User login
COVID-19 and public health preparedness in the United States
Background
On Dec. 31, 2019, the Chinese city of Wuhan reported an outbreak of pneumonia from an unknown cause. The outbreak was found to be linked to the Hunan seafood market because of a shared history of exposure by many patients. After a full-scale investigation, China’s Center for Disease Control activated a level 2 emergency response on Jan. 4, 2020. A novel coronavirus was officially identified as a causative pathogen for the outbreak.1
Coronavirus, first discovered in the 1960s, is a respiratory RNA virus, most commonly associated with the “common cold.” However, we have had two highly pathogenic forms of coronavirus that originated from animal reservoirs, leading to global epidemics. This includes SARS-CoV in 2002-2004 and MERS-CoV in 2012 with more than 10,000 combined cases. The primary host has been bats, but mammals like camels, cattle, cats, and palm civets have been intermediate hosts in previous epidemics.2
The International Committee on Taxonomy of Viruses named the 2019-nCoV officially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease, COVID-19, on Feb. 11, 2020.3 Currently, the presentation includes fever, cough, trouble breathing, fatigue, and, rarely, watery diarrhea. More severe presentations include respiratory failure and death. Based on the incubation period of illness for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses, as well as observational data from reports of travel-related COVID-19, CDC estimates that symptoms of COVID-19 occur within 2-14 days after exposure. Asymptomatic transmission is also documented in some cases.4
On Jan. 13, the first case of COVID-19 outside of China was identified in Thailand. On Jan. 21, the first case of COVID-19 was identified in the United States. On Jan. 23, Chinese authorities suspended travel in and out of Wuhan, followed by other cities in the Hubei Province, leading to a quarantine of 50 million people. By Jan. 30, the World Health Organization had identified COVID-19 as the highest level of an epidemic alert referred to as a PHEIC: Public Health Emergency of International Concern. On Feb. 2, the first death outside China from coronavirus was reported in the Philippines. As of March 4 there have been 95,000 confirmed cases and 3,246 deaths globally. Within China, there have been 80,200 cases with 2,981 deaths.5
Cases have now been diagnosed in increasing numbers in Italy, Japan, South Korea, Iran, and 76 countries. Of note, the fatalities were of patients already in critical condition, who were typically older (more than 60 years old, especially more than 80) and immunocompromised with comorbid conditions (cardiovascular disease, diabetes, chronic respiratory disease, cancer).6 To put this in perspective, since 2010, CDC reports 140,000-810,000 hospitalizations and 12,000-61,000 deaths from the influenza virus annually in the US.7
The current situation in the United States
In the United States, as of March 4, 2020, there are currently 152 confirmed cases in 16 states. The first U.S. case of coronavirus without any of the travel-related and exposure risk factors was identified on Feb. 27 in California, indicating the first instance of community spread.8 The first death was reported in Washington state on Feb. 28, after which the state’s governor declared a state of emergency.9 On March 1, Washington state health officials investigated an outbreak of coronavirus at a long-term nursing facility in which two people tested positive for the disease, heralding the probable first nosocomial transmission of the virus in the United States. Since then, there have been 10 deaths in Washington state related to the coronavirus.
Current interventions in the United States
The U.S. Centers for Disease Control and Prevention is leading a multiagency effort to combat the COVID-19 potential pandemic. A Feb. 24 report in Morbidity and Mortality Weekly Report revealed that 1,336 CDC staff members have been involved in the COVID-19 response.10 CDC staff members have been deployed to 39 locations in the United States and internationally. CDC staff members are working with state and local health departments and other public health authorities to assist with case identification, contact tracing, evaluation of persons under investigation (PUI) for COVID-19, and medical management of cases, as well as with research and academic institutions to understand the virulence, risk for transmission, and other characteristics of this novel virus. The CDC is also working with other agencies of the U.S. government including the U.S. Department of Defense, Department of Health & Human Services and the U.S. Department of State to safely evacuate U.S. citizens, residents, and their families from international locations with high incidence and transmission of COVID-19.
Specific real-time updated guidance has been developed and posted online for health care settings for patient management, infection control and prevention, laboratory testing, environmental cleaning, worker safety, and international travel. The CDC has developed communications materials in English and Spanish for communities and guidance for health care settings, public health, laboratories, schools, and businesses to prepare for a potential pandemic. Travel advisories to countries affected by the epidemic are regularly updated to inform travelers and clinicians about current health issues that need to be considered before travel.11 A level 3 travel notice (avoid all nonessential travel) for China has been in effect since Jan. 27, and on Feb. 29 this was upgraded to a level 4 travel notice.12 Airport screening has been implemented in the 11 U.S. international airports to which flights from China have been diverted, and a total of 46,016 air travelers had been screened by Feb. 23. Incoming passengers are screened for fever, cough, and shortness of breath.
Currently, the CDC has a comprehensive algorithm for further investigation of a PUI – fever, cough, shortness of breath, and a history of travel to areas with increased coronavirus circulation within 14 days of onset of symptoms, OR a close household contact of a confirmed case. When there is a PUI, the current protocol indicates health care providers should alert a local or state health department official. After the health department completes a case investigation, the CDC will help transport specimens (upper respiratory and lower respiratory specimens, and sometimes stool or urine) as soon as possible to the centralized lab for polymerase chain reaction (PCR) testing.13 CDC laboratories are currently using real-time reverse transcription–PCR (RT-PCR). The CDC is also developing a serologic test to assist with surveillance for SARS-CoV-2 circulation in the U.S. population. There is also a safe repository of viral isolates set up to help with sharing of isolates with academic institutions for research purposes.14
At hospitals and outpatient offices in the United States, we are preparing for potential cases by reminding frontline health care workers to routinely ask about travel history in addition to relevant symptoms. By eliciting the history early, they should be able to identify and isolate PUIs, appropriately minimizing exposure. Some facilities are displaying signage in waiting rooms to alert patients to provide relevant history, helping to improve triage. COVID-19 symptoms are like those of influenza (e.g., fever, cough, and shortness of breath), and the current outbreak is occurring during a time of year when respiratory illnesses from influenza and other viruses are highly prevalent. To prevent influenza and possible unnecessary evaluation for COVID-19, all persons aged 6 months and older are strongly encouraged to receive an annual influenza vaccine.
To decrease the risk for respiratory disease, persons can practice recommended preventive measures. Persons ill with symptoms of COVID-19 who have had contact with a person with COVID-19, or recent travel to countries with apparent community spread, should proactively communicate with their health care provider before showing up at the health care facility to help make arrangements to prevent possible transmission in the health care setting. In a medical emergency, they should inform emergency medical personnel about possible COVID-19 exposure. If found positive, the current recommendation is to place patients on airborne isolation. N95 masks are being recommended for health care professionals. Hospitals are reinforcing effective infection control procedures, updating pandemic preparedness protocols, and ensuring adequate supplies in the case of an enormous influx of patients.15
Challenges and opportunities
Many challenges present in the process of getting prepared for a potential outbreak. Personal protective equipment such as N-95 masks are in short supply, as they are in high demand in the general public.16 The CDC currently does not recommend that members of the general public use face masks, given low levels of circulation of SARS-CoV-2 currently in the United States. The CDC has developed several documents regarding infection control, hospital preparedness assessments, personal protective equipment (PPE) supply planning, clinical evaluation and management, and respirator conservation strategies.
The RT-PCR test developed by the CDC has had some setbacks, with recent testing kits showing “inconclusive results.” The testing was initially available only through the CDC lab in Atlanta, with a 48-hour turnaround. This led to potential delays in diagnosis and the timely isolation and treatment of infected patients. On March 3, the CDC broadened the guidelines for coronavirus testing, allowing clinicians to order a test for any patients who have symptoms of COVID-19 infection. The greatest need is for decentralized testing in local and state labs, as well as validated testing in local hospitals and commercial labs. The ability to develop and scale-up diagnostic abilities is critically important.
There is also concern about overwhelming hospitals with a strain on the availability of beds, ventilators, and airborne isolation rooms. The CDC is recommending leveraging telehealth tools to direct people to the right level of health care for their medical needs. Hospitalization should only be for the sickest patients.17
Funding for a pandemic response is of paramount importance. Proposed 2021 federal budget cuts include $2.9 billion in cuts to the National Institutes of Health, and $708 million in cuts to the CDC, which makes the situation look especially worrisome as we face a potentially severe pandemic. The Infectious Diseases Society of America identifies antimicrobial resistance, NIH research, global health security, global HIV epidemic, and CDC vaccine programs as five “deeply underfunded” areas in the federal budget.18
The NIH has recently begun the first randomized clinical trial, treating patients at the University of Nebraska with laboratory-confirmed SARS-CoV-2 with a broad-spectrum antiviral drug called remdesivir. Patients from the Diamond Princess Cruise ship are also participating in this clinical trial. This study will hopefully shed light on potential treatments for coronavirus to stop or alleviate the consequences in real time. Similar clinical trials are also occurring in China.19
Vaccine development is underway in many public and private research facilities, but it will take approximately 6-18 months before they will be available for use. In the absence of a vaccine or therapeutic, community mitigation measures are the primary method to respond to the widespread transmission, and supportive care is the current medical treatment. In the case of a pandemic, the mitigation measures might include school dismissals and social distancing in other settings, like suspension of mass gatherings, telework and remote-meeting options in workplaces.
Many respected medical journals in the United States have made access to SARS-CoV-2 articles and literature readily and freely available, which is a remarkable step. Multiple societies and journals have made information available in real time and have used media effectively (e.g., podcasts, e-learning) to disseminate information to the general public. Articles have been made available in other languages, including Chinese.
Conclusions
In summary, there have been 3,280 total deaths attributable to SARS-CoV-2 to date globally, mostly among geriatric patients with comorbidities. To provide some perspective on the statistics, influenza has killed almost 14,000 patients this season alone (much more than coronavirus). COVID-19 is undoubtedly a global public health threat. We in the U.S. health care system are taking swift public health actions, including isolation of patients and contacts to prevent secondary spread, but it is unclear if this is enough to stop an outbreak from becoming a pandemic.
The CDC is warning of significant social and economic disruption in the coming weeks, with more expected community spread and confirmed cases. It is challenging to prepare for a pandemic when the transmission dynamics are not clearly known, the duration of infectiousness is not well defined, and asymptomatic transmission is a possibility. It is time for the public to be informed from trusted sources and avoid unverified information, especially on social media which can lead to confusion and panic. The spread of COVID-19 infection in the United States is inevitable, and there must be sufficient, well-coordinated planning that can curtail the spread and reduce the impact.
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. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson. Ms. Sathya Areti is a 3rd-year medical student at the Virginia Commonwealth University School of Medicine (class of 2021), planning to apply into Internal Medicine-Pediatrics. Dr. Swetha Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is also a member of the Wellspan Pharmacy and Therapeutics committee.
References
1. Phelan AL et al. The novel coronavirus originating in Wuhan, China: Challenges for global health governance. JAMA. 2020;323(8):709-10. doi: 10.1001/jama.2020.1097.
2. del Rio C, Malani PN. 2019 Novel coronavirus – Important information for clinicians. JAMA. Published online Feb. 5, 2020. doi: 10.1001/jama.2020.1490.
3. Gorbalenya AE et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. Published Jan. 1, 2020. doi: 10.1101/2020.02.07.937862.
4. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
5. Coronavirus disease 2019 (COVID-19). Situation Report – 40. Published Feb. 29, 2020.
6. Kaiyuan Sun, et al. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population level observational study, Feb. 20, 2020. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30026-1.
7. Rolfes MA et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018;12(1):132-7. doi: 10.1111/irv.12486.
8. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
9. Jablon R, Baumann L. Washington governor declares state of emergency over virus. AP News. Published Feb. 29, 2020.
10. Jernigan DB, CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-219. doi: 10.15585/mmwr.mm6908e1.
11. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb 24, 2020.
12. Hines M. Coronavirus: Travel advisory for Italy, South Korea raised to level 4, ‘Do Not Travel’. USA Today. Published Feb. 29, 2020.
13. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb. 24, 2020.
14. CDC Tests for COVID-19. Centers for Disease Control and Prevention. Published Feb. 25, 2020.
15. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-19. doi: 10.15585/mmwr.mm6908e1.
16. Gunia A. The global shortage of medical masks won’t be easing soon. Time. Published Feb. 27, 2020.
17. CDC in action: Preparing communities for potential spread of COVID-19. Centers for Disease Control and Prevention. Published Feb. 23, 2020.
18. Kadets L. White House budget cuts vital domestic and global public health programs. IDSA Home. Published 2020.
19. NIH clinical trial of remdesivir to treat COVID-19 begins. National Institutes of Health. Feb. 25, 2020.
Background
On Dec. 31, 2019, the Chinese city of Wuhan reported an outbreak of pneumonia from an unknown cause. The outbreak was found to be linked to the Hunan seafood market because of a shared history of exposure by many patients. After a full-scale investigation, China’s Center for Disease Control activated a level 2 emergency response on Jan. 4, 2020. A novel coronavirus was officially identified as a causative pathogen for the outbreak.1
Coronavirus, first discovered in the 1960s, is a respiratory RNA virus, most commonly associated with the “common cold.” However, we have had two highly pathogenic forms of coronavirus that originated from animal reservoirs, leading to global epidemics. This includes SARS-CoV in 2002-2004 and MERS-CoV in 2012 with more than 10,000 combined cases. The primary host has been bats, but mammals like camels, cattle, cats, and palm civets have been intermediate hosts in previous epidemics.2
The International Committee on Taxonomy of Viruses named the 2019-nCoV officially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease, COVID-19, on Feb. 11, 2020.3 Currently, the presentation includes fever, cough, trouble breathing, fatigue, and, rarely, watery diarrhea. More severe presentations include respiratory failure and death. Based on the incubation period of illness for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses, as well as observational data from reports of travel-related COVID-19, CDC estimates that symptoms of COVID-19 occur within 2-14 days after exposure. Asymptomatic transmission is also documented in some cases.4
On Jan. 13, the first case of COVID-19 outside of China was identified in Thailand. On Jan. 21, the first case of COVID-19 was identified in the United States. On Jan. 23, Chinese authorities suspended travel in and out of Wuhan, followed by other cities in the Hubei Province, leading to a quarantine of 50 million people. By Jan. 30, the World Health Organization had identified COVID-19 as the highest level of an epidemic alert referred to as a PHEIC: Public Health Emergency of International Concern. On Feb. 2, the first death outside China from coronavirus was reported in the Philippines. As of March 4 there have been 95,000 confirmed cases and 3,246 deaths globally. Within China, there have been 80,200 cases with 2,981 deaths.5
Cases have now been diagnosed in increasing numbers in Italy, Japan, South Korea, Iran, and 76 countries. Of note, the fatalities were of patients already in critical condition, who were typically older (more than 60 years old, especially more than 80) and immunocompromised with comorbid conditions (cardiovascular disease, diabetes, chronic respiratory disease, cancer).6 To put this in perspective, since 2010, CDC reports 140,000-810,000 hospitalizations and 12,000-61,000 deaths from the influenza virus annually in the US.7
The current situation in the United States
In the United States, as of March 4, 2020, there are currently 152 confirmed cases in 16 states. The first U.S. case of coronavirus without any of the travel-related and exposure risk factors was identified on Feb. 27 in California, indicating the first instance of community spread.8 The first death was reported in Washington state on Feb. 28, after which the state’s governor declared a state of emergency.9 On March 1, Washington state health officials investigated an outbreak of coronavirus at a long-term nursing facility in which two people tested positive for the disease, heralding the probable first nosocomial transmission of the virus in the United States. Since then, there have been 10 deaths in Washington state related to the coronavirus.
Current interventions in the United States
The U.S. Centers for Disease Control and Prevention is leading a multiagency effort to combat the COVID-19 potential pandemic. A Feb. 24 report in Morbidity and Mortality Weekly Report revealed that 1,336 CDC staff members have been involved in the COVID-19 response.10 CDC staff members have been deployed to 39 locations in the United States and internationally. CDC staff members are working with state and local health departments and other public health authorities to assist with case identification, contact tracing, evaluation of persons under investigation (PUI) for COVID-19, and medical management of cases, as well as with research and academic institutions to understand the virulence, risk for transmission, and other characteristics of this novel virus. The CDC is also working with other agencies of the U.S. government including the U.S. Department of Defense, Department of Health & Human Services and the U.S. Department of State to safely evacuate U.S. citizens, residents, and their families from international locations with high incidence and transmission of COVID-19.
Specific real-time updated guidance has been developed and posted online for health care settings for patient management, infection control and prevention, laboratory testing, environmental cleaning, worker safety, and international travel. The CDC has developed communications materials in English and Spanish for communities and guidance for health care settings, public health, laboratories, schools, and businesses to prepare for a potential pandemic. Travel advisories to countries affected by the epidemic are regularly updated to inform travelers and clinicians about current health issues that need to be considered before travel.11 A level 3 travel notice (avoid all nonessential travel) for China has been in effect since Jan. 27, and on Feb. 29 this was upgraded to a level 4 travel notice.12 Airport screening has been implemented in the 11 U.S. international airports to which flights from China have been diverted, and a total of 46,016 air travelers had been screened by Feb. 23. Incoming passengers are screened for fever, cough, and shortness of breath.
Currently, the CDC has a comprehensive algorithm for further investigation of a PUI – fever, cough, shortness of breath, and a history of travel to areas with increased coronavirus circulation within 14 days of onset of symptoms, OR a close household contact of a confirmed case. When there is a PUI, the current protocol indicates health care providers should alert a local or state health department official. After the health department completes a case investigation, the CDC will help transport specimens (upper respiratory and lower respiratory specimens, and sometimes stool or urine) as soon as possible to the centralized lab for polymerase chain reaction (PCR) testing.13 CDC laboratories are currently using real-time reverse transcription–PCR (RT-PCR). The CDC is also developing a serologic test to assist with surveillance for SARS-CoV-2 circulation in the U.S. population. There is also a safe repository of viral isolates set up to help with sharing of isolates with academic institutions for research purposes.14
At hospitals and outpatient offices in the United States, we are preparing for potential cases by reminding frontline health care workers to routinely ask about travel history in addition to relevant symptoms. By eliciting the history early, they should be able to identify and isolate PUIs, appropriately minimizing exposure. Some facilities are displaying signage in waiting rooms to alert patients to provide relevant history, helping to improve triage. COVID-19 symptoms are like those of influenza (e.g., fever, cough, and shortness of breath), and the current outbreak is occurring during a time of year when respiratory illnesses from influenza and other viruses are highly prevalent. To prevent influenza and possible unnecessary evaluation for COVID-19, all persons aged 6 months and older are strongly encouraged to receive an annual influenza vaccine.
