Vaccines

THE CASE

A 52-year-old man sought care at the emergency department for intermittent fevers that started within 6 days of receiving his second dose of the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech). After an unremarkable work-up, he was discharged home. Six days later, he returned to the emergency department with a fever of 102 °F and new-onset, progressive tremors in all 4 of his extremities.

The patient had a history of rheumatoid arthritis, for which he was taking oral methotrexate 15 mg once weekly and golimumab 50 mg SQ once monthly, and atrial fibrillation. He’d also had mechanical aortic and mitral valves implanted and was taking warfarin (9 mg/d on weekdays, 6 mg/d on Saturday and Sunday). Aside from his fever, his vital signs were normal. He also had horizontal nystagmus (chronically present) and diffuse tremors/myoclonic movements throughout his upper and lower extremities. The tremors were present at rest and worsened with intention/activity, which affected the patient’s ability to walk and perform activities of daily living.

He was admitted the next day to the family medicine service for further evaluation. Neurology and infectious disease consultations were requested, and a broad initial work-up was undertaken. Hyperreflexia was present in all of his extremities, but his neurologic examination was otherwise normal. Initial laboratory tests demonstrated leukocytosis and elevated liver transaminases. His international normalized ratio (INR) and prothrombin time (PT) also were elevated (> 8 [goal, 2.5-3.5 for mechanical heart valves] and > 90 seconds [normal range, 9.7-13.0 seconds], respectively), thus his warfarin was held and oral vitamin K was started (initial dose of 2.5 mg, which was increased to 5 mg when his INR did not decrease enough).

By Day 2, his INR and PT had normalized enough to reinitiate his warfarin dosing. Results from the viral antibody and polymerase chain reaction testing indicated the presence of cytomegalovirus (CMV) infection with viremia; blood cultures for bacterial infection were negative. Brain magnetic resonance imaging was ordered and identified a small, acute left-side cerebellar stroke. Lumbar puncture also was ordered but deferred until his INR was below 1.5 (on Day 8), at which point it confirmed the absence of CMV or herpes simplex virus in his central nervous system.

THE DIAGNOSIS

The patient started oral valganciclovir 900 mg twice daily to ameliorate his tremors, but he did not tolerate it well, vomiting after dosing. He was switched to IV ganciclovir 5 mg/kg every 12 hours; however, his tremors were not improving, leading the team to suspect an etiology other than viral infection. A presumptive diagnosis of autoimmune movement disorder was made, and serum tests were ordered; the results were positive for antiphospholipid antibodies, including anticardiolipin and anti-ß₂ glycoprotein-I antibodies. A final diagnosis of autoimmune antiphospholipid antibody syndrome (APS)–related movement disorder¹ with coagulopathy was reached, and the patient was started on methylprednisolone 1 g/d IV.

We suspected the CMV viremia was reactivated by the COVID-19 vaccine and caused the APS that led to the movement disorder, coagulopathy, and likely, the thrombotic cerebellar stroke. The case was reported to the Vaccine Adverse Event Reporting System (VAERS).²

DISCUSSION

Clinically evident APS is rare, with an estimated annual incidence of 2.1 per 100,000 according to a 2019 longitudinal cohort study.³ Notably, all identified cases in this cohort had either a venous or arterial thrombotic event—a characterizing feature of APS—with 45% of patients diagnosed with stroke or transient ischemic attack.^3,4

Continue to: The development of antiphospholipid antibodies...

The development of antiphospholipid antibodies has been independently associated with rheumatoid arthritis,⁵ COVID-19,⁶ and CMV infection,⁷ as well as with vaccination for influenza and tetanus.⁸ There also are reports of antiphospholipid antibodies occurring in patients who have received ­adenovirus-vectored and mRNA COVID-19 vaccines.^9-11

Movement disorders occurring with APS are unusual, with approximately 1.3% to 4.5% of patients with APS demonstrating this manifestation.¹² One of multiple autoimmune-related movement disorders, APS-­related movement disorder is most commonly associated with systemic lupus erythematosus (SLE), although it can occur outside an SLE diagnosis.⁴

Limited evidence suggests that COVID-19 vaccination can cause reactivation of dormant herpesviruses.

While APS-related movement disorder occurs with the presence of antiphospholipid antibodies, the pathogenesis of the movement disorder is unclear.⁴ Patients are typically young women, and the associated movements are choreiform. The condition often occurs with coagulopathy and arterial thrombosis.⁴ Psychiatric manifestations also can occur, including changes in behavior—up to and including psychosis.⁴

Evidence of COVID-19 vaccination reactivating herpesviruses exists, although it is rare and usually does not cause serious health outcomes.¹³ The annual incidence of reactivation related to vaccination is estimated to be 0.7 per 100,000 for varicella zoster virus and 0.03 per 100,000 for herpes simplex virus.¹³ The literature also suggests that the occurrence of Bell palsy—the onset of which may be related to the reactivation of a latent virus—may increase in relation to particular COVID-19 vaccines.^14,15 Although there is no confirmed explanation for these reactivation events at this time, different theories related to altering the focus of immune cells from latent disease to the newly generated antigen have been suggested.¹⁶

To date, reactivation has not been demonstrated with CMV specifically. However, based on the literature reviewed here on the reactivation of herpesviruses and the temporal relationship to infection in our patient, we propose that the BNT162b2 mRNA vaccination reactivated his CMV infection and led to his APS-related movement disorder.

Continue to: Treatment is focused on resolved the autoimmune condition

Treatment is focused on resolving the autoimmune condition, usually with corticosteroids. Longer-term treatment of the movement disorder with antiepileptics such as carbamazepine and valproic acid may be necessary.⁴

Our patient received methylprednisolone IV 1 g/d for 3 days and responded quickly to the treatment. He was discharged to a post-acute rehabilitation hospital on Day 16 with a plan for 21 days of antiviral treatment for an acute CMV infection, 1 month of oral steroid taper for the APS, and continued warfarin treatment. This regimen resulted in complete resolution of his movement disorder and negative testing of antiphospholipid antibodies 16 days after he was discharged from the hospital.

THE TAKEAWAY

This case illustrates the possible reactivation of a herpesvirus (CMV) related to COVID-19 vaccination, as well as the development of APS-related movement disorder and coagulopathy related to acute CMV infection with viremia. Vaccination for the COVID-19 virus is seen as the best intervention available for preventing serious illness and death associated with COVID-19 infection. Thus, it is important to be aware of these unusual events when vaccinating large populations. This case also demonstrates the need to understand the interplay of immune status and possible disorders associated with autoimmune conditions. Keeping an open mind when evaluating patients with post-vaccination complaints is beneficial—especially given the volume of distrust and misinformation associated with COVID-19 vaccination.

CORRESPONDENCE
Aaron Lear, MD, MSc, CAQ, Cleveland Clinic Akron General Center for Family Medicine, 1 Akron General Avenue, Building 301, Akron, OH 44307; [email protected]

THE CASE

A 52-year-old man sought care at the emergency department for intermittent fevers that started within 6 days of receiving his second dose of the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech). After an unremarkable work-up, he was discharged home. Six days later, he returned to the emergency department with a fever of 102 °F and new-onset, progressive tremors in all 4 of his extremities.

The patient had a history of rheumatoid arthritis, for which he was taking oral methotrexate 15 mg once weekly and golimumab 50 mg SQ once monthly, and atrial fibrillation. He’d also had mechanical aortic and mitral valves implanted and was taking warfarin (9 mg/d on weekdays, 6 mg/d on Saturday and Sunday). Aside from his fever, his vital signs were normal. He also had horizontal nystagmus (chronically present) and diffuse tremors/myoclonic movements throughout his upper and lower extremities. The tremors were present at rest and worsened with intention/activity, which affected the patient’s ability to walk and perform activities of daily living.

He was admitted the next day to the family medicine service for further evaluation. Neurology and infectious disease consultations were requested, and a broad initial work-up was undertaken. Hyperreflexia was present in all of his extremities, but his neurologic examination was otherwise normal. Initial laboratory tests demonstrated leukocytosis and elevated liver transaminases. His international normalized ratio (INR) and prothrombin time (PT) also were elevated (> 8 [goal, 2.5-3.5 for mechanical heart valves] and > 90 seconds [normal range, 9.7-13.0 seconds], respectively), thus his warfarin was held and oral vitamin K was started (initial dose of 2.5 mg, which was increased to 5 mg when his INR did not decrease enough).

By Day 2, his INR and PT had normalized enough to reinitiate his warfarin dosing. Results from the viral antibody and polymerase chain reaction testing indicated the presence of cytomegalovirus (CMV) infection with viremia; blood cultures for bacterial infection were negative. Brain magnetic resonance imaging was ordered and identified a small, acute left-side cerebellar stroke. Lumbar puncture also was ordered but deferred until his INR was below 1.5 (on Day 8), at which point it confirmed the absence of CMV or herpes simplex virus in his central nervous system.

THE DIAGNOSIS

The patient started oral valganciclovir 900 mg twice daily to ameliorate his tremors, but he did not tolerate it well, vomiting after dosing. He was switched to IV ganciclovir 5 mg/kg every 12 hours; however, his tremors were not improving, leading the team to suspect an etiology other than viral infection. A presumptive diagnosis of autoimmune movement disorder was made, and serum tests were ordered; the results were positive for antiphospholipid antibodies, including anticardiolipin and anti-ß₂ glycoprotein-I antibodies. A final diagnosis of autoimmune antiphospholipid antibody syndrome (APS)–related movement disorder¹ with coagulopathy was reached, and the patient was started on methylprednisolone 1 g/d IV.

We suspected the CMV viremia was reactivated by the COVID-19 vaccine and caused the APS that led to the movement disorder, coagulopathy, and likely, the thrombotic cerebellar stroke. The case was reported to the Vaccine Adverse Event Reporting System (VAERS).²

DISCUSSION

Clinically evident APS is rare, with an estimated annual incidence of 2.1 per 100,000 according to a 2019 longitudinal cohort study.³ Notably, all identified cases in this cohort had either a venous or arterial thrombotic event—a characterizing feature of APS—with 45% of patients diagnosed with stroke or transient ischemic attack.^3,4

Continue to: The development of antiphospholipid antibodies...

The development of antiphospholipid antibodies has been independently associated with rheumatoid arthritis,⁵ COVID-19,⁶ and CMV infection,⁷ as well as with vaccination for influenza and tetanus.⁸ There also are reports of antiphospholipid antibodies occurring in patients who have received ­adenovirus-vectored and mRNA COVID-19 vaccines.^9-11

Movement disorders occurring with APS are unusual, with approximately 1.3% to 4.5% of patients with APS demonstrating this manifestation.¹² One of multiple autoimmune-related movement disorders, APS-­related movement disorder is most commonly associated with systemic lupus erythematosus (SLE), although it can occur outside an SLE diagnosis.⁴

Limited evidence suggests that COVID-19 vaccination can cause reactivation of dormant herpesviruses.

While APS-related movement disorder occurs with the presence of antiphospholipid antibodies, the pathogenesis of the movement disorder is unclear.⁴ Patients are typically young women, and the associated movements are choreiform. The condition often occurs with coagulopathy and arterial thrombosis.⁴ Psychiatric manifestations also can occur, including changes in behavior—up to and including psychosis.⁴

Evidence of COVID-19 vaccination reactivating herpesviruses exists, although it is rare and usually does not cause serious health outcomes.¹³ The annual incidence of reactivation related to vaccination is estimated to be 0.7 per 100,000 for varicella zoster virus and 0.03 per 100,000 for herpes simplex virus.¹³ The literature also suggests that the occurrence of Bell palsy—the onset of which may be related to the reactivation of a latent virus—may increase in relation to particular COVID-19 vaccines.^14,15 Although there is no confirmed explanation for these reactivation events at this time, different theories related to altering the focus of immune cells from latent disease to the newly generated antigen have been suggested.¹⁶

To date, reactivation has not been demonstrated with CMV specifically. However, based on the literature reviewed here on the reactivation of herpesviruses and the temporal relationship to infection in our patient, we propose that the BNT162b2 mRNA vaccination reactivated his CMV infection and led to his APS-related movement disorder.

Continue to: Treatment is focused on resolved the autoimmune condition

Treatment is focused on resolving the autoimmune condition, usually with corticosteroids. Longer-term treatment of the movement disorder with antiepileptics such as carbamazepine and valproic acid may be necessary.⁴

Our patient received methylprednisolone IV 1 g/d for 3 days and responded quickly to the treatment. He was discharged to a post-acute rehabilitation hospital on Day 16 with a plan for 21 days of antiviral treatment for an acute CMV infection, 1 month of oral steroid taper for the APS, and continued warfarin treatment. This regimen resulted in complete resolution of his movement disorder and negative testing of antiphospholipid antibodies 16 days after he was discharged from the hospital.

THE TAKEAWAY

This case illustrates the possible reactivation of a herpesvirus (CMV) related to COVID-19 vaccination, as well as the development of APS-related movement disorder and coagulopathy related to acute CMV infection with viremia. Vaccination for the COVID-19 virus is seen as the best intervention available for preventing serious illness and death associated with COVID-19 infection. Thus, it is important to be aware of these unusual events when vaccinating large populations. This case also demonstrates the need to understand the interplay of immune status and possible disorders associated with autoimmune conditions. Keeping an open mind when evaluating patients with post-vaccination complaints is beneficial—especially given the volume of distrust and misinformation associated with COVID-19 vaccination.

CORRESPONDENCE
Aaron Lear, MD, MSc, CAQ, Cleveland Clinic Akron General Center for Family Medicine, 1 Akron General Avenue, Building 301, Akron, OH 44307; [email protected]

THE CASE

A 52-year-old man sought care at the emergency department for intermittent fevers that started within 6 days of receiving his second dose of the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech). After an unremarkable work-up, he was discharged home. Six days later, he returned to the emergency department with a fever of 102 °F and new-onset, progressive tremors in all 4 of his extremities.

The patient had a history of rheumatoid arthritis, for which he was taking oral methotrexate 15 mg once weekly and golimumab 50 mg SQ once monthly, and atrial fibrillation. He’d also had mechanical aortic and mitral valves implanted and was taking warfarin (9 mg/d on weekdays, 6 mg/d on Saturday and Sunday). Aside from his fever, his vital signs were normal. He also had horizontal nystagmus (chronically present) and diffuse tremors/myoclonic movements throughout his upper and lower extremities. The tremors were present at rest and worsened with intention/activity, which affected the patient’s ability to walk and perform activities of daily living.

