealth: Clinicians (such as physicians, social workers, occupational therapists) should leverage and maximize the use of telemedicine to minimize direct or prolonged exposure to infectious disease risks.
• Nursing: It is important to establish appropriate ratios of nursing and support staff for a COVID-19–positive psychiatry unit given the unique work flows related to isolation precautions and to ensure patient and staff safety. These ratios may take into account patient-specific needs, including the need for additional staff to perform constant observation for high-risk patients, management of agitated patients, and sufficient staff to allow for relief and break-time from PPE. Admission and routine care processes should be adapted in order to limit equipment entering the room, such as computer workstations on wheels.
• Medication administration procedures: Develop work flows related to PPE and infection control when retrieving and administering medications.
• Workspace: Designate appropriate workspace for PCU clinicians to access computers and documents and to minimize use of non–COVID-19 unit work areas.

6. Restraints and management of agitated patients: PCUs should develop plans for addressing agitated patients, including contingency plans for whether seclusion or restraints should be administered in the patient’s individual room or in a dedicated restraint room in the PCU. Staff training should include protocols specifically designed for managing agitated patients in the PCU.

7. Discharge processes: If patients remain medically well and clear their COVID-19 PCR tests, it is conceivable that they might be transferred to a non–COVID-19 psychiatric unit if sufficient isolation time has passed and the infectious disease consultants deem it appropriate. It is also possible that patients would be discharged from a PCU to home or other residential setting. Such patients should be assessed for ability to comply with continued self-quarantine if necessary. Discharge planning must take into consideration follow-up plans for COVID-19 illness and primary care appointments, as well as needed psychiatric follow-up.

8. Patients’ rights: The apparently highly infectious and transmissible nature of SARS-CoV-2 creates novel tensions between a wide range of individual rights and the rights of others. In addition to manifesting in our general society, there are potentially unique tensions in acute inpatient psychiatric settings. Certain patients’ rights may require modification in a PCU (for example, access to outdoor space, personal belongings, visitors, and possibly civil commitment judicial hearings). These discussions may require input from hospital compliance officers, ethics committees, risk managers, and the local department of mental health and also may be partly solved by using video communication platforms.

References

1. Kim MJ. “ ‘It was a medical disaster’: The psychiatric ward that saw 100 patients with new coronavirus.” Independent. 2020 Mar 1.

2. Korean Society of Infectious Diseases et al. J Korean Med Sci. 2020 Mar 16;35(10):e112.

3. Centers for Disease Control and Prevention. Symptom-based strategy to discontinue isolation for persons with COVID-19. Decision Memo. 2020 May 3.

4. He X et al. Nature Medicine. 2020. 26:672-5.
 

Dr. Cheung is associate medical director and chief quality officer at the Stewart and Lynda Resnick Neuropsychiatric Hospital at the University of California, Los Angeles. He has no conflicts of interest. Dr. Strouse is medical director, UCLA Stewart and Lynda Resnick Neuropsychiatric Hospital and Maddie Katz Professor at the UCLA department of psychiatry/Semel Institute. He has no conflicts of interest. Dr. Li is associate medical director of quality improvement at Yale-New Haven Psychiatric Hospital in Connecticut. She also serves as medical director of clinical operations at the Yale-New Haven Health System. Dr. Li is a 2019-2020 Health and Aging Policy Fellow and receives funding support from the program.

Each day, we’re inundated with news about the COVID-19 pandemic and how it continues to strain our health care system and resources. With more than 1.15 million positive cases in the United States and over 67,000 deaths as of this writing, it has been a scary yet humbling experience for everyone. There is no doubt this pandemic will be a defining moment in health care for several reasons. From supply chain disruptions and personal protective equipment (PPE) and ventilator shortages to exhausted caregivers – both physically and mentally – this event has pushed the envelope on finding answers from federal and state authorities. Hospital administrations are working harder than ever to rise to the challenge and do what is best for their frontline staff and, more importantly, the patients and the communities they serve.

The provider experience during COVID-19

Hospitalists are in a unique situation as frontline providers. Managing daily throughput of patients has always been a key role for the specialty. They also play an integral role in their own care teams alongside nurses, trainees, case managers, pharmacists, and others in cohorted COVID-19 units. Now more than ever, such a geographic placement of patients is quickly emerging as a must-have staffing model to reduce risk of cross-contamination and preserving critical PPE supplies. This heightened awareness, coupled with anxiety, sometimes leads to added stress and burnout risk for hospitalists.

Communication is critical in creating situational awareness and reducing anxiety within the teams. This is exactly where hospitalists can lead:

• Active presence in hospital incident command centers and infection control boards
• Close coordination with emergency medicine colleagues and bed placement navigators
• Developing protocols for appropriate testing
• Frequent daily huddles to discuss current state- and hospital-level testing guidelines
• Close involvement in the hospital operations committee
• Advocating for or securing more testing or supplies, especially PPE
• Effective communication about changes in PPE requirements and conservation strategies as per the Centers for Disease Control and Prevention, State Department of Health, and the hospital infection control board
• Crisis-driven changes, including development and review of triage and treatment protocols and elective procedure cancellations
• Census numbers and capacity/staffing adjustments within the team to meet temporary dips and surges in on-service patient volumes
• Frontline caregiver mental and physical health assessment

Daily huddles at key times (e.g., at shift start and end times) can help to identify these barriers. If operational issues arise, there should be a clear channel to escalate them to senior leadership.

Hospitalists could also use several strategies proven to improve staff morale and resilience. For instance, take this time to connect with friends and family virtually, unplug when off from work, explore one’s spiritual self through meditation and prayers, spend time with nature, exercise daily, seek humor, and develop or work on one’s hobby.
 

The patient experience during COVID-19

Some intriguing data is also being released about patient experience during the pandemic. A Press Ganey analysis of 350,000 comments between January and March 2020 shows that patients are looking for more information about their condition, primarily COVID-19 test delays and result notification time. There is also hypervigilance in patients’ minds about hand hygiene and overall cleanliness of the hospital. Patients also seek clarification and transparent explanation of their caregiver’s bedside mannerisms – for example, why did they gown up before entering – and their daily care plans.

