What are the implications of the COVID-19 pandemic on respiratory syncytial virus (RSV) infection prophylaxis with palivizumab?
Respiratory syncytial virus (RSV) is a common respiratory pathogen of infancy and early childhood.1,2 In the United States, annual RSV epidemics usually begin in the fall and extend through spring, with peak activity typically occurring sometime in January or early February. The clinical manifestations of RSV vary with age, health status, and whether the infection is primary or secondary. The majority of patients who are infected with RSV will present with mild and self-limiting symptoms consistent with an upper respiratory tract infection. Severe disease is rare and usually occurs in very young infants (<6 months and those born prematurely), children, and older adults with certain underlying conditions.
In early 2020, public health measures introduced to mitigate the impact of the COVID-19 pandemic, such as widespread masking and physical distancing, greatly reduced the transmission of common respiratory viruses in the United States.3 Notably, influenza viruses and RSV had historically low activity following the start of the pandemic. From October 3, 2020 to May 22, 2021, the cumulative incidence of laboratory-confirmed influenza-associated hospitalizations was 0.8 per 100,000 persons, compared to a range of 62.0 to 102.9 per 100,000 persons during the previous 4 seasons. Regarding RSV activity, from January 4, 2020 to April 4, 2020, the weekly percentage of RSV positive cases decreased from 15.3% to 1.4% and remained less than 1% for the next year; as a comparison, the weekly percentage of positive RSV cases ranged from 3.0% to upwards of 16% during the previous 4 RSV seasons. From October 2020 to April 2021, the cumulative incidence of RSV-associated hospitalization was 0.3 per 100,000 persons, compared with 27.1 and 33.4 per 100,000 persons during the previous 2 seasons.
It is interesting to note that over 75% of RSV-associated hospitalizations occurring between October 2020 and May 2021 occurred in April and May 2021. The offseason increase in RSV activity starting in spring 2021 likely correlated to the loosening of COVID-19 mitigation practices in many parts of the United States.3 In June 2021, the CDC issued a health advisory warning clinicians of increased interseasonal RSV activity in parts of the Southern United States.4 An important topic not addressed by this health advisory is whether or not the change in RSV seasonality impacts the use of palivizumab, an important prophylactic agent against RSV that prevents morbidity in patients at high risk of severe disease.5
In 2014, the American Academy of Pediatrics (AAP) published a guideline outlining eligibility requirements for the use of palivizumab and appropriate duration of therapy;6 recommendations from these guidelines are summarized in a previously published FAQ.7 The 2014 AAP guideline was reaffirmed by the AAP in 2019.8 In August 2021, the AAP published interim guidance for use of palivizumab prophylaxis to prevent hospitalization from severe RSV infection during the current atypical interseasonal RSV spread.9 In their interim guidance, the AAP makes the following recommendation regarding expanded use of palivizumab prophylaxis:
“The need for palivizumab administration to eligible infants during this atypical interseason should be supported where activity approaches fall-winter season and should be reassessed at least monthly.”
In their interim guidance, the AAP acknowledges the importance of maintaining flexible approaches to palivizumab use during the atypical interseasonal change in RSV epidemiology brought on by the COVID-19 pandemic.9
Neither the 2021 interim guidance from the AAP nor the CDC Health Advisory issued in June 2021 discuss whether or not the interseasonal increase in RSV activity impacts the maximum number of palivizumab doses that should be administered.4,9 Per the 2014 guideline from the AAP, no more than 5 monthly doses of palivizumab are recommended per qualifying patient in the continental United States.6 Pharmacokinetic studies have demonstrated that 5 monthly doses will provide more than 6 months of serum palivizumab concentrations above the desired level for most children. It remains to be seen how changes in seasonality of RSV activity will continue to impact the treatment timeline for palivizumab prophylaxis. A search for literature describing prolonged palivizumab prophylaxis provided some evidence for extended dosing regimens, but data were limited to patients living in subtropical regions, where RSV seasons are traditionally longer than those seen in the US.10, 11,12, 13 Personal communication with the manufacturer of palivizumab (Sobi, Inc) in October 2021 did not result in additional recommendations regarding the maximum number of palivizumab doses.