He was admitted the next day to the family medicine service for further evaluation. Neurology and infectious disease consultations were requested, and a broad initial work-up was undertaken. Hyperreflexia was present in all of his extremities, but his neurologic examination was otherwise normal. Initial laboratory tests demonstrated leukocytosis and elevated liver transaminases. His international normalized ratio (INR) and prothrombin time (PT) also were elevated (> 8 [goal, 2.5-3.5 for mechanical heart valves] and > 90 seconds [normal range, 9.7-13.0 seconds], respectively), thus his warfarin was held and oral vitamin K was started (initial dose of 2.5 mg, which was increased to 5 mg when his INR did not decrease enough).

By Day 2, his INR and PT had normalized enough to reinitiate his warfarin dosing. Results from the viral antibody and polymerase chain reaction testing indicated the presence of cytomegalovirus (CMV) infection with viremia; blood cultures for bacterial infection were negative. Brain magnetic resonance imaging was ordered and identified a small, acute left-side cerebellar stroke. Lumbar puncture also was ordered but deferred until his INR was below 1.5 (on Day 8), at which point it confirmed the absence of CMV or herpes simplex virus in his central nervous system.

THE DIAGNOSIS

The patient started oral valganciclovir 900 mg twice daily to ameliorate his tremors, but he did not tolerate it well, vomiting after dosing. He was switched to IV ganciclovir 5 mg/kg every 12 hours; however, his tremors were not improving, leading the team to suspect an etiology other than viral infection. A presumptive diagnosis of autoimmune movement disorder was made, and serum tests were ordered; the results were positive for antiphospholipid antibodies, including anticardiolipin and anti-ß₂ glycoprotein-I antibodies. A final diagnosis of autoimmune antiphospholipid antibody syndrome (APS)–related movement disorder¹ with coagulopathy was reached, and the patient was started on methylprednisolone 1 g/d IV.

We suspected the CMV viremia was reactivated by the COVID-19 vaccine and caused the APS that led to the movement disorder, coagulopathy, and likely, the thrombotic cerebellar stroke. The case was reported to the Vaccine Adverse Event Reporting System (VAERS).²

DISCUSSION

Clinically evident APS is rare, with an estimated annual incidence of 2.1 per 100,000 according to a 2019 longitudinal cohort study.³ Notably, all identified cases in this cohort had either a venous or arterial thrombotic event—a characterizing feature of APS—with 45% of patients diagnosed with stroke or transient ischemic attack.^3,4

Continue to: The development of antiphospholipid antibodies...

The development of antiphospholipid antibodies has been independently associated with rheumatoid arthritis,⁵ COVID-19,⁶ and CMV infection,⁷ as well as with vaccination for influenza and tetanus.⁸ There also are reports of antiphospholipid antibodies occurring in patients who have received ­adenovirus-vectored and mRNA COVID-19 vaccines.^9-11

Movement disorders occurring with APS are unusual, with approximately 1.3% to 4.5% of patients with APS demonstrating this manifestation.¹² One of multiple autoimmune-related movement disorders, APS-­related movement disorder is most commonly associated with systemic lupus erythematosus (SLE), although it can occur outside an SLE diagnosis.⁴

Limited evidence suggests that COVID-19 vaccination can cause reactivation of dormant herpesviruses.

While APS-related movement disorder occurs with the presence of antiphospholipid antibodies, the pathogenesis of the movement disorder is unclear.⁴ Patients are typically young women, and the associated movements are choreiform. The condition often occurs with coagulopathy and arterial thrombosis.⁴ Psychiatric manifestations also can occur, including changes in behavior—up to and including psychosis.⁴

Evidence of COVID-19 vaccination reactivating herpesviruses exists, although it is rare and usually does not cause serious health outcomes.¹³ The annual incidence of reactivation related to vaccination is estimated to be 0.7 per 100,000 for varicella zoster virus and 0.03 per 100,000 for herpes simplex virus.¹³ The literature also suggests that the occurrence of Bell palsy—the onset of which may be related to the reactivation of a latent virus—may increase in relation to particular COVID-19 vaccines.^14,15 Although there is no confirmed explanation for these reactivation events at this time, different theories related to altering the focus of immune cells from latent disease to the newly generated antigen have been suggested.¹⁶

To date, reactivation has not been demonstrated with CMV specifically. However, based on the literature reviewed here on the reactivation of herpesviruses and the temporal relationship to infection in our patient, we propose that the BNT162b2 mRNA vaccination reactivated his CMV infection and led to his APS-related movement disorder.

Continue to: Treatment is focused on resolved the autoimmune condition

Treatment is focused on resolving the autoimmune condition, usually with corticosteroids. Longer-term treatment of the movement disorder with antiepileptics such as carbamazepine and valproic acid may be necessary.⁴

Our patient received methylprednisolone IV 1 g/d for 3 days and responded quickly to the treatment. He was discharged to a post-acute rehabilitation hospital on Day 16 with a plan for 21 days of antiviral treatment for an acute CMV infection, 1 month of oral steroid taper for the APS, and continued warfarin treatment. This regimen resulted in complete resolution of his movement disorder and negative testing of antiphospholipid antibodies 16 days after he was discharged from the hospital.

THE TAKEAWAY

This case illustrates the possible reactivation of a herpesvirus (CMV) related to COVID-19 vaccination, as well as the development of APS-related movement disorder and coagulopathy related to acute CMV infection with viremia. Vaccination for the COVID-19 virus is seen as the best intervention available for preventing serious illness and death associated with COVID-19 infection. Thus, it is important to be aware of these unusual events when vaccinating large populations. This case also demonstrates the need to understand the interplay of immune status and possible disorders associated with autoimmune conditions. Keeping an open mind when evaluating patients with post-vaccination complaints is beneficial—especially given the volume of distrust and misinformation associated with COVID-19 vaccination.

CORRESPONDENCE
Aaron Lear, MD, MSc, CAQ, Cleveland Clinic Akron General Center for Family Medicine, 1 Akron General Avenue, Building 301, Akron, OH 44307; [email protected]

When the Advisory Committee on Immunization Practices (ACIP) met in June and adopted recommendations for influenza vaccines for the 2023-2024 season, the major discussions focused on the timing of vaccine administration, the composition of the vaccine, and what (if any) special precautions are needed when administering an egg-based vaccine to a person with a history of egg allergy. Here are the takeaways.

When should flu vaccine be administered?

Influenza activity usually peaks between December and the end of March; only twice between 1982 and 2022 did it peak before December. Thus, most people should receive the vaccine in September or October, a recommendation that has not changed from last year. This is early enough to provide adequate protection in most influenza seasons, but late enough to allow protection to persist through the entire season. Vaccination should continue to be offered to those who are unvaccinated throughout the influenza season, as long as influenza viruses are circulating.

Earlier administration is not recommended for most people and is recommended against for those ages 65 years and older (because their immunity from the vaccine may wane faster) and for pregnant people in their first or second trimester (because the vaccine is more effective in preventing influenza in newborns if administered in the third trimester). Evidence regarding waning immunity is inconsistent; however, some studies have shown greater loss of immunity in the elderly compared to younger age groups, as time from vaccination increases.¹

What’s in this year’s vaccines?

The composition of the vaccines used in North America was determined by the World Health Organization in February, based on the most commonly circulating strains. All vaccines approved for use in the 2023-2024 season are quadrivalent and contain 1 influenza A (H1N1) strain, 1 influenza A (H3N2) strain, and 2 influenza B strains. The specifics of each strain are listed in TABLE 1.² The 2 influenza A strains are slightly different for the egg-based and non-egg-based vaccines.² There is no known effectiveness advantage of one antigen strain vs the other.

Should you take special precautions with egg allergy?

There is new wording to the recommendations on the use of egg-based influenza vaccines for those with a history of egg allergy (TABLE 2²). Previously, the ACIP had recommended that if an egg-based vaccine is given to a person with a history of egg allergy, it should be administered in an inpatient or outpatient medical setting (eg, hospital, clinic, health department, physician office) and should be supervised by a health care provider who is able to recognize and manage severe allergic reactions. These added precautions were out of step with other organizations, including the American Academy of Pediatrics and allergy-related specialty societies, all of whom recommend no special procedures or precautions when administering any influenza vaccine to those with a history of egg allergy.³

Why the change? Several factors contributed to ACIP’s decision to reword its recommendation. One is that the ovalbumin content of all current influenza vaccines ­(TABLE 3³) is considered too low to trigger an allergic reaction.

Another is the paucity of evidence that egg-based vaccines convey increased risk beyond that for any other vaccine. Although 1% to 3% of children are reported to have an egg allergy, there is no evidence that they are at increased risk for a serious allergic reaction if administered an egg-based vaccine.³ A systematic review of 31 studies (mostly low-quality observational studies and case series) conducted by the ACIP Influenza Work Group found no risk for severe anaphylaxis, hospitalization, or death, even in those with a history of an anaphylactic reaction to eggs.² A review of Vaccine Adverse Events Reporting System (VAERS) data identified 18 cases of reported anaphylaxis after receipt of an inactivated influenza vaccine over a 5-year period, but clinical review confirmed only 7.²

Continue to: And finally, appropriate precautions already...

And finally, appropriate precautions already are recommended for administration of any vaccine. The CDC guidance for best practices for administering vaccines states: “Although allergic reactions are a common concern for vaccine providers, these reactions are uncommon and anaphylaxis following vaccines is rare, occurring at a rate of approximately one per million doses for many vaccines. Epinephrine and equipment for managing an airway should be available for immediate use.”⁴

What does this mean in practice? Family physicians who administer influenza vaccines do not need to use special precautions for any influenza vaccine, or use non-egg-based vaccines, for those who have a history of egg allergy. However, they should be prepared to respond to a severe allergic reaction just as they would for any other vaccine. Any vestigial practices pertaining to egg allergy and influenza vaccines—such as vaccine skin testing prior to vaccination (with dilution of vaccine if positive), vaccination deferral or administration via alternative dosing protocols, and split dosing of vaccine—are unnecessary and should be abandoned. 

When the Advisory Committee on Immunization Practices (ACIP) met in June and adopted recommendations for influenza vaccines for the 2023-2024 season, the major discussions focused on the timing of vaccine administration, the composition of the vaccine, and what (if any) special precautions are needed when administering an egg-based vaccine to a person with a history of egg allergy. Here are the takeaways.

When should flu vaccine be administered?

Influenza activity usually peaks between December and the end of March; only twice between 1982 and 2022 did it peak before December. Thus, most people should receive the vaccine in September or October, a recommendation that has not changed from last year. This is early enough to provide adequate protection in most influenza seasons, but late enough to allow protection to persist through the entire season. Vaccination should continue to be offered to those who are unvaccinated throughout the influenza season, as long as influenza viruses are circulating.

Earlier administration is not recommended for most people and is recommended against for those ages 65 years and older (because their immunity from the vaccine may wane faster) and for pregnant people in their first or second trimester (because the vaccine is more effective in preventing influenza in newborns if administered in the third trimester). Evidence regarding waning immunity is inconsistent; however, some studies have shown greater loss of immunity in the elderly compared to younger age groups, as time from vaccination increases.¹

What’s in this year’s vaccines?

The composition of the vaccines used in North America was determined by the World Health Organization in February, based on the most commonly circulating strains. All vaccines approved for use in the 2023-2024 season are quadrivalent and contain 1 influenza A (H1N1) strain, 1 influenza A (H3N2) strain, and 2 influenza B strains. The specifics of each strain are listed in TABLE 1.² The 2 influenza A strains are slightly different for the egg-based and non-egg-based vaccines.² There is no known effectiveness advantage of one antigen strain vs the other.

Should you take special precautions with egg allergy?

There is new wording to the recommendations on the use of egg-based influenza vaccines for those with a history of egg allergy (TABLE 2²). Previously, the ACIP had recommended that if an egg-based vaccine is given to a person with a history of egg allergy, it should be administered in an inpatient or outpatient medical setting (eg, hospital, clinic, health department, physician office) and should be supervised by a health care provider who is able to recognize and manage severe allergic reactions. These added precautions were out of step with other organizations, including the American Academy of Pediatrics and allergy-related specialty societies, all of whom recommend no special procedures or precautions when administering any influenza vaccine to those with a history of egg allergy.³

Why the change? Several factors contributed to ACIP’s decision to reword its recommendation. One is that the ovalbumin content of all current influenza vaccines ­(TABLE 3³) is considered too low to trigger an allergic reaction.

Another is the paucity of evidence that egg-based vaccines convey increased risk beyond that for any other vaccine. Although 1% to 3% of children are reported to have an egg allergy, there is no evidence that they are at increased risk for a serious allergic reaction if administered an egg-based vaccine.³ A systematic review of 31 studies (mostly low-quality observational studies and case series) conducted by the ACIP Influenza Work Group found no risk for severe anaphylaxis, hospitalization, or death, even in those with a history of an anaphylactic reaction to eggs.² A review of Vaccine Adverse Events Reporting System (VAERS) data identified 18 cases of reported anaphylaxis after receipt of an inactivated influenza vaccine over a 5-year period, but clinical review confirmed only 7.²

Continue to: And finally, appropriate precautions already...

And finally, appropriate precautions already are recommended for administration of any vaccine. The CDC guidance for best practices for administering vaccines states: “Although allergic reactions are a common concern for vaccine providers, these reactions are uncommon and anaphylaxis following vaccines is rare, occurring at a rate of approximately one per million doses for many vaccines. Epinephrine and equipment for managing an airway should be available for immediate use.”⁴

What does this mean in practice? Family physicians who administer influenza vaccines do not need to use special precautions for any influenza vaccine, or use non-egg-based vaccines, for those who have a history of egg allergy. However, they should be prepared to respond to a severe allergic reaction just as they would for any other vaccine. Any vestigial practices pertaining to egg allergy and influenza vaccines—such as vaccine skin testing prior to vaccination (with dilution of vaccine if positive), vaccination deferral or administration via alternative dosing protocols, and split dosing of vaccine—are unnecessary and should be abandoned. 

When the Advisory Committee on Immunization Practices (ACIP) met in June and adopted recommendations for influenza vaccines for the 2023-2024 season, the major discussions focused on the timing of vaccine administration, the composition of the vaccine, and what (if any) special precautions are needed when administering an egg-based vaccine to a person with a history of egg allergy. Here are the takeaways.

When should flu vaccine be administered?

Influenza activity usually peaks between December and the end of March; only twice between 1982 and 2022 did it peak before December. Thus, most people should receive the vaccine in September or October, a recommendation that has not changed from last year. This is early enough to provide adequate protection in most influenza seasons, but late enough to allow protection to persist through the entire season. Vaccination should continue to be offered to those who are unvaccinated throughout the influenza season, as long as influenza viruses are circulating.