Patients have been appreciative of providers and recognize the personal risk frontline staff put themselves through. Communication transparency seems to mitigate concerns about delays of care especially caused by operational challenges as a result of the pandemic.

In surveys specifically related to experiences including COVID-19, patients were more likely to rate more areas of service lower than in surveys that did not mention COVID-19. The patients also seemed to put more value on the quality of instructions and information they received and on perception of providers’ respect and listening abilities. These insights could prove invaluable in improving care delivery by hospitalists.

Isolation of patients has been shown in multiple studies to have negative outcomes. These patients are up to twice as likely to have an adverse event, and seven times more likely to have treatment-related avoidable adversity, poorer perceived patient experience, and overall perception of being cared for “less.” Add to this a higher level of depression and mental strain, and these patients quickly become “unsatisfied.”

At the ED level, the willingness to let family be present for care was the key area of concern listed – a metric that has changed rapidly since the early days of the pandemic.

The bottom line is these are trying times for everyone – both for providers and patients. Both look up to health system and group leadership for reassurance. Patients and families recognize the risks frontline providers are assuming. However, transparent communication across all levels is the key. Silos are disappearing and team based care is taking center stage.

Beyond the current public health crisis, these efforts will go a long way to create unshakable trust between health systems, providers, patients, and their loved ones.

Dr. Singh is currently the chief of inpatient operations at Adena Health System in Chillicothe, Ohio, where he also has key roles in medical informatics and health IT. He is also the president-elect of the Central Ohio Chapter of SHM.

Each day, we’re inundated with news about the COVID-19 pandemic and how it continues to strain our health care system and resources. With more than 1.15 million positive cases in the United States and over 67,000 deaths as of this writing, it has been a scary yet humbling experience for everyone. There is no doubt this pandemic will be a defining moment in health care for several reasons. From supply chain disruptions and personal protective equipment (PPE) and ventilator shortages to exhausted caregivers – both physically and mentally – this event has pushed the envelope on finding answers from federal and state authorities. Hospital administrations are working harder than ever to rise to the challenge and do what is best for their frontline staff and, more importantly, the patients and the communities they serve.

The provider experience during COVID-19

Hospitalists are in a unique situation as frontline providers. Managing daily throughput of patients has always been a key role for the specialty. They also play an integral role in their own care teams alongside nurses, trainees, case managers, pharmacists, and others in cohorted COVID-19 units. Now more than ever, such a geographic placement of patients is quickly emerging as a must-have staffing model to reduce risk of cross-contamination and preserving critical PPE supplies. This heightened awareness, coupled with anxiety, sometimes leads to added stress and burnout risk for hospitalists.

Communication is critical in creating situational awareness and reducing anxiety within the teams. This is exactly where hospitalists can lead:

• Active presence in hospital incident command centers and infection control boards
• Close coordination with emergency medicine colleagues and bed placement navigators
• Developing protocols for appropriate testing
• Frequent daily huddles to discuss current state- and hospital-level testing guidelines
• Close involvement in the hospital operations committee
• Advocating for or securing more testing or supplies, especially PPE
• Effective communication about changes in PPE requirements and conservation strategies as per the Centers for Disease Control and Prevention, State Department of Health, and the hospital infection control board
• Crisis-driven changes, including development and review of triage and treatment protocols and elective procedure cancellations
• Census numbers and capacity/staffing adjustments within the team to meet temporary dips and surges in on-service patient volumes
• Frontline caregiver mental and physical health assessment

Daily huddles at key times (e.g., at shift start and end times) can help to identify these barriers. If operational issues arise, there should be a clear channel to escalate them to senior leadership.

Hospitalists could also use several strategies proven to improve staff morale and resilience. For instance, take this time to connect with friends and family virtually, unplug when off from work, explore one’s spiritual self through meditation and prayers, spend time with nature, exercise daily, seek humor, and develop or work on one’s hobby.
 

The patient experience during COVID-19

Some intriguing data is also being released about patient experience during the pandemic. A Press Ganey analysis of 350,000 comments between January and March 2020 shows that patients are looking for more information about their condition, primarily COVID-19 test delays and result notification time. There is also hypervigilance in patients’ minds about hand hygiene and overall cleanliness of the hospital. Patients also seek clarification and transparent explanation of their caregiver’s bedside mannerisms – for example, why did they gown up before entering – and their daily care plans.

Patients have been appreciative of providers and recognize the personal risk frontline staff put themselves through. Communication transparency seems to mitigate concerns about delays of care especially caused by operational challenges as a result of the pandemic.

In surveys specifically related to experiences including COVID-19, patients were more likely to rate more areas of service lower than in surveys that did not mention COVID-19. The patients also seemed to put more value on the quality of instructions and information they received and on perception of providers’ respect and listening abilities. These insights could prove invaluable in improving care delivery by hospitalists.

Isolation of patients has been shown in multiple studies to have negative outcomes. These patients are up to twice as likely to have an adverse event, and seven times more likely to have treatment-related avoidable adversity, poorer perceived patient experience, and overall perception of being cared for “less.” Add to this a higher level of depression and mental strain, and these patients quickly become “unsatisfied.”

At the ED level, the willingness to let family be present for care was the key area of concern listed – a metric that has changed rapidly since the early days of the pandemic.

The bottom line is these are trying times for everyone – both for providers and patients. Both look up to health system and group leadership for reassurance. Patients and families recognize the risks frontline providers are assuming. However, transparent communication across all levels is the key. Silos are disappearing and team based care is taking center stage.

Beyond the current public health crisis, these efforts will go a long way to create unshakable trust between health systems, providers, patients, and their loved ones.

Dr. Singh is currently the chief of inpatient operations at Adena Health System in Chillicothe, Ohio, where he also has key roles in medical informatics and health IT. He is also the president-elect of the Central Ohio Chapter of SHM.