To decrease the risk for respiratory disease, persons can practice recommended preventive measures. Persons ill with symptoms of COVID-19 who have had contact with a person with COVID-19, or recent travel to countries with apparent community spread, should proactively communicate with their health care provider before showing up at the health care facility to help make arrangements to prevent possible transmission in the health care setting. In a medical emergency, they should inform emergency medical personnel about possible COVID-19 exposure. If found positive, the current recommendation is to place patients on airborne isolation. N95 masks are being recommended for health care professionals. Hospitals are reinforcing effective infection control procedures, updating pandemic preparedness protocols, and ensuring adequate supplies in the case of an enormous influx of patients.15
Challenges and opportunities
Many challenges present in the process of getting prepared for a potential outbreak. Personal protective equipment such as N-95 masks are in short supply, as they are in high demand in the general public.16 The CDC currently does not recommend that members of the general public use face masks, given low levels of circulation of SARS-CoV-2 currently in the United States. The CDC has developed several documents regarding infection control, hospital preparedness assessments, personal protective equipment (PPE) supply planning, clinical evaluation and management, and respirator conservation strategies.
The RT-PCR test developed by the CDC has had some setbacks, with recent testing kits showing “inconclusive results.” The testing was initially available only through the CDC lab in Atlanta, with a 48-hour turnaround. This led to potential delays in diagnosis and the timely isolation and treatment of infected patients. On March 3, the CDC broadened the guidelines for coronavirus testing, allowing clinicians to order a test for any patients who have symptoms of COVID-19 infection. The greatest need is for decentralized testing in local and state labs, as well as validated testing in local hospitals and commercial labs. The ability to develop and scale-up diagnostic abilities is critically important.
There is also concern about overwhelming hospitals with a strain on the availability of beds, ventilators, and airborne isolation rooms. The CDC is recommending leveraging telehealth tools to direct people to the right level of health care for their medical needs. Hospitalization should only be for the sickest patients.17
Funding for a pandemic response is of paramount importance. Proposed 2021 federal budget cuts include $2.9 billion in cuts to the National Institutes of Health, and $708 million in cuts to the CDC, which makes the situation look especially worrisome as we face a potentially severe pandemic. The Infectious Diseases Society of America identifies antimicrobial resistance, NIH research, global health security, global HIV epidemic, and CDC vaccine programs as five “deeply underfunded” areas in the federal budget.18
The NIH has recently begun the first randomized clinical trial, treating patients at the University of Nebraska with laboratory-confirmed SARS-CoV-2 with a broad-spectrum antiviral drug called remdesivir. Patients from the Diamond Princess Cruise ship are also participating in this clinical trial. This study will hopefully shed light on potential treatments for coronavirus to stop or alleviate the consequences in real time. Similar clinical trials are also occurring in China.19
Vaccine development is underway in many public and private research facilities, but it will take approximately 6-18 months before they will be available for use. In the absence of a vaccine or therapeutic, community mitigation measures are the primary method to respond to the widespread transmission, and supportive care is the current medical treatment. In the case of a pandemic, the mitigation measures might include school dismissals and social distancing in other settings, like suspension of mass gatherings, telework and remote-meeting options in workplaces.
Many respected medical journals in the United States have made access to SARS-CoV-2 articles and literature readily and freely available, which is a remarkable step. Multiple societies and journals have made information available in real time and have used media effectively (e.g., podcasts, e-learning) to disseminate information to the general public. Articles have been made available in other languages, including Chinese.
Conclusions
In summary, there have been 3,280 total deaths attributable to SARS-CoV-2 to date globally, mostly among geriatric patients with comorbidities. To provide some perspective on the statistics, influenza has killed almost 14,000 patients this season alone (much more than coronavirus). COVID-19 is undoubtedly a global public health threat. We in the U.S. health care system are taking swift public health actions, including isolation of patients and contacts to prevent secondary spread, but it is unclear if this is enough to stop an outbreak from becoming a pandemic.
The CDC is warning of significant social and economic disruption in the coming weeks, with more expected community spread and confirmed cases. It is challenging to prepare for a pandemic when the transmission dynamics are not clearly known, the duration of infectiousness is not well defined, and asymptomatic transmission is a possibility. It is time for the public to be informed from trusted sources and avoid unverified information, especially on social media which can lead to confusion and panic. The spread of COVID-19 infection in the United States is inevitable, and there must be sufficient, well-coordinated planning that can curtail the spread and reduce the impact.
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. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson. Ms. Sathya Areti is a 3rd-year medical student at the Virginia Commonwealth University School of Medicine (class of 2021), planning to apply into Internal Medicine-Pediatrics. Dr. Swetha Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is also a member of the Wellspan Pharmacy and Therapeutics committee.
References
1. Phelan AL et al. The novel coronavirus originating in Wuhan, China: Challenges for global health governance. JAMA. 2020;323(8):709-10. doi: 10.1001/jama.2020.1097.
2. del Rio C, Malani PN. 2019 Novel coronavirus – Important information for clinicians. JAMA. Published online Feb. 5, 2020. doi: 10.1001/jama.2020.1490.
3. Gorbalenya AE et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. Published Jan. 1, 2020. doi: 10.1101/2020.02.07.937862.
4. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
5. Coronavirus disease 2019 (COVID-19). Situation Report – 40. Published Feb. 29, 2020.
6. Kaiyuan Sun, et al. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population level observational study, Feb. 20, 2020. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30026-1.
7. Rolfes MA et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018;12(1):132-7. doi: 10.1111/irv.12486.
8. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
9. Jablon R, Baumann L. Washington governor declares state of emergency over virus. AP News. Published Feb. 29, 2020.
10. Jernigan DB, CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-219. doi: 10.15585/mmwr.mm6908e1.
11. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb 24, 2020.
12. Hines M. Coronavirus: Travel advisory for Italy, South Korea raised to level 4, ‘Do Not Travel’. USA Today. Published Feb. 29, 2020.
13. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb. 24, 2020.
14. CDC Tests for COVID-19. Centers for Disease Control and Prevention. Published Feb. 25, 2020.
15. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-19. doi: 10.15585/mmwr.mm6908e1.
16. Gunia A. The global shortage of medical masks won’t be easing soon. Time. Published Feb. 27, 2020.
17. CDC in action: Preparing communities for potential spread of COVID-19. Centers for Disease Control and Prevention. Published Feb. 23, 2020.
18. Kadets L. White House budget cuts vital domestic and global public health programs. IDSA Home. Published 2020.
19. NIH clinical trial of remdesivir to treat COVID-19 begins. National Institutes of Health. Feb. 25, 2020.
Background
On Dec. 31, 2019, the Chinese city of Wuhan reported an outbreak of pneumonia from an unknown cause. The outbreak was found to be linked to the Hunan seafood market because of a shared history of exposure by many patients. After a full-scale investigation, China’s Center for Disease Control activated a level 2 emergency response on Jan. 4, 2020. A novel coronavirus was officially identified as a causative pathogen for the outbreak.1
Coronavirus, first discovered in the 1960s, is a respiratory RNA virus, most commonly associated with the “common cold.” However, we have had two highly pathogenic forms of coronavirus that originated from animal reservoirs, leading to global epidemics. This includes SARS-CoV in 2002-2004 and MERS-CoV in 2012 with more than 10,000 combined cases. The primary host has been bats, but mammals like camels, cattle, cats, and palm civets have been intermediate hosts in previous epidemics.2
The International Committee on Taxonomy of Viruses named the 2019-nCoV officially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease, COVID-19, on Feb. 11, 2020.3 Currently, the presentation includes fever, cough, trouble breathing, fatigue, and, rarely, watery diarrhea. More severe presentations include respiratory failure and death. Based on the incubation period of illness for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses, as well as observational data from reports of travel-related COVID-19, CDC estimates that symptoms of COVID-19 occur within 2-14 days after exposure. Asymptomatic transmission is also documented in some cases.4
On Jan. 13, the first case of COVID-19 outside of China was identified in Thailand. On Jan. 21, the first case of COVID-19 was identified in the United States. On Jan. 23, Chinese authorities suspended travel in and out of Wuhan, followed by other cities in the Hubei Province, leading to a quarantine of 50 million people. By Jan. 30, the World Health Organization had identified COVID-19 as the highest level of an epidemic alert referred to as a PHEIC: Public Health Emergency of International Concern. On Feb. 2, the first death outside China from coronavirus was reported in the Philippines. As of March 4 there have been 95,000 confirmed cases and 3,246 deaths globally. Within China, there have been 80,200 cases with 2,981 deaths.5
Cases have now been diagnosed in increasing numbers in Italy, Japan, South Korea, Iran, and 76 countries. Of note, the fatalities were of patients already in critical condition, who were typically older (more than 60 years old, especially more than 80) and immunocompromised with comorbid conditions (cardiovascular disease, diabetes, chronic respiratory disease, cancer).6 To put this in perspective, since 2010, CDC reports 140,000-810,000 hospitalizations and 12,000-61,000 deaths from the influenza virus annually in the US.7
The current situation in the United States
In the United States, as of March 4, 2020, there are currently 152 confirmed cases in 16 states. The first U.S. case of coronavirus without any of the travel-related and exposure risk factors was identified on Feb. 27 in California, indicating the first instance of community spread.8 The first death was reported in Washington state on Feb. 28, after which the state’s governor declared a state of emergency.9 On March 1, Washington state health officials investigated an outbreak of coronavirus at a long-term nursing facility in which two people tested positive for the disease, heralding the probable first nosocomial transmission of the virus in the United States. Since then, there have been 10 deaths in Washington state related to the coronavirus.
Current interventions in the United States
The U.S. Centers for Disease Control and Prevention is leading a multiagency effort to combat the COVID-19 potential pandemic. A Feb. 24 report in Morbidity and Mortality Weekly Report revealed that 1,336 CDC staff members have been involved in the COVID-19 response.10 CDC staff members have been deployed to 39 locations in the United States and internationally. CDC staff members are working with state and local health departments and other public health authorities to assist with case identification, contact tracing, evaluation of persons under investigation (PUI) for COVID-19, and medical management of cases, as well as with research and academic institutions to understand the virulence, risk for transmission, and other characteristics of this novel virus. The CDC is also working with other agencies of the U.S. government including the U.S. Department of Defense, Department of Health & Human Services and the U.S. Department of State to safely evacuate U.S. citizens, residents, and their families from international locations with high incidence and transmission of COVID-19.
Specific real-time updated guidance has been developed and posted online for health care settings for patient management, infection control and prevention, laboratory testing, environmental cleaning, worker safety, and international travel. The CDC has developed communications materials in English and Spanish for communities and guidance for health care settings, public health, laboratories, schools, and businesses to prepare for a potential pandemic. Travel advisories to countries affected by the epidemic are regularly updated to inform travelers and clinicians about current health issues that need to be considered before travel.11 A level 3 travel notice (avoid all nonessential travel) for China has been in effect since Jan. 27, and on Feb. 29 this was upgraded to a level 4 travel notice.12 Airport screening has been implemented in the 11 U.S. international airports to which flights from China have been diverted, and a total of 46,016 air travelers had been screened by Feb. 23. Incoming passengers are screened for fever, cough, and shortness of breath.
Currently, the CDC has a comprehensive algorithm for further investigation of a PUI – fever, cough, shortness of breath, and a history of travel to areas with increased coronavirus circulation within 14 days of onset of symptoms, OR a close household contact of a confirmed case. When there is a PUI, the current protocol indicates health care providers should alert a local or state health department official. After the health department completes a case investigation, the CDC will help transport specimens (upper respiratory and lower respiratory specimens, and sometimes stool or urine) as soon as possible to the centralized lab for polymerase chain reaction (PCR) testing.13 CDC laboratories are currently using real-time reverse transcription–PCR (RT-PCR). The CDC is also developing a serologic test to assist with surveillance for SARS-CoV-2 circulation in the U.S. population. There is also a safe repository of viral isolates set up to help with sharing of isolates with academic institutions for research purposes.14
At hospitals and outpatient offices in the United States, we are preparing for potential cases by reminding frontline health care workers to routinely ask about travel history in addition to relevant symptoms. By eliciting the history early, they should be able to identify and isolate PUIs, appropriately minimizing exposure. Some facilities are displaying signage in waiting rooms to alert patients to provide relevant history, helping to improve triage. COVID-19 symptoms are like those of influenza (e.g., fever, cough, and shortness of breath), and the current outbreak is occurring during a time of year when respiratory illnesses from influenza and other viruses are highly prevalent. To prevent influenza and possible unnecessary evaluation for COVID-19, all persons aged 6 months and older are strongly encouraged to receive an annual influenza vaccine.
To decrease the risk for respiratory disease, persons can practice recommended preventive measures. Persons ill with symptoms of COVID-19 who have had contact with a person with COVID-19, or recent travel to countries with apparent community spread, should proactively communicate with their health care provider before showing up at the health care facility to help make arrangements to prevent possible transmission in the health care setting. In a medical emergency, they should inform emergency medical personnel about possible COVID-19 exposure. If found positive, the current recommendation is to place patients on airborne isolation. N95 masks are being recommended for health care professionals. Hospitals are reinforcing effective infection control procedures, updating pandemic preparedness protocols, and ensuring adequate supplies in the case of an enormous influx of patients.15
Challenges and opportunities
Many challenges present in the process of getting prepared for a potential outbreak. Personal protective equipment such as N-95 masks are in short supply, as they are in high demand in the general public.16 The CDC currently does not recommend that members of the general public use face masks, given low levels of circulation of SARS-CoV-2 currently in the United States. The CDC has developed several documents regarding infection control, hospital preparedness assessments, personal protective equipment (PPE) supply planning, clinical evaluation and management, and respirator conservation strategies.
The RT-PCR test developed by the CDC has had some setbacks, with recent testing kits showing “inconclusive results.” The testing was initially available only through the CDC lab in Atlanta, with a 48-hour turnaround. This led to potential delays in diagnosis and the timely isolation and treatment of infected patients. On March 3, the CDC broadened the guidelines for coronavirus testing, allowing clinicians to order a test for any patients who have symptoms of COVID-19 infection. The greatest need is for decentralized testing in local and state labs, as well as validated testing in local hospitals and commercial labs. The ability to develop and scale-up diagnostic abilities is critically important.
There is also concern about overwhelming hospitals with a strain on the availability of beds, ventilators, and airborne isolation rooms. The CDC is recommending leveraging telehealth tools to direct people to the right level of health care for their medical needs. Hospitalization should only be for the sickest patients.17
Funding for a pandemic response is of paramount importance. Proposed 2021 federal budget cuts include $2.9 billion in cuts to the National Institutes of Health, and $708 million in cuts to the CDC, which makes the situation look especially worrisome as we face a potentially severe pandemic. The Infectious Diseases Society of America identifies antimicrobial resistance, NIH research, global health security, global HIV epidemic, and CDC vaccine programs as five “deeply underfunded” areas in the federal budget.18
The NIH has recently begun the first randomized clinical trial, treating patients at the University of Nebraska with laboratory-confirmed SARS-CoV-2 with a broad-spectrum antiviral drug called remdesivir. Patients from the Diamond Princess Cruise ship are also participating in this clinical trial. This study will hopefully shed light on potential treatments for coronavirus to stop or alleviate the consequences in real time. Similar clinical trials are also occurring in China.19
Vaccine development is underway in many public and private research facilities, but it will take approximately 6-18 months before they will be available for use. In the absence of a vaccine or therapeutic, community mitigation measures are the primary method to respond to the widespread transmission, and supportive care is the current medical treatment. In the case of a pandemic, the mitigation measures might include school dismissals and social distancing in other settings, like suspension of mass gatherings, telework and remote-meeting options in workplaces.
Many respected medical journals in the United States have made access to SARS-CoV-2 articles and literature readily and freely available, which is a remarkable step. Multiple societies and journals have made information available in real time and have used media effectively (e.g., podcasts, e-learning) to disseminate information to the general public. Articles have been made available in other languages, including Chinese.
Conclusions
In summary, there have been 3,280 total deaths attributable to SARS-CoV-2 to date globally, mostly among geriatric patients with comorbidities. To provide some perspective on the statistics, influenza has killed almost 14,000 patients this season alone (much more than coronavirus). COVID-19 is undoubtedly a global public health threat. We in the U.S. health care system are taking swift public health actions, including isolation of patients and contacts to prevent secondary spread, but it is unclear if this is enough to stop an outbreak from becoming a pandemic.
The CDC is warning of significant social and economic disruption in the coming weeks, with more expected community spread and confirmed cases. It is challenging to prepare for a pandemic when the transmission dynamics are not clearly known, the duration of infectiousness is not well defined, and asymptomatic transmission is a possibility. It is time for the public to be informed from trusted sources and avoid unverified information, especially on social media which can lead to confusion and panic. The spread of COVID-19 infection in the United States is inevitable, and there must be sufficient, well-coordinated planning that can curtail the spread and reduce the impact.
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. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson. Ms. Sathya Areti is a 3rd-year medical student at the Virginia Commonwealth University School of Medicine (class of 2021), planning to apply into Internal Medicine-Pediatrics. Dr. Swetha Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is also a member of the Wellspan Pharmacy and Therapeutics committee.
References
1. Phelan AL et al. The novel coronavirus originating in Wuhan, China: Challenges for global health governance. JAMA. 2020;323(8):709-10. doi: 10.1001/jama.2020.1097.
2. del Rio C, Malani PN. 2019 Novel coronavirus – Important information for clinicians. JAMA. Published online Feb. 5, 2020. doi: 10.1001/jama.2020.1490.
3. Gorbalenya AE et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. Published Jan. 1, 2020. doi: 10.1101/2020.02.07.937862.
4. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
5. Coronavirus disease 2019 (COVID-19). Situation Report – 40. Published Feb. 29, 2020.
6. Kaiyuan Sun, et al. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population level observational study, Feb. 20, 2020. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30026-1.
7. Rolfes MA et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018;12(1):132-7. doi: 10.1111/irv.12486.
8. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
9. Jablon R, Baumann L. Washington governor declares state of emergency over virus. AP News. Published Feb. 29, 2020.
10. Jernigan DB, CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-219. doi: 10.15585/mmwr.mm6908e1.
11. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb 24, 2020.
12. Hines M. Coronavirus: Travel advisory for Italy, South Korea raised to level 4, ‘Do Not Travel’. USA Today. Published Feb. 29, 2020.
13. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb. 24, 2020.
14. CDC Tests for COVID-19. Centers for Disease Control and Prevention. Published Feb. 25, 2020.
15. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-19. doi: 10.15585/mmwr.mm6908e1.
16. Gunia A. The global shortage of medical masks won’t be easing soon. Time. Published Feb. 27, 2020.
17. CDC in action: Preparing communities for potential spread of COVID-19. Centers for Disease Control and Prevention. Published Feb. 23, 2020.
18. Kadets L. White House budget cuts vital domestic and global public health programs. IDSA Home. Published 2020.
19. NIH clinical trial of remdesivir to treat COVID-19 begins. National Institutes of Health. Feb. 25, 2020.
Infection control protects hospital staff from COVID-19, study shows
Hospital-related infections have been widely reported during the ongoing coronavirus outbreak, with healthcare professionals bearing a disproportionate risk. However, a proactive response in Hong Kong’s public hospital system appears to have bucked this trend and successfully protected both patients and staff from SARS-CoV-2, according to a study published online today in Infection Control & Hospital Epidemiology.
During the first 42 days of the outbreak, the 43 hospitals in the network tested 1275 suspected cases and treated 42 patients with confirmed COVID-19, the disease caused by SARS-CoV-2 infection. Yet, there were no nosocomial infections or infections among healthcare personnel, report Vincent C.C. Cheng, MD, FRCPath, the hospital’s infection control officer, and colleagues.
Cheng and colleagues note that 11 out of 413 healthcare workers who treat patients with confirmed infections had unprotected exposure and were in quarantine for 14 days, but none became ill.
In comparison, they note, the 2003 SARS outbreak saw almost 60% of nosocomial cases occurring in healthcare workers.
Proactive bundle
The Hong Kong success story may be due to a stepped-up proactive bundle of measures that included enhanced laboratory surveillance, early airborne infection isolation, and rapid-turnaround molecular diagnostics. Other strategies included staff forums and one-on-one discussions about infection control, employee training in protective equipment use, hand-hygiene compliance enforcement, and contact tracing for workers with unprotected exposure.
In addition, surgical masks were provided for all healthcare workers, patients, and visitors to clinical areas, a practice previously associated with reduced in-hospital transmission during influenza outbreaks, the authors note.
Hospitals also mandated use of personal protective equipment (PPE) for aerosol-generating procedures (AGPs), such as endotracheal intubation, open suctioning, and high-flow oxygen use, as AGPs had been linked to nosocomial transmission to healthcare workers during the 2003 SARS outbreak.
The infection control measures, which were part of a preparedness plan developed after the SARS outbreak, were initiated on December 31, when the first reports of a cluster of infections came from Wuhan, China.
As the outbreak evolved, the Hong Kong hospitals quickly widened the epidemiologic criteria for screening, from initially including only those who had been to a wet market in Wuhan within 14 days of symptom onset, to eventually including anyone who had been to Hubei province, been in a medical facility in mainland China, or in contact with a known case.
All suspected cases were sent to an airborne-infection isolation room (AIIR) or a ward with at least a meter of space between patients.
“Appropriate hospital infection control measures could prevent nosocomial transmission of SARS-CoV-2,” the authors write. “Vigilance in hand hygiene practice, wearing of surgical mask in the hospital, and appropriate use of PPE in patient care, especially [when] performing AGPs, are the key infection control measures to prevent nosocomial transmission of SARS-CoV-2 even before the availability of effective antiviral agents and vaccine.”
Asked for his perspective on the report, Aaron E. Glatt, MD, chairman of the department of medicine and chief of infectious diseases at Mount Sinai South Nassau in Oceanside, New York, said that apart from the widespread issuing of surgical masks to workers, patients, and visitors, the measures taken in Hong Kong are not different from standard infection-control practices in American hospitals. Glatt, who is also a hospital epidemiologist, said it was unclear how much impact the masks would have.
“Although the infection control was impressive, I don’t see any evidence of a difference in care,” he told Medscape Medical News.
Could zero infection transmission be achieved in the more far-flung and variable settings of hospitals across the United States? “The ability to get zero transmission is only possible if people adhere to the strictest infection-control guidelines,” Glatt said. “That is clearly the goal, and it will take time to see if our existing strict guidelines are sufficient to maintain zero or close to zero contamination and transmission rates in our hospitals.”
Rather than looking to change US practices, he stressed adherence to widely established tenets of care. “It’s critically important to keep paying close attention to the basics, to the simple blocking and tackling, and to identify which patients are at risk, and therefore, when workers need protective equipment,” he said.
“Follow the recommended standards,” continued Glatt, who is also a spokesperson for the Infectious Diseases Society of America and did not participate in this study.
In a finding from an ancillary pilot experiment, the Hong Kong researchers found exhaled air from a patient with a moderate coronavirus load showed no evidence of the virus, whether the patient was breathing normally or heavily, speaking, or coughing. And spot tests around the room detected the virus in just one location.
“We may not be able to make a definite conclusion based on the analysis of a single patient,” the authors write. “However, it may help to reassure our staff that the exhaled air may be rapidly diluted inside the AIIR with 12 air changes per hour, or probably the SARS-CoV-2 may not be predominantly transmitted by [the] airborne route.”
However, a recent Singapore study showed widespread environmental contamination by SARS-CoV-2 through respiratory droplets and fecal shedding, underlining the need for strict adherence to environmental and hand hygiene. Post-cleaning samples tested negative, suggesting that standard decontamination practices are effective.
This work was partly supported by the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases of the Department of Health, Hong Kong Special Administrative Region; and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Education of China. The authors and Glatt have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Hospital-related infections have been widely reported during the ongoing coronavirus outbreak, with healthcare professionals bearing a disproportionate risk. However, a proactive response in Hong Kong’s public hospital system appears to have bucked this trend and successfully protected both patients and staff from SARS-CoV-2, according to a study published online today in Infection Control & Hospital Epidemiology.
During the first 42 days of the outbreak, the 43 hospitals in the network tested 1275 suspected cases and treated 42 patients with confirmed COVID-19, the disease caused by SARS-CoV-2 infection. Yet, there were no nosocomial infections or infections among healthcare personnel, report Vincent C.C. Cheng, MD, FRCPath, the hospital’s infection control officer, and colleagues.
Cheng and colleagues note that 11 out of 413 healthcare workers who treat patients with confirmed infections had unprotected exposure and were in quarantine for 14 days, but none became ill.
In comparison, they note, the 2003 SARS outbreak saw almost 60% of nosocomial cases occurring in healthcare workers.
Proactive bundle
The Hong Kong success story may be due to a stepped-up proactive bundle of measures that included enhanced laboratory surveillance, early airborne infection isolation, and rapid-turnaround molecular diagnostics. Other strategies included staff forums and one-on-one discussions about infection control, employee training in protective equipment use, hand-hygiene compliance enforcement, and contact tracing for workers with unprotected exposure.
In addition, surgical masks were provided for all healthcare workers, patients, and visitors to clinical areas, a practice previously associated with reduced in-hospital transmission during influenza outbreaks, the authors note.
Hospitals also mandated use of personal protective equipment (PPE) for aerosol-generating procedures (AGPs), such as endotracheal intubation, open suctioning, and high-flow oxygen use, as AGPs had been linked to nosocomial transmission to healthcare workers during the 2003 SARS outbreak.
The infection control measures, which were part of a preparedness plan developed after the SARS outbreak, were initiated on December 31, when the first reports of a cluster of infections came from Wuhan, China.
As the outbreak evolved, the Hong Kong hospitals quickly widened the epidemiologic criteria for screening, from initially including only those who had been to a wet market in Wuhan within 14 days of symptom onset, to eventually including anyone who had been to Hubei province, been in a medical facility in mainland China, or in contact with a known case.
All suspected cases were sent to an airborne-infection isolation room (AIIR) or a ward with at least a meter of space between patients.
“Appropriate hospital infection control measures could prevent nosocomial transmission of SARS-CoV-2,” the authors write. “Vigilance in hand hygiene practice, wearing of surgical mask in the hospital, and appropriate use of PPE in patient care, especially [when] performing AGPs, are the key infection control measures to prevent nosocomial transmission of SARS-CoV-2 even before the availability of effective antiviral agents and vaccine.”
Asked for his perspective on the report, Aaron E. Glatt, MD, chairman of the department of medicine and chief of infectious diseases at Mount Sinai South Nassau in Oceanside, New York, said that apart from the widespread issuing of surgical masks to workers, patients, and visitors, the measures taken in Hong Kong are not different from standard infection-control practices in American hospitals. Glatt, who is also a hospital epidemiologist, said it was unclear how much impact the masks would have.
“Although the infection control was impressive, I don’t see any evidence of a difference in care,” he told Medscape Medical News.
Could zero infection transmission be achieved in the more far-flung and variable settings of hospitals across the United States? “The ability to get zero transmission is only possible if people adhere to the strictest infection-control guidelines,” Glatt said. “That is clearly the goal, and it will take time to see if our existing strict guidelines are sufficient to maintain zero or close to zero contamination and transmission rates in our hospitals.”
Rather than looking to change US practices, he stressed adherence to widely established tenets of care. “It’s critically important to keep paying close attention to the basics, to the simple blocking and tackling, and to identify which patients are at risk, and therefore, when workers need protective equipment,” he said.
“Follow the recommended standards,” continued Glatt, who is also a spokesperson for the Infectious Diseases Society of America and did not participate in this study.
In a finding from an ancillary pilot experiment, the Hong Kong researchers found exhaled air from a patient with a moderate coronavirus load showed no evidence of the virus, whether the patient was breathing normally or heavily, speaking, or coughing. And spot tests around the room detected the virus in just one location.
“We may not be able to make a definite conclusion based on the analysis of a single patient,” the authors write. “However, it may help to reassure our staff that the exhaled air may be rapidly diluted inside the AIIR with 12 air changes per hour, or probably the SARS-CoV-2 may not be predominantly transmitted by [the] airborne route.”
However, a recent Singapore study showed widespread environmental contamination by SARS-CoV-2 through respiratory droplets and fecal shedding, underlining the need for strict adherence to environmental and hand hygiene. Post-cleaning samples tested negative, suggesting that standard decontamination practices are effective.
This work was partly supported by the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases of the Department of Health, Hong Kong Special Administrative Region; and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Education of China. The authors and Glatt have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Hospital-related infections have been widely reported during the ongoing coronavirus outbreak, with healthcare professionals bearing a disproportionate risk. However, a proactive response in Hong Kong’s public hospital system appears to have bucked this trend and successfully protected both patients and staff from SARS-CoV-2, according to a study published online today in Infection Control & Hospital Epidemiology.
During the first 42 days of the outbreak, the 43 hospitals in the network tested 1275 suspected cases and treated 42 patients with confirmed COVID-19, the disease caused by SARS-CoV-2 infection. Yet, there were no nosocomial infections or infections among healthcare personnel, report Vincent C.C. Cheng, MD, FRCPath, the hospital’s infection control officer, and colleagues.
Cheng and colleagues note that 11 out of 413 healthcare workers who treat patients with confirmed infections had unprotected exposure and were in quarantine for 14 days, but none became ill.
In comparison, they note, the 2003 SARS outbreak saw almost 60% of nosocomial cases occurring in healthcare workers.
Proactive bundle
The Hong Kong success story may be due to a stepped-up proactive bundle of measures that included enhanced laboratory surveillance, early airborne infection isolation, and rapid-turnaround molecular diagnostics. Other strategies included staff forums and one-on-one discussions about infection control, employee training in protective equipment use, hand-hygiene compliance enforcement, and contact tracing for workers with unprotected exposure.
In addition, surgical masks were provided for all healthcare workers, patients, and visitors to clinical areas, a practice previously associated with reduced in-hospital transmission during influenza outbreaks, the authors note.
Hospitals also mandated use of personal protective equipment (PPE) for aerosol-generating procedures (AGPs), such as endotracheal intubation, open suctioning, and high-flow oxygen use, as AGPs had been linked to nosocomial transmission to healthcare workers during the 2003 SARS outbreak.
The infection control measures, which were part of a preparedness plan developed after the SARS outbreak, were initiated on December 31, when the first reports of a cluster of infections came from Wuhan, China.
As the outbreak evolved, the Hong Kong hospitals quickly widened the epidemiologic criteria for screening, from initially including only those who had been to a wet market in Wuhan within 14 days of symptom onset, to eventually including anyone who had been to Hubei province, been in a medical facility in mainland China, or in contact with a known case.
All suspected cases were sent to an airborne-infection isolation room (AIIR) or a ward with at least a meter of space between patients.
“Appropriate hospital infection control measures could prevent nosocomial transmission of SARS-CoV-2,” the authors write. “Vigilance in hand hygiene practice, wearing of surgical mask in the hospital, and appropriate use of PPE in patient care, especially [when] performing AGPs, are the key infection control measures to prevent nosocomial transmission of SARS-CoV-2 even before the availability of effective antiviral agents and vaccine.”
Asked for his perspective on the report, Aaron E. Glatt, MD, chairman of the department of medicine and chief of infectious diseases at Mount Sinai South Nassau in Oceanside, New York, said that apart from the widespread issuing of surgical masks to workers, patients, and visitors, the measures taken in Hong Kong are not different from standard infection-control practices in American hospitals. Glatt, who is also a hospital epidemiologist, said it was unclear how much impact the masks would have.
“Although the infection control was impressive, I don’t see any evidence of a difference in care,” he told Medscape Medical News.
Could zero infection transmission be achieved in the more far-flung and variable settings of hospitals across the United States? “The ability to get zero transmission is only possible if people adhere to the strictest infection-control guidelines,” Glatt said. “That is clearly the goal, and it will take time to see if our existing strict guidelines are sufficient to maintain zero or close to zero contamination and transmission rates in our hospitals.”
Rather than looking to change US practices, he stressed adherence to widely established tenets of care. “It’s critically important to keep paying close attention to the basics, to the simple blocking and tackling, and to identify which patients are at risk, and therefore, when workers need protective equipment,” he said.
“Follow the recommended standards,” continued Glatt, who is also a spokesperson for the Infectious Diseases Society of America and did not participate in this study.
In a finding from an ancillary pilot experiment, the Hong Kong researchers found exhaled air from a patient with a moderate coronavirus load showed no evidence of the virus, whether the patient was breathing normally or heavily, speaking, or coughing. And spot tests around the room detected the virus in just one location.
“We may not be able to make a definite conclusion based on the analysis of a single patient,” the authors write. “However, it may help to reassure our staff that the exhaled air may be rapidly diluted inside the AIIR with 12 air changes per hour, or probably the SARS-CoV-2 may not be predominantly transmitted by [the] airborne route.”
However, a recent Singapore study showed widespread environmental contamination by SARS-CoV-2 through respiratory droplets and fecal shedding, underlining the need for strict adherence to environmental and hand hygiene. Post-cleaning samples tested negative, suggesting that standard decontamination practices are effective.
This work was partly supported by the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases of the Department of Health, Hong Kong Special Administrative Region; and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Education of China. The authors and Glatt have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
CMS issues guidance on containing spread of coronavirus
The first guidance document, “Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge,” issued March 4, provides some basic guidance, including identifying which patients are at risk, how facilities should screen for COVID-19, how facilities should monitor or restrict health care facility staff, and other recommendations for infection prevention and control.
“Hospitals should identify visitors and patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility,” the guidance document notes. “For patients, implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth if that has not already been done) and isolate the patient in an examination room with the door closed. If the patient cannot be immediately moved to an examination room, ensure they are not allowed to wait among other patients seeking care.”
The document offers further information regarding the care of patients and provides numerous links to existing guidance from the Centers for Disease Control and Prevention.
The second document, “Guidance for Infection Control and Prevention of Coronavirus Disease 2019 (COVID-19) in Nursing Homes,” issued the same day, provides information on how to limit and monitor visitors as well as monitor and restrict health staff. It details when to transfer residents with suspected or confirmed coronavirus infection, and when a nursing home should accept a resident diagnosed with COVID-19.
Facilities “should contact their local health department if they have questions or suspect a resident of a nursing home has COVID-19,” the document states. “Per CDC, prompt detection, triage and isolation of potentially infectious patients are essential to prevent unnecessary exposure among patients, healthcare personnel, and visitors at the facility.”
The CMS also announced that it is suspending all nonemergency survey activity.
“CMS is suspending nonemergency inspections across the country, allowing inspectors to turn their focus on the most serious health and safety threats like infectious diseases and abuse,” the agency stated in a March 4 memo. “This shift in approach will also allow inspectors to focus on addressing the spread of ... COVID-19. CMS is issuing this memorandum to State Survey Agencies to provide important guidelines for the inspection process in situations in which a COVID-19 is suspected.”
In a statement, CMS Administrator Seema Verma said these actions “represent a call to action across the health care system. All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention.”
The first guidance document, “Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge,” issued March 4, provides some basic guidance, including identifying which patients are at risk, how facilities should screen for COVID-19, how facilities should monitor or restrict health care facility staff, and other recommendations for infection prevention and control.
“Hospitals should identify visitors and patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility,” the guidance document notes. “For patients, implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth if that has not already been done) and isolate the patient in an examination room with the door closed. If the patient cannot be immediately moved to an examination room, ensure they are not allowed to wait among other patients seeking care.”
The document offers further information regarding the care of patients and provides numerous links to existing guidance from the Centers for Disease Control and Prevention.
The second document, “Guidance for Infection Control and Prevention of Coronavirus Disease 2019 (COVID-19) in Nursing Homes,” issued the same day, provides information on how to limit and monitor visitors as well as monitor and restrict health staff. It details when to transfer residents with suspected or confirmed coronavirus infection, and when a nursing home should accept a resident diagnosed with COVID-19.