Earlier administration is not recommended for most people and is recommended against for those ages 65 years and older (because their immunity from the vaccine may wane faster) and for pregnant people in their first or second trimester (because the vaccine is more effective in preventing influenza in newborns if administered in the third trimester). Evidence regarding waning immunity is inconsistent; however, some studies have shown greater loss of immunity in the elderly compared to younger age groups, as time from vaccination increases.¹

What’s in this year’s vaccines?

The composition of the vaccines used in North America was determined by the World Health Organization in February, based on the most commonly circulating strains. All vaccines approved for use in the 2023-2024 season are quadrivalent and contain 1 influenza A (H1N1) strain, 1 influenza A (H3N2) strain, and 2 influenza B strains. The specifics of each strain are listed in TABLE 1.² The 2 influenza A strains are slightly different for the egg-based and non-egg-based vaccines.² There is no known effectiveness advantage of one antigen strain vs the other.

Should you take special precautions with egg allergy?

There is new wording to the recommendations on the use of egg-based influenza vaccines for those with a history of egg allergy (TABLE 2²). Previously, the ACIP had recommended that if an egg-based vaccine is given to a person with a history of egg allergy, it should be administered in an inpatient or outpatient medical setting (eg, hospital, clinic, health department, physician office) and should be supervised by a health care provider who is able to recognize and manage severe allergic reactions. These added precautions were out of step with other organizations, including the American Academy of Pediatrics and allergy-related specialty societies, all of whom recommend no special procedures or precautions when administering any influenza vaccine to those with a history of egg allergy.³

Why the change? Several factors contributed to ACIP’s decision to reword its recommendation. One is that the ovalbumin content of all current influenza vaccines ­(TABLE 3³) is considered too low to trigger an allergic reaction.

Another is the paucity of evidence that egg-based vaccines convey increased risk beyond that for any other vaccine. Although 1% to 3% of children are reported to have an egg allergy, there is no evidence that they are at increased risk for a serious allergic reaction if administered an egg-based vaccine.³ A systematic review of 31 studies (mostly low-quality observational studies and case series) conducted by the ACIP Influenza Work Group found no risk for severe anaphylaxis, hospitalization, or death, even in those with a history of an anaphylactic reaction to eggs.² A review of Vaccine Adverse Events Reporting System (VAERS) data identified 18 cases of reported anaphylaxis after receipt of an inactivated influenza vaccine over a 5-year period, but clinical review confirmed only 7.²

Continue to: And finally, appropriate precautions already...

And finally, appropriate precautions already are recommended for administration of any vaccine. The CDC guidance for best practices for administering vaccines states: “Although allergic reactions are a common concern for vaccine providers, these reactions are uncommon and anaphylaxis following vaccines is rare, occurring at a rate of approximately one per million doses for many vaccines. Epinephrine and equipment for managing an airway should be available for immediate use.”⁴

What does this mean in practice? Family physicians who administer influenza vaccines do not need to use special precautions for any influenza vaccine, or use non-egg-based vaccines, for those who have a history of egg allergy. However, they should be prepared to respond to a severe allergic reaction just as they would for any other vaccine. Any vestigial practices pertaining to egg allergy and influenza vaccines—such as vaccine skin testing prior to vaccination (with dilution of vaccine if positive), vaccination deferral or administration via alternative dosing protocols, and split dosing of vaccine—are unnecessary and should be abandoned. 

Maternal pertussis vaccinations, given during pregnancy, prevent an estimated 65% of pertussis infections in infants, new research indicates.

The study, led by Annette K. Regan, PhD, MPH, a perinatal and pediatric infectious disease epidemiologist at Curtin University, Perth, Australia, was published online in Pediatrics.

Dr. Regan – who is also with the University of San Francisco and the University of California, Los Angeles – and colleagues reviewed data on 279,418 infants born to 252,444 mothers in Australia.

There, about 52% of the women in this study received the Tdap vaccine through a maternal pertussis vaccination program.

Duration of effectiveness in infants was one of the main questions the study sought to answer.

The authors wrote that they assessed vaccine effectiveness through 18 months of age. “We observed significant protection against disease until at least 8 months of age, 2 months longer than reported in previous studies.” From 70% to 90% of all pertussis-attributable hospitalizations and death occur in infancy.
 

Answering the ‘blunting’ question

This study also set out to clarify an important clinical question regarding a potential “blunting” effect in infants. Previous work had suggested that maternal antibodies from the vaccination could interfere with the effectiveness of infants’ DtaP (the version of Tdap for infants) and other vaccines.

Dr. Regan and colleagues found that, “although we observed slightly lower VE [vaccine effectiveness] point estimates for the third dose of infant pertussis vaccine among maternally vaccinated compared with unvaccinated infants (76.5% vs. 92.9%, P = .002), we did not observe higher rates of pertussis infection (hazard ratio, 0.70; 95% confidence interval, 0.61-3.39).
 

Best time to give mothers the vaccine

Another clinical debate has centered on when to give the mother the vaccine during pregnancy. The authors concluded: “Our findings support the infant health benefits of recommendations to administer a booster dose of pertussis vaccine near 28 weeks of gestational age.”

That 28-week mark was associated with lower risk of infection in infants through 8 months of age, they wrote.
 

Positive results in the United States

In an invited commentary, Kathryn M. Edwards, MD, with the division of infectious diseases, department of pediatrics, at Vanderbilt University Medical Center, Nashville, Tenn., highlighted similar positive findings for maternal pertussis vaccination in the United States.

The Centers for Disease Control and Prevention did an ecologic study of infant pertussis cases reported between Jan. 1, 2000, and Dec. 31, 2019. Rates were compared for the years before maternal Tdap vaccinations were recommended against the 7-year period after they were implemented.

That study found that in the period before maternal Tdap vaccination, annual pertussis incidence did not change among infants younger than 2 months and increased slightly in infants 6-12 months.

However, during the period after maternal Tdap vaccination had started (2012-2019), pertussis incidence significantly decreased in infants younger than 2 months and was unchanged in infants 6-12 months.

“As with the Australian data, the U.S. data support the overall benefit of the maternal Tdap program and, as with the Australian data, do not suggest that blunting has led to an increase in cases within the first year of life,” Dr. Edwards wrote.

The CDC notes that pertussis cases are rising and outbreaks are happening across the United States.

“On average, about 1,000 infants are hospitalized and typically between 5 and 15 infants die each year in the United States due to pertussis,” the CDC states.
 

Uptake low despite positive data

Dr. Edwards noted that, despite positive data supporting maternal vaccination to reduce pertussis, uptake rates are low – between 50% and 60% in Australia, the United Kingdom, and the United States. “Active engagement to increase these rates should be implemented.”

Maternal vaccination might also be implemented soon to protect against other diseases including respiratory syncytial virus and group B streptococcal disease after promising study data, she said.

As with pertussis, the potential “blunting” effect will need to be carefully monitored, she said, “as was done in the carefully conducted study of pertussis reported in this issue of Pediatrics.”

One coauthor has received institutional honoraria for participation in advisory groups for Merck Sharpe & Dohme and Pfizer unrelated to this work. Another coauthor was supported by scholarships provided by the Wesfarmers Centre of Vaccines and Infectious Disease at the Telethon Kids Institute. Dr. Edwards reported receiving grants from the CDC and consulting for Bionet, Dynavax, and IBM. She is a member of the data safety and monitoring board for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, Merck, Roche, Novavax, and Brighton Collaboration.

Maternal pertussis vaccinations, given during pregnancy, prevent an estimated 65% of pertussis infections in infants, new research indicates.

The study, led by Annette K. Regan, PhD, MPH, a perinatal and pediatric infectious disease epidemiologist at Curtin University, Perth, Australia, was published online in Pediatrics.

Dr. Regan – who is also with the University of San Francisco and the University of California, Los Angeles – and colleagues reviewed data on 279,418 infants born to 252,444 mothers in Australia.

There, about 52% of the women in this study received the Tdap vaccine through a maternal pertussis vaccination program.

Duration of effectiveness in infants was one of the main questions the study sought to answer.

The authors wrote that they assessed vaccine effectiveness through 18 months of age. “We observed significant protection against disease until at least 8 months of age, 2 months longer than reported in previous studies.” From 70% to 90% of all pertussis-attributable hospitalizations and death occur in infancy.
 

Answering the ‘blunting’ question

This study also set out to clarify an important clinical question regarding a potential “blunting” effect in infants. Previous work had suggested that maternal antibodies from the vaccination could interfere with the effectiveness of infants’ DtaP (the version of Tdap for infants) and other vaccines.

Dr. Regan and colleagues found that, “although we observed slightly lower VE [vaccine effectiveness] point estimates for the third dose of infant pertussis vaccine among maternally vaccinated compared with unvaccinated infants (76.5% vs. 92.9%, P = .002), we did not observe higher rates of pertussis infection (hazard ratio, 0.70; 95% confidence interval, 0.61-3.39).
 

Best time to give mothers the vaccine

Another clinical debate has centered on when to give the mother the vaccine during pregnancy. The authors concluded: “Our findings support the infant health benefits of recommendations to administer a booster dose of pertussis vaccine near 28 weeks of gestational age.”

That 28-week mark was associated with lower risk of infection in infants through 8 months of age, they wrote.
 

Positive results in the United States

In an invited commentary, Kathryn M. Edwards, MD, with the division of infectious diseases, department of pediatrics, at Vanderbilt University Medical Center, Nashville, Tenn., highlighted similar positive findings for maternal pertussis vaccination in the United States.

The Centers for Disease Control and Prevention did an ecologic study of infant pertussis cases reported between Jan. 1, 2000, and Dec. 31, 2019. Rates were compared for the years before maternal Tdap vaccinations were recommended against the 7-year period after they were implemented.

That study found that in the period before maternal Tdap vaccination, annual pertussis incidence did not change among infants younger than 2 months and increased slightly in infants 6-12 months.

However, during the period after maternal Tdap vaccination had started (2012-2019), pertussis incidence significantly decreased in infants younger than 2 months and was unchanged in infants 6-12 months.

“As with the Australian data, the U.S. data support the overall benefit of the maternal Tdap program and, as with the Australian data, do not suggest that blunting has led to an increase in cases within the first year of life,” Dr. Edwards wrote.

The CDC notes that pertussis cases are rising and outbreaks are happening across the United States.

“On average, about 1,000 infants are hospitalized and typically between 5 and 15 infants die each year in the United States due to pertussis,” the CDC states.
 

Uptake low despite positive data

Dr. Edwards noted that, despite positive data supporting maternal vaccination to reduce pertussis, uptake rates are low – between 50% and 60% in Australia, the United Kingdom, and the United States. “Active engagement to increase these rates should be implemented.”

Maternal vaccination might also be implemented soon to protect against other diseases including respiratory syncytial virus and group B streptococcal disease after promising study data, she said.

As with pertussis, the potential “blunting” effect will need to be carefully monitored, she said, “as was done in the carefully conducted study of pertussis reported in this issue of Pediatrics.”

One coauthor has received institutional honoraria for participation in advisory groups for Merck Sharpe & Dohme and Pfizer unrelated to this work. Another coauthor was supported by scholarships provided by the Wesfarmers Centre of Vaccines and Infectious Disease at the Telethon Kids Institute. Dr. Edwards reported receiving grants from the CDC and consulting for Bionet, Dynavax, and IBM. She is a member of the data safety and monitoring board for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, Merck, Roche, Novavax, and Brighton Collaboration.

Maternal pertussis vaccinations, given during pregnancy, prevent an estimated 65% of pertussis infections in infants, new research indicates.

The study, led by Annette K. Regan, PhD, MPH, a perinatal and pediatric infectious disease epidemiologist at Curtin University, Perth, Australia, was published online in Pediatrics.

Dr. Regan – who is also with the University of San Francisco and the University of California, Los Angeles – and colleagues reviewed data on 279,418 infants born to 252,444 mothers in Australia.

There, about 52% of the women in this study received the Tdap vaccine through a maternal pertussis vaccination program.

Duration of effectiveness in infants was one of the main questions the study sought to answer.

The authors wrote that they assessed vaccine effectiveness through 18 months of age. “We observed significant protection against disease until at least 8 months of age, 2 months longer than reported in previous studies.” From 70% to 90% of all pertussis-attributable hospitalizations and death occur in infancy.
 

Answering the ‘blunting’ question

This study also set out to clarify an important clinical question regarding a potential “blunting” effect in infants. Previous work had suggested that maternal antibodies from the vaccination could interfere with the effectiveness of infants’ DtaP (the version of Tdap for infants) and other vaccines.

Dr. Regan and colleagues found that, “although we observed slightly lower VE [vaccine effectiveness] point estimates for the third dose of infant pertussis vaccine among maternally vaccinated compared with unvaccinated infants (76.5% vs. 92.9%, P = .002), we did not observe higher rates of pertussis infection (hazard ratio, 0.70; 95% confidence interval, 0.61-3.39).
 

Best time to give mothers the vaccine

Another clinical debate has centered on when to give the mother the vaccine during pregnancy. The authors concluded: “Our findings support the infant health benefits of recommendations to administer a booster dose of pertussis vaccine near 28 weeks of gestational age.”

That 28-week mark was associated with lower risk of infection in infants through 8 months of age, they wrote.
 

Positive results in the United States

In an invited commentary, Kathryn M. Edwards, MD, with the division of infectious diseases, department of pediatrics, at Vanderbilt University Medical Center, Nashville, Tenn., highlighted similar positive findings for maternal pertussis vaccination in the United States.

The Centers for Disease Control and Prevention did an ecologic study of infant pertussis cases reported between Jan. 1, 2000, and Dec. 31, 2019. Rates were compared for the years before maternal Tdap vaccinations were recommended against the 7-year period after they were implemented.

That study found that in the period before maternal Tdap vaccination, annual pertussis incidence did not change among infants younger than 2 months and increased slightly in infants 6-12 months.

However, during the period after maternal Tdap vaccination had started (2012-2019), pertussis incidence significantly decreased in infants younger than 2 months and was unchanged in infants 6-12 months.

“As with the Australian data, the U.S. data support the overall benefit of the maternal Tdap program and, as with the Australian data, do not suggest that blunting has led to an increase in cases within the first year of life,” Dr. Edwards wrote.

The CDC notes that pertussis cases are rising and outbreaks are happening across the United States.

“On average, about 1,000 infants are hospitalized and typically between 5 and 15 infants die each year in the United States due to pertussis,” the CDC states.
 