Each day, we’re inundated with news about the COVID-19 pandemic and how it continues to strain our health care system and resources. With more than 1.15 million positive cases in the United States and over 67,000 deaths as of this writing, it has been a scary yet humbling experience for everyone. There is no doubt this pandemic will be a defining moment in health care for several reasons. From supply chain disruptions and personal protective equipment (PPE) and ventilator shortages to exhausted caregivers – both physically and mentally – this event has pushed the envelope on finding answers from federal and state authorities. Hospital administrations are working harder than ever to rise to the challenge and do what is best for their frontline staff and, more importantly, the patients and the communities they serve.

The provider experience during COVID-19

Hospitalists are in a unique situation as frontline providers. Managing daily throughput of patients has always been a key role for the specialty. They also play an integral role in their own care teams alongside nurses, trainees, case managers, pharmacists, and others in cohorted COVID-19 units. Now more than ever, such a geographic placement of patients is quickly emerging as a must-have staffing model to reduce risk of cross-contamination and preserving critical PPE supplies. This heightened awareness, coupled with anxiety, sometimes leads to added stress and burnout risk for hospitalists.

Communication is critical in creating situational awareness and reducing anxiety within the teams. This is exactly where hospitalists can lead:

• Active presence in hospital incident command centers and infection control boards
• Close coordination with emergency medicine colleagues and bed placement navigators
• Developing protocols for appropriate testing
• Frequent daily huddles to discuss current state- and hospital-level testing guidelines
• Close involvement in the hospital operations committee
• Advocating for or securing more testing or supplies, especially PPE
• Effective communication about changes in PPE requirements and conservation strategies as per the Centers for Disease Control and Prevention, State Department of Health, and the hospital infection control board
• Crisis-driven changes, including development and review of triage and treatment protocols and elective procedure cancellations
• Census numbers and capacity/staffing adjustments within the team to meet temporary dips and surges in on-service patient volumes
• Frontline caregiver mental and physical health assessment

Daily huddles at key times (e.g., at shift start and end times) can help to identify these barriers. If operational issues arise, there should be a clear channel to escalate them to senior leadership.

Hospitalists could also use several strategies proven to improve staff morale and resilience. For instance, take this time to connect with friends and family virtually, unplug when off from work, explore one’s spiritual self through meditation and prayers, spend time with nature, exercise daily, seek humor, and develop or work on one’s hobby.
 

The patient experience during COVID-19

Some intriguing data is also being released about patient experience during the pandemic. A Press Ganey analysis of 350,000 comments between January and March 2020 shows that patients are looking for more information about their condition, primarily COVID-19 test delays and result notification time. There is also hypervigilance in patients’ minds about hand hygiene and overall cleanliness of the hospital. Patients also seek clarification and transparent explanation of their caregiver’s bedside mannerisms – for example, why did they gown up before entering – and their daily care plans.

Patients have been appreciative of providers and recognize the personal risk frontline staff put themselves through. Communication transparency seems to mitigate concerns about delays of care especially caused by operational challenges as a result of the pandemic.

In surveys specifically related to experiences including COVID-19, patients were more likely to rate more areas of service lower than in surveys that did not mention COVID-19. The patients also seemed to put more value on the quality of instructions and information they received and on perception of providers’ respect and listening abilities. These insights could prove invaluable in improving care delivery by hospitalists.

Isolation of patients has been shown in multiple studies to have negative outcomes. These patients are up to twice as likely to have an adverse event, and seven times more likely to have treatment-related avoidable adversity, poorer perceived patient experience, and overall perception of being cared for “less.” Add to this a higher level of depression and mental strain, and these patients quickly become “unsatisfied.”

At the ED level, the willingness to let family be present for care was the key area of concern listed – a metric that has changed rapidly since the early days of the pandemic.

The bottom line is these are trying times for everyone – both for providers and patients. Both look up to health system and group leadership for reassurance. Patients and families recognize the risks frontline providers are assuming. However, transparent communication across all levels is the key. Silos are disappearing and team based care is taking center stage.

Beyond the current public health crisis, these efforts will go a long way to create unshakable trust between health systems, providers, patients, and their loved ones.

Dr. Singh is currently the chief of inpatient operations at Adena Health System in Chillicothe, Ohio, where he also has key roles in medical informatics and health IT. He is also the president-elect of the Central Ohio Chapter of SHM.

Stadnytskyi and colleagues explored the size of droplets created by speech using a highly sensitive laser system. They reported in PNAS that speaking resulted in the generation of a high number of medium-sized droplets (10- to 100-µm in diameter). Under the conditions of their experiment (27% humidity and 23° C) they reported that speech probably generates droplets that originate at a size of 12 to 21 µm in diameter and quickly dehydrate to an estimated diameter of 4 µm. The 4 µm-sized particles had a falling rate of only 0.06 cm·s⁻¹ and remained airborne for 8 to 14 minutes.¹

As reported by Hamner and colleagues, on March 10, 2020, 61 persons attended a 2.5-hour choir practice. One choir member had symptoms of an upper respiratory infection that began on March 7. Eventually that choir member tested positive for SARS-CoV-2. Of the 60 remaining persons, 52 (86.7%) eventually developed an upper respiratory illness. In total, 33 cases of SARS-CoV-2 were confirmed by nucleic acid testing and 20 probable cases were diagnosed (these individuals declined testing). The  choir attendees developed symptoms at a median of 3 days following the practice, with a range of 1 to 12 days. Three of the 53 ill people were hospitalized, and two died.²

The Stadnytskyi study suggests that speech generates large respiratory droplets that dehydrate into very small droplets that may remain in the air for an extended period of time. If the SARS-CoV-2 virus were in the original large droplet, the rapid dehydration of the droplet would result in prolonged airborne presence of the virus and enhance its infectivity.

The Hamner study highlights the importance of vocalization and respiratory particles in transmitting the SARS-CoV-2 virus. For clinicians and patients, both studies support many recommendations to reduce viral transmission, including:

• all clinicians and patients need to wear face masks
• all clinicians and patients should avoid face-to-face contact if alternative approaches to communication are possible
• all clinicians and patients should avoid gathering in large groups or crowded public spaces and need to maintain physical distancing.

The COVID pandemic has dramatically changed how we practice medicine and socialize.