Facilities “should contact their local health department if they have questions or suspect a resident of a nursing home has COVID-19,” the document states. “Per CDC, prompt detection, triage and isolation of potentially infectious patients are essential to prevent unnecessary exposure among patients, healthcare personnel, and visitors at the facility.”
The CMS also announced that it is suspending all nonemergency survey activity.
“CMS is suspending nonemergency inspections across the country, allowing inspectors to turn their focus on the most serious health and safety threats like infectious diseases and abuse,” the agency stated in a March 4 memo. “This shift in approach will also allow inspectors to focus on addressing the spread of ... COVID-19. CMS is issuing this memorandum to State Survey Agencies to provide important guidelines for the inspection process in situations in which a COVID-19 is suspected.”
In a statement, CMS Administrator Seema Verma said these actions “represent a call to action across the health care system. All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention.”
The first guidance document, “Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge,” issued March 4, provides some basic guidance, including identifying which patients are at risk, how facilities should screen for COVID-19, how facilities should monitor or restrict health care facility staff, and other recommendations for infection prevention and control.
“Hospitals should identify visitors and patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility,” the guidance document notes. “For patients, implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth if that has not already been done) and isolate the patient in an examination room with the door closed. If the patient cannot be immediately moved to an examination room, ensure they are not allowed to wait among other patients seeking care.”
The document offers further information regarding the care of patients and provides numerous links to existing guidance from the Centers for Disease Control and Prevention.
The second document, “Guidance for Infection Control and Prevention of Coronavirus Disease 2019 (COVID-19) in Nursing Homes,” issued the same day, provides information on how to limit and monitor visitors as well as monitor and restrict health staff. It details when to transfer residents with suspected or confirmed coronavirus infection, and when a nursing home should accept a resident diagnosed with COVID-19.
Facilities “should contact their local health department if they have questions or suspect a resident of a nursing home has COVID-19,” the document states. “Per CDC, prompt detection, triage and isolation of potentially infectious patients are essential to prevent unnecessary exposure among patients, healthcare personnel, and visitors at the facility.”
The CMS also announced that it is suspending all nonemergency survey activity.
“CMS is suspending nonemergency inspections across the country, allowing inspectors to turn their focus on the most serious health and safety threats like infectious diseases and abuse,” the agency stated in a March 4 memo. “This shift in approach will also allow inspectors to focus on addressing the spread of ... COVID-19. CMS is issuing this memorandum to State Survey Agencies to provide important guidelines for the inspection process in situations in which a COVID-19 is suspected.”
In a statement, CMS Administrator Seema Verma said these actions “represent a call to action across the health care system. All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention.”
FDA issues stronger warning on neuropsychiatric event risk linked to montelukast
The Food and Drug Administration has issued , a prescription drug for asthma and allergy.
The new boxed warning advises health care providers to avoid prescribing montelukast for patients with mild symptoms, particularly those with allergic rhinitis, the FDA said in a press release. The drug was first approved in 1998, and the product labeling was updated in 2008 to include information about neuropsychiatric adverse events reported with usage of montelukast.
While the Sentinel study, along with other observational studies, did not find an increased risk of mental health side effects with montelukast treatment, compared with inhaled corticosteroids, those studies had limitations that may have affected results, the FDA said in the Drug Safety Communication. However, the FDA has continued to receive reports of neuropsychiatric events – including agitation, depression, sleeping problems, and suicidal thoughts and actions – in patients receiving the medication.
“The incidence of neuropsychiatric events associated with montelukast is unknown, but some reports are serious, and many patients and health care professionals are not fully aware of these risks,” Sally Seymour, MD, director of the division of pulmonary, allergy and rheumatology products in the FDA’s Center for Drug Evaluation and Research, said in the press release. “There are many other safe and effective medications to treat allergies with extensive history of use and safety, such that many products are available over the counter without a prescription.”
In addition to the boxed warning, the FDA now requires a new medication guide to be given to patients with each montelukast prescription, the FDA said.
The Food and Drug Administration has issued , a prescription drug for asthma and allergy.
The new boxed warning advises health care providers to avoid prescribing montelukast for patients with mild symptoms, particularly those with allergic rhinitis, the FDA said in a press release. The drug was first approved in 1998, and the product labeling was updated in 2008 to include information about neuropsychiatric adverse events reported with usage of montelukast.
While the Sentinel study, along with other observational studies, did not find an increased risk of mental health side effects with montelukast treatment, compared with inhaled corticosteroids, those studies had limitations that may have affected results, the FDA said in the Drug Safety Communication. However, the FDA has continued to receive reports of neuropsychiatric events – including agitation, depression, sleeping problems, and suicidal thoughts and actions – in patients receiving the medication.
“The incidence of neuropsychiatric events associated with montelukast is unknown, but some reports are serious, and many patients and health care professionals are not fully aware of these risks,” Sally Seymour, MD, director of the division of pulmonary, allergy and rheumatology products in the FDA’s Center for Drug Evaluation and Research, said in the press release. “There are many other safe and effective medications to treat allergies with extensive history of use and safety, such that many products are available over the counter without a prescription.”
In addition to the boxed warning, the FDA now requires a new medication guide to be given to patients with each montelukast prescription, the FDA said.
The Food and Drug Administration has issued , a prescription drug for asthma and allergy.
The new boxed warning advises health care providers to avoid prescribing montelukast for patients with mild symptoms, particularly those with allergic rhinitis, the FDA said in a press release. The drug was first approved in 1998, and the product labeling was updated in 2008 to include information about neuropsychiatric adverse events reported with usage of montelukast.
While the Sentinel study, along with other observational studies, did not find an increased risk of mental health side effects with montelukast treatment, compared with inhaled corticosteroids, those studies had limitations that may have affected results, the FDA said in the Drug Safety Communication. However, the FDA has continued to receive reports of neuropsychiatric events – including agitation, depression, sleeping problems, and suicidal thoughts and actions – in patients receiving the medication.
“The incidence of neuropsychiatric events associated with montelukast is unknown, but some reports are serious, and many patients and health care professionals are not fully aware of these risks,” Sally Seymour, MD, director of the division of pulmonary, allergy and rheumatology products in the FDA’s Center for Drug Evaluation and Research, said in the press release. “There are many other safe and effective medications to treat allergies with extensive history of use and safety, such that many products are available over the counter without a prescription.”
In addition to the boxed warning, the FDA now requires a new medication guide to be given to patients with each montelukast prescription, the FDA said.
FDA moves to expand coronavirus testing capacity; CDC clarifies testing criteria
The White House Coronavirus Task Force appeared at a press briefing March 2 to provide updates about testing strategies and public health coordination to address the current outbreak of the coronavirus COVID-19. Speaking at the briefing, led by Vice President Mike Pence, Centers for Disease Control and Prevention (CDC) director Robert Redfield, MD, said, “Working with our public health partners we continue to be able to identify new community cases and use our public health efforts to aggressively confirm, isolate, and do contact tracking.” Calling state, local, tribal, and territorial public health departments “the backbone of the public health system in our country,” Dr. Redfield noted that he expected many more confirmed COVID-19 cases to emerge.
At least some of the expected increase in confirmed cases of COVID-19 will occur because of expanded testing capacity, noted several of the task force members. On Feb. 29, the Food and Drug Administration issued a the virus that is causing the current outbreak of COVID-19.
Highly qualified laboratories, including both those run by public agencies and private labs, are now authorized to begin using their own validated test for the virus as long as they submit an Emergency Use Authorization (EUA) to the Food and Drug Administration within 15 days of notifying the agency of validation.
“To effectively respond to the COVID-19 outbreak, rapid detection of cases and contacts, appropriate clinical management and infection control, and implementation of community mitigation efforts are critical. This can best be achieved with wide availability of testing capabilities in health care settings, reference and commercial laboratories, and at the point of care,” the agency wrote in a press announcement of the expedited test expansion.
On Feb. 4, the Secretary of the Department of Health & Human Services declared a coronavirus public health emergency. The FDA was then authorized to allow individual laboratories with validated coronavirus tests to begin testing samples immediately. The goal is a more rapid and expanded testing capacity in the United States.
“The global emergence of COVID-19 is concerning, and we appreciate the efforts of the FDA to help bring more testing capability to the U.S.,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), said in the press release.
The new guidance that permits the immediate use of clinical tests after individual development and validation, said the FDA, only applies to labs already certified to perform high complexity testing under Clinical Laboratory Improvement Amendments. Many governmental, academic, and private laboratories fall into this category, however.
“Under this policy, we expect certain laboratories who develop validated tests for coronavirus would begin using them right away prior to FDA review,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health. “We believe this action will support laboratories across the country working on this urgent public health situation,” he added in the press release.
“By the end of this week, close to a million tests will be available,” FDA Commissioner Stephen M. Hahn, MD, said during the March 2 briefing.*
Updated criteria
The CDC is maintaining updated criteria for the virus testing on its website. Testing criteria are based both on clinical features and epidemiologic risk.
Individuals with less severe clinical features – those who have either fever or signs and symptoms of lower respiratory disease such as cough or shortness of breath, but who don’t require hospitalization – should be tested if they have high epidemiologic risk. “High risk” is defined by the CDC as any individual, including health care workers, who has had close contact with a person with confirmed COVID-19 within the past 2 weeks. For health care workers, testing can be considered even if they have relatively mild respiratory symptoms or have had contact with a person who is suspected, but not yet confirmed, to have coronavirus.
In its testing guidance, the CDC recognizes that defining close contact is difficult. General guidelines are that individuals are considered to have been in close contact with a person who has COVID-19 if they were within about six feet of the person for a prolonged period, or cared for or have spent a prolonged amount of time in the same room or house as a person with confirmed COVID-19.
Individuals who have both fever and signs or symptoms of lower respiratory illness who require hospitalization should be tested if they have a history of travel from any affected geographic area within 14 days of the onset of their symptoms. The CDC now defines “affected geographic area” as any country or region that has at least a CDC Level 2 Travel Health Notice for COVID-19, so that the testing criteria themselves don’t need to be updated when new geographic areas are included in these alerts. As of March 3, China, Iran, Italy, Japan, and South Korea all have Level 2 or 3 travel alerts.
The CDC now recommends that any patient who has severe acute lower respiratory illness that requires hospitalization and doesn’t have an alternative diagnosis should be tested, even without any identified source of exposure.
“Despite seeing these new cases, the risk to the American people is low,” said the CDC’s Dr. Redfield. In response to a question from the press about how fast the coronavirus will spread across the United States, Dr. Redfield said, “From the beginning we’ve anticipated seeing community cases pop up.” He added that as these cases arise, testing and public health strategies will focus on unearthing linkages and contacts to learn how the virus is spreading. “We’ll use the public health strategies that we can to limit that transmission,” he said.
*An earlier version of this article misattributed this quote.
The White House Coronavirus Task Force appeared at a press briefing March 2 to provide updates about testing strategies and public health coordination to address the current outbreak of the coronavirus COVID-19. Speaking at the briefing, led by Vice President Mike Pence, Centers for Disease Control and Prevention (CDC) director Robert Redfield, MD, said, “Working with our public health partners we continue to be able to identify new community cases and use our public health efforts to aggressively confirm, isolate, and do contact tracking.” Calling state, local, tribal, and territorial public health departments “the backbone of the public health system in our country,” Dr. Redfield noted that he expected many more confirmed COVID-19 cases to emerge.
At least some of the expected increase in confirmed cases of COVID-19 will occur because of expanded testing capacity, noted several of the task force members. On Feb. 29, the Food and Drug Administration issued a the virus that is causing the current outbreak of COVID-19.
Highly qualified laboratories, including both those run by public agencies and private labs, are now authorized to begin using their own validated test for the virus as long as they submit an Emergency Use Authorization (EUA) to the Food and Drug Administration within 15 days of notifying the agency of validation.
“To effectively respond to the COVID-19 outbreak, rapid detection of cases and contacts, appropriate clinical management and infection control, and implementation of community mitigation efforts are critical. This can best be achieved with wide availability of testing capabilities in health care settings, reference and commercial laboratories, and at the point of care,” the agency wrote in a press announcement of the expedited test expansion.
On Feb. 4, the Secretary of the Department of Health & Human Services declared a coronavirus public health emergency. The FDA was then authorized to allow individual laboratories with validated coronavirus tests to begin testing samples immediately. The goal is a more rapid and expanded testing capacity in the United States.
“The global emergence of COVID-19 is concerning, and we appreciate the efforts of the FDA to help bring more testing capability to the U.S.,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), said in the press release.
The new guidance that permits the immediate use of clinical tests after individual development and validation, said the FDA, only applies to labs already certified to perform high complexity testing under Clinical Laboratory Improvement Amendments. Many governmental, academic, and private laboratories fall into this category, however.
“Under this policy, we expect certain laboratories who develop validated tests for coronavirus would begin using them right away prior to FDA review,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health. “We believe this action will support laboratories across the country working on this urgent public health situation,” he added in the press release.
“By the end of this week, close to a million tests will be available,” FDA Commissioner Stephen M. Hahn, MD, said during the March 2 briefing.*
Updated criteria
The CDC is maintaining updated criteria for the virus testing on its website. Testing criteria are based both on clinical features and epidemiologic risk.
Individuals with less severe clinical features – those who have either fever or signs and symptoms of lower respiratory disease such as cough or shortness of breath, but who don’t require hospitalization – should be tested if they have high epidemiologic risk. “High risk” is defined by the CDC as any individual, including health care workers, who has had close contact with a person with confirmed COVID-19 within the past 2 weeks. For health care workers, testing can be considered even if they have relatively mild respiratory symptoms or have had contact with a person who is suspected, but not yet confirmed, to have coronavirus.
In its testing guidance, the CDC recognizes that defining close contact is difficult. General guidelines are that individuals are considered to have been in close contact with a person who has COVID-19 if they were within about six feet of the person for a prolonged period, or cared for or have spent a prolonged amount of time in the same room or house as a person with confirmed COVID-19.
Individuals who have both fever and signs or symptoms of lower respiratory illness who require hospitalization should be tested if they have a history of travel from any affected geographic area within 14 days of the onset of their symptoms. The CDC now defines “affected geographic area” as any country or region that has at least a CDC Level 2 Travel Health Notice for COVID-19, so that the testing criteria themselves don’t need to be updated when new geographic areas are included in these alerts. As of March 3, China, Iran, Italy, Japan, and South Korea all have Level 2 or 3 travel alerts.
The CDC now recommends that any patient who has severe acute lower respiratory illness that requires hospitalization and doesn’t have an alternative diagnosis should be tested, even without any identified source of exposure.
“Despite seeing these new cases, the risk to the American people is low,” said the CDC’s Dr. Redfield. In response to a question from the press about how fast the coronavirus will spread across the United States, Dr. Redfield said, “From the beginning we’ve anticipated seeing community cases pop up.” He added that as these cases arise, testing and public health strategies will focus on unearthing linkages and contacts to learn how the virus is spreading. “We’ll use the public health strategies that we can to limit that transmission,” he said.
*An earlier version of this article misattributed this quote.
The White House Coronavirus Task Force appeared at a press briefing March 2 to provide updates about testing strategies and public health coordination to address the current outbreak of the coronavirus COVID-19. Speaking at the briefing, led by Vice President Mike Pence, Centers for Disease Control and Prevention (CDC) director Robert Redfield, MD, said, “Working with our public health partners we continue to be able to identify new community cases and use our public health efforts to aggressively confirm, isolate, and do contact tracking.” Calling state, local, tribal, and territorial public health departments “the backbone of the public health system in our country,” Dr. Redfield noted that he expected many more confirmed COVID-19 cases to emerge.
At least some of the expected increase in confirmed cases of COVID-19 will occur because of expanded testing capacity, noted several of the task force members. On Feb. 29, the Food and Drug Administration issued a the virus that is causing the current outbreak of COVID-19.
Highly qualified laboratories, including both those run by public agencies and private labs, are now authorized to begin using their own validated test for the virus as long as they submit an Emergency Use Authorization (EUA) to the Food and Drug Administration within 15 days of notifying the agency of validation.
“To effectively respond to the COVID-19 outbreak, rapid detection of cases and contacts, appropriate clinical management and infection control, and implementation of community mitigation efforts are critical. This can best be achieved with wide availability of testing capabilities in health care settings, reference and commercial laboratories, and at the point of care,” the agency wrote in a press announcement of the expedited test expansion.
On Feb. 4, the Secretary of the Department of Health & Human Services declared a coronavirus public health emergency. The FDA was then authorized to allow individual laboratories with validated coronavirus tests to begin testing samples immediately. The goal is a more rapid and expanded testing capacity in the United States.
“The global emergence of COVID-19 is concerning, and we appreciate the efforts of the FDA to help bring more testing capability to the U.S.,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), said in the press release.
The new guidance that permits the immediate use of clinical tests after individual development and validation, said the FDA, only applies to labs already certified to perform high complexity testing under Clinical Laboratory Improvement Amendments. Many governmental, academic, and private laboratories fall into this category, however.
“Under this policy, we expect certain laboratories who develop validated tests for coronavirus would begin using them right away prior to FDA review,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health. “We believe this action will support laboratories across the country working on this urgent public health situation,” he added in the press release.
“By the end of this week, close to a million tests will be available,” FDA Commissioner Stephen M. Hahn, MD, said during the March 2 briefing.*
Updated criteria
The CDC is maintaining updated criteria for the virus testing on its website. Testing criteria are based both on clinical features and epidemiologic risk.
Individuals with less severe clinical features – those who have either fever or signs and symptoms of lower respiratory disease such as cough or shortness of breath, but who don’t require hospitalization – should be tested if they have high epidemiologic risk. “High risk” is defined by the CDC as any individual, including health care workers, who has had close contact with a person with confirmed COVID-19 within the past 2 weeks. For health care workers, testing can be considered even if they have relatively mild respiratory symptoms or have had contact with a person who is suspected, but not yet confirmed, to have coronavirus.
In its testing guidance, the CDC recognizes that defining close contact is difficult. General guidelines are that individuals are considered to have been in close contact with a person who has COVID-19 if they were within about six feet of the person for a prolonged period, or cared for or have spent a prolonged amount of time in the same room or house as a person with confirmed COVID-19.