Uptake low despite positive data

Dr. Edwards noted that, despite positive data supporting maternal vaccination to reduce pertussis, uptake rates are low – between 50% and 60% in Australia, the United Kingdom, and the United States. “Active engagement to increase these rates should be implemented.”

Maternal vaccination might also be implemented soon to protect against other diseases including respiratory syncytial virus and group B streptococcal disease after promising study data, she said.

As with pertussis, the potential “blunting” effect will need to be carefully monitored, she said, “as was done in the carefully conducted study of pertussis reported in this issue of Pediatrics.”

One coauthor has received institutional honoraria for participation in advisory groups for Merck Sharpe & Dohme and Pfizer unrelated to this work. Another coauthor was supported by scholarships provided by the Wesfarmers Centre of Vaccines and Infectious Disease at the Telethon Kids Institute. Dr. Edwards reported receiving grants from the CDC and consulting for Bionet, Dynavax, and IBM. She is a member of the data safety and monitoring board for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, Merck, Roche, Novavax, and Brighton Collaboration.

Click to read more from Pulmonology Data Trends 2023.

Click to read more from Pulmonology Data Trends 2023.

Click to read more from Pulmonology Data Trends 2023.

In July 2023, nirsevimab (Beyfortus), a monoclonal antibody, was approved by the Food and Drug Administration for the prevention of respiratory syncytial virus (RSV) disease in infants and children younger than 2 years of age. On Aug. 3, 2023, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention recommended routine use of it for all infants younger than 8 months of age born during or entering their first RSV season. Its use is also recommended for certain children 8-19 months of age who are at increased risk for severe RSV disease at the start of their second RSV season. Hearing the approval, I immediately had a flashback to residency, recalling the multiple infants admitted each fall and winter exhibiting classic symptoms including cough, rhinorrhea, nasal flaring, retractions, and wheezing with many having oxygen requirements and others needing intubation. Only supportive care was available.

RSV is the leading cause of infant hospitalizations. Annually, the CDC estimates there are 50,000-80,000 RSV hospitalizations and 100-300 RSV-related deaths in the United States in persons younger than 5 years of age. While premature infants have the highest rates of hospitalization (three times a term infant) about 79% of hospitalized children younger than 2 years have no underlying medical risks.¹ The majority of children will experience RSV as an upper respiratory infection within the first 2 years of life. However, severe disease requiring hospitalization is more likely to occur in premature infants and children younger than 6 months; children younger than 2 with congenital heart disease and/or chronic lung disease; children with severe cystic fibrosis; as well as the immunocompromised child and individuals with neuromuscular disorders that preclude clearing mucous secretions or have difficulty swallowing.

Palivizumab (Synagis), the first monoclonal antibody to prevent RSV in infants was licensed in 1998. Its use was limited to infants meeting specific criteria developed by the American Academy of Pediatrics. Only 5% of infants had access to it. It was a short-acting agent requiring monthly injections, which were very costly ($1,661-$2,584 per dose). Eligible infants could receive up to five injections per season. Several studies proved its use was not cost beneficial.

What are the advantages of nirsevimab? It’s a long-acting monoclonal antibody. Only one dose is required per season. Costs will significantly diminish. It is recommended for all infants younger than 8 months of age born during RSV season. Those children 8-19 months at risk for severe RSV disease can receive it prior to the start of their second RSV season. During RSV season (October 1 to March 31), the initial dose should be administered to newborns just prior to hospital discharge. Older infants and newborns who did not receive it prior to hospital discharge can receive it at their medical home. Newborns should receive it within the first week of life. It is covered by the Vaccine for Children Program. Simultaneous administration with routine childhood immunizations is recommended. Finally, RSV season may vary in tropical areas (Southern Florida, Puerto Rico. etc.) and Alaska. The timing of nirsevimab administration should be based on local RSV activity provided by state and local authorities.

In addition, the FDA approved an RSV vaccine (Abrysvo) for use in adults at least 60 years of age and in pregnant women at 32-36 weeks’ gestation. The latter is administered to prevent lower respiratory tract infection in infants from birth to 6 months. Recommendations have been published for administration in nonpregnant adults. Specific information is forthcoming in terms timing of administration of nirsevimab in infants whose mothers receive Abrysvo.

RSV season is quickly approaching. Detailed recommendations for administration and FAQ questions related to nirsevimab and palivizumab can be found at https://www.aap.org or https://www.cdc.gov/vaccines/hcp/acip-recs/index.html.
 

Influenza

So, what about influenza? Vaccine composition has been tweaked to match the circulating viruses but the recommended age for annual routine administration remains unchanged. All persons at least 6 months of age should be vaccinated. Children between 6 months and 8 years need two doses at least 4 weeks apart when receiving vaccine for the first time. Immunizing everyone in the household is encouraged especially if there are household contacts at risk for developing severe disease, including infants too young to be vaccinated. Keep in mind children may be coinfected with multiple viruses. Adams and colleagues reviewed the prevalence of coinfection of influenza and Sars-CoV-2 in persons younger than 18 years reported to three CDC surveillance platforms during the 2021-2022 season.² Thirty-two of 575 hospitalized (6%) coinfections were analyzed and 7 of 44 (16%) deaths. Compared with patients without coinfections, the coinfected patients were more likely to require mechanical ventilation (13% vs. 4%) or CPAP (16% vs. 6%). Only 4 of 23 who were influenza vaccine eligible were vaccinated. Of seven coinfected children who died, none had received influenza vaccine and only one received an antiviral. Only 5 of 31 (16%) infected only with influenza were vaccinated.³

Influenza activity was lower than usual during the 2021-2022 season. However, this report revealed underuse of both influenza vaccine and antiviral therapy, both of which are routinely recommended.
 

COVID-19

What’s new with COVID-19? On Sept. 12, 2023, ACIP recommended that everyone at least 6 months of age receive the 2023-2024 (monovalent, XBB containing) COVID-19 vaccines. Children at least 5 years of age need one dose and those younger need one or two doses depending on the number of doses previously received. Why the change? Circulating variants continue to change. There is a current uptick in cases including hospitalizations (7.7%) and deaths (4.5%) and it’s just the beginning of the season.⁴ Symptoms, risk groups and complications have not changed. The primary goal is to prevent infection, hospitalization, long term complications, and death.

We are now armed with the most up-to-date interventions to help prevent the acquisition of these three viruses. Our next step is recommending and delivering them to our patients.
 

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported no relevant financial disclosures.

References

1.Suh M et al. J Infect Dis. 2022;226(Suppl 2):S154-36. doi: 10.1093/infdis/jiac120.

2. Adams K et al. MMWR Morb Mortal Wkly Rep. 2022;71:1589-96. doi: http://dx.doi.org/10.15585/mmwr.mm7150a4.

3. Pingali C et al. MMWR Morb Mortal Wkly Rep. 2023 Aug 25;72:912-9. doi: http://dx.doi.org/10.15585/mmwr.mm7234a3.

4. CDC Covid Data Tracker.

In July 2023, nirsevimab (Beyfortus), a monoclonal antibody, was approved by the Food and Drug Administration for the prevention of respiratory syncytial virus (RSV) disease in infants and children younger than 2 years of age. On Aug. 3, 2023, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention recommended routine use of it for all infants younger than 8 months of age born during or entering their first RSV season. Its use is also recommended for certain children 8-19 months of age who are at increased risk for severe RSV disease at the start of their second RSV season. Hearing the approval, I immediately had a flashback to residency, recalling the multiple infants admitted each fall and winter exhibiting classic symptoms including cough, rhinorrhea, nasal flaring, retractions, and wheezing with many having oxygen requirements and others needing intubation. Only supportive care was available.

RSV is the leading cause of infant hospitalizations. Annually, the CDC estimates there are 50,000-80,000 RSV hospitalizations and 100-300 RSV-related deaths in the United States in persons younger than 5 years of age. While premature infants have the highest rates of hospitalization (three times a term infant) about 79% of hospitalized children younger than 2 years have no underlying medical risks.¹ The majority of children will experience RSV as an upper respiratory infection within the first 2 years of life. However, severe disease requiring hospitalization is more likely to occur in premature infants and children younger than 6 months; children younger than 2 with congenital heart disease and/or chronic lung disease; children with severe cystic fibrosis; as well as the immunocompromised child and individuals with neuromuscular disorders that preclude clearing mucous secretions or have difficulty swallowing.

Palivizumab (Synagis), the first monoclonal antibody to prevent RSV in infants was licensed in 1998. Its use was limited to infants meeting specific criteria developed by the American Academy of Pediatrics. Only 5% of infants had access to it. It was a short-acting agent requiring monthly injections, which were very costly ($1,661-$2,584 per dose). Eligible infants could receive up to five injections per season. Several studies proved its use was not cost beneficial.

What are the advantages of nirsevimab? It’s a long-acting monoclonal antibody. Only one dose is required per season. Costs will significantly diminish. It is recommended for all infants younger than 8 months of age born during RSV season. Those children 8-19 months at risk for severe RSV disease can receive it prior to the start of their second RSV season. During RSV season (October 1 to March 31), the initial dose should be administered to newborns just prior to hospital discharge. Older infants and newborns who did not receive it prior to hospital discharge can receive it at their medical home. Newborns should receive it within the first week of life. It is covered by the Vaccine for Children Program. Simultaneous administration with routine childhood immunizations is recommended. Finally, RSV season may vary in tropical areas (Southern Florida, Puerto Rico. etc.) and Alaska. The timing of nirsevimab administration should be based on local RSV activity provided by state and local authorities.

In addition, the FDA approved an RSV vaccine (Abrysvo) for use in adults at least 60 years of age and in pregnant women at 32-36 weeks’ gestation. The latter is administered to prevent lower respiratory tract infection in infants from birth to 6 months. Recommendations have been published for administration in nonpregnant adults. Specific information is forthcoming in terms timing of administration of nirsevimab in infants whose mothers receive Abrysvo.

RSV season is quickly approaching. Detailed recommendations for administration and FAQ questions related to nirsevimab and palivizumab can be found at https://www.aap.org or https://www.cdc.gov/vaccines/hcp/acip-recs/index.html.
 

Influenza

So, what about influenza? Vaccine composition has been tweaked to match the circulating viruses but the recommended age for annual routine administration remains unchanged. All persons at least 6 months of age should be vaccinated. Children between 6 months and 8 years need two doses at least 4 weeks apart when receiving vaccine for the first time. Immunizing everyone in the household is encouraged especially if there are household contacts at risk for developing severe disease, including infants too young to be vaccinated. Keep in mind children may be coinfected with multiple viruses. Adams and colleagues reviewed the prevalence of coinfection of influenza and Sars-CoV-2 in persons younger than 18 years reported to three CDC surveillance platforms during the 2021-2022 season.² Thirty-two of 575 hospitalized (6%) coinfections were analyzed and 7 of 44 (16%) deaths. Compared with patients without coinfections, the coinfected patients were more likely to require mechanical ventilation (13% vs. 4%) or CPAP (16% vs. 6%). Only 4 of 23 who were influenza vaccine eligible were vaccinated. Of seven coinfected children who died, none had received influenza vaccine and only one received an antiviral. Only 5 of 31 (16%) infected only with influenza were vaccinated.³

Influenza activity was lower than usual during the 2021-2022 season. However, this report revealed underuse of both influenza vaccine and antiviral therapy, both of which are routinely recommended.
 

COVID-19

What’s new with COVID-19? On Sept. 12, 2023, ACIP recommended that everyone at least 6 months of age receive the 2023-2024 (monovalent, XBB containing) COVID-19 vaccines. Children at least 5 years of age need one dose and those younger need one or two doses depending on the number of doses previously received. Why the change? Circulating variants continue to change. There is a current uptick in cases including hospitalizations (7.7%) and deaths (4.5%) and it’s just the beginning of the season.⁴ Symptoms, risk groups and complications have not changed. The primary goal is to prevent infection, hospitalization, long term complications, and death.

We are now armed with the most up-to-date interventions to help prevent the acquisition of these three viruses. Our next step is recommending and delivering them to our patients.
 

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported no relevant financial disclosures.

References

1.Suh M et al. J Infect Dis. 2022;226(Suppl 2):S154-36. doi: 10.1093/infdis/jiac120.

2. Adams K et al. MMWR Morb Mortal Wkly Rep. 2022;71:1589-96. doi: http://dx.doi.org/10.15585/mmwr.mm7150a4.

3. Pingali C et al. MMWR Morb Mortal Wkly Rep. 2023 Aug 25;72:912-9. doi: http://dx.doi.org/10.15585/mmwr.mm7234a3.

4. CDC Covid Data Tracker.

In July 2023, nirsevimab (Beyfortus), a monoclonal antibody, was approved by the Food and Drug Administration for the prevention of respiratory syncytial virus (RSV) disease in infants and children younger than 2 years of age. On Aug. 3, 2023, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention recommended routine use of it for all infants younger than 8 months of age born during or entering their first RSV season. Its use is also recommended for certain children 8-19 months of age who are at increased risk for severe RSV disease at the start of their second RSV season. Hearing the approval, I immediately had a flashback to residency, recalling the multiple infants admitted each fall and winter exhibiting classic symptoms including cough, rhinorrhea, nasal flaring, retractions, and wheezing with many having oxygen requirements and others needing intubation. Only supportive care was available.

RSV is the leading cause of infant hospitalizations. Annually, the CDC estimates there are 50,000-80,000 RSV hospitalizations and 100-300 RSV-related deaths in the United States in persons younger than 5 years of age. While premature infants have the highest rates of hospitalization (three times a term infant) about 79% of hospitalized children younger than 2 years have no underlying medical risks.¹ The majority of children will experience RSV as an upper respiratory infection within the first 2 years of life. However, severe disease requiring hospitalization is more likely to occur in premature infants and children younger than 6 months; children younger than 2 with congenital heart disease and/or chronic lung disease; children with severe cystic fibrosis; as well as the immunocompromised child and individuals with neuromuscular disorders that preclude clearing mucous secretions or have difficulty swallowing.

Palivizumab (Synagis), the first monoclonal antibody to prevent RSV in infants was licensed in 1998. Its use was limited to infants meeting specific criteria developed by the American Academy of Pediatrics. Only 5% of infants had access to it. It was a short-acting agent requiring monthly injections, which were very costly ($1,661-$2,584 per dose). Eligible infants could receive up to five injections per season. Several studies proved its use was not cost beneficial.