Stadnytskyi and colleagues explored the size of droplets created by speech using a highly sensitive laser system. They reported in PNAS that speaking resulted in the generation of a high number of medium-sized droplets (10- to 100-µm in diameter). Under the conditions of their experiment (27% humidity and 23° C) they reported that speech probably generates droplets that originate at a size of 12 to 21 µm in diameter and quickly dehydrate to an estimated diameter of 4 µm. The 4 µm-sized particles had a falling rate of only 0.06 cm·s⁻¹ and remained airborne for 8 to 14 minutes.¹

As reported by Hamner and colleagues, on March 10, 2020, 61 persons attended a 2.5-hour choir practice. One choir member had symptoms of an upper respiratory infection that began on March 7. Eventually that choir member tested positive for SARS-CoV-2. Of the 60 remaining persons, 52 (86.7%) eventually developed an upper respiratory illness. In total, 33 cases of SARS-CoV-2 were confirmed by nucleic acid testing and 20 probable cases were diagnosed (these individuals declined testing). The  choir attendees developed symptoms at a median of 3 days following the practice, with a range of 1 to 12 days. Three of the 53 ill people were hospitalized, and two died.²

The Stadnytskyi study suggests that speech generates large respiratory droplets that dehydrate into very small droplets that may remain in the air for an extended period of time. If the SARS-CoV-2 virus were in the original large droplet, the rapid dehydration of the droplet would result in prolonged airborne presence of the virus and enhance its infectivity.

The Hamner study highlights the importance of vocalization and respiratory particles in transmitting the SARS-CoV-2 virus. For clinicians and patients, both studies support many recommendations to reduce viral transmission, including:

• all clinicians and patients need to wear face masks
• all clinicians and patients should avoid face-to-face contact if alternative approaches to communication are possible
• all clinicians and patients should avoid gathering in large groups or crowded public spaces and need to maintain physical distancing.

The COVID pandemic has dramatically changed how we practice medicine and socialize.

Stadnytskyi and colleagues explored the size of droplets created by speech using a highly sensitive laser system. They reported in PNAS that speaking resulted in the generation of a high number of medium-sized droplets (10- to 100-µm in diameter). Under the conditions of their experiment (27% humidity and 23° C) they reported that speech probably generates droplets that originate at a size of 12 to 21 µm in diameter and quickly dehydrate to an estimated diameter of 4 µm. The 4 µm-sized particles had a falling rate of only 0.06 cm·s⁻¹ and remained airborne for 8 to 14 minutes.¹

As reported by Hamner and colleagues, on March 10, 2020, 61 persons attended a 2.5-hour choir practice. One choir member had symptoms of an upper respiratory infection that began on March 7. Eventually that choir member tested positive for SARS-CoV-2. Of the 60 remaining persons, 52 (86.7%) eventually developed an upper respiratory illness. In total, 33 cases of SARS-CoV-2 were confirmed by nucleic acid testing and 20 probable cases were diagnosed (these individuals declined testing). The  choir attendees developed symptoms at a median of 3 days following the practice, with a range of 1 to 12 days. Three of the 53 ill people were hospitalized, and two died.²

The Stadnytskyi study suggests that speech generates large respiratory droplets that dehydrate into very small droplets that may remain in the air for an extended period of time. If the SARS-CoV-2 virus were in the original large droplet, the rapid dehydration of the droplet would result in prolonged airborne presence of the virus and enhance its infectivity.

The Hamner study highlights the importance of vocalization and respiratory particles in transmitting the SARS-CoV-2 virus. For clinicians and patients, both studies support many recommendations to reduce viral transmission, including:

• all clinicians and patients need to wear face masks
• all clinicians and patients should avoid face-to-face contact if alternative approaches to communication are possible
• all clinicians and patients should avoid gathering in large groups or crowded public spaces and need to maintain physical distancing.

The COVID pandemic has dramatically changed how we practice medicine and socialize.

Inexpensively obtained as a silk industry by-product, sericin is a glycoprotein found to confer various biologic effects.¹ The globular protein sericin has also long been known to exhibit antityrosinase and immunomodulatory activities.^2,3 This column focuses on the wide range of emerging and potential applications of sericin in cutaneous treatments.

Protection against solar radiation and photoaging

Sailesh Patnaik/CCA-SA 4.0 International

Studies in mice to evaluate the potential antioxidant and skin-protective effects of sericin by Zhaorigetu et al. in 2003 revealed that, by diminishing oxidative stress, cyclooxygenase-2 protein, and cell proliferation, sericin exerted a photoprotective effect against acute harm and tumor promotion elicited by UVB.⁴

Using mouse skin models, Dash et al. showed in 2008 that the silk protein sericin derived from the tropical tasar silkworm is a robust antioxidant and photoprotective agent, displaying a capacity to block UVB-induced apoptosis in irradiated (30 mJ/cm² UVB) human keratinocytes and, as compared with the mulberry silkworm, yielding protection against oxidative stress.^5,6

In 2015, Berardesca et al. conducted a randomized, double-blind, vehicle-controlled, split-face study over 8 weeks in 40 women (ages 40-70 years) to assess the antiaging effects of topically applied combination therapy including gold silk sericin, niacinamide, and signaline. The investigators observed significant improvements in stratum corneum hydration, barrier function, skin elasticity, and roughness as compared with skin treated with the control formulation. They concluded that this combination formulation featuring gold silk sericin warrants attention in the arsenal for ameliorating signs of aging female facial skin.⁷

A year earlier, Aramwit and Bang introduced a bacterial nanocellulose gel shown to effectively release silk sericin for facial treatment. Formulated at a pH of 4.5, the bioactive mask exhibited an ultrafine and pure fiber network structure. The authors noted that the gel was less adhesive than the commercially available paper mask, while the silk sericin product displayed greater moisture absorption capacity. In vitro cytotoxicity assessments also revealed that the product is safe for facial treatments.⁸

Cosmeceutical antioxidant for hyperpigmentation

In 2019, Kumar et al. demonstrated the inhibitory effect of topically applied silk sericin derived from Antheraea assamensis against UV-induced melanogenesis in mouse melanoma. They suggested that the formulation shows promise as a cosmeceutical antioxidant agent designed to address hyperpigmentation.³