Individuals who have both fever and signs or symptoms of lower respiratory illness who require hospitalization should be tested if they have a history of travel from any affected geographic area within 14 days of the onset of their symptoms. The CDC now defines “affected geographic area” as any country or region that has at least a CDC Level 2 Travel Health Notice for COVID-19, so that the testing criteria themselves don’t need to be updated when new geographic areas are included in these alerts. As of March 3, China, Iran, Italy, Japan, and South Korea all have Level 2 or 3 travel alerts.
The CDC now recommends that any patient who has severe acute lower respiratory illness that requires hospitalization and doesn’t have an alternative diagnosis should be tested, even without any identified source of exposure.
“Despite seeing these new cases, the risk to the American people is low,” said the CDC’s Dr. Redfield. In response to a question from the press about how fast the coronavirus will spread across the United States, Dr. Redfield said, “From the beginning we’ve anticipated seeing community cases pop up.” He added that as these cases arise, testing and public health strategies will focus on unearthing linkages and contacts to learn how the virus is spreading. “We’ll use the public health strategies that we can to limit that transmission,” he said.
*An earlier version of this article misattributed this quote.
FROM A PRESS BRIEFING BY THE WHITE HOUSE CORONAVIRUS TASK FORCE
Pembro ups survival in NSCLC: ‘Really extraordinary’ results
More than a third (35%) of patients with relapsed non–small cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda, Merck) were still alive at 3 years, according to long-term results from a pivotal clinical trial.
The results also showed that, among the 10% of patients who completed all 35 cycles of pembrolizumab, the 3-year overall survival was approximately 99%, with progression-free survival (PFS) at around 70%.
“It is too soon to say that pembrolizumab is a potential cure...and we know that it doesn’t work for all patients, but the agent remains very, very promising,” said lead investigator Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut.
These new results come from the KEYNOTE-010 trial, conducted in more than 1000 patients with NSCLC who had progressed on chemotherapy, randomized to receive immunotherapy with pembrolizumab or chemotherapy with docetaxel.
The results were published online on February 20 in the Journal of Clinical Oncology and were previously presented at the 2018 annual meeting of the European Society of Medical Oncology.
Overall survival at 3 years was 35% in patients with PD-L1 expression ≥ 50% in the tumor, and 23% in those with PD-L1 ≥ 1%.
This compares with 3-year overall survival of 11-13% with docetaxel.
These results are “really extraordinary,” Herbst commented to Medscape Medical News.
The 3-year overall survival rate of 35% in patients with PD-L1 ≥ 50% “is huge,” he said. “It really shows the durability of the response.”
Herbst commented that the “almost 100%” survival at 3 years among patients who completed 35 cycles of pembrolizumab shows that this treatment period (of about 2 years) is “probably about the right time to treat.”
“Currently, the agent is being used in all potential settings, before any other treatment, after other treatment, and with other treatments,” he said.
“Our hope is to find the very best way to use pembrolizumab to treat individual lung cancer patients, assessing how much PD-L1 a tumor expresses, what stage the patient is in, as well as other variables and biomarkers we are working on. This is the story of tailored therapy,” Herbst said.
Approached for comment, Solange Peters, MD, PhD, Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said that the results are “very good” and “confirm the paradigms we have been seeing in melanoma,” with good long-term control, which is “very reassuring.”
However, she told Medscape Medical News that the trial raises an important question: «How long do you need to expose your patient with lung cancer to immunotherapy in order to get this long-term control?»
She said the “good news” is that, for the 10% of patients who completed 2 years of treatment per protocol, almost all of them are still alive at 3 years, “which is not observed with chemotherapy.”
The question for Peters is “more about the definition of long-term control,” as it was seen that almost one in three patients nevertheless had some form of progression.
This suggests that you have a group of people “who are nicely controlled, you stop the drug, and 1 year later a third of them have progressed.”
Peters said: “So how long do you need to treat these patients? I would say I still don’t know.”
“If I were one of these patients probably I would still want to continue [on the drug]. Of course, some might have progressed even while remaining on the drug, but the proportion who would have progressed is probably smaller than this one.”
Responses on Re-introduction of Therapy
The study also allowed patients who had completed 35 cycles of pembrolizumab to be restarted on the drug if they experienced progression.
The team found that, among 14 patients, 43% had a partial response and 36% had stable disease.
Herbst highlighted this finding and told Medscape Medical News that this «could be very important to physicians because they might want to think about using the drug again» in patients who have progressed on it.
He believes that the progression was not because of any resistance per se but rather a slowing down of the adaptive immune response.
“It’s just that it needs a boost,” he said, while noting that tissue specimens will nevertheless be required to demonstrate the theory.
Peters agreed that these results are “very promising,” but questioned their overall significance, as it is “a very small number of patients” from a subset whose disease was controlled while on treatment and then progressed after stopping.
She also pointed out that, in another study in patients with lung cancer (CheckMate-153), some patients were rechallenged with immunotherapy after having stopped treatment at 1 year “with very poor results.”
Peters said studies in melanoma have shown “rechallenge can be useful in a significant proportion of patients, but still you have not demonstrated that stopping and rechallenging is the same as not stopping.”
Study Details
KEYNOTE-010 involved patients with NSCLC from 202 centers in 24 countries with stage IIIB/IV disease expressing PD-L1 who had experienced disease progression after at least two cycles of platinum-based chemotherapy.
They were randomized 1:1:1 to open-label pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks.
Pembrolizumab was continued for 35 treatment cycles over 2 years and docetaxel was continued for the maximum duration allowed by local regulators.
Patients who stopped pembrolizumab after a complete response or completing all 35 cycles, and who subsequently experienced disease progression, could receive up to 17 additional cycles over 1 year if they had not received another anticancer therapy in the meantime.
Among the 1,034 patients originally recruited between August 2013 and February 2015, 691 were assigned to pembrolizumab at 3 mg/kg or 10 mg/kg and 343 to docetaxel.
For the intention-to-treat analysis in 1033 patients, the mean duration of follow-up was 42.6 months, with a median treatment duration of 3.5 months in the pembrolizumab group and 2.0 months in the docetaxel group.
Compared with docetaxel, pembrolizumab was associated with a significant reduction in the risk of death, at a hazard ratio of 0.53 in patients with PD-L1 ≥ 50% and 0.69 in those with PD-L1 ≥ 1% (both P < .0001).
In patients with PD-L1 ≥ 50%, median overall survival was 16.9 months in those given pembrolizumab and 8.2 months with docetaxel. Among those with PD-L1 ≥ 1%, median overall survival was 11.8 months with pembrolizumab versus 8.4 months with docetaxel.
Overall survival on Kaplan-Meier analysis was 34.5% with pembrolizumab and 12.7% with docetaxel in the PD-L1 ≥ 50% group, and 22.9% versus 11.0% in the PD-L1 ≥ 1% group.
PFS significantly improved with pembrolizumab versus docetaxel, at a hazard ratio of 0.57 (P < .00001) among patients with PD-L1 ≥ 50% and 0.83 (P < .005) in those with PD-L1 ≥ 1%.
In terms of safety, 17.7% of patients who completed 2 years of pembrolizumab had grade 3-5 treatment-related adverse events, compared with 16.6% among all pembrolizumab-treated patients and 36.6% of those given docetaxel.
The team reports that 79 patients completed 35 cycles of pembrolizumab, with a median follow-up of 43.4 months.
Compared with the overall patient group, these patients were less likely to be aged ≥ 65 years and to have received two or more prior treatment lines, although they were more likely to be current or former smokers and to have squamous tumor histology.
Patients who completed 35 cycles had an objective response rate of 94.9%, and 91.0% were still alive at the data cutoff. Overall survival rates were 98.7% at 12 months and 86.3% at 24 months.
Of 71 patients eligible for analysis, 23 experienced progression after completing pembrolizumab, at PFS rates at 12 and 24 months of 72.5% and 57.7%, respectively.
A total of 14 patients were given a second course of pembrolizumab, of whom six had a partial response and five had stable disease. At the data cutoff, five patients had completed 17 additional cycles and 11 were alive.
Pembro Approved at Fixed Dose
One notable aspect of the study is that patients in the pembrolizumab arm were given two different doses of the drug based on body weight, whereas the drug is approved in the United States at a fixed dose of 200 mg.
Herbst told Medscape Medical News he considers the 200-mg dose to be appropriate.
“I didn’t think that the 3-mg versus 10-mg dose per kg that we used in our study made much difference in an average-sized person,” he said, adding that the 200-mg dose “is something a little bit more than 3 mg/kg.”
“So I think that this is clearly the right dos, and I don’t think more would make any difference,” he said.
The study was funded by Merck, the manufacturer of pembrolizumab. Herbst has reported having a consulting or advisory role for many pharmaceutical companies. Other coauthors have also reported relationships with industry, and some of the authors are Merck employees. Peters has reported receiving education grants, providing consultation, attending advisory boards, and/or providing lectures for many pharmaceutical companies.
This article first appeared on Medscape.com.
More than a third (35%) of patients with relapsed non–small cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda, Merck) were still alive at 3 years, according to long-term results from a pivotal clinical trial.
The results also showed that, among the 10% of patients who completed all 35 cycles of pembrolizumab, the 3-year overall survival was approximately 99%, with progression-free survival (PFS) at around 70%.
“It is too soon to say that pembrolizumab is a potential cure...and we know that it doesn’t work for all patients, but the agent remains very, very promising,” said lead investigator Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut.
These new results come from the KEYNOTE-010 trial, conducted in more than 1000 patients with NSCLC who had progressed on chemotherapy, randomized to receive immunotherapy with pembrolizumab or chemotherapy with docetaxel.
The results were published online on February 20 in the Journal of Clinical Oncology and were previously presented at the 2018 annual meeting of the European Society of Medical Oncology.
Overall survival at 3 years was 35% in patients with PD-L1 expression ≥ 50% in the tumor, and 23% in those with PD-L1 ≥ 1%.
This compares with 3-year overall survival of 11-13% with docetaxel.
These results are “really extraordinary,” Herbst commented to Medscape Medical News.
The 3-year overall survival rate of 35% in patients with PD-L1 ≥ 50% “is huge,” he said. “It really shows the durability of the response.”
Herbst commented that the “almost 100%” survival at 3 years among patients who completed 35 cycles of pembrolizumab shows that this treatment period (of about 2 years) is “probably about the right time to treat.”
“Currently, the agent is being used in all potential settings, before any other treatment, after other treatment, and with other treatments,” he said.
“Our hope is to find the very best way to use pembrolizumab to treat individual lung cancer patients, assessing how much PD-L1 a tumor expresses, what stage the patient is in, as well as other variables and biomarkers we are working on. This is the story of tailored therapy,” Herbst said.
Approached for comment, Solange Peters, MD, PhD, Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said that the results are “very good” and “confirm the paradigms we have been seeing in melanoma,” with good long-term control, which is “very reassuring.”
However, she told Medscape Medical News that the trial raises an important question: «How long do you need to expose your patient with lung cancer to immunotherapy in order to get this long-term control?»
She said the “good news” is that, for the 10% of patients who completed 2 years of treatment per protocol, almost all of them are still alive at 3 years, “which is not observed with chemotherapy.”
The question for Peters is “more about the definition of long-term control,” as it was seen that almost one in three patients nevertheless had some form of progression.
This suggests that you have a group of people “who are nicely controlled, you stop the drug, and 1 year later a third of them have progressed.”
Peters said: “So how long do you need to treat these patients? I would say I still don’t know.”
“If I were one of these patients probably I would still want to continue [on the drug]. Of course, some might have progressed even while remaining on the drug, but the proportion who would have progressed is probably smaller than this one.”
Responses on Re-introduction of Therapy
The study also allowed patients who had completed 35 cycles of pembrolizumab to be restarted on the drug if they experienced progression.
The team found that, among 14 patients, 43% had a partial response and 36% had stable disease.
Herbst highlighted this finding and told Medscape Medical News that this «could be very important to physicians because they might want to think about using the drug again» in patients who have progressed on it.
He believes that the progression was not because of any resistance per se but rather a slowing down of the adaptive immune response.
“It’s just that it needs a boost,” he said, while noting that tissue specimens will nevertheless be required to demonstrate the theory.
Peters agreed that these results are “very promising,” but questioned their overall significance, as it is “a very small number of patients” from a subset whose disease was controlled while on treatment and then progressed after stopping.
She also pointed out that, in another study in patients with lung cancer (CheckMate-153), some patients were rechallenged with immunotherapy after having stopped treatment at 1 year “with very poor results.”
Peters said studies in melanoma have shown “rechallenge can be useful in a significant proportion of patients, but still you have not demonstrated that stopping and rechallenging is the same as not stopping.”
Study Details
KEYNOTE-010 involved patients with NSCLC from 202 centers in 24 countries with stage IIIB/IV disease expressing PD-L1 who had experienced disease progression after at least two cycles of platinum-based chemotherapy.
They were randomized 1:1:1 to open-label pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks.
Pembrolizumab was continued for 35 treatment cycles over 2 years and docetaxel was continued for the maximum duration allowed by local regulators.
Patients who stopped pembrolizumab after a complete response or completing all 35 cycles, and who subsequently experienced disease progression, could receive up to 17 additional cycles over 1 year if they had not received another anticancer therapy in the meantime.
Among the 1,034 patients originally recruited between August 2013 and February 2015, 691 were assigned to pembrolizumab at 3 mg/kg or 10 mg/kg and 343 to docetaxel.
For the intention-to-treat analysis in 1033 patients, the mean duration of follow-up was 42.6 months, with a median treatment duration of 3.5 months in the pembrolizumab group and 2.0 months in the docetaxel group.
Compared with docetaxel, pembrolizumab was associated with a significant reduction in the risk of death, at a hazard ratio of 0.53 in patients with PD-L1 ≥ 50% and 0.69 in those with PD-L1 ≥ 1% (both P < .0001).
In patients with PD-L1 ≥ 50%, median overall survival was 16.9 months in those given pembrolizumab and 8.2 months with docetaxel. Among those with PD-L1 ≥ 1%, median overall survival was 11.8 months with pembrolizumab versus 8.4 months with docetaxel.
Overall survival on Kaplan-Meier analysis was 34.5% with pembrolizumab and 12.7% with docetaxel in the PD-L1 ≥ 50% group, and 22.9% versus 11.0% in the PD-L1 ≥ 1% group.
PFS significantly improved with pembrolizumab versus docetaxel, at a hazard ratio of 0.57 (P < .00001) among patients with PD-L1 ≥ 50% and 0.83 (P < .005) in those with PD-L1 ≥ 1%.
In terms of safety, 17.7% of patients who completed 2 years of pembrolizumab had grade 3-5 treatment-related adverse events, compared with 16.6% among all pembrolizumab-treated patients and 36.6% of those given docetaxel.
The team reports that 79 patients completed 35 cycles of pembrolizumab, with a median follow-up of 43.4 months.
Compared with the overall patient group, these patients were less likely to be aged ≥ 65 years and to have received two or more prior treatment lines, although they were more likely to be current or former smokers and to have squamous tumor histology.
Patients who completed 35 cycles had an objective response rate of 94.9%, and 91.0% were still alive at the data cutoff. Overall survival rates were 98.7% at 12 months and 86.3% at 24 months.
Of 71 patients eligible for analysis, 23 experienced progression after completing pembrolizumab, at PFS rates at 12 and 24 months of 72.5% and 57.7%, respectively.
A total of 14 patients were given a second course of pembrolizumab, of whom six had a partial response and five had stable disease. At the data cutoff, five patients had completed 17 additional cycles and 11 were alive.
Pembro Approved at Fixed Dose
One notable aspect of the study is that patients in the pembrolizumab arm were given two different doses of the drug based on body weight, whereas the drug is approved in the United States at a fixed dose of 200 mg.
Herbst told Medscape Medical News he considers the 200-mg dose to be appropriate.
“I didn’t think that the 3-mg versus 10-mg dose per kg that we used in our study made much difference in an average-sized person,” he said, adding that the 200-mg dose “is something a little bit more than 3 mg/kg.”
“So I think that this is clearly the right dos, and I don’t think more would make any difference,” he said.
The study was funded by Merck, the manufacturer of pembrolizumab. Herbst has reported having a consulting or advisory role for many pharmaceutical companies. Other coauthors have also reported relationships with industry, and some of the authors are Merck employees. Peters has reported receiving education grants, providing consultation, attending advisory boards, and/or providing lectures for many pharmaceutical companies.
This article first appeared on Medscape.com.
More than a third (35%) of patients with relapsed non–small cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda, Merck) were still alive at 3 years, according to long-term results from a pivotal clinical trial.
The results also showed that, among the 10% of patients who completed all 35 cycles of pembrolizumab, the 3-year overall survival was approximately 99%, with progression-free survival (PFS) at around 70%.
“It is too soon to say that pembrolizumab is a potential cure...and we know that it doesn’t work for all patients, but the agent remains very, very promising,” said lead investigator Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut.
These new results come from the KEYNOTE-010 trial, conducted in more than 1000 patients with NSCLC who had progressed on chemotherapy, randomized to receive immunotherapy with pembrolizumab or chemotherapy with docetaxel.
The results were published online on February 20 in the Journal of Clinical Oncology and were previously presented at the 2018 annual meeting of the European Society of Medical Oncology.
Overall survival at 3 years was 35% in patients with PD-L1 expression ≥ 50% in the tumor, and 23% in those with PD-L1 ≥ 1%.
This compares with 3-year overall survival of 11-13% with docetaxel.
These results are “really extraordinary,” Herbst commented to Medscape Medical News.
The 3-year overall survival rate of 35% in patients with PD-L1 ≥ 50% “is huge,” he said. “It really shows the durability of the response.”
Herbst commented that the “almost 100%” survival at 3 years among patients who completed 35 cycles of pembrolizumab shows that this treatment period (of about 2 years) is “probably about the right time to treat.”
“Currently, the agent is being used in all potential settings, before any other treatment, after other treatment, and with other treatments,” he said.
“Our hope is to find the very best way to use pembrolizumab to treat individual lung cancer patients, assessing how much PD-L1 a tumor expresses, what stage the patient is in, as well as other variables and biomarkers we are working on. This is the story of tailored therapy,” Herbst said.