What are the advantages of nirsevimab? It’s a long-acting monoclonal antibody. Only one dose is required per season. Costs will significantly diminish. It is recommended for all infants younger than 8 months of age born during RSV season. Those children 8-19 months at risk for severe RSV disease can receive it prior to the start of their second RSV season. During RSV season (October 1 to March 31), the initial dose should be administered to newborns just prior to hospital discharge. Older infants and newborns who did not receive it prior to hospital discharge can receive it at their medical home. Newborns should receive it within the first week of life. It is covered by the Vaccine for Children Program. Simultaneous administration with routine childhood immunizations is recommended. Finally, RSV season may vary in tropical areas (Southern Florida, Puerto Rico. etc.) and Alaska. The timing of nirsevimab administration should be based on local RSV activity provided by state and local authorities.

In addition, the FDA approved an RSV vaccine (Abrysvo) for use in adults at least 60 years of age and in pregnant women at 32-36 weeks’ gestation. The latter is administered to prevent lower respiratory tract infection in infants from birth to 6 months. Recommendations have been published for administration in nonpregnant adults. Specific information is forthcoming in terms timing of administration of nirsevimab in infants whose mothers receive Abrysvo.

RSV season is quickly approaching. Detailed recommendations for administration and FAQ questions related to nirsevimab and palivizumab can be found at https://www.aap.org or https://www.cdc.gov/vaccines/hcp/acip-recs/index.html.
 

Influenza

So, what about influenza? Vaccine composition has been tweaked to match the circulating viruses but the recommended age for annual routine administration remains unchanged. All persons at least 6 months of age should be vaccinated. Children between 6 months and 8 years need two doses at least 4 weeks apart when receiving vaccine for the first time. Immunizing everyone in the household is encouraged especially if there are household contacts at risk for developing severe disease, including infants too young to be vaccinated. Keep in mind children may be coinfected with multiple viruses. Adams and colleagues reviewed the prevalence of coinfection of influenza and Sars-CoV-2 in persons younger than 18 years reported to three CDC surveillance platforms during the 2021-2022 season.² Thirty-two of 575 hospitalized (6%) coinfections were analyzed and 7 of 44 (16%) deaths. Compared with patients without coinfections, the coinfected patients were more likely to require mechanical ventilation (13% vs. 4%) or CPAP (16% vs. 6%). Only 4 of 23 who were influenza vaccine eligible were vaccinated. Of seven coinfected children who died, none had received influenza vaccine and only one received an antiviral. Only 5 of 31 (16%) infected only with influenza were vaccinated.³

Influenza activity was lower than usual during the 2021-2022 season. However, this report revealed underuse of both influenza vaccine and antiviral therapy, both of which are routinely recommended.
 

COVID-19

What’s new with COVID-19? On Sept. 12, 2023, ACIP recommended that everyone at least 6 months of age receive the 2023-2024 (monovalent, XBB containing) COVID-19 vaccines. Children at least 5 years of age need one dose and those younger need one or two doses depending on the number of doses previously received. Why the change? Circulating variants continue to change. There is a current uptick in cases including hospitalizations (7.7%) and deaths (4.5%) and it’s just the beginning of the season.⁴ Symptoms, risk groups and complications have not changed. The primary goal is to prevent infection, hospitalization, long term complications, and death.

We are now armed with the most up-to-date interventions to help prevent the acquisition of these three viruses. Our next step is recommending and delivering them to our patients.
 

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported no relevant financial disclosures.

References

1.Suh M et al. J Infect Dis. 2022;226(Suppl 2):S154-36. doi: 10.1093/infdis/jiac120.

2. Adams K et al. MMWR Morb Mortal Wkly Rep. 2022;71:1589-96. doi: http://dx.doi.org/10.15585/mmwr.mm7150a4.

3. Pingali C et al. MMWR Morb Mortal Wkly Rep. 2023 Aug 25;72:912-9. doi: http://dx.doi.org/10.15585/mmwr.mm7234a3.

4. CDC Covid Data Tracker.

Nonmenstruating women were more likely to experience unexpected vaginal bleeding after receiving COVID-19 vaccinations, according to a new study.

The researchers suggested it could have been connected to the SARS-CoV-2 spike protein in the vaccines. The study was published in Science Advances.

After vaccinations became widely available, many women reported heavier menstrual bleeding than normal. Researchers at the Norwegian Institute of Public Health in Oslo examined the data, particularly among women who do not have periods, such as those who have been through menopause or are taking contraceptives.

The researchers used an ongoing population health survey called the Norwegian Mother, Father, and Child Cohort Study, Nature reported. They examined more than 21,000 responses from postmenopausal, perimenopausal, and nonmenstruating premenopausal women. Some were on long-term hormonal contraceptives.

They learned that 252 postmenopausal women, 1,008 perimenopausal women, and 924 premenopausal women reported having unexpected vaginal bleeding.

About half said the bleeding occurred within 4 weeks of the first or second shot or both. The risk of bleeding was up three to five times for premenopausal and perimenopausal women, and two to three times for postmenopausal women, the researchers found.

Postmenopausal bleeding is usually serious and can be a sign of cancer. “Knowing a patient’s vaccination status could put their bleeding incidence into context,” said Kate Clancy, a biological anthropologist at the University of Illinois at Urbana-Champaign.

The study received funding through the Norwegian Institute of Public Health and Research Council of Norway. The researchers reported no conflicts of interest.

A version of this article first appeared on WebMD.com.

Nonmenstruating women were more likely to experience unexpected vaginal bleeding after receiving COVID-19 vaccinations, according to a new study.

The researchers suggested it could have been connected to the SARS-CoV-2 spike protein in the vaccines. The study was published in Science Advances.

After vaccinations became widely available, many women reported heavier menstrual bleeding than normal. Researchers at the Norwegian Institute of Public Health in Oslo examined the data, particularly among women who do not have periods, such as those who have been through menopause or are taking contraceptives.

The researchers used an ongoing population health survey called the Norwegian Mother, Father, and Child Cohort Study, Nature reported. They examined more than 21,000 responses from postmenopausal, perimenopausal, and nonmenstruating premenopausal women. Some were on long-term hormonal contraceptives.

They learned that 252 postmenopausal women, 1,008 perimenopausal women, and 924 premenopausal women reported having unexpected vaginal bleeding.

About half said the bleeding occurred within 4 weeks of the first or second shot or both. The risk of bleeding was up three to five times for premenopausal and perimenopausal women, and two to three times for postmenopausal women, the researchers found.

Postmenopausal bleeding is usually serious and can be a sign of cancer. “Knowing a patient’s vaccination status could put their bleeding incidence into context,” said Kate Clancy, a biological anthropologist at the University of Illinois at Urbana-Champaign.

The study received funding through the Norwegian Institute of Public Health and Research Council of Norway. The researchers reported no conflicts of interest.

A version of this article first appeared on WebMD.com.

Nonmenstruating women were more likely to experience unexpected vaginal bleeding after receiving COVID-19 vaccinations, according to a new study.

The researchers suggested it could have been connected to the SARS-CoV-2 spike protein in the vaccines. The study was published in Science Advances.

After vaccinations became widely available, many women reported heavier menstrual bleeding than normal. Researchers at the Norwegian Institute of Public Health in Oslo examined the data, particularly among women who do not have periods, such as those who have been through menopause or are taking contraceptives.

The researchers used an ongoing population health survey called the Norwegian Mother, Father, and Child Cohort Study, Nature reported. They examined more than 21,000 responses from postmenopausal, perimenopausal, and nonmenstruating premenopausal women. Some were on long-term hormonal contraceptives.

They learned that 252 postmenopausal women, 1,008 perimenopausal women, and 924 premenopausal women reported having unexpected vaginal bleeding.

About half said the bleeding occurred within 4 weeks of the first or second shot or both. The risk of bleeding was up three to five times for premenopausal and perimenopausal women, and two to three times for postmenopausal women, the researchers found.

Postmenopausal bleeding is usually serious and can be a sign of cancer. “Knowing a patient’s vaccination status could put their bleeding incidence into context,” said Kate Clancy, a biological anthropologist at the University of Illinois at Urbana-Champaign.

The study received funding through the Norwegian Institute of Public Health and Research Council of Norway. The researchers reported no conflicts of interest.

A version of this article first appeared on WebMD.com.

Key clinical point: In patients with migraine, COVID-19 vaccination worsened the overall migraine symptoms in the first month post-vaccination; however, COVID-19 infection solely increased the number of acute medication intake days in the first month following infection.

Major finding: COVID-19 vaccination led to a significant increase in the number of monthly migraine days (MMD), monthly headache days (MHD), and monthly acute medication days (MAMD) by 1.06, 1.52, and 0.72, respectively (all P < .001) in the first month post-vaccination. COVID-19 infection solely increased MAMD by 1.11 (P = .027) in the first month following infection, with no significant effects on MMD and MHD.

Study details: This longitudinal cohort study identified 547 patients with migraine, of whom 147 were included in the vaccine analysis and 59 in the infection analysis.

Disclosures: This study did not receive any funding. BWH van der Arend and GM Terwindt declared receiving independent support and consultancy or industry support from various sources. The other authors declared no conflicts of interest.

Source: van der Arend BWH et al. Effect of COVID vaccination on monthly migraine days: A longitudinal cohort study. Cephalalgia. 2023;43(9) (Sep 8). doi: 10.1177/03331024231198792

Key clinical point: In patients with migraine, COVID-19 vaccination worsened the overall migraine symptoms in the first month post-vaccination; however, COVID-19 infection solely increased the number of acute medication intake days in the first month following infection.

Major finding: COVID-19 vaccination led to a significant increase in the number of monthly migraine days (MMD), monthly headache days (MHD), and monthly acute medication days (MAMD) by 1.06, 1.52, and 0.72, respectively (all P < .001) in the first month post-vaccination. COVID-19 infection solely increased MAMD by 1.11 (P = .027) in the first month following infection, with no significant effects on MMD and MHD.

Study details: This longitudinal cohort study identified 547 patients with migraine, of whom 147 were included in the vaccine analysis and 59 in the infection analysis.

Disclosures: This study did not receive any funding. BWH van der Arend and GM Terwindt declared receiving independent support and consultancy or industry support from various sources. The other authors declared no conflicts of interest.

Source: van der Arend BWH et al. Effect of COVID vaccination on monthly migraine days: A longitudinal cohort study. Cephalalgia. 2023;43(9) (Sep 8). doi: 10.1177/03331024231198792

Key clinical point: In patients with migraine, COVID-19 vaccination worsened the overall migraine symptoms in the first month post-vaccination; however, COVID-19 infection solely increased the number of acute medication intake days in the first month following infection.

Major finding: COVID-19 vaccination led to a significant increase in the number of monthly migraine days (MMD), monthly headache days (MHD), and monthly acute medication days (MAMD) by 1.06, 1.52, and 0.72, respectively (all P < .001) in the first month post-vaccination. COVID-19 infection solely increased MAMD by 1.11 (P = .027) in the first month following infection, with no significant effects on MMD and MHD.

Study details: This longitudinal cohort study identified 547 patients with migraine, of whom 147 were included in the vaccine analysis and 59 in the infection analysis.

Disclosures: This study did not receive any funding. BWH van der Arend and GM Terwindt declared receiving independent support and consultancy or industry support from various sources. The other authors declared no conflicts of interest.

Source: van der Arend BWH et al. Effect of COVID vaccination on monthly migraine days: A longitudinal cohort study. Cephalalgia. 2023;43(9) (Sep 8). doi: 10.1177/03331024231198792

Widely used billing codes have been updated for 2024, including new ones for respiratory syncytial virus (RSV) vaccines and medications, and new Spanish translations.

The American Medical Association recently released the Current Procedural Terminology (CPT) 2024 Code Set. The update included 349 editorial changes, including 230 additions, 49 deletions, and 70 revisions. With more than 11,100 codes in use, the CPT system continues “to grow and evolve with the rapid pace of innovation in medical science and health technology,” AMA said.

The AMA said the CPT update includes five new codes created to report product-specific RSV products (90380, 90381, 90683, 90679, and 90678) for better tracking, reporting and analysis that supports data-driven planning and allocation, AMA said.

There’s been a flurry of new U.S. vaccines and drugs to address RSV. The Food and Drug Administration in May granted the first U.S. approval of an RSV vaccine to Arexy, manufactured by GSK. The FDA cleared it for prevention of lower respiratory tract disease caused by RSV in adults age 60 years and older.

In June, Pfizer won FDA approval of Abrysvo, another vaccine meant to protect adults older than 60 years from RSV. The following month, the FDA approved nirsevimab (Beyfortus, AstraZeneca/Sanofi), for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. (This is not a vaccine, but a monoclonal antibody used for prevention. There has been confusion on this issue in part because monoclonal antibodies are often used for treatment rather than prevention.)

The FDA also has approved Abrysvo for use in pregnant individuals.

In addition, new CPT codes aim to streamline COVID-19 immunizations reporting. A new code (90480) was approved for reporting the administration of any COVID-19 vaccine for any patient. New provisional codes (91318-91322) will identify monovalent vaccine products from Moderna and Pfizer for immunization against COVID-19.

These provisional codes will be effective for use when the monovalent vaccine products from Moderna and Pfizer receive FDA approval, AMA said.
 

More codes explained in Spanish

The 2024 update includes more code descriptions in Spanish. Many hospitals, health plans, and medical offices already incorporate CPT descriptors in English-language medical documents, insurance forms, price sheets, and patient portals. This expansion is intended to help patients who may not read English well or at all.

“Providing approximately 41 million Spanish-speaking individuals in the United States with an easy-to-understand description of medical procedures and services can help build a more inclusive health care environment, where language is no longer a barrier and patients can actively engage in their own care,” Lori Prestesater, AMA’s senior vice president of health solutions, said in a statement.

In addition, the 2024 update includes clarifications sought by the Centers for Medicare & Medicaid Services about the reporting of evaluation and management (E/M) services. The revisions include:

• Removal of time ranges from office or other outpatient visit codes (99202-99205, 99212-99215) and format alignment with other E/M codes.
• Definition of the “substantive portion” of a split/shared E/M visit in which a physician and a nonphysician practitioner work jointly to furnish all the work related to the visit.
• Instructions for reporting hospital inpatient or observation care services and admission and discharge services for the use of codes. 99234-99236 when the patient stay crosses over two calendar dates.

A version of this article appeared on Medscape.com.

Widely used billing codes have been updated for 2024, including new ones for respiratory syncytial virus (RSV) vaccines and medications, and new Spanish translations.