The previous year, Aramwit et al. demonstrated using an in vitro model that urea-extracted sericin displays a capacity to inhibit melanogenesis by hindering tyrosinase activity, attenuating inflammation and allergic reactions, and reducing the expression of microphthalmia-associated transcription factor, a marker of melanogenesis regulation, in melanocytes and keratinocytes.²

Potential use as an adjunct psoriasis treatment

A combination of naringin (from Citrus maxima) and sericin (from Bombyx mori) was evaluated in 2019 by Deenonpoe et al. for the treatment of psoriasis. They isolated human peripheral blood mononuclear cells from 10 healthy subjects and 10 patients with psoriasis. The combination formulation was much more effective than either compound alone in significantly reducing mRNA expression and the synthesis of proinflammatory cytokines in samples from psoriasis patients. The investigators concluded that the down-regulation of proinflammatory cytokines imparted by the naringin/sericin product points toward its possible clinical use as a complementary treatment for psoriasis and other inflammation-mediated conditions.⁹

Uremic pruritus and burn wounds

A randomized, double-blind, placebo-controlled 6-week study in 2012 conducted by Aramwit et al. assessed the use of sericin cream versus a cream base placebo in the treatment of uremic pruritus in 50 hemodialysis patients, 47 of whom completed the study. Significant differences in the creams were identified, with hydration vastly improved in patients using the sericin cream. Significant reductions in pruritus and dyspigmentation were also observed in the treatment group, with an overall quality of life improvement noted in relation to pain score.¹⁰

Gail Hampshire/Wikimedia Commons CC BY 2.0

The ensuing year, Aramwit et al. showed that silk sericin promoted wound healing in vitro and, when added to silver sulfadiazine cream and evaluated in a randomized, double-blind, standard-controlled study, demonstrated clinical efficacy in healing burn wounds.¹¹

Wound healing

An expanding body of research suggests the role of sericin in wound healing. In 2007, Aramwit et al. found that sericin, which boasts notable hydrophilic qualities, was effective as a wound-healing agent in rats. The tested sericin cream successfully reduced wound size and wound healing time was substantially shorter than in animals treated with control formula. Treatment for 15 days yielded complete healing, no ulceration, and higher collagen levels, as determined by histologic examination, in comparison with control.¹² Other studies using sericin hydrogel as well as a sericin-based nanofibrous matrix with chitosan have demonstrated success in wound healing in mice.^13,14

Human studies

In 2018, Napavichayanun et al. reported on the clinical efficacy and safety of bacterial cellulose wound dressings including silk sericin and PHMB as compared with Bactigras (an antiseptic dressing) as a control in split-thickness skin graft donor-site wound treatment. In this single-blinded, randomized, controlled study of 21 patients, pain scores were significantly lower and wound quality higher in the skin treated with the sericin product. The test formulation was protected against infection without inducing adverse effects.¹⁵

Previously, a silk sericin–releasing wound dressing introduced in 2014 was found to significantly diminish pain and promote more rapid healing in patients with split-thickness skin graft donor sites as compared with treatment with the Bactigras wound dressing.¹⁶

Sericin in tissue repair and as a drug delivery carrier

Sericin is associated with antioxidant and moisturizing properties as well as a mitogenic influence on mammalian cells, with a particular impact on keratinocytes and fibroblasts that render it useful in biomaterials designed for skin tissue repair.¹⁷

Wang et al. have cross-linked dialdehyde carboxymethyl cellulose with silk sericin derived from the B. mori cocoon to develop a film with impressive blood compatibility and cytocompatibility that shows potential for use as a wound dressing, artificial skin, and in tissue engineering.¹⁸

Similarly, Liang et al. have been successful in preparing a medical tissue glue incorporating a gelatin, sericin, and carboxymethyl chitosan blend solution, cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. The tissue glue has been found to offer notable biocompatibility and structural traits at low cost.¹⁹

Sericin protein also evinces potential as a biocompatible, bioviable carrier for drug delivery. Suktham et al. showed that resveratrol-loaded sericin nanoparticles robustly hindered growth of colorectal adenocarcinoma cells while cytotoxic to skin fibroblasts, suggesting the viability or potential of sericin nanoparticles as bionanocarriers in a drug delivery system.²⁰ In addition, Tao et al. found silk sericin to be effective when blended with poly(vinyl alcohol) in a hydrogel with antibacterial properties as a drug delivery carrier with potential for use as wound dressing.²¹

Conclusion

There is a plethora of new evidence to justify the inclusion of sericin in dermatologic research and skin care, specifically wound care. Much more research is necessary, though, to explore how the antioxidant and moisturizing activities of the protein may be harnessed to confer skin-protective effects, especially against UV damage.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers,“The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

2. Aramwit P et al. Biol Res. 2018 Nov 29;51(1):54.

3. Kumar JP, Mandal BB. Photochem Photobiol Sci. 2019 Oct 9:18(10):2497-508.

4. Zhaorigetu S et al. J Photochem Photobiol B. 2003 Oct 15;71(1-3):11-7.

5. Dash R et al. Mol Cell Biochem. 2008 Apr;311(1-2):111-9.

6. Dash R et al. BMB Rep. 2008 Mar 31;41(3):236-41.

7. Berardesca E et al. Int J Cosmet Sci. 2015 Dec;37(6):606-12.

8. Aramwit P, Bang N. BMC Biotechnol. 2014 Dec 9;14:104.

9. Deenonpoe R et al. BMC Complement Altern Med. 2019 Jul 10;19(1):168.

10. Aramwit P et al. BMC Nephrol. 2012 Sep 24;13:119.

11. Aramwit P et al. Arch Dermatol Res. 2013 Sep;305(7):585-94.

12. Aramwit P, Sangcakul A. Biosci Biotechnol Biochem. 2007 Oct;71(10):2473-7.

13. Qi C et al. Biomater Sci. 2018 Nov 1;6(11):2859-70.

14. Sapru S et al. Acta Biomater. 2018 Sep 15;78:137-50.

15. Napavichayanun S et al. Arch Dermatol Res. 2018 Dec;310(10):795-805.

16. Siritientong T et al. Pharm Res. 2014 Jan;31(1):104-16.

17. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

18. Wang P et al. Carbohydr Polym. 2019 May 15;212:403-11.

19. Liang M et al. J Appl Biomater Funct Mater. 2018 Apr;16(2):97-106.

20. Suktham K et al. Int J Pharm. 2018 Feb 15;537(1-2):48-56.

21. Tao G et al. Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:341-51.

Inexpensively obtained as a silk industry by-product, sericin is a glycoprotein found to confer various biologic effects.¹ The globular protein sericin has also long been known to exhibit antityrosinase and immunomodulatory activities.^2,3 This column focuses on the wide range of emerging and potential applications of sericin in cutaneous treatments.