Approached for comment, Solange Peters, MD, PhD, Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said that the results are “very good” and “confirm the paradigms we have been seeing in melanoma,” with good long-term control, which is “very reassuring.”
However, she told Medscape Medical News that the trial raises an important question: «How long do you need to expose your patient with lung cancer to immunotherapy in order to get this long-term control?»
She said the “good news” is that, for the 10% of patients who completed 2 years of treatment per protocol, almost all of them are still alive at 3 years, “which is not observed with chemotherapy.”
The question for Peters is “more about the definition of long-term control,” as it was seen that almost one in three patients nevertheless had some form of progression.
This suggests that you have a group of people “who are nicely controlled, you stop the drug, and 1 year later a third of them have progressed.”
Peters said: “So how long do you need to treat these patients? I would say I still don’t know.”
“If I were one of these patients probably I would still want to continue [on the drug]. Of course, some might have progressed even while remaining on the drug, but the proportion who would have progressed is probably smaller than this one.”
Responses on Re-introduction of Therapy
The study also allowed patients who had completed 35 cycles of pembrolizumab to be restarted on the drug if they experienced progression.
The team found that, among 14 patients, 43% had a partial response and 36% had stable disease.
Herbst highlighted this finding and told Medscape Medical News that this «could be very important to physicians because they might want to think about using the drug again» in patients who have progressed on it.
He believes that the progression was not because of any resistance per se but rather a slowing down of the adaptive immune response.
“It’s just that it needs a boost,” he said, while noting that tissue specimens will nevertheless be required to demonstrate the theory.
Peters agreed that these results are “very promising,” but questioned their overall significance, as it is “a very small number of patients” from a subset whose disease was controlled while on treatment and then progressed after stopping.
She also pointed out that, in another study in patients with lung cancer (CheckMate-153), some patients were rechallenged with immunotherapy after having stopped treatment at 1 year “with very poor results.”
Peters said studies in melanoma have shown “rechallenge can be useful in a significant proportion of patients, but still you have not demonstrated that stopping and rechallenging is the same as not stopping.”
Study Details
KEYNOTE-010 involved patients with NSCLC from 202 centers in 24 countries with stage IIIB/IV disease expressing PD-L1 who had experienced disease progression after at least two cycles of platinum-based chemotherapy.
They were randomized 1:1:1 to open-label pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks.
Pembrolizumab was continued for 35 treatment cycles over 2 years and docetaxel was continued for the maximum duration allowed by local regulators.
Patients who stopped pembrolizumab after a complete response or completing all 35 cycles, and who subsequently experienced disease progression, could receive up to 17 additional cycles over 1 year if they had not received another anticancer therapy in the meantime.
Among the 1,034 patients originally recruited between August 2013 and February 2015, 691 were assigned to pembrolizumab at 3 mg/kg or 10 mg/kg and 343 to docetaxel.
For the intention-to-treat analysis in 1033 patients, the mean duration of follow-up was 42.6 months, with a median treatment duration of 3.5 months in the pembrolizumab group and 2.0 months in the docetaxel group.
Compared with docetaxel, pembrolizumab was associated with a significant reduction in the risk of death, at a hazard ratio of 0.53 in patients with PD-L1 ≥ 50% and 0.69 in those with PD-L1 ≥ 1% (both P < .0001).
In patients with PD-L1 ≥ 50%, median overall survival was 16.9 months in those given pembrolizumab and 8.2 months with docetaxel. Among those with PD-L1 ≥ 1%, median overall survival was 11.8 months with pembrolizumab versus 8.4 months with docetaxel.
Overall survival on Kaplan-Meier analysis was 34.5% with pembrolizumab and 12.7% with docetaxel in the PD-L1 ≥ 50% group, and 22.9% versus 11.0% in the PD-L1 ≥ 1% group.
PFS significantly improved with pembrolizumab versus docetaxel, at a hazard ratio of 0.57 (P < .00001) among patients with PD-L1 ≥ 50% and 0.83 (P < .005) in those with PD-L1 ≥ 1%.
In terms of safety, 17.7% of patients who completed 2 years of pembrolizumab had grade 3-5 treatment-related adverse events, compared with 16.6% among all pembrolizumab-treated patients and 36.6% of those given docetaxel.
The team reports that 79 patients completed 35 cycles of pembrolizumab, with a median follow-up of 43.4 months.
Compared with the overall patient group, these patients were less likely to be aged ≥ 65 years and to have received two or more prior treatment lines, although they were more likely to be current or former smokers and to have squamous tumor histology.
Patients who completed 35 cycles had an objective response rate of 94.9%, and 91.0% were still alive at the data cutoff. Overall survival rates were 98.7% at 12 months and 86.3% at 24 months.
Of 71 patients eligible for analysis, 23 experienced progression after completing pembrolizumab, at PFS rates at 12 and 24 months of 72.5% and 57.7%, respectively.
A total of 14 patients were given a second course of pembrolizumab, of whom six had a partial response and five had stable disease. At the data cutoff, five patients had completed 17 additional cycles and 11 were alive.
Pembro Approved at Fixed Dose
One notable aspect of the study is that patients in the pembrolizumab arm were given two different doses of the drug based on body weight, whereas the drug is approved in the United States at a fixed dose of 200 mg.
Herbst told Medscape Medical News he considers the 200-mg dose to be appropriate.
“I didn’t think that the 3-mg versus 10-mg dose per kg that we used in our study made much difference in an average-sized person,” he said, adding that the 200-mg dose “is something a little bit more than 3 mg/kg.”
“So I think that this is clearly the right dos, and I don’t think more would make any difference,” he said.
The study was funded by Merck, the manufacturer of pembrolizumab. Herbst has reported having a consulting or advisory role for many pharmaceutical companies. Other coauthors have also reported relationships with industry, and some of the authors are Merck employees. Peters has reported receiving education grants, providing consultation, attending advisory boards, and/or providing lectures for many pharmaceutical companies.
This article first appeared on Medscape.com.
What medical conferences are being canceled by coronavirus?
In a typical year, March marks the start of conference season, made all the more attractive by collegial gatherings and travel to warmer climes. But 2020 has already proven anything but typical as the number of novel coronavirus cases continues to increase around the globe. As a potential pandemic looms, these meetings – full of handshakes and crowded lecture halls – are also nirvana for opportunistic viruses. As are the airports, airplanes, and cabs required to get there.
So, as COVID-19 continues to spread, medical and scientific societies must make some difficult decisions. In Europe, at least a few societies have already suspended their upcoming meetings, while France has temporarily banned all gatherings over 5000 people.
In the United States, however, most medical conferences are moving forward as planned – at least for now. But one conference of 10,000 attendees, the American Physical Society annual meeting, which was scheduled for March 2-6 in Denver, was canceled the day before the meeting started. Although it’s not a medical conference, it speaks to the “rapidly escalating health concerns” that all conference organizers must grapple with.
APS Physics Meetings
@APSMeetings
Due to rapidly escalating health concerns relating to the spread of the coronavirus disease (COVID-19), the 2020 APS March Meeting in Denver, CO, has been canceled. Please do not travel to Denver to attend the March Meeting. More information will follow shortly. #apsmarch
734 9:59 PM - Feb 29, 2020
Just one smaller medical meeting, the Ataxia Conference, which was scheduled for March 6-7 in Denver, has been canceled.
Most societies hosting these meetings have put out statements to their attendees saying that they’re monitoring the situation and will adapt as necessary. The United States and Canadian Academy of Pathology, which is holding its annual meeting in Los Angeles this week, sent out an email beforehand asking international travelers to consider staying home. The Healthcare Information and Management Systems Society (HIMSS) Global Health Conference, which is slated to have about 50,000 attendees from around the world, has declared itself a “handshake-free” conference but otherwise intends to move ahead as planned.
All of these conferences will be pushing forward without at least one prominent group of attendees. New York University’s Langone Health has removed its employees from the decision-making process and instead is taking a proactive stance: The health system just declared a 60-day (minimum) ban preventing employees from attending any meetings or conferences and from all domestic and international work-related travel.
Here’s what some of the societies have said to attendees about their intent to proceed or modify their plans:
- Conference on Retroviruses and Opportunistic Infections (CROI), Boston, 3/8/20 - 3/11/20: Monitoring the situation and seeking input from local, state, and federal infectious-disease and public-health experts. Final decision expected by the evening of March 3.
- American Academy of Allergy, Asthma & Immunology (AAAAI), Philadelphia, 3/13/20 - 3/16/20: Monitoring developments but no plans to cancel or postpone at this time.
- American Academy of Orthopedic Surgeons (AAOS), Orlando, 3/24/20 - 3/28/20: Proceeding as planned.
- American Academy of Dermatology (AAD), Denver, 3/20/20 - 3/24/20: The AAD’s 2020 Annual Meeting is scheduled to take place as planned. The organization will increase the number of hand-sanitizing stations throughout the convention center, and it is adding a nursing station specifically designated for anyone with flu-like symptoms.
- American College of Cardiology (ACC), Chicago, 3/28/20 - 3/30/20: The organization is working with attendees, faculty, exhibitors, and other stakeholders in affected countries to ensure access to research and education from the meeting, but is otherwise proceeding as planned.
- Endocrine Society (ENDO), San Francisco, 3/28/20 - 3/31/20: ENDO 2020 will take place as scheduled, but this is an evolving situation worldwide. The society will continue to monitor and provide updates on its FAQ page.
- American College of Physicians Internal Medicine (ACP IM), Los Angeles, 4/23/20 - 4/25/20: ACP leadership is closely monitoring the COVID-19 situation and is actively working with the Centers for Disease Control and Prevention (CDC) to ensure authoritative communication of safety updates and recommendations as the situation evolves.
- American Association for Cancer Research (AACR), San Diego, 4/24/20 - 4/29/20: At this time, there is no plan to cancel or postpone any scheduled AACR meetings. The organization is tracking all travel restrictions as well as information and guidance from the CDC and World Health Organization.
- American Academy of Neurology (AAN), Toronto, 4/25/20 - 5/1/20: The group is continuing to closely monitor the situation in Toronto and will provide updates as the situation warrants.
This article originally appeared on Medscape.com.
In a typical year, March marks the start of conference season, made all the more attractive by collegial gatherings and travel to warmer climes. But 2020 has already proven anything but typical as the number of novel coronavirus cases continues to increase around the globe. As a potential pandemic looms, these meetings – full of handshakes and crowded lecture halls – are also nirvana for opportunistic viruses. As are the airports, airplanes, and cabs required to get there.
So, as COVID-19 continues to spread, medical and scientific societies must make some difficult decisions. In Europe, at least a few societies have already suspended their upcoming meetings, while France has temporarily banned all gatherings over 5000 people.
In the United States, however, most medical conferences are moving forward as planned – at least for now. But one conference of 10,000 attendees, the American Physical Society annual meeting, which was scheduled for March 2-6 in Denver, was canceled the day before the meeting started. Although it’s not a medical conference, it speaks to the “rapidly escalating health concerns” that all conference organizers must grapple with.
APS Physics Meetings
@APSMeetings
Due to rapidly escalating health concerns relating to the spread of the coronavirus disease (COVID-19), the 2020 APS March Meeting in Denver, CO, has been canceled. Please do not travel to Denver to attend the March Meeting. More information will follow shortly. #apsmarch
734 9:59 PM - Feb 29, 2020
Just one smaller medical meeting, the Ataxia Conference, which was scheduled for March 6-7 in Denver, has been canceled.
Most societies hosting these meetings have put out statements to their attendees saying that they’re monitoring the situation and will adapt as necessary. The United States and Canadian Academy of Pathology, which is holding its annual meeting in Los Angeles this week, sent out an email beforehand asking international travelers to consider staying home. The Healthcare Information and Management Systems Society (HIMSS) Global Health Conference, which is slated to have about 50,000 attendees from around the world, has declared itself a “handshake-free” conference but otherwise intends to move ahead as planned.
All of these conferences will be pushing forward without at least one prominent group of attendees. New York University’s Langone Health has removed its employees from the decision-making process and instead is taking a proactive stance: The health system just declared a 60-day (minimum) ban preventing employees from attending any meetings or conferences and from all domestic and international work-related travel.
Here’s what some of the societies have said to attendees about their intent to proceed or modify their plans:
- Conference on Retroviruses and Opportunistic Infections (CROI), Boston, 3/8/20 - 3/11/20: Monitoring the situation and seeking input from local, state, and federal infectious-disease and public-health experts. Final decision expected by the evening of March 3.
- American Academy of Allergy, Asthma & Immunology (AAAAI), Philadelphia, 3/13/20 - 3/16/20: Monitoring developments but no plans to cancel or postpone at this time.
- American Academy of Orthopedic Surgeons (AAOS), Orlando, 3/24/20 - 3/28/20: Proceeding as planned.
- American Academy of Dermatology (AAD), Denver, 3/20/20 - 3/24/20: The AAD’s 2020 Annual Meeting is scheduled to take place as planned. The organization will increase the number of hand-sanitizing stations throughout the convention center, and it is adding a nursing station specifically designated for anyone with flu-like symptoms.
- American College of Cardiology (ACC), Chicago, 3/28/20 - 3/30/20: The organization is working with attendees, faculty, exhibitors, and other stakeholders in affected countries to ensure access to research and education from the meeting, but is otherwise proceeding as planned.
- Endocrine Society (ENDO), San Francisco, 3/28/20 - 3/31/20: ENDO 2020 will take place as scheduled, but this is an evolving situation worldwide. The society will continue to monitor and provide updates on its FAQ page.
- American College of Physicians Internal Medicine (ACP IM), Los Angeles, 4/23/20 - 4/25/20: ACP leadership is closely monitoring the COVID-19 situation and is actively working with the Centers for Disease Control and Prevention (CDC) to ensure authoritative communication of safety updates and recommendations as the situation evolves.
- American Association for Cancer Research (AACR), San Diego, 4/24/20 - 4/29/20: At this time, there is no plan to cancel or postpone any scheduled AACR meetings. The organization is tracking all travel restrictions as well as information and guidance from the CDC and World Health Organization.
- American Academy of Neurology (AAN), Toronto, 4/25/20 - 5/1/20: The group is continuing to closely monitor the situation in Toronto and will provide updates as the situation warrants.
This article originally appeared on Medscape.com.
In a typical year, March marks the start of conference season, made all the more attractive by collegial gatherings and travel to warmer climes. But 2020 has already proven anything but typical as the number of novel coronavirus cases continues to increase around the globe. As a potential pandemic looms, these meetings – full of handshakes and crowded lecture halls – are also nirvana for opportunistic viruses. As are the airports, airplanes, and cabs required to get there.
So, as COVID-19 continues to spread, medical and scientific societies must make some difficult decisions. In Europe, at least a few societies have already suspended their upcoming meetings, while France has temporarily banned all gatherings over 5000 people.
In the United States, however, most medical conferences are moving forward as planned – at least for now. But one conference of 10,000 attendees, the American Physical Society annual meeting, which was scheduled for March 2-6 in Denver, was canceled the day before the meeting started. Although it’s not a medical conference, it speaks to the “rapidly escalating health concerns” that all conference organizers must grapple with.
APS Physics Meetings
@APSMeetings
Due to rapidly escalating health concerns relating to the spread of the coronavirus disease (COVID-19), the 2020 APS March Meeting in Denver, CO, has been canceled. Please do not travel to Denver to attend the March Meeting. More information will follow shortly. #apsmarch
734 9:59 PM - Feb 29, 2020
Just one smaller medical meeting, the Ataxia Conference, which was scheduled for March 6-7 in Denver, has been canceled.
Most societies hosting these meetings have put out statements to their attendees saying that they’re monitoring the situation and will adapt as necessary. The United States and Canadian Academy of Pathology, which is holding its annual meeting in Los Angeles this week, sent out an email beforehand asking international travelers to consider staying home. The Healthcare Information and Management Systems Society (HIMSS) Global Health Conference, which is slated to have about 50,000 attendees from around the world, has declared itself a “handshake-free” conference but otherwise intends to move ahead as planned.
All of these conferences will be pushing forward without at least one prominent group of attendees. New York University’s Langone Health has removed its employees from the decision-making process and instead is taking a proactive stance: The health system just declared a 60-day (minimum) ban preventing employees from attending any meetings or conferences and from all domestic and international work-related travel.
Here’s what some of the societies have said to attendees about their intent to proceed or modify their plans:
- Conference on Retroviruses and Opportunistic Infections (CROI), Boston, 3/8/20 - 3/11/20: Monitoring the situation and seeking input from local, state, and federal infectious-disease and public-health experts. Final decision expected by the evening of March 3.
- American Academy of Allergy, Asthma & Immunology (AAAAI), Philadelphia, 3/13/20 - 3/16/20: Monitoring developments but no plans to cancel or postpone at this time.
- American Academy of Orthopedic Surgeons (AAOS), Orlando, 3/24/20 - 3/28/20: Proceeding as planned.
- American Academy of Dermatology (AAD), Denver, 3/20/20 - 3/24/20: The AAD’s 2020 Annual Meeting is scheduled to take place as planned. The organization will increase the number of hand-sanitizing stations throughout the convention center, and it is adding a nursing station specifically designated for anyone with flu-like symptoms.
- American College of Cardiology (ACC), Chicago, 3/28/20 - 3/30/20: The organization is working with attendees, faculty, exhibitors, and other stakeholders in affected countries to ensure access to research and education from the meeting, but is otherwise proceeding as planned.
- Endocrine Society (ENDO), San Francisco, 3/28/20 - 3/31/20: ENDO 2020 will take place as scheduled, but this is an evolving situation worldwide. The society will continue to monitor and provide updates on its FAQ page.
- American College of Physicians Internal Medicine (ACP IM), Los Angeles, 4/23/20 - 4/25/20: ACP leadership is closely monitoring the COVID-19 situation and is actively working with the Centers for Disease Control and Prevention (CDC) to ensure authoritative communication of safety updates and recommendations as the situation evolves.
- American Association for Cancer Research (AACR), San Diego, 4/24/20 - 4/29/20: At this time, there is no plan to cancel or postpone any scheduled AACR meetings. The organization is tracking all travel restrictions as well as information and guidance from the CDC and World Health Organization.