The American Medical Association recently released the Current Procedural Terminology (CPT) 2024 Code Set. The update included 349 editorial changes, including 230 additions, 49 deletions, and 70 revisions. With more than 11,100 codes in use, the CPT system continues “to grow and evolve with the rapid pace of innovation in medical science and health technology,” AMA said.

The AMA said the CPT update includes five new codes created to report product-specific RSV products (90380, 90381, 90683, 90679, and 90678) for better tracking, reporting and analysis that supports data-driven planning and allocation, AMA said.

There’s been a flurry of new U.S. vaccines and drugs to address RSV. The Food and Drug Administration in May granted the first U.S. approval of an RSV vaccine to Arexy, manufactured by GSK. The FDA cleared it for prevention of lower respiratory tract disease caused by RSV in adults age 60 years and older.

In June, Pfizer won FDA approval of Abrysvo, another vaccine meant to protect adults older than 60 years from RSV. The following month, the FDA approved nirsevimab (Beyfortus, AstraZeneca/Sanofi), for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. (This is not a vaccine, but a monoclonal antibody used for prevention. There has been confusion on this issue in part because monoclonal antibodies are often used for treatment rather than prevention.)

The FDA also has approved Abrysvo for use in pregnant individuals.

In addition, new CPT codes aim to streamline COVID-19 immunizations reporting. A new code (90480) was approved for reporting the administration of any COVID-19 vaccine for any patient. New provisional codes (91318-91322) will identify monovalent vaccine products from Moderna and Pfizer for immunization against COVID-19.

These provisional codes will be effective for use when the monovalent vaccine products from Moderna and Pfizer receive FDA approval, AMA said.
 

More codes explained in Spanish

The 2024 update includes more code descriptions in Spanish. Many hospitals, health plans, and medical offices already incorporate CPT descriptors in English-language medical documents, insurance forms, price sheets, and patient portals. This expansion is intended to help patients who may not read English well or at all.

“Providing approximately 41 million Spanish-speaking individuals in the United States with an easy-to-understand description of medical procedures and services can help build a more inclusive health care environment, where language is no longer a barrier and patients can actively engage in their own care,” Lori Prestesater, AMA’s senior vice president of health solutions, said in a statement.

In addition, the 2024 update includes clarifications sought by the Centers for Medicare & Medicaid Services about the reporting of evaluation and management (E/M) services. The revisions include:

• Removal of time ranges from office or other outpatient visit codes (99202-99205, 99212-99215) and format alignment with other E/M codes.
• Definition of the “substantive portion” of a split/shared E/M visit in which a physician and a nonphysician practitioner work jointly to furnish all the work related to the visit.
• Instructions for reporting hospital inpatient or observation care services and admission and discharge services for the use of codes. 99234-99236 when the patient stay crosses over two calendar dates.

A version of this article appeared on Medscape.com.

Widely used billing codes have been updated for 2024, including new ones for respiratory syncytial virus (RSV) vaccines and medications, and new Spanish translations.

The American Medical Association recently released the Current Procedural Terminology (CPT) 2024 Code Set. The update included 349 editorial changes, including 230 additions, 49 deletions, and 70 revisions. With more than 11,100 codes in use, the CPT system continues “to grow and evolve with the rapid pace of innovation in medical science and health technology,” AMA said.

The AMA said the CPT update includes five new codes created to report product-specific RSV products (90380, 90381, 90683, 90679, and 90678) for better tracking, reporting and analysis that supports data-driven planning and allocation, AMA said.

There’s been a flurry of new U.S. vaccines and drugs to address RSV. The Food and Drug Administration in May granted the first U.S. approval of an RSV vaccine to Arexy, manufactured by GSK. The FDA cleared it for prevention of lower respiratory tract disease caused by RSV in adults age 60 years and older.

In June, Pfizer won FDA approval of Abrysvo, another vaccine meant to protect adults older than 60 years from RSV. The following month, the FDA approved nirsevimab (Beyfortus, AstraZeneca/Sanofi), for the prevention of RSV in neonates and infants entering their first RSV season, and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. (This is not a vaccine, but a monoclonal antibody used for prevention. There has been confusion on this issue in part because monoclonal antibodies are often used for treatment rather than prevention.)

The FDA also has approved Abrysvo for use in pregnant individuals.

In addition, new CPT codes aim to streamline COVID-19 immunizations reporting. A new code (90480) was approved for reporting the administration of any COVID-19 vaccine for any patient. New provisional codes (91318-91322) will identify monovalent vaccine products from Moderna and Pfizer for immunization against COVID-19.

These provisional codes will be effective for use when the monovalent vaccine products from Moderna and Pfizer receive FDA approval, AMA said.
 

More codes explained in Spanish

The 2024 update includes more code descriptions in Spanish. Many hospitals, health plans, and medical offices already incorporate CPT descriptors in English-language medical documents, insurance forms, price sheets, and patient portals. This expansion is intended to help patients who may not read English well or at all.

“Providing approximately 41 million Spanish-speaking individuals in the United States with an easy-to-understand description of medical procedures and services can help build a more inclusive health care environment, where language is no longer a barrier and patients can actively engage in their own care,” Lori Prestesater, AMA’s senior vice president of health solutions, said in a statement.

In addition, the 2024 update includes clarifications sought by the Centers for Medicare & Medicaid Services about the reporting of evaluation and management (E/M) services. The revisions include:

• Removal of time ranges from office or other outpatient visit codes (99202-99205, 99212-99215) and format alignment with other E/M codes.
• Definition of the “substantive portion” of a split/shared E/M visit in which a physician and a nonphysician practitioner work jointly to furnish all the work related to the visit.
• Instructions for reporting hospital inpatient or observation care services and admission and discharge services for the use of codes. 99234-99236 when the patient stay crosses over two calendar dates.

A version of this article appeared on Medscape.com.

Hospitalizations for COVID-19 in the United States have increased for 8 weeks in a row.

Data from Florida and Georgia signal that respiratory syncytial virus (RSV) season has begun.

As for flu shots, experts say patients with long COVID should get them in 2023, although federal health agencies have not addressed that specific question.

Paul G. Auwaerter, MD, MBA, an infectious disease consultant, said many patients in his primary care practice worry about “the big three” – COVID, influenza, and RSV.

This news organization spoke with Dr. Auwaerter, as well as family physician Santina J. G. Wheat, MD, MPH, and clinical pharmacist Spencer H. Durham, PharmD, about their approach to 2023’s respiratory virus season.

They discussed how to handle COVID boosters, the use of Paxlovid, vaccine hesitancy, and the correct order of operations for patients getting vaccinated against all three diseases.
 

Paul G. Auwaerter, MD, MBA, clinical director of the division of infectious diseases and the Sherrilyn and Ken Fisher Professor of Medicine at Johns Hopkins University, BaltimoreQuestion: How should primary care physicians be preparing to handle what everyone is predicting will be a major surge in cases of respiratory infections?

Auwaerter: Although I’m an infectious disease consultant, I still have a small primary care practice. So, I field questions for my patients all the time, and many patients, especially those with health problems, are worried about the big three: RSV, COVID, and influenza – at least, my more motivated patients are.

People frequently ask if they need the COVID booster. I think that’s been something many people think maybe they can avoid. The good news is that the early in vitro data suggest that the XBB1.5x-based vaccine seems to offer sufficient neutralizing activity against the circulating newer variants since the vaccine was approved earlier this year. I am suggesting that everyone get a booster, especially those at high risk, because we know that the risk for hospitalization decreases based on earlier studies for 4-6 months after a COVID booster. We can simultaneously administer the revised COVID booster vaccine and the annual influenza vaccine. The timing is good, as influenza immunization should be accomplished by October or early November at the latest. Like many parts of the country, we in Maryland are in the middle of a COVID boomlet. I have issued more Paxlovid prescriptions since mid-August than I did all spring and early summer.

Q: Are you seeing a lot of rebound COVID in your patients taking Paxlovid [nirmatrelvir/ritonavir]?

Dr. Auwaerter: I think the frequency is probably around 10%. It has been quoted much higher – at 20% – but careful studies have put it down at just single digits. I think it just depends on symptomatology and how you ask the question. But I think it’s important that I try to persuade people to take a direct-acting antiviral if they’re in a high-risk category rather than tough it out. Increasing data suggest taking an antiviral also reduces the risk for long COVID. Also, we know that rebound symptoms are not always infectious virus. Sometimes, they’re just inflammatory. Unless a person is immune suppressed, they rarely have a culturable virus 7-8 days after onset of symptoms. So, for most people, I don’t administer second courses of Paxlovid, although I know some physicians do. One has to realize the risk for hospitalization from a rebound is tiny, and many people don’t even have infectious virus when they take the second course of a drug such as Paxlovid.

Q: You mentioned motivated patients, which seems to be an important factor to consider, particularly for new vaccines.

Dr. Auwaerter: There are always early adopters who are less afraid. And then some people say: This is a brand-new vaccine; I’m going to wait for a year to let this shake out, and make sure it seems safe. People more engaged in their health have asked me about the RSV vaccine. For anyone who has cardiopulmonary problems and other major health problems, I’ve advised it. But if someone’s in good health and 65 or 70, the RSV illness is probably pretty mild if they get it. For them, I would say the vaccine is optional.

For people over 75, I have been advising the RSV vaccine because that is a group we tend to see hospitalized with RSV; they’re the highest-risk group, similar to COVID. The older you are, the more likely this infection will land you in the hospital. You can acquire RSV even if you don’t have young grandchildren around.

Q: You have called respiratory virus seasons unstable? What does it mean, and what is the significance for clinicians?

Dr. Auwaerter: It’s less predictable than in the past. If you had a cough and fever, you could think it was influenza if you knew you had influenza circulating in your community. Maybe you thought about RSV for your immunocompromised or older patients, but we didn’t have any therapy for it anyway. I sometimes refer to the respiratory virus season as a cage match between the major infections. Last year, RSV came out first, and we got some influenza and COVID. What does the situation look like this year? I don’t know at this point, but we are seeing more COVID earlier. What’s different is we continue to have the emergence of viral variants of SARS-CoV-2. Also, with both influenza and COVID, it’s harder to make a clinical judgment about what people have.

I think we have to rely more on tests to treat these patients. Options include having point of care testing in the office for rapid results (molecular assays preferred) for both influenza and SARS-CoV-2 or home antigen testing. There are home kits that do test for both if influenza is known to be circulating significantly in the community. But there are still barriers. For one, COVID and COVID/influenza antigen kits are no longer free, although some health insurance companies do provide COVID kits free of charge. In offices, you don’t want to have ill people with respiratory infections in your waiting room unless you can isolate or have negative pressure rooms. Do you ask for masking in your offices? Telemedicine has been a big help since the pandemic in managing nonsevere respiratory infections at home; however, you must be licensed in the state to practice, which limits helping your out-of-state patients.

Q: How has the advent of in-home antigen tests changed practice?

Dr. Auwaerter: Home antigen tests have been groundbreaking in facilitating care. When I see patients via telemedicine, I don’t want to prescribe medications for influenza and COVID to people simultaneously. I want to pick one or the other – and now I’m able to ask for a COVID test or a COVID/influenza test if the patient or family is able to get a kit. Some offices do have real-time molecular testing, which is the ideal and the CDC-recommended approach, but they’re expensive, and not everyone has access to them.

Q: People talk about the “tripledemic,” but does doing so ignore the fourth horseman of the respiratory apocalypse: pneumococcal pneumonia?

Dr. Auwaerter: Pneumonia remains a leading cause of hospitalization, except we’ve seen much more viral than bacterial pneumonia in recent years of the pandemic. We’ve lost sight, and pneumococcal pneumonia is important, especially in older patients. What we have seen pretty clearly is a rise in group A streptococcal infections. This is another consequence of the pandemic, where people did not socialize for a year or 2. There was much less group A strep infection in younger children, and even in adults, the amount of invasive group A streptococcal infections has clearly taken a jump, according to the NHS in Great Britain. Our pediatric practices here at Johns Hopkins are seeing far more cases of acute rheumatic fever than they’ve seen in decades. And I think, again, this is a consequence of the frequency of group A strep infections definitely taking an uptick. And that was no doubt probably from social mitigation measures and just an interruption in normal circumstances that bacterial and respiratory pathogens tend to circulate and colonize.

Q: Do you have any concerns about immunogenicity or side effects associated with receiving several vaccines at once?

Dr. Auwaerter: I think three injections at once is only for the heroic, and there is actually no guidance for getting all three at the moment. COVID, RSV, and influenza are not live vaccines. I’ve been recommending the new COVID booster and flu together, and then wait 2 weeks and then get RSV or vice-versa. A part of the reason is RSV is new. People have gotten COVID and flu vaccines before; they’re no different than in the past in terms of anticipating adverse effects. But RSV is new, so I’ve usually been recommending that as a standalone to gauge if there are issues as an RSV booster may be recommended at some point down the road.

Q: Unfortunately, some people are going to see or hear misinformation that the COVID boosters have not been properly tested or proven safe. What’s your response to the patient who says something to that effect?

Dr. Auwaerter: My response is, the basic components of the vaccine are the same, right? If you have the mRNA vaccine, you’re getting the vaccine components, the lipids, and the mRNA coding for spike proteins, which has just been modified slightly to adjust to the Omicron subvariant composition. We do the same thing with the influenza vaccine every year, and we don’t see much change in the side effect profile. I think it’s important for my staff in the office and myself to be very comfortable to field questions such as these.

We try to inform all of our staff about a vaccine, especially a new one like RSV, just so they have some comfort level with it, whether they’re getting it or not. Vaccine-hesitant patients need very little to dissuade and to take a pass – to the probable detriment of their health and their family’s health. We know the influenza vaccine helps reduce absenteeism and transmission in addition to reducing serious illness in high-risk patients. Even COVID vaccine efficacy is not as robust as initially reported, falling from 95% to under 70% depending on the study – you are provided with protection against serious illness and hospitalization. The same goes for influenza, and that’s how we try to pitch it to people. Are they going to get the flu? Maybe, but you didn’t land in the hospital. That’s why it’s these vaccines are so important.
 

Spencer H. Durham, PharmD, associate clinical professor in the department of pharmacy practice at Auburn (Ala.) University, and clinical pharmacist, Internal Medicine & Infectious Diseases, at the UAB Heersink School of Medicine in Huntsville.Q: What is known, if anything, about the risks/desirability of giving three vaccinations at once to patients (particularly older patients) – flu, COVID-19 and RSV? Any potential vaccine interactions physicians should know about?