Protection against solar radiation and photoaging

Sailesh Patnaik/CCA-SA 4.0 International

Studies in mice to evaluate the potential antioxidant and skin-protective effects of sericin by Zhaorigetu et al. in 2003 revealed that, by diminishing oxidative stress, cyclooxygenase-2 protein, and cell proliferation, sericin exerted a photoprotective effect against acute harm and tumor promotion elicited by UVB.⁴

Using mouse skin models, Dash et al. showed in 2008 that the silk protein sericin derived from the tropical tasar silkworm is a robust antioxidant and photoprotective agent, displaying a capacity to block UVB-induced apoptosis in irradiated (30 mJ/cm² UVB) human keratinocytes and, as compared with the mulberry silkworm, yielding protection against oxidative stress.^5,6

In 2015, Berardesca et al. conducted a randomized, double-blind, vehicle-controlled, split-face study over 8 weeks in 40 women (ages 40-70 years) to assess the antiaging effects of topically applied combination therapy including gold silk sericin, niacinamide, and signaline. The investigators observed significant improvements in stratum corneum hydration, barrier function, skin elasticity, and roughness as compared with skin treated with the control formulation. They concluded that this combination formulation featuring gold silk sericin warrants attention in the arsenal for ameliorating signs of aging female facial skin.⁷

A year earlier, Aramwit and Bang introduced a bacterial nanocellulose gel shown to effectively release silk sericin for facial treatment. Formulated at a pH of 4.5, the bioactive mask exhibited an ultrafine and pure fiber network structure. The authors noted that the gel was less adhesive than the commercially available paper mask, while the silk sericin product displayed greater moisture absorption capacity. In vitro cytotoxicity assessments also revealed that the product is safe for facial treatments.⁸

Cosmeceutical antioxidant for hyperpigmentation

In 2019, Kumar et al. demonstrated the inhibitory effect of topically applied silk sericin derived from Antheraea assamensis against UV-induced melanogenesis in mouse melanoma. They suggested that the formulation shows promise as a cosmeceutical antioxidant agent designed to address hyperpigmentation.³

The previous year, Aramwit et al. demonstrated using an in vitro model that urea-extracted sericin displays a capacity to inhibit melanogenesis by hindering tyrosinase activity, attenuating inflammation and allergic reactions, and reducing the expression of microphthalmia-associated transcription factor, a marker of melanogenesis regulation, in melanocytes and keratinocytes.²

Potential use as an adjunct psoriasis treatment

A combination of naringin (from Citrus maxima) and sericin (from Bombyx mori) was evaluated in 2019 by Deenonpoe et al. for the treatment of psoriasis. They isolated human peripheral blood mononuclear cells from 10 healthy subjects and 10 patients with psoriasis. The combination formulation was much more effective than either compound alone in significantly reducing mRNA expression and the synthesis of proinflammatory cytokines in samples from psoriasis patients. The investigators concluded that the down-regulation of proinflammatory cytokines imparted by the naringin/sericin product points toward its possible clinical use as a complementary treatment for psoriasis and other inflammation-mediated conditions.⁹

Uremic pruritus and burn wounds

A randomized, double-blind, placebo-controlled 6-week study in 2012 conducted by Aramwit et al. assessed the use of sericin cream versus a cream base placebo in the treatment of uremic pruritus in 50 hemodialysis patients, 47 of whom completed the study. Significant differences in the creams were identified, with hydration vastly improved in patients using the sericin cream. Significant reductions in pruritus and dyspigmentation were also observed in the treatment group, with an overall quality of life improvement noted in relation to pain score.¹⁰

Gail Hampshire/Wikimedia Commons CC BY 2.0

The ensuing year, Aramwit et al. showed that silk sericin promoted wound healing in vitro and, when added to silver sulfadiazine cream and evaluated in a randomized, double-blind, standard-controlled study, demonstrated clinical efficacy in healing burn wounds.¹¹

Wound healing

An expanding body of research suggests the role of sericin in wound healing. In 2007, Aramwit et al. found that sericin, which boasts notable hydrophilic qualities, was effective as a wound-healing agent in rats. The tested sericin cream successfully reduced wound size and wound healing time was substantially shorter than in animals treated with control formula. Treatment for 15 days yielded complete healing, no ulceration, and higher collagen levels, as determined by histologic examination, in comparison with control.¹² Other studies using sericin hydrogel as well as a sericin-based nanofibrous matrix with chitosan have demonstrated success in wound healing in mice.^13,14

Human studies

In 2018, Napavichayanun et al. reported on the clinical efficacy and safety of bacterial cellulose wound dressings including silk sericin and PHMB as compared with Bactigras (an antiseptic dressing) as a control in split-thickness skin graft donor-site wound treatment. In this single-blinded, randomized, controlled study of 21 patients, pain scores were significantly lower and wound quality higher in the skin treated with the sericin product. The test formulation was protected against infection without inducing adverse effects.¹⁵

Previously, a silk sericin–releasing wound dressing introduced in 2014 was found to significantly diminish pain and promote more rapid healing in patients with split-thickness skin graft donor sites as compared with treatment with the Bactigras wound dressing.¹⁶