- American Academy of Neurology (AAN), Toronto, 4/25/20 - 5/1/20: The group is continuing to closely monitor the situation in Toronto and will provide updates as the situation warrants.
This article originally appeared on Medscape.com.
Upcoming vaccine may offset surge in polio subtypes
Although wild poliovirus type 3 has not been detected globally for 7 years, the number of wild type 1 cases increased from 33 in 2018 to 173 in 2019. In response, a modified oral vaccine is being developed, according to Stephen Cochi, MD, of the Centers for Disease Control and Prevention’s Center for Global Health.
Several factors, including a Taliban ban on house-to-house vaccination in Afghanistan and a delay of large-scale vaccinations in Pakistan contributed to the surge in polio infections, Dr. Cochi said in a presentation at the February meeting of the CDC’s Advisory Committee on Immunization Practices (ACIP).
In addition, circulating vaccine-derived polioviruses (cVDPV) outbreaks have occurred in multiple countries including sub-Saharan Africa, China, Pakistan, and the Philippines. These outbreaks threaten the success of the bivalent oral polio vaccine introduced in April 2016 in 155 countries, Dr. Cochi said.
Outbreaks tend to occur just outside targeted areas for campaigns, caused by decreasing population immunity, he said.
The novel OPV2 (nOPV2) is a genetic modification of the existing OPV2 vaccine designed to improve genetic stability, Dr. Cochi explained. The modifications would “decrease the risk of seeding new cVDPVs and the risk of vaccine-associated paralytic poliomyelitis (VAPP),” he said.
The Emergency Use Listing (EUL) was developed by the World Health Organization in response to the Ebola virus outbreak in 2014-2016 and is the fastest way to obtain regulatory review and approval of drug products, said Dr. Cochi.
A pilot plant has been established in Indonesia, and upon EUL approval, 4-8 million doses of the nOPV2 should be available for use in the second quarter of 2020, he concluded.
Dr. Cochi had no relevant financial conflicts to disclose.
Although wild poliovirus type 3 has not been detected globally for 7 years, the number of wild type 1 cases increased from 33 in 2018 to 173 in 2019. In response, a modified oral vaccine is being developed, according to Stephen Cochi, MD, of the Centers for Disease Control and Prevention’s Center for Global Health.
Several factors, including a Taliban ban on house-to-house vaccination in Afghanistan and a delay of large-scale vaccinations in Pakistan contributed to the surge in polio infections, Dr. Cochi said in a presentation at the February meeting of the CDC’s Advisory Committee on Immunization Practices (ACIP).
In addition, circulating vaccine-derived polioviruses (cVDPV) outbreaks have occurred in multiple countries including sub-Saharan Africa, China, Pakistan, and the Philippines. These outbreaks threaten the success of the bivalent oral polio vaccine introduced in April 2016 in 155 countries, Dr. Cochi said.
Outbreaks tend to occur just outside targeted areas for campaigns, caused by decreasing population immunity, he said.
The novel OPV2 (nOPV2) is a genetic modification of the existing OPV2 vaccine designed to improve genetic stability, Dr. Cochi explained. The modifications would “decrease the risk of seeding new cVDPVs and the risk of vaccine-associated paralytic poliomyelitis (VAPP),” he said.
The Emergency Use Listing (EUL) was developed by the World Health Organization in response to the Ebola virus outbreak in 2014-2016 and is the fastest way to obtain regulatory review and approval of drug products, said Dr. Cochi.
A pilot plant has been established in Indonesia, and upon EUL approval, 4-8 million doses of the nOPV2 should be available for use in the second quarter of 2020, he concluded.
Dr. Cochi had no relevant financial conflicts to disclose.
Although wild poliovirus type 3 has not been detected globally for 7 years, the number of wild type 1 cases increased from 33 in 2018 to 173 in 2019. In response, a modified oral vaccine is being developed, according to Stephen Cochi, MD, of the Centers for Disease Control and Prevention’s Center for Global Health.
Several factors, including a Taliban ban on house-to-house vaccination in Afghanistan and a delay of large-scale vaccinations in Pakistan contributed to the surge in polio infections, Dr. Cochi said in a presentation at the February meeting of the CDC’s Advisory Committee on Immunization Practices (ACIP).
In addition, circulating vaccine-derived polioviruses (cVDPV) outbreaks have occurred in multiple countries including sub-Saharan Africa, China, Pakistan, and the Philippines. These outbreaks threaten the success of the bivalent oral polio vaccine introduced in April 2016 in 155 countries, Dr. Cochi said.
Outbreaks tend to occur just outside targeted areas for campaigns, caused by decreasing population immunity, he said.
The novel OPV2 (nOPV2) is a genetic modification of the existing OPV2 vaccine designed to improve genetic stability, Dr. Cochi explained. The modifications would “decrease the risk of seeding new cVDPVs and the risk of vaccine-associated paralytic poliomyelitis (VAPP),” he said.
The Emergency Use Listing (EUL) was developed by the World Health Organization in response to the Ebola virus outbreak in 2014-2016 and is the fastest way to obtain regulatory review and approval of drug products, said Dr. Cochi.
A pilot plant has been established in Indonesia, and upon EUL approval, 4-8 million doses of the nOPV2 should be available for use in the second quarter of 2020, he concluded.
Dr. Cochi had no relevant financial conflicts to disclose.
FROM AN ACIP MEETING
Washington State grapples with coronavirus outbreak
As the first COVID-19 outbreak in the United States emerges in Washington State, the city of Seattle, King County, and Washington State health officials provided the beginnings of a roadmap for how the region will address the rapidly evolving health crisis.
Health officials announced that four new cases were reported over the weekend in King County, Wash. There have now been 10 hospitalizations and 6 COVID-19 deaths at Evergreen Health, Kirkland, Wash. Of the deaths, five were King County residents and one was a resident of Snohomish County. Three patients died on March 1; all were in their 70s or 80s with comorbidities. Two had been residents of the Life Care senior residential facility that is at the center of the Kirkland outbreak. The number of cases in Washington now totals 18, with four cases in Snohomish County and the balance in neighboring King County.
Approximately 29 cases are under investigation with test results pending; a Centers for Disease Control and Prevention (CDC) team is on-site.
Speaking at a news conference March 2, officials sought to strike a balance between giving the community a realistic appraisal of the likely scope of the COVID-19 outbreak and avoiding sparking a panic.
“This is a complex and unprecedented challenge nationally, globally, and locally. The vast majority of the infected have mild or moderate disease and do not need hospitalization,” said Jeffrey Duchin, MD, health officer and chief, Communicable Disease EPI/Immunization Section, Public Health, Seattle and King County, and a professor of infectious diseases at the University of Washington, Seattle. “On the other hand, it’s obvious that this infection can cause very serious disease in people who are older and have underlying health conditions. We expect cases to continue to increase. We are taking the situation extremely seriously; the risk for all of us becoming infected is increasing. ...There is the potential for many to become ill at the same time.”
Among the measures being taken immediately are the purchase by King County of a hotel to house individuals who require isolation and those who are convalescing from the virus. Officials are also placing a number of prefabricated stand-alone housing units on public grounds in Seattle, with the recognition that the area has a large transient and homeless community. The stand-alone units will house homeless individuals who need isolation, treatment, or recuperation but who aren’t ill enough to be hospitalized.
Dr. Duchin said that testing capacity is ramping up rapidly in Washington State: The state lab can now accommodate up to about 200 tests daily, and expects to be able to do up to 1,000 daily soon. The University of Washington’s testing capacity will come online March 2 or 3 as a testing facility with similar initial and future peak testing capacities.
The testing strategy will continue to include very ill individuals with pneumonia or other respiratory illness of unknown etiology, but will also expand to include less ill people. This shift is being made in accordance with a shift in CDC guidelines, because of increased testing capacity, and to provide a better picture of the severity, scope, geography, and timing of the current COVID-19 outbreak in the greater Seattle area.
No school closures or cancellation of gatherings are currently recommended by public health authorities. There are currently no COVID-19 cases in Washington schools. The expectation is that any recommendations regarding closures will be re-evaluated as the outbreak progresses.
Repeatedly, officials asked the general public to employ basic measures such as handwashing and avoidance of touching the face, and to spare masks for the ill and for those who care for them. “The vast majority of people will not have serious illness. In turn we need to do everything we can to help those health care workers. I’m asking the public to do things like save the masks for our health care workers. …We need assets for our front-line health care workers and also for those who may be needing them,” said King County Health Department director Patty Hayes, RN, MN.
Now is also the time for households to initiate basic emergency preparedness measures, such as having adequate food and medication, and to make arrangements for childcare in the event of school closures, said several officials.
“We can decrease the impact on our health care system by reducing our individual risk. We are making individual- and community-level recommendations to limit the spread of disease. These are very similar to what we recommend for influenza,” said Dr. Duchin.
Ettore Palazzo, MD, chief medical and quality officer at EvergreenHealth, gave a sense of how the hospital is coping with being Ground Zero for COVID-19 in the United States. “We have made adjustments for airborne precautions,” he said, including transforming the entire critical care unit to a negative pressure unit. “We have these capabilities in other parts of the hospital as well.” Staff are working hard, but thus far staffing has kept pace with demand, he said, but all are feeling the strain already.
Dr. Duchin made the point that Washington is relatively well equipped to handle the increasingly likely scenario of a large spike in coronavirus cases, since it’s part of the Northwest Healthcare Response Network. The network is planning for sharing resources such as staff, respirators, and intensive care unit beds as circumstances warrant.
“What you just heard illustrates the challenge of this disease,” said Dr. Duchin, summing up. “The public health service and clinical health care delivery systems don’t have the capacity to track down every case in the community. I’m guessing we will see more cases of coronavirus than we see of influenza. At some point we will be shifting from counting every case” to focusing on outbreaks and the critically ill in hospitals, he said.
“We are still trying to contain the outbreak, but we are at the same time pivoting to a more community-based approach,” similar to the approach with influenza, said Dr. Duchin.
A summary of deaths and ongoing cases, drawn from the press release, is below:
The four new cases are:
• A male in his 50s, hospitalized at Highline Hospital. He has no known exposures. He is in stable but critical condition. He had no underlying health conditions.
• A male in his 70s, a resident of Life Care, hospitalized at EvergreenHealth in Kirkland. The man had underlying health conditions, and died March 1.
• A female in her 70s, a resident of Life Care, hospitalized at EvergreenHealth in Kirkland. The woman had underlying health conditions, and died March 1.
• A female in her 80s, a resident of Life Care, was hospitalized at EvergreenHealth. She is in critical condition.
In addition, a woman in her 80s, who was already reported as in critical condition at Evergreen, has died. She died on March 1.
Ten other cases, already reported earlier by Public Health, include:
• A female in her 80s, hospitalized at EvergreenHealth in Kirkland. This person has now died, and is reported as such above.
• A female in her 90s, hospitalized at EvergreenHealth in Kirkland. The woman has underlying health conditions, and is in critical condition.
• A male in his 70s, hospitalized at EvergreenHealth in Kirkland. The man has underlying health conditions, and is in critical condition.
• A male in his 70s was hospitalized at EvergreenHealth. He had underlying health conditions and died on Feb. 29.
• A man in his 60s, hospitalized at Valley Medical Center in Renton.
• A man in 60s, hospitalized at Virginia Mason Medical Center.
• A woman in her 50s, who had traveled to South Korea; recovering at home.
• A woman in her 70s, who was a resident of Life Care in Kirkland, hospitalized at EvergreenHealth.
• A woman in her 40s, employed by Life Care, who is hospitalized at Overlake Medical Center.
• A man in his 50s, who was hospitalized and died at EvergreenHealth.
As the first COVID-19 outbreak in the United States emerges in Washington State, the city of Seattle, King County, and Washington State health officials provided the beginnings of a roadmap for how the region will address the rapidly evolving health crisis.
Health officials announced that four new cases were reported over the weekend in King County, Wash. There have now been 10 hospitalizations and 6 COVID-19 deaths at Evergreen Health, Kirkland, Wash. Of the deaths, five were King County residents and one was a resident of Snohomish County. Three patients died on March 1; all were in their 70s or 80s with comorbidities. Two had been residents of the Life Care senior residential facility that is at the center of the Kirkland outbreak. The number of cases in Washington now totals 18, with four cases in Snohomish County and the balance in neighboring King County.
Approximately 29 cases are under investigation with test results pending; a Centers for Disease Control and Prevention (CDC) team is on-site.
Speaking at a news conference March 2, officials sought to strike a balance between giving the community a realistic appraisal of the likely scope of the COVID-19 outbreak and avoiding sparking a panic.
“This is a complex and unprecedented challenge nationally, globally, and locally. The vast majority of the infected have mild or moderate disease and do not need hospitalization,” said Jeffrey Duchin, MD, health officer and chief, Communicable Disease EPI/Immunization Section, Public Health, Seattle and King County, and a professor of infectious diseases at the University of Washington, Seattle. “On the other hand, it’s obvious that this infection can cause very serious disease in people who are older and have underlying health conditions. We expect cases to continue to increase. We are taking the situation extremely seriously; the risk for all of us becoming infected is increasing. ...There is the potential for many to become ill at the same time.”
Among the measures being taken immediately are the purchase by King County of a hotel to house individuals who require isolation and those who are convalescing from the virus. Officials are also placing a number of prefabricated stand-alone housing units on public grounds in Seattle, with the recognition that the area has a large transient and homeless community. The stand-alone units will house homeless individuals who need isolation, treatment, or recuperation but who aren’t ill enough to be hospitalized.
Dr. Duchin said that testing capacity is ramping up rapidly in Washington State: The state lab can now accommodate up to about 200 tests daily, and expects to be able to do up to 1,000 daily soon. The University of Washington’s testing capacity will come online March 2 or 3 as a testing facility with similar initial and future peak testing capacities.
The testing strategy will continue to include very ill individuals with pneumonia or other respiratory illness of unknown etiology, but will also expand to include less ill people. This shift is being made in accordance with a shift in CDC guidelines, because of increased testing capacity, and to provide a better picture of the severity, scope, geography, and timing of the current COVID-19 outbreak in the greater Seattle area.
No school closures or cancellation of gatherings are currently recommended by public health authorities. There are currently no COVID-19 cases in Washington schools. The expectation is that any recommendations regarding closures will be re-evaluated as the outbreak progresses.
Repeatedly, officials asked the general public to employ basic measures such as handwashing and avoidance of touching the face, and to spare masks for the ill and for those who care for them. “The vast majority of people will not have serious illness. In turn we need to do everything we can to help those health care workers. I’m asking the public to do things like save the masks for our health care workers. …We need assets for our front-line health care workers and also for those who may be needing them,” said King County Health Department director Patty Hayes, RN, MN.
Now is also the time for households to initiate basic emergency preparedness measures, such as having adequate food and medication, and to make arrangements for childcare in the event of school closures, said several officials.
“We can decrease the impact on our health care system by reducing our individual risk. We are making individual- and community-level recommendations to limit the spread of disease. These are very similar to what we recommend for influenza,” said Dr. Duchin.
Ettore Palazzo, MD, chief medical and quality officer at EvergreenHealth, gave a sense of how the hospital is coping with being Ground Zero for COVID-19 in the United States. “We have made adjustments for airborne precautions,” he said, including transforming the entire critical care unit to a negative pressure unit. “We have these capabilities in other parts of the hospital as well.” Staff are working hard, but thus far staffing has kept pace with demand, he said, but all are feeling the strain already.
Dr. Duchin made the point that Washington is relatively well equipped to handle the increasingly likely scenario of a large spike in coronavirus cases, since it’s part of the Northwest Healthcare Response Network. The network is planning for sharing resources such as staff, respirators, and intensive care unit beds as circumstances warrant.
“What you just heard illustrates the challenge of this disease,” said Dr. Duchin, summing up. “The public health service and clinical health care delivery systems don’t have the capacity to track down every case in the community. I’m guessing we will see more cases of coronavirus than we see of influenza. At some point we will be shifting from counting every case” to focusing on outbreaks and the critically ill in hospitals, he said.
“We are still trying to contain the outbreak, but we are at the same time pivoting to a more community-based approach,” similar to the approach with influenza, said Dr. Duchin.
A summary of deaths and ongoing cases, drawn from the press release, is below:
The four new cases are:
• A male in his 50s, hospitalized at Highline Hospital. He has no known exposures. He is in stable but critical condition. He had no underlying health conditions.
• A male in his 70s, a resident of Life Care, hospitalized at EvergreenHealth in Kirkland. The man had underlying health conditions, and died March 1.
• A female in her 70s, a resident of Life Care, hospitalized at EvergreenHealth in Kirkland. The woman had underlying health conditions, and died March 1.
• A female in her 80s, a resident of Life Care, was hospitalized at EvergreenHealth. She is in critical condition.
In addition, a woman in her 80s, who was already reported as in critical condition at Evergreen, has died. She died on March 1.
Ten other cases, already reported earlier by Public Health, include:
• A female in her 80s, hospitalized at EvergreenHealth in Kirkland. This person has now died, and is reported as such above.
• A female in her 90s, hospitalized at EvergreenHealth in Kirkland. The woman has underlying health conditions, and is in critical condition.
• A male in his 70s, hospitalized at EvergreenHealth in Kirkland. The man has underlying health conditions, and is in critical condition.
• A male in his 70s was hospitalized at EvergreenHealth. He had underlying health conditions and died on Feb. 29.
• A man in his 60s, hospitalized at Valley Medical Center in Renton.
• A man in 60s, hospitalized at Virginia Mason Medical Center.
• A woman in her 50s, who had traveled to South Korea; recovering at home.
• A woman in her 70s, who was a resident of Life Care in Kirkland, hospitalized at EvergreenHealth.
• A woman in her 40s, employed by Life Care, who is hospitalized at Overlake Medical Center.
• A man in his 50s, who was hospitalized and died at EvergreenHealth.
As the first COVID-19 outbreak in the United States emerges in Washington State, the city of Seattle, King County, and Washington State health officials provided the beginnings of a roadmap for how the region will address the rapidly evolving health crisis.