Dr. Durham: There are currently no data about giving all three of these vaccines together at the same time. However, there is both data and practical experience of giving both the flu and COVID vaccines at the same time. The best approach right now for these three vaccines would be to get the flu and COVID vaccines at the same time, then give the RSV vaccine at a different date. In general, they should be separated by about 2 weeks, although it does not matter in what order they are given (that is, patients could get RSV first, then flu/COVID, or they could get flu/COVID first, followed by RSV).

Having said this, there is no theoretical reason why patients couldn’t get all three at once, so if there is only one opportunity to vaccinate a patient, then it would be okay to give all three. But, if the patient can come for two separate visits, the recommendation would currently be to separate these. In the future, there likely will be data on giving all three vaccines at once, so it may not be an issue to administer all three at the same time.

Lastly, I would point out that the RSV vaccine is not necessarily recommended for everyone age 60 and above. The Advisory Committee on Immunization Practices recommends using shared clinical decision-making to determine if that vaccine is right for the patient. In general, the flu and COVID vaccines are recommended for everyone, although the specific COVID recommendations for fall 2023 have not yet been released. There are no particular vaccine interactions that are concerning with these vaccines.

Q: What if any special considerations are there regarding the storage, handling, and ordering of these vaccines? Should primary care practices take any special steps they might not already be taking?

Dr. Durham: I don’t think there are any special considerations that providers might not already be doing. All of the vaccines do require refrigeration, but each individual product may vary some on beyond-use dates or how long they are good after being reconstituted. All providers administering these vaccines should carefully examine the labeling of each individual product to ensure correct storage and handling. In addition, the Centers for Disease Control and Prevention has an online toolkit for vaccine storage and handling and can be found at https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html.

Santina J. G. Wheat, MD, MPH, vice chair of diversity, equity, and inclusion, department of family and community medicine, and associate professor of family and community medicine, Northwestern University, ChicagoQ: What can primary care doctors/family physicians and their staff do to increase patient access to the vaccines? Any lessons learned from the earlier phases of the pandemic that might pertain not only to COVID-19 but also to RSV and/or influenza?

Dr. Wheat: I think the most important thing family physicians can do is speak with their patients about the importance of vaccines and specific recommendations they have for the situations of individuals and families. When vaccines started becoming available, I had many patients who wanted to hear from me – as their primary physician – what I truly thought and what I was planning to do for my own family.

I also think if our teams can know where vaccines are easily accessible, that makes it much easier for our patients. I have heard great stories and seen my own clinical support staff look at websites with patients to help them find the best location to get vaccines. In particular, about the RSV vaccine, I have had a handful of patients already come to ask me about my recommendations. When vaccines are available at my location, I find it much easier for my patients to be willing to get vaccinated. Similarly, if I am sending patients to pick up a prescription and they can get it at the same time, I have found success in them being willing to be vaccinated while picking up their prescription. In both instances, they do not need to make an additional stop; they are just able to be vaccinated while already at the clinic or pharmacy.

Q: Do you see any extra difficulties involved in trying to get groups of patients – in this case, older people – to be receptive to three vaccines, especially in this climate where it appears a growing number of people are hostile to immunization?

Dr. Wheat: Recently, I have found myself negotiating vaccines with patients not just with these, but as recommendations have changed for vaccines such as the pneumococcal vaccines and the hepatitis B vaccines. I think primary care providers can recommend all of them, but still help patients prioritize what is most important for that patient and family. For example, if welcoming a new baby soon, they might prioritize the vaccines for pertussis or influenza over the hepatitis vaccine with a plan to revisit the conversations later.

I have had some patients tell me they have gotten enough vaccines – and we know that even before the pandemic there was resistance to the influenza vaccine for some. I think we need to be prepared to address the concerns and, at times, the apathy. We also need to ask every time, because we never know which visit will be the one when a patient agrees.

Dr. Auwaerter reported financial relationships with Pfizer, Shionogi, Gilead, and Wellstat. Dr. Durham and Dr. Wheat disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Hospitalizations for COVID-19 in the United States have increased for 8 weeks in a row.

Data from Florida and Georgia signal that respiratory syncytial virus (RSV) season has begun.

As for flu shots, experts say patients with long COVID should get them in 2023, although federal health agencies have not addressed that specific question.

Paul G. Auwaerter, MD, MBA, an infectious disease consultant, said many patients in his primary care practice worry about “the big three” – COVID, influenza, and RSV.

This news organization spoke with Dr. Auwaerter, as well as family physician Santina J. G. Wheat, MD, MPH, and clinical pharmacist Spencer H. Durham, PharmD, about their approach to 2023’s respiratory virus season.

They discussed how to handle COVID boosters, the use of Paxlovid, vaccine hesitancy, and the correct order of operations for patients getting vaccinated against all three diseases.
 

Paul G. Auwaerter, MD, MBA, clinical director of the division of infectious diseases and the Sherrilyn and Ken Fisher Professor of Medicine at Johns Hopkins University, BaltimoreQuestion: How should primary care physicians be preparing to handle what everyone is predicting will be a major surge in cases of respiratory infections?

Auwaerter: Although I’m an infectious disease consultant, I still have a small primary care practice. So, I field questions for my patients all the time, and many patients, especially those with health problems, are worried about the big three: RSV, COVID, and influenza – at least, my more motivated patients are.

People frequently ask if they need the COVID booster. I think that’s been something many people think maybe they can avoid. The good news is that the early in vitro data suggest that the XBB1.5x-based vaccine seems to offer sufficient neutralizing activity against the circulating newer variants since the vaccine was approved earlier this year. I am suggesting that everyone get a booster, especially those at high risk, because we know that the risk for hospitalization decreases based on earlier studies for 4-6 months after a COVID booster. We can simultaneously administer the revised COVID booster vaccine and the annual influenza vaccine. The timing is good, as influenza immunization should be accomplished by October or early November at the latest. Like many parts of the country, we in Maryland are in the middle of a COVID boomlet. I have issued more Paxlovid prescriptions since mid-August than I did all spring and early summer.

Q: Are you seeing a lot of rebound COVID in your patients taking Paxlovid [nirmatrelvir/ritonavir]?

Dr. Auwaerter: I think the frequency is probably around 10%. It has been quoted much higher – at 20% – but careful studies have put it down at just single digits. I think it just depends on symptomatology and how you ask the question. But I think it’s important that I try to persuade people to take a direct-acting antiviral if they’re in a high-risk category rather than tough it out. Increasing data suggest taking an antiviral also reduces the risk for long COVID. Also, we know that rebound symptoms are not always infectious virus. Sometimes, they’re just inflammatory. Unless a person is immune suppressed, they rarely have a culturable virus 7-8 days after onset of symptoms. So, for most people, I don’t administer second courses of Paxlovid, although I know some physicians do. One has to realize the risk for hospitalization from a rebound is tiny, and many people don’t even have infectious virus when they take the second course of a drug such as Paxlovid.

Q: You mentioned motivated patients, which seems to be an important factor to consider, particularly for new vaccines.

Dr. Auwaerter: There are always early adopters who are less afraid. And then some people say: This is a brand-new vaccine; I’m going to wait for a year to let this shake out, and make sure it seems safe. People more engaged in their health have asked me about the RSV vaccine. For anyone who has cardiopulmonary problems and other major health problems, I’ve advised it. But if someone’s in good health and 65 or 70, the RSV illness is probably pretty mild if they get it. For them, I would say the vaccine is optional.

For people over 75, I have been advising the RSV vaccine because that is a group we tend to see hospitalized with RSV; they’re the highest-risk group, similar to COVID. The older you are, the more likely this infection will land you in the hospital. You can acquire RSV even if you don’t have young grandchildren around.

Q: You have called respiratory virus seasons unstable? What does it mean, and what is the significance for clinicians?

Dr. Auwaerter: It’s less predictable than in the past. If you had a cough and fever, you could think it was influenza if you knew you had influenza circulating in your community. Maybe you thought about RSV for your immunocompromised or older patients, but we didn’t have any therapy for it anyway. I sometimes refer to the respiratory virus season as a cage match between the major infections. Last year, RSV came out first, and we got some influenza and COVID. What does the situation look like this year? I don’t know at this point, but we are seeing more COVID earlier. What’s different is we continue to have the emergence of viral variants of SARS-CoV-2. Also, with both influenza and COVID, it’s harder to make a clinical judgment about what people have.

I think we have to rely more on tests to treat these patients. Options include having point of care testing in the office for rapid results (molecular assays preferred) for both influenza and SARS-CoV-2 or home antigen testing. There are home kits that do test for both if influenza is known to be circulating significantly in the community. But there are still barriers. For one, COVID and COVID/influenza antigen kits are no longer free, although some health insurance companies do provide COVID kits free of charge. In offices, you don’t want to have ill people with respiratory infections in your waiting room unless you can isolate or have negative pressure rooms. Do you ask for masking in your offices? Telemedicine has been a big help since the pandemic in managing nonsevere respiratory infections at home; however, you must be licensed in the state to practice, which limits helping your out-of-state patients.

Q: How has the advent of in-home antigen tests changed practice?

Dr. Auwaerter: Home antigen tests have been groundbreaking in facilitating care. When I see patients via telemedicine, I don’t want to prescribe medications for influenza and COVID to people simultaneously. I want to pick one or the other – and now I’m able to ask for a COVID test or a COVID/influenza test if the patient or family is able to get a kit. Some offices do have real-time molecular testing, which is the ideal and the CDC-recommended approach, but they’re expensive, and not everyone has access to them.

Q: People talk about the “tripledemic,” but does doing so ignore the fourth horseman of the respiratory apocalypse: pneumococcal pneumonia?

Dr. Auwaerter: Pneumonia remains a leading cause of hospitalization, except we’ve seen much more viral than bacterial pneumonia in recent years of the pandemic. We’ve lost sight, and pneumococcal pneumonia is important, especially in older patients. What we have seen pretty clearly is a rise in group A streptococcal infections. This is another consequence of the pandemic, where people did not socialize for a year or 2. There was much less group A strep infection in younger children, and even in adults, the amount of invasive group A streptococcal infections has clearly taken a jump, according to the NHS in Great Britain. Our pediatric practices here at Johns Hopkins are seeing far more cases of acute rheumatic fever than they’ve seen in decades. And I think, again, this is a consequence of the frequency of group A strep infections definitely taking an uptick. And that was no doubt probably from social mitigation measures and just an interruption in normal circumstances that bacterial and respiratory pathogens tend to circulate and colonize.

Q: Do you have any concerns about immunogenicity or side effects associated with receiving several vaccines at once?

Dr. Auwaerter: I think three injections at once is only for the heroic, and there is actually no guidance for getting all three at the moment. COVID, RSV, and influenza are not live vaccines. I’ve been recommending the new COVID booster and flu together, and then wait 2 weeks and then get RSV or vice-versa. A part of the reason is RSV is new. People have gotten COVID and flu vaccines before; they’re no different than in the past in terms of anticipating adverse effects. But RSV is new, so I’ve usually been recommending that as a standalone to gauge if there are issues as an RSV booster may be recommended at some point down the road.

Q: Unfortunately, some people are going to see or hear misinformation that the COVID boosters have not been properly tested or proven safe. What’s your response to the patient who says something to that effect?

Dr. Auwaerter: My response is, the basic components of the vaccine are the same, right? If you have the mRNA vaccine, you’re getting the vaccine components, the lipids, and the mRNA coding for spike proteins, which has just been modified slightly to adjust to the Omicron subvariant composition. We do the same thing with the influenza vaccine every year, and we don’t see much change in the side effect profile. I think it’s important for my staff in the office and myself to be very comfortable to field questions such as these.

We try to inform all of our staff about a vaccine, especially a new one like RSV, just so they have some comfort level with it, whether they’re getting it or not. Vaccine-hesitant patients need very little to dissuade and to take a pass – to the probable detriment of their health and their family’s health. We know the influenza vaccine helps reduce absenteeism and transmission in addition to reducing serious illness in high-risk patients. Even COVID vaccine efficacy is not as robust as initially reported, falling from 95% to under 70% depending on the study – you are provided with protection against serious illness and hospitalization. The same goes for influenza, and that’s how we try to pitch it to people. Are they going to get the flu? Maybe, but you didn’t land in the hospital. That’s why it’s these vaccines are so important.
 

Spencer H. Durham, PharmD, associate clinical professor in the department of pharmacy practice at Auburn (Ala.) University, and clinical pharmacist, Internal Medicine & Infectious Diseases, at the UAB Heersink School of Medicine in Huntsville.Q: What is known, if anything, about the risks/desirability of giving three vaccinations at once to patients (particularly older patients) – flu, COVID-19 and RSV? Any potential vaccine interactions physicians should know about?

Dr. Durham: There are currently no data about giving all three of these vaccines together at the same time. However, there is both data and practical experience of giving both the flu and COVID vaccines at the same time. The best approach right now for these three vaccines would be to get the flu and COVID vaccines at the same time, then give the RSV vaccine at a different date. In general, they should be separated by about 2 weeks, although it does not matter in what order they are given (that is, patients could get RSV first, then flu/COVID, or they could get flu/COVID first, followed by RSV).

Having said this, there is no theoretical reason why patients couldn’t get all three at once, so if there is only one opportunity to vaccinate a patient, then it would be okay to give all three. But, if the patient can come for two separate visits, the recommendation would currently be to separate these. In the future, there likely will be data on giving all three vaccines at once, so it may not be an issue to administer all three at the same time.

Lastly, I would point out that the RSV vaccine is not necessarily recommended for everyone age 60 and above. The Advisory Committee on Immunization Practices recommends using shared clinical decision-making to determine if that vaccine is right for the patient. In general, the flu and COVID vaccines are recommended for everyone, although the specific COVID recommendations for fall 2023 have not yet been released. There are no particular vaccine interactions that are concerning with these vaccines.

Q: What if any special considerations are there regarding the storage, handling, and ordering of these vaccines? Should primary care practices take any special steps they might not already be taking?

Dr. Durham: I don’t think there are any special considerations that providers might not already be doing. All of the vaccines do require refrigeration, but each individual product may vary some on beyond-use dates or how long they are good after being reconstituted. All providers administering these vaccines should carefully examine the labeling of each individual product to ensure correct storage and handling. In addition, the Centers for Disease Control and Prevention has an online toolkit for vaccine storage and handling and can be found at https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html.

Santina J. G. Wheat, MD, MPH, vice chair of diversity, equity, and inclusion, department of family and community medicine, and associate professor of family and community medicine, Northwestern University, ChicagoQ: What can primary care doctors/family physicians and their staff do to increase patient access to the vaccines? Any lessons learned from the earlier phases of the pandemic that might pertain not only to COVID-19 but also to RSV and/or influenza?