Sericin in tissue repair and as a drug delivery carrier

Sericin is associated with antioxidant and moisturizing properties as well as a mitogenic influence on mammalian cells, with a particular impact on keratinocytes and fibroblasts that render it useful in biomaterials designed for skin tissue repair.¹⁷

Wang et al. have cross-linked dialdehyde carboxymethyl cellulose with silk sericin derived from the B. mori cocoon to develop a film with impressive blood compatibility and cytocompatibility that shows potential for use as a wound dressing, artificial skin, and in tissue engineering.¹⁸

Similarly, Liang et al. have been successful in preparing a medical tissue glue incorporating a gelatin, sericin, and carboxymethyl chitosan blend solution, cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. The tissue glue has been found to offer notable biocompatibility and structural traits at low cost.¹⁹

Sericin protein also evinces potential as a biocompatible, bioviable carrier for drug delivery. Suktham et al. showed that resveratrol-loaded sericin nanoparticles robustly hindered growth of colorectal adenocarcinoma cells while cytotoxic to skin fibroblasts, suggesting the viability or potential of sericin nanoparticles as bionanocarriers in a drug delivery system.²⁰ In addition, Tao et al. found silk sericin to be effective when blended with poly(vinyl alcohol) in a hydrogel with antibacterial properties as a drug delivery carrier with potential for use as wound dressing.²¹

Conclusion

There is a plethora of new evidence to justify the inclusion of sericin in dermatologic research and skin care, specifically wound care. Much more research is necessary, though, to explore how the antioxidant and moisturizing activities of the protein may be harnessed to confer skin-protective effects, especially against UV damage.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers,“The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

2. Aramwit P et al. Biol Res. 2018 Nov 29;51(1):54.

3. Kumar JP, Mandal BB. Photochem Photobiol Sci. 2019 Oct 9:18(10):2497-508.

4. Zhaorigetu S et al. J Photochem Photobiol B. 2003 Oct 15;71(1-3):11-7.

5. Dash R et al. Mol Cell Biochem. 2008 Apr;311(1-2):111-9.

6. Dash R et al. BMB Rep. 2008 Mar 31;41(3):236-41.

7. Berardesca E et al. Int J Cosmet Sci. 2015 Dec;37(6):606-12.

8. Aramwit P, Bang N. BMC Biotechnol. 2014 Dec 9;14:104.

9. Deenonpoe R et al. BMC Complement Altern Med. 2019 Jul 10;19(1):168.

10. Aramwit P et al. BMC Nephrol. 2012 Sep 24;13:119.

11. Aramwit P et al. Arch Dermatol Res. 2013 Sep;305(7):585-94.

12. Aramwit P, Sangcakul A. Biosci Biotechnol Biochem. 2007 Oct;71(10):2473-7.

13. Qi C et al. Biomater Sci. 2018 Nov 1;6(11):2859-70.

14. Sapru S et al. Acta Biomater. 2018 Sep 15;78:137-50.

15. Napavichayanun S et al. Arch Dermatol Res. 2018 Dec;310(10):795-805.

16. Siritientong T et al. Pharm Res. 2014 Jan;31(1):104-16.

17. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

18. Wang P et al. Carbohydr Polym. 2019 May 15;212:403-11.

19. Liang M et al. J Appl Biomater Funct Mater. 2018 Apr;16(2):97-106.

20. Suktham K et al. Int J Pharm. 2018 Feb 15;537(1-2):48-56.

21. Tao G et al. Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:341-51.

Inexpensively obtained as a silk industry by-product, sericin is a glycoprotein found to confer various biologic effects.¹ The globular protein sericin has also long been known to exhibit antityrosinase and immunomodulatory activities.^2,3 This column focuses on the wide range of emerging and potential applications of sericin in cutaneous treatments.

Protection against solar radiation and photoaging

Sailesh Patnaik/CCA-SA 4.0 International

Studies in mice to evaluate the potential antioxidant and skin-protective effects of sericin by Zhaorigetu et al. in 2003 revealed that, by diminishing oxidative stress, cyclooxygenase-2 protein, and cell proliferation, sericin exerted a photoprotective effect against acute harm and tumor promotion elicited by UVB.⁴

Using mouse skin models, Dash et al. showed in 2008 that the silk protein sericin derived from the tropical tasar silkworm is a robust antioxidant and photoprotective agent, displaying a capacity to block UVB-induced apoptosis in irradiated (30 mJ/cm² UVB) human keratinocytes and, as compared with the mulberry silkworm, yielding protection against oxidative stress.^5,6

In 2015, Berardesca et al. conducted a randomized, double-blind, vehicle-controlled, split-face study over 8 weeks in 40 women (ages 40-70 years) to assess the antiaging effects of topically applied combination therapy including gold silk sericin, niacinamide, and signaline. The investigators observed significant improvements in stratum corneum hydration, barrier function, skin elasticity, and roughness as compared with skin treated with the control formulation. They concluded that this combination formulation featuring gold silk sericin warrants attention in the arsenal for ameliorating signs of aging female facial skin.⁷

A year earlier, Aramwit and Bang introduced a bacterial nanocellulose gel shown to effectively release silk sericin for facial treatment. Formulated at a pH of 4.5, the bioactive mask exhibited an ultrafine and pure fiber network structure. The authors noted that the gel was less adhesive than the commercially available paper mask, while the silk sericin product displayed greater moisture absorption capacity. In vitro cytotoxicity assessments also revealed that the product is safe for facial treatments.⁸

Cosmeceutical antioxidant for hyperpigmentation

In 2019, Kumar et al. demonstrated the inhibitory effect of topically applied silk sericin derived from Antheraea assamensis against UV-induced melanogenesis in mouse melanoma. They suggested that the formulation shows promise as a cosmeceutical antioxidant agent designed to address hyperpigmentation.³

The previous year, Aramwit et al. demonstrated using an in vitro model that urea-extracted sericin displays a capacity to inhibit melanogenesis by hindering tyrosinase activity, attenuating inflammation and allergic reactions, and reducing the expression of microphthalmia-associated transcription factor, a marker of melanogenesis regulation, in melanocytes and keratinocytes.²