Health officials announced that four new cases were reported over the weekend in King County, Wash. There have now been 10 hospitalizations and 6 COVID-19 deaths at Evergreen Health, Kirkland, Wash. Of the deaths, five were King County residents and one was a resident of Snohomish County. Three patients died on March 1; all were in their 70s or 80s with comorbidities. Two had been residents of the Life Care senior residential facility that is at the center of the Kirkland outbreak. The number of cases in Washington now totals 18, with four cases in Snohomish County and the balance in neighboring King County.
Approximately 29 cases are under investigation with test results pending; a Centers for Disease Control and Prevention (CDC) team is on-site.
Speaking at a news conference March 2, officials sought to strike a balance between giving the community a realistic appraisal of the likely scope of the COVID-19 outbreak and avoiding sparking a panic.
“This is a complex and unprecedented challenge nationally, globally, and locally. The vast majority of the infected have mild or moderate disease and do not need hospitalization,” said Jeffrey Duchin, MD, health officer and chief, Communicable Disease EPI/Immunization Section, Public Health, Seattle and King County, and a professor of infectious diseases at the University of Washington, Seattle. “On the other hand, it’s obvious that this infection can cause very serious disease in people who are older and have underlying health conditions. We expect cases to continue to increase. We are taking the situation extremely seriously; the risk for all of us becoming infected is increasing. ...There is the potential for many to become ill at the same time.”
Among the measures being taken immediately are the purchase by King County of a hotel to house individuals who require isolation and those who are convalescing from the virus. Officials are also placing a number of prefabricated stand-alone housing units on public grounds in Seattle, with the recognition that the area has a large transient and homeless community. The stand-alone units will house homeless individuals who need isolation, treatment, or recuperation but who aren’t ill enough to be hospitalized.
Dr. Duchin said that testing capacity is ramping up rapidly in Washington State: The state lab can now accommodate up to about 200 tests daily, and expects to be able to do up to 1,000 daily soon. The University of Washington’s testing capacity will come online March 2 or 3 as a testing facility with similar initial and future peak testing capacities.
The testing strategy will continue to include very ill individuals with pneumonia or other respiratory illness of unknown etiology, but will also expand to include less ill people. This shift is being made in accordance with a shift in CDC guidelines, because of increased testing capacity, and to provide a better picture of the severity, scope, geography, and timing of the current COVID-19 outbreak in the greater Seattle area.
No school closures or cancellation of gatherings are currently recommended by public health authorities. There are currently no COVID-19 cases in Washington schools. The expectation is that any recommendations regarding closures will be re-evaluated as the outbreak progresses.
Repeatedly, officials asked the general public to employ basic measures such as handwashing and avoidance of touching the face, and to spare masks for the ill and for those who care for them. “The vast majority of people will not have serious illness. In turn we need to do everything we can to help those health care workers. I’m asking the public to do things like save the masks for our health care workers. …We need assets for our front-line health care workers and also for those who may be needing them,” said King County Health Department director Patty Hayes, RN, MN.
Now is also the time for households to initiate basic emergency preparedness measures, such as having adequate food and medication, and to make arrangements for childcare in the event of school closures, said several officials.
“We can decrease the impact on our health care system by reducing our individual risk. We are making individual- and community-level recommendations to limit the spread of disease. These are very similar to what we recommend for influenza,” said Dr. Duchin.
Ettore Palazzo, MD, chief medical and quality officer at EvergreenHealth, gave a sense of how the hospital is coping with being Ground Zero for COVID-19 in the United States. “We have made adjustments for airborne precautions,” he said, including transforming the entire critical care unit to a negative pressure unit. “We have these capabilities in other parts of the hospital as well.” Staff are working hard, but thus far staffing has kept pace with demand, he said, but all are feeling the strain already.
Dr. Duchin made the point that Washington is relatively well equipped to handle the increasingly likely scenario of a large spike in coronavirus cases, since it’s part of the Northwest Healthcare Response Network. The network is planning for sharing resources such as staff, respirators, and intensive care unit beds as circumstances warrant.
“What you just heard illustrates the challenge of this disease,” said Dr. Duchin, summing up. “The public health service and clinical health care delivery systems don’t have the capacity to track down every case in the community. I’m guessing we will see more cases of coronavirus than we see of influenza. At some point we will be shifting from counting every case” to focusing on outbreaks and the critically ill in hospitals, he said.
“We are still trying to contain the outbreak, but we are at the same time pivoting to a more community-based approach,” similar to the approach with influenza, said Dr. Duchin.
A summary of deaths and ongoing cases, drawn from the press release, is below:
The four new cases are:
• A male in his 50s, hospitalized at Highline Hospital. He has no known exposures. He is in stable but critical condition. He had no underlying health conditions.
• A male in his 70s, a resident of Life Care, hospitalized at EvergreenHealth in Kirkland. The man had underlying health conditions, and died March 1.
• A female in her 70s, a resident of Life Care, hospitalized at EvergreenHealth in Kirkland. The woman had underlying health conditions, and died March 1.
• A female in her 80s, a resident of Life Care, was hospitalized at EvergreenHealth. She is in critical condition.
In addition, a woman in her 80s, who was already reported as in critical condition at Evergreen, has died. She died on March 1.
Ten other cases, already reported earlier by Public Health, include:
• A female in her 80s, hospitalized at EvergreenHealth in Kirkland. This person has now died, and is reported as such above.
• A female in her 90s, hospitalized at EvergreenHealth in Kirkland. The woman has underlying health conditions, and is in critical condition.
• A male in his 70s, hospitalized at EvergreenHealth in Kirkland. The man has underlying health conditions, and is in critical condition.
• A male in his 70s was hospitalized at EvergreenHealth. He had underlying health conditions and died on Feb. 29.
• A man in his 60s, hospitalized at Valley Medical Center in Renton.
• A man in 60s, hospitalized at Virginia Mason Medical Center.
• A woman in her 50s, who had traveled to South Korea; recovering at home.
• A woman in her 70s, who was a resident of Life Care in Kirkland, hospitalized at EvergreenHealth.
• A woman in her 40s, employed by Life Care, who is hospitalized at Overlake Medical Center.
• A man in his 50s, who was hospitalized and died at EvergreenHealth.
FROM A KING COUNTY, WASH. NEWS BRIEFING
No sedation fails to improve mortality in mechanically ventilated patients
ORLANDO – For critically ill, according to results of a multicenter, randomized trial.
The lack of sedation did significantly improve certain secondary endpoints, including a reduced number of thromboembolic events and preservation of physical function, according to Palle Toft, PhD, DMSc, of Odense (Denmark) University Hospital.
However, the 90-day mortality rate was 42.4% in the no-sedation group versus 37.0% in the sedation group in the NONSEDA study, which was intended to test the hypothesis that mortality would be lower in the no-sedation group.
That 5.4 percentage point difference between arms in NONSEDA was not statistically significant (P = .65) in results of the study, presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine and concurrently published in the New England Journal of Medicine.
Yet that mortality trend is in the “opposite direction” of an earlier, single-center trial by Dr. Toft and colleagues, noted Claude Guérin, MD, PhD, in a related editorial that also appeared in the journal. In that earlier study, the reported hospital mortality rates were 36% for no sedation and 47% for sedation with daily interruption.
“The results from this trial [NONSEDA] are important because they arouse concern about omitting sedation in mechanically ventilated patients and reinforce the need to monitor sedation clinically, with the aim of discontinuing it as early as possible or at least interrupting it daily,” Dr. Guérin wrote in his editorial.
That said, the earlier, single-center trial was not statistically powered to show between-group differences in mortality, Dr. Toft and coauthors wrote in their journal article.
In his presentation, Dr. Toft emphasized that light sedation with a wake-up trial was “comparable” with no sedation with regard to mortality.
“I think my main message is that we have to individualize patient treatment,” Dr. Toft told attendees at a late-breaking literature session. “Many patients would benefit from nonsedation, and some would benefit by light sedation with a daily wake-up trial. We have to respect patient autonomy, and try to establish a two-way communication with patients in 2020.”
Sandra L. Kane-Gill, PharmD, treasurer of SCCM and assistant professor of pharmacy and therapeutics at the University of Pittsburgh, said that current SCCM guidelines recommend using light sedation in critically ill, mechanically ventilated adults.
“I think we should stay consistent with what the guidelines are saying,” Dr. Kane-Gill said in an interview. “How you do that may vary, but targeting light sedation is consistent with what the evidence is suggesting in those guidelines.”
The depth of sedation between the no-sedation group in the light sedation group in the present study was not as great as the investigators had anticipated, which may explain the lack of statistically significant difference in mortality, according to Dr. Kane-Gill.
According to the report, 38.4% of patients in the no-sedation group received medication for sedation during their ICU stay, while Richmond Agitation and Sedation Scores increased in both groups, indicating a more alert state in both groups.
The multicenter NONSEDA trial included 700 mechanically ventilated ICU patients randomized either to no sedation or to light sedation, such that the patient was arousable, with daily interruption.
Previous studies have shown that daily interruption of sedation reduced mechanical ventilation duration, ICU stay length, and mortality in comparison with no interruption, the investigators noted.
While mortality at 90 days did not differ significantly between the no-sedation and light-sedation approaches, no sedation reduced thromboembolic events, Dr. Toft said at the meeting. The number of thrombolic events within 90 days was 10 (5%) in the sedation group and 1 (0.5%) in the no-sedation group (P less than .05), according to the reported data.
Likewise, several measures of physical function significantly improved in an a prior defined subgroup of 200 patients, he said. Those measures included hand grip at extubation and ICU discharge, as well as scores on the Barthel Index for Activities of Daily Living.
Nonsedation might improve kidney function, based on other reported outcomes of the study, Dr. Toft said. The number of coma- and delirium-free days was 3.0 in the no-sedation group versus 1.0 in the sedation group (P less than .01), he added.
The benefits of no sedation may extend beyond objective changes in health outcomes, according to Dr. Toft. “The patients are able to communicate with the staff, they might be able to enjoy food, in the evening they can look at the television instead of being sedated – and they can be mobilized and they can write their opinion about the treatments to the doctor, and in this way, you have two-way communication,” he explained in his presentation.
Dr. Toft reported that he had no financial relationships to disclose.
SOURCE: Toft P et al. N Engl J Med. 2019 Feb 16. doi: 10.1056/NEJMoa1906759.
ORLANDO – For critically ill, according to results of a multicenter, randomized trial.
The lack of sedation did significantly improve certain secondary endpoints, including a reduced number of thromboembolic events and preservation of physical function, according to Palle Toft, PhD, DMSc, of Odense (Denmark) University Hospital.
However, the 90-day mortality rate was 42.4% in the no-sedation group versus 37.0% in the sedation group in the NONSEDA study, which was intended to test the hypothesis that mortality would be lower in the no-sedation group.
That 5.4 percentage point difference between arms in NONSEDA was not statistically significant (P = .65) in results of the study, presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine and concurrently published in the New England Journal of Medicine.
Yet that mortality trend is in the “opposite direction” of an earlier, single-center trial by Dr. Toft and colleagues, noted Claude Guérin, MD, PhD, in a related editorial that also appeared in the journal. In that earlier study, the reported hospital mortality rates were 36% for no sedation and 47% for sedation with daily interruption.
“The results from this trial [NONSEDA] are important because they arouse concern about omitting sedation in mechanically ventilated patients and reinforce the need to monitor sedation clinically, with the aim of discontinuing it as early as possible or at least interrupting it daily,” Dr. Guérin wrote in his editorial.
That said, the earlier, single-center trial was not statistically powered to show between-group differences in mortality, Dr. Toft and coauthors wrote in their journal article.
In his presentation, Dr. Toft emphasized that light sedation with a wake-up trial was “comparable” with no sedation with regard to mortality.
“I think my main message is that we have to individualize patient treatment,” Dr. Toft told attendees at a late-breaking literature session. “Many patients would benefit from nonsedation, and some would benefit by light sedation with a daily wake-up trial. We have to respect patient autonomy, and try to establish a two-way communication with patients in 2020.”
Sandra L. Kane-Gill, PharmD, treasurer of SCCM and assistant professor of pharmacy and therapeutics at the University of Pittsburgh, said that current SCCM guidelines recommend using light sedation in critically ill, mechanically ventilated adults.
“I think we should stay consistent with what the guidelines are saying,” Dr. Kane-Gill said in an interview. “How you do that may vary, but targeting light sedation is consistent with what the evidence is suggesting in those guidelines.”
The depth of sedation between the no-sedation group in the light sedation group in the present study was not as great as the investigators had anticipated, which may explain the lack of statistically significant difference in mortality, according to Dr. Kane-Gill.
According to the report, 38.4% of patients in the no-sedation group received medication for sedation during their ICU stay, while Richmond Agitation and Sedation Scores increased in both groups, indicating a more alert state in both groups.
The multicenter NONSEDA trial included 700 mechanically ventilated ICU patients randomized either to no sedation or to light sedation, such that the patient was arousable, with daily interruption.
Previous studies have shown that daily interruption of sedation reduced mechanical ventilation duration, ICU stay length, and mortality in comparison with no interruption, the investigators noted.
While mortality at 90 days did not differ significantly between the no-sedation and light-sedation approaches, no sedation reduced thromboembolic events, Dr. Toft said at the meeting. The number of thrombolic events within 90 days was 10 (5%) in the sedation group and 1 (0.5%) in the no-sedation group (P less than .05), according to the reported data.
Likewise, several measures of physical function significantly improved in an a prior defined subgroup of 200 patients, he said. Those measures included hand grip at extubation and ICU discharge, as well as scores on the Barthel Index for Activities of Daily Living.
Nonsedation might improve kidney function, based on other reported outcomes of the study, Dr. Toft said. The number of coma- and delirium-free days was 3.0 in the no-sedation group versus 1.0 in the sedation group (P less than .01), he added.
The benefits of no sedation may extend beyond objective changes in health outcomes, according to Dr. Toft. “The patients are able to communicate with the staff, they might be able to enjoy food, in the evening they can look at the television instead of being sedated – and they can be mobilized and they can write their opinion about the treatments to the doctor, and in this way, you have two-way communication,” he explained in his presentation.
Dr. Toft reported that he had no financial relationships to disclose.
SOURCE: Toft P et al. N Engl J Med. 2019 Feb 16. doi: 10.1056/NEJMoa1906759.
ORLANDO – For critically ill, according to results of a multicenter, randomized trial.
The lack of sedation did significantly improve certain secondary endpoints, including a reduced number of thromboembolic events and preservation of physical function, according to Palle Toft, PhD, DMSc, of Odense (Denmark) University Hospital.
However, the 90-day mortality rate was 42.4% in the no-sedation group versus 37.0% in the sedation group in the NONSEDA study, which was intended to test the hypothesis that mortality would be lower in the no-sedation group.
That 5.4 percentage point difference between arms in NONSEDA was not statistically significant (P = .65) in results of the study, presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine and concurrently published in the New England Journal of Medicine.
Yet that mortality trend is in the “opposite direction” of an earlier, single-center trial by Dr. Toft and colleagues, noted Claude Guérin, MD, PhD, in a related editorial that also appeared in the journal. In that earlier study, the reported hospital mortality rates were 36% for no sedation and 47% for sedation with daily interruption.
“The results from this trial [NONSEDA] are important because they arouse concern about omitting sedation in mechanically ventilated patients and reinforce the need to monitor sedation clinically, with the aim of discontinuing it as early as possible or at least interrupting it daily,” Dr. Guérin wrote in his editorial.
That said, the earlier, single-center trial was not statistically powered to show between-group differences in mortality, Dr. Toft and coauthors wrote in their journal article.
In his presentation, Dr. Toft emphasized that light sedation with a wake-up trial was “comparable” with no sedation with regard to mortality.
“I think my main message is that we have to individualize patient treatment,” Dr. Toft told attendees at a late-breaking literature session. “Many patients would benefit from nonsedation, and some would benefit by light sedation with a daily wake-up trial. We have to respect patient autonomy, and try to establish a two-way communication with patients in 2020.”
Sandra L. Kane-Gill, PharmD, treasurer of SCCM and assistant professor of pharmacy and therapeutics at the University of Pittsburgh, said that current SCCM guidelines recommend using light sedation in critically ill, mechanically ventilated adults.
“I think we should stay consistent with what the guidelines are saying,” Dr. Kane-Gill said in an interview. “How you do that may vary, but targeting light sedation is consistent with what the evidence is suggesting in those guidelines.”
The depth of sedation between the no-sedation group in the light sedation group in the present study was not as great as the investigators had anticipated, which may explain the lack of statistically significant difference in mortality, according to Dr. Kane-Gill.
According to the report, 38.4% of patients in the no-sedation group received medication for sedation during their ICU stay, while Richmond Agitation and Sedation Scores increased in both groups, indicating a more alert state in both groups.
The multicenter NONSEDA trial included 700 mechanically ventilated ICU patients randomized either to no sedation or to light sedation, such that the patient was arousable, with daily interruption.
Previous studies have shown that daily interruption of sedation reduced mechanical ventilation duration, ICU stay length, and mortality in comparison with no interruption, the investigators noted.
While mortality at 90 days did not differ significantly between the no-sedation and light-sedation approaches, no sedation reduced thromboembolic events, Dr. Toft said at the meeting. The number of thrombolic events within 90 days was 10 (5%) in the sedation group and 1 (0.5%) in the no-sedation group (P less than .05), according to the reported data.
Likewise, several measures of physical function significantly improved in an a prior defined subgroup of 200 patients, he said. Those measures included hand grip at extubation and ICU discharge, as well as scores on the Barthel Index for Activities of Daily Living.
Nonsedation might improve kidney function, based on other reported outcomes of the study, Dr. Toft said. The number of coma- and delirium-free days was 3.0 in the no-sedation group versus 1.0 in the sedation group (P less than .01), he added.
The benefits of no sedation may extend beyond objective changes in health outcomes, according to Dr. Toft. “The patients are able to communicate with the staff, they might be able to enjoy food, in the evening they can look at the television instead of being sedated – and they can be mobilized and they can write their opinion about the treatments to the doctor, and in this way, you have two-way communication,” he explained in his presentation.
Dr. Toft reported that he had no financial relationships to disclose.
SOURCE: Toft P et al. N Engl J Med. 2019 Feb 16. doi: 10.1056/NEJMoa1906759.
REPORTING FROM CCC49