Dr. Wheat: I think the most important thing family physicians can do is speak with their patients about the importance of vaccines and specific recommendations they have for the situations of individuals and families. When vaccines started becoming available, I had many patients who wanted to hear from me – as their primary physician – what I truly thought and what I was planning to do for my own family.

I also think if our teams can know where vaccines are easily accessible, that makes it much easier for our patients. I have heard great stories and seen my own clinical support staff look at websites with patients to help them find the best location to get vaccines. In particular, about the RSV vaccine, I have had a handful of patients already come to ask me about my recommendations. When vaccines are available at my location, I find it much easier for my patients to be willing to get vaccinated. Similarly, if I am sending patients to pick up a prescription and they can get it at the same time, I have found success in them being willing to be vaccinated while picking up their prescription. In both instances, they do not need to make an additional stop; they are just able to be vaccinated while already at the clinic or pharmacy.

Q: Do you see any extra difficulties involved in trying to get groups of patients – in this case, older people – to be receptive to three vaccines, especially in this climate where it appears a growing number of people are hostile to immunization?

Dr. Wheat: Recently, I have found myself negotiating vaccines with patients not just with these, but as recommendations have changed for vaccines such as the pneumococcal vaccines and the hepatitis B vaccines. I think primary care providers can recommend all of them, but still help patients prioritize what is most important for that patient and family. For example, if welcoming a new baby soon, they might prioritize the vaccines for pertussis or influenza over the hepatitis vaccine with a plan to revisit the conversations later.

I have had some patients tell me they have gotten enough vaccines – and we know that even before the pandemic there was resistance to the influenza vaccine for some. I think we need to be prepared to address the concerns and, at times, the apathy. We also need to ask every time, because we never know which visit will be the one when a patient agrees.

Dr. Auwaerter reported financial relationships with Pfizer, Shionogi, Gilead, and Wellstat. Dr. Durham and Dr. Wheat disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Hospitalizations for COVID-19 in the United States have increased for 8 weeks in a row.

Data from Florida and Georgia signal that respiratory syncytial virus (RSV) season has begun.

As for flu shots, experts say patients with long COVID should get them in 2023, although federal health agencies have not addressed that specific question.

Paul G. Auwaerter, MD, MBA, an infectious disease consultant, said many patients in his primary care practice worry about “the big three” – COVID, influenza, and RSV.

This news organization spoke with Dr. Auwaerter, as well as family physician Santina J. G. Wheat, MD, MPH, and clinical pharmacist Spencer H. Durham, PharmD, about their approach to 2023’s respiratory virus season.

They discussed how to handle COVID boosters, the use of Paxlovid, vaccine hesitancy, and the correct order of operations for patients getting vaccinated against all three diseases.
 

Paul G. Auwaerter, MD, MBA, clinical director of the division of infectious diseases and the Sherrilyn and Ken Fisher Professor of Medicine at Johns Hopkins University, BaltimoreQuestion: How should primary care physicians be preparing to handle what everyone is predicting will be a major surge in cases of respiratory infections?

Auwaerter: Although I’m an infectious disease consultant, I still have a small primary care practice. So, I field questions for my patients all the time, and many patients, especially those with health problems, are worried about the big three: RSV, COVID, and influenza – at least, my more motivated patients are.

People frequently ask if they need the COVID booster. I think that’s been something many people think maybe they can avoid. The good news is that the early in vitro data suggest that the XBB1.5x-based vaccine seems to offer sufficient neutralizing activity against the circulating newer variants since the vaccine was approved earlier this year. I am suggesting that everyone get a booster, especially those at high risk, because we know that the risk for hospitalization decreases based on earlier studies for 4-6 months after a COVID booster. We can simultaneously administer the revised COVID booster vaccine and the annual influenza vaccine. The timing is good, as influenza immunization should be accomplished by October or early November at the latest. Like many parts of the country, we in Maryland are in the middle of a COVID boomlet. I have issued more Paxlovid prescriptions since mid-August than I did all spring and early summer.

Q: Are you seeing a lot of rebound COVID in your patients taking Paxlovid [nirmatrelvir/ritonavir]?

Dr. Auwaerter: I think the frequency is probably around 10%. It has been quoted much higher – at 20% – but careful studies have put it down at just single digits. I think it just depends on symptomatology and how you ask the question. But I think it’s important that I try to persuade people to take a direct-acting antiviral if they’re in a high-risk category rather than tough it out. Increasing data suggest taking an antiviral also reduces the risk for long COVID. Also, we know that rebound symptoms are not always infectious virus. Sometimes, they’re just inflammatory. Unless a person is immune suppressed, they rarely have a culturable virus 7-8 days after onset of symptoms. So, for most people, I don’t administer second courses of Paxlovid, although I know some physicians do. One has to realize the risk for hospitalization from a rebound is tiny, and many people don’t even have infectious virus when they take the second course of a drug such as Paxlovid.

Q: You mentioned motivated patients, which seems to be an important factor to consider, particularly for new vaccines.

Dr. Auwaerter: There are always early adopters who are less afraid. And then some people say: This is a brand-new vaccine; I’m going to wait for a year to let this shake out, and make sure it seems safe. People more engaged in their health have asked me about the RSV vaccine. For anyone who has cardiopulmonary problems and other major health problems, I’ve advised it. But if someone’s in good health and 65 or 70, the RSV illness is probably pretty mild if they get it. For them, I would say the vaccine is optional.

For people over 75, I have been advising the RSV vaccine because that is a group we tend to see hospitalized with RSV; they’re the highest-risk group, similar to COVID. The older you are, the more likely this infection will land you in the hospital. You can acquire RSV even if you don’t have young grandchildren around.

Q: You have called respiratory virus seasons unstable? What does it mean, and what is the significance for clinicians?

Dr. Auwaerter: It’s less predictable than in the past. If you had a cough and fever, you could think it was influenza if you knew you had influenza circulating in your community. Maybe you thought about RSV for your immunocompromised or older patients, but we didn’t have any therapy for it anyway. I sometimes refer to the respiratory virus season as a cage match between the major infections. Last year, RSV came out first, and we got some influenza and COVID. What does the situation look like this year? I don’t know at this point, but we are seeing more COVID earlier. What’s different is we continue to have the emergence of viral variants of SARS-CoV-2. Also, with both influenza and COVID, it’s harder to make a clinical judgment about what people have.

I think we have to rely more on tests to treat these patients. Options include having point of care testing in the office for rapid results (molecular assays preferred) for both influenza and SARS-CoV-2 or home antigen testing. There are home kits that do test for both if influenza is known to be circulating significantly in the community. But there are still barriers. For one, COVID and COVID/influenza antigen kits are no longer free, although some health insurance companies do provide COVID kits free of charge. In offices, you don’t want to have ill people with respiratory infections in your waiting room unless you can isolate or have negative pressure rooms. Do you ask for masking in your offices? Telemedicine has been a big help since the pandemic in managing nonsevere respiratory infections at home; however, you must be licensed in the state to practice, which limits helping your out-of-state patients.

Q: How has the advent of in-home antigen tests changed practice?

Dr. Auwaerter: Home antigen tests have been groundbreaking in facilitating care. When I see patients via telemedicine, I don’t want to prescribe medications for influenza and COVID to people simultaneously. I want to pick one or the other – and now I’m able to ask for a COVID test or a COVID/influenza test if the patient or family is able to get a kit. Some offices do have real-time molecular testing, which is the ideal and the CDC-recommended approach, but they’re expensive, and not everyone has access to them.

Q: People talk about the “tripledemic,” but does doing so ignore the fourth horseman of the respiratory apocalypse: pneumococcal pneumonia?

Dr. Auwaerter: Pneumonia remains a leading cause of hospitalization, except we’ve seen much more viral than bacterial pneumonia in recent years of the pandemic. We’ve lost sight, and pneumococcal pneumonia is important, especially in older patients. What we have seen pretty clearly is a rise in group A streptococcal infections. This is another consequence of the pandemic, where people did not socialize for a year or 2. There was much less group A strep infection in younger children, and even in adults, the amount of invasive group A streptococcal infections has clearly taken a jump, according to the NHS in Great Britain. Our pediatric practices here at Johns Hopkins are seeing far more cases of acute rheumatic fever than they’ve seen in decades. And I think, again, this is a consequence of the frequency of group A strep infections definitely taking an uptick. And that was no doubt probably from social mitigation measures and just an interruption in normal circumstances that bacterial and respiratory pathogens tend to circulate and colonize.

Q: Do you have any concerns about immunogenicity or side effects associated with receiving several vaccines at once?

Dr. Auwaerter: I think three injections at once is only for the heroic, and there is actually no guidance for getting all three at the moment. COVID, RSV, and influenza are not live vaccines. I’ve been recommending the new COVID booster and flu together, and then wait 2 weeks and then get RSV or vice-versa. A part of the reason is RSV is new. People have gotten COVID and flu vaccines before; they’re no different than in the past in terms of anticipating adverse effects. But RSV is new, so I’ve usually been recommending that as a standalone to gauge if there are issues as an RSV booster may be recommended at some point down the road.

Q: Unfortunately, some people are going to see or hear misinformation that the COVID boosters have not been properly tested or proven safe. What’s your response to the patient who says something to that effect?

Dr. Auwaerter: My response is, the basic components of the vaccine are the same, right? If you have the mRNA vaccine, you’re getting the vaccine components, the lipids, and the mRNA coding for spike proteins, which has just been modified slightly to adjust to the Omicron subvariant composition. We do the same thing with the influenza vaccine every year, and we don’t see much change in the side effect profile. I think it’s important for my staff in the office and myself to be very comfortable to field questions such as these.

We try to inform all of our staff about a vaccine, especially a new one like RSV, just so they have some comfort level with it, whether they’re getting it or not. Vaccine-hesitant patients need very little to dissuade and to take a pass – to the probable detriment of their health and their family’s health. We know the influenza vaccine helps reduce absenteeism and transmission in addition to reducing serious illness in high-risk patients. Even COVID vaccine efficacy is not as robust as initially reported, falling from 95% to under 70% depending on the study – you are provided with protection against serious illness and hospitalization. The same goes for influenza, and that’s how we try to pitch it to people. Are they going to get the flu? Maybe, but you didn’t land in the hospital. That’s why it’s these vaccines are so important.
 

Spencer H. Durham, PharmD, associate clinical professor in the department of pharmacy practice at Auburn (Ala.) University, and clinical pharmacist, Internal Medicine & Infectious Diseases, at the UAB Heersink School of Medicine in Huntsville.Q: What is known, if anything, about the risks/desirability of giving three vaccinations at once to patients (particularly older patients) – flu, COVID-19 and RSV? Any potential vaccine interactions physicians should know about?

Dr. Durham: There are currently no data about giving all three of these vaccines together at the same time. However, there is both data and practical experience of giving both the flu and COVID vaccines at the same time. The best approach right now for these three vaccines would be to get the flu and COVID vaccines at the same time, then give the RSV vaccine at a different date. In general, they should be separated by about 2 weeks, although it does not matter in what order they are given (that is, patients could get RSV first, then flu/COVID, or they could get flu/COVID first, followed by RSV).

Having said this, there is no theoretical reason why patients couldn’t get all three at once, so if there is only one opportunity to vaccinate a patient, then it would be okay to give all three. But, if the patient can come for two separate visits, the recommendation would currently be to separate these. In the future, there likely will be data on giving all three vaccines at once, so it may not be an issue to administer all three at the same time.

Lastly, I would point out that the RSV vaccine is not necessarily recommended for everyone age 60 and above. The Advisory Committee on Immunization Practices recommends using shared clinical decision-making to determine if that vaccine is right for the patient. In general, the flu and COVID vaccines are recommended for everyone, although the specific COVID recommendations for fall 2023 have not yet been released. There are no particular vaccine interactions that are concerning with these vaccines.

Q: What if any special considerations are there regarding the storage, handling, and ordering of these vaccines? Should primary care practices take any special steps they might not already be taking?

Dr. Durham: I don’t think there are any special considerations that providers might not already be doing. All of the vaccines do require refrigeration, but each individual product may vary some on beyond-use dates or how long they are good after being reconstituted. All providers administering these vaccines should carefully examine the labeling of each individual product to ensure correct storage and handling. In addition, the Centers for Disease Control and Prevention has an online toolkit for vaccine storage and handling and can be found at https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html.

Santina J. G. Wheat, MD, MPH, vice chair of diversity, equity, and inclusion, department of family and community medicine, and associate professor of family and community medicine, Northwestern University, ChicagoQ: What can primary care doctors/family physicians and their staff do to increase patient access to the vaccines? Any lessons learned from the earlier phases of the pandemic that might pertain not only to COVID-19 but also to RSV and/or influenza?

Dr. Wheat: I think the most important thing family physicians can do is speak with their patients about the importance of vaccines and specific recommendations they have for the situations of individuals and families. When vaccines started becoming available, I had many patients who wanted to hear from me – as their primary physician – what I truly thought and what I was planning to do for my own family.

I also think if our teams can know where vaccines are easily accessible, that makes it much easier for our patients. I have heard great stories and seen my own clinical support staff look at websites with patients to help them find the best location to get vaccines. In particular, about the RSV vaccine, I have had a handful of patients already come to ask me about my recommendations. When vaccines are available at my location, I find it much easier for my patients to be willing to get vaccinated. Similarly, if I am sending patients to pick up a prescription and they can get it at the same time, I have found success in them being willing to be vaccinated while picking up their prescription. In both instances, they do not need to make an additional stop; they are just able to be vaccinated while already at the clinic or pharmacy.

Q: Do you see any extra difficulties involved in trying to get groups of patients – in this case, older people – to be receptive to three vaccines, especially in this climate where it appears a growing number of people are hostile to immunization?

Dr. Wheat: Recently, I have found myself negotiating vaccines with patients not just with these, but as recommendations have changed for vaccines such as the pneumococcal vaccines and the hepatitis B vaccines. I think primary care providers can recommend all of them, but still help patients prioritize what is most important for that patient and family. For example, if welcoming a new baby soon, they might prioritize the vaccines for pertussis or influenza over the hepatitis vaccine with a plan to revisit the conversations later.

I have had some patients tell me they have gotten enough vaccines – and we know that even before the pandemic there was resistance to the influenza vaccine for some. I think we need to be prepared to address the concerns and, at times, the apathy. We also need to ask every time, because we never know which visit will be the one when a patient agrees.

Dr. Auwaerter reported financial relationships with Pfizer, Shionogi, Gilead, and Wellstat. Dr. Durham and Dr. Wheat disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.