Potential use as an adjunct psoriasis treatment

A combination of naringin (from Citrus maxima) and sericin (from Bombyx mori) was evaluated in 2019 by Deenonpoe et al. for the treatment of psoriasis. They isolated human peripheral blood mononuclear cells from 10 healthy subjects and 10 patients with psoriasis. The combination formulation was much more effective than either compound alone in significantly reducing mRNA expression and the synthesis of proinflammatory cytokines in samples from psoriasis patients. The investigators concluded that the down-regulation of proinflammatory cytokines imparted by the naringin/sericin product points toward its possible clinical use as a complementary treatment for psoriasis and other inflammation-mediated conditions.⁹

Uremic pruritus and burn wounds

A randomized, double-blind, placebo-controlled 6-week study in 2012 conducted by Aramwit et al. assessed the use of sericin cream versus a cream base placebo in the treatment of uremic pruritus in 50 hemodialysis patients, 47 of whom completed the study. Significant differences in the creams were identified, with hydration vastly improved in patients using the sericin cream. Significant reductions in pruritus and dyspigmentation were also observed in the treatment group, with an overall quality of life improvement noted in relation to pain score.¹⁰

Gail Hampshire/Wikimedia Commons CC BY 2.0

The ensuing year, Aramwit et al. showed that silk sericin promoted wound healing in vitro and, when added to silver sulfadiazine cream and evaluated in a randomized, double-blind, standard-controlled study, demonstrated clinical efficacy in healing burn wounds.¹¹

Wound healing

An expanding body of research suggests the role of sericin in wound healing. In 2007, Aramwit et al. found that sericin, which boasts notable hydrophilic qualities, was effective as a wound-healing agent in rats. The tested sericin cream successfully reduced wound size and wound healing time was substantially shorter than in animals treated with control formula. Treatment for 15 days yielded complete healing, no ulceration, and higher collagen levels, as determined by histologic examination, in comparison with control.¹² Other studies using sericin hydrogel as well as a sericin-based nanofibrous matrix with chitosan have demonstrated success in wound healing in mice.^13,14

Human studies

In 2018, Napavichayanun et al. reported on the clinical efficacy and safety of bacterial cellulose wound dressings including silk sericin and PHMB as compared with Bactigras (an antiseptic dressing) as a control in split-thickness skin graft donor-site wound treatment. In this single-blinded, randomized, controlled study of 21 patients, pain scores were significantly lower and wound quality higher in the skin treated with the sericin product. The test formulation was protected against infection without inducing adverse effects.¹⁵

Previously, a silk sericin–releasing wound dressing introduced in 2014 was found to significantly diminish pain and promote more rapid healing in patients with split-thickness skin graft donor sites as compared with treatment with the Bactigras wound dressing.¹⁶

Sericin in tissue repair and as a drug delivery carrier

Sericin is associated with antioxidant and moisturizing properties as well as a mitogenic influence on mammalian cells, with a particular impact on keratinocytes and fibroblasts that render it useful in biomaterials designed for skin tissue repair.¹⁷

Wang et al. have cross-linked dialdehyde carboxymethyl cellulose with silk sericin derived from the B. mori cocoon to develop a film with impressive blood compatibility and cytocompatibility that shows potential for use as a wound dressing, artificial skin, and in tissue engineering.¹⁸

Similarly, Liang et al. have been successful in preparing a medical tissue glue incorporating a gelatin, sericin, and carboxymethyl chitosan blend solution, cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. The tissue glue has been found to offer notable biocompatibility and structural traits at low cost.¹⁹

Sericin protein also evinces potential as a biocompatible, bioviable carrier for drug delivery. Suktham et al. showed that resveratrol-loaded sericin nanoparticles robustly hindered growth of colorectal adenocarcinoma cells while cytotoxic to skin fibroblasts, suggesting the viability or potential of sericin nanoparticles as bionanocarriers in a drug delivery system.²⁰ In addition, Tao et al. found silk sericin to be effective when blended with poly(vinyl alcohol) in a hydrogel with antibacterial properties as a drug delivery carrier with potential for use as wound dressing.²¹

Conclusion

There is a plethora of new evidence to justify the inclusion of sericin in dermatologic research and skin care, specifically wound care. Much more research is necessary, though, to explore how the antioxidant and moisturizing activities of the protein may be harnessed to confer skin-protective effects, especially against UV damage.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers,“The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

2. Aramwit P et al. Biol Res. 2018 Nov 29;51(1):54.

3. Kumar JP, Mandal BB. Photochem Photobiol Sci. 2019 Oct 9:18(10):2497-508.

4. Zhaorigetu S et al. J Photochem Photobiol B. 2003 Oct 15;71(1-3):11-7.

5. Dash R et al. Mol Cell Biochem. 2008 Apr;311(1-2):111-9.

6. Dash R et al. BMB Rep. 2008 Mar 31;41(3):236-41.

7. Berardesca E et al. Int J Cosmet Sci. 2015 Dec;37(6):606-12.

8. Aramwit P, Bang N. BMC Biotechnol. 2014 Dec 9;14:104.

9. Deenonpoe R et al. BMC Complement Altern Med. 2019 Jul 10;19(1):168.

10. Aramwit P et al. BMC Nephrol. 2012 Sep 24;13:119.

11. Aramwit P et al. Arch Dermatol Res. 2013 Sep;305(7):585-94.

12. Aramwit P, Sangcakul A. Biosci Biotechnol Biochem. 2007 Oct;71(10):2473-7.

13. Qi C et al. Biomater Sci. 2018 Nov 1;6(11):2859-70.

14. Sapru S et al. Acta Biomater. 2018 Sep 15;78:137-50.

15. Napavichayanun S et al. Arch Dermatol Res. 2018 Dec;310(10):795-805.

16. Siritientong T et al. Pharm Res. 2014 Jan;31(1):104-16.

17. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

18. Wang P et al. Carbohydr Polym. 2019 May 15;212:403-11.

19. Liang M et al. J Appl Biomater Funct Mater. 2018 Apr;16(2):97-106.

20. Suktham K et al. Int J Pharm. 2018 Feb 15;537(1-2):48-56.

21. Tao G et al. Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:341-51.