There remains uncertainly in how the seasonality and circulation of common respiratory viruses such as RSV will progress as a result of evolving public health measures brought on by the dynamic nature of the COVID-19 pandemic. Therefore, clinicians should remain vigilant for off-season increases in viral activity. At the time of writing, the AAP strongly recommends consideration for use of palivizumab in patients who would otherwise be candidates, if they are residing in a region of the United States experiencing RSV circulation at rates consistent with a typical fall-winter season. Whether or not this recommendation impacts the maximum recommended number of palivizumab doses is unclear.
- Respiratory Syncytial Virus. In: Kimberlin DW, Long SS, Jackson MA, eds. Red Book– Report of the Committee on Infectious Diseases.31st ed: American Academy of Pediatrics; 2018: 1049-1050.
- Respiratory Syncytial Virus Infection (RSV). Centers for Disease Control and Prevention. Updated December 18, 2020. Accessed October 10, 2021. https://www.cdc.gov/rsv/index.html
- Olsen SJ, Winn AK, Budd AP, et al. Changes in influenza and other respiratory virus activity during the COVID-19 Pandemic – United States, 2020-2021. MMWR Morb Mortal Wkly Rep. 2021;70(29):1013-1019. doi:10.15585/mmwr.mm7029a1
- Centers for Disease Control (CDC) Health Alert Network. Increased interseasonal respiratory syncytial virus (RSV) activity in parts of the southern United States. CDC. June 10, 2021. Accessed October 11, 2021. https://emergency.cdc.gov/han/2021/han00443.asp
- Synagis [package insert]. Sobi Inc; November 2020.
- American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134(2):415-420. doi:10.1542/peds.2014-1665
- What is the new guidance regarding palivizumab (Synagis®) administration for respiratory syncytial virus? University of Illinois at Chicago Drug Information Group. September 2014. Accessed October 11, 2021. https://dig.pharmacy.uic.edu/faqs/2014-2/september-2014-faqs/
- American Academy of Pediatrics (AAP). AAP Publications Reaffirmed. AAP. Accessed October 11, 2021. https://pediatrics.aappublications.org/content/144/2/e20191767.
- American Academy of Pediatrics. Interim guidance for use of palivizumab prophylaxis to prevent hospitalization from severe respiratory syncytial virus infection during the current atypical interseasonal RSV spread. Updated September 23, 2021. Accessed October 11, 2021.https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/interim-guidance-for-use-of-palivizumab-prophylaxis-to-prevent-hospitalization/
- Ashkenazi-Hoffnung L, Dotan M, Livni G, Amir J, Bilavsky E. Nosocomial respiratory syncytial virus infections in the palivizumab-prophylaxis era with implications regarding high-risk infants. Am J Infect Control. 2014;42(9):991-995. doi:10.1016/j.ajic.2014.05.030
- Hsu CH, Lin CY, Chi H, et al. Prolonged seasonality of respiratory syncytial virus infection among preterm infants in a subtropical climate. PLoS One. 2014;9(10):e110166. doi:10.1371/journal.pone.0110166
- Al-Alaiyan S, Pollack P, Notario GF. Safety and pharmacokinetics of extended use of palivizumab in Saudi Arabian infants and children. Drugs Context. 2015;4:212270. doi:10.7573/dic.212270
- Hendaus MA, Alhammadi AH, Chandra P, Muneer E, Khalifa MS. Identifying agents triggering bronchiolitis in the State of Qatar. Int J Gen Med. 2018;11:143-149. Published 2018 Apr 10. doi:10.2147/IJGM.S154424
Katherine Sarna, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy
The information presented is current as of October 10, 2021. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.