1340. The Burden of Influenza and Rhinovirus Among Hospitalized Adults Post the COVID-19 Pandemic

Abstract Background Acute respiratory tract infections (ARIs) are a significant cause of morbidity in adults. Influenza is associated with about 490,600 hospitalizations and 34,200 deaths in the US in the 2018-2019 season. The burden of rhinovirus among adults hospitalized with ARI is less well known. We compared the burden of influenza and rhinovirus from 2 consecutive winter respiratory viral seasons in hospitalized adults and healthy controls pre-COVID-19 and one season mid-COVID-19 to determine the impact of rhinovirus as a pathogen. Methods From Oct 2018 to Apr 2021, prospective surveillance of adults ≥50 years old admitted with ARI or COPD/CHF exacerbations at any age was conducted at two Atlanta hospitals. Adults were eligible if they lived within an eight-county region around Atlanta and if their symptom duration was < 14 days. In the seasons from Oct 2018 to Mar 2020, asymptomatic adults ≥50 years old were enrolled as controls. Standard of care test results were included and those enrolled contributed nasopharyngeal swabs that were tested for respiratory pathogens using BioFire® FilmArray® Respiratory Viral Panel (RVP). Results During the first two seasons, 1566 hospitalized adults were enrolled. Rhinovirus was detected in 7.5% (118) and influenza was detected in 7.7% (121). Rhinovirus was also detected in 2.2% of 466 healthy adult controls while influenza was detected in 0%. During Season 3, the peak of the COVID-19 pandemic, influenza declined to 0% of ARI hospitalizations. Rhinovirus also declined (p=0.01) but still accounted for 5.1% of all ARIs screened (Figure 1). Rhinovirus was detected at a greater rate in Season 3 than in asymptomatic controls in the first 2 seasons (p=0.008). In the first two seasons, Influenza was detected in 8.6% (24/276) of those admitted to the ICU. Rhinovirus was detected in 6.1% (17/276) of those admitted to the ICU but declined to 3.1% (8/258) in Season 3. Figure 1. Percent Positive Cases of Influenza and Rhinovirus between Season 1&2 (hospitalized and healthy controls) vs Season 3 (hospitalized) Conclusion Dramatic declines occurred in influenza in adults hospitalized with ARI, CHF, or COPD in Atlanta during the COVID-19 pandemic and with enhanced public health measures. Although rhinovirus declined during the COVID-19 pandemic, it continued to be identified at a rate higher than in historical controls. Additional data are needed to understand the role of rhinovirus in adult ARI, CHF, and COPD exacerbations. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory; Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

. Percent of PAIVED participants reporting ILI by week of season.

Conclusion.
The low incidence of reported ILI in PAIVED participants during the COVID-19 pandemic is consistent with national influenza surveillance reports of influenza and outpatient ILI activity, suggesting that mitigation measures taken to reduce transmission of SARS-CoV-2 reduced the spread of other respiratory viruses.

Disclaimer.
Disclosures. Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) Jitu Modi, MD, GSK (Speaker's Bureau) Background. The COVID-19 pandemic led to the implementation of several strategies (e.g., masking, physical distancing, daycare/school and business closures, hand hygiene, surface disinfection) intended to mitigate the spread of disease in the community. Our objective was to evaluate the impact of these strategies on the activity of respiratory viral pathogens (other than SARS-CoV-2) and norovirus.

Impact of COVID-19 Pandemic on Activity of Other Respiratory Viral Pathogen and Norovirus
Methods. At University of North Carolina (UNC) Hospitals, we compared the percent positivity for respiratory viral pathogens and norovirus by calendar year for 2014-2019 and the first three months of 2020 to the percent positivity in the subsequent months of 2020 and the first quarter of 2021. Patients were included in the study if they had a positive specimen obtained in a clinic, ED or as an inpatient. Three molecular tests were used to detect these viruses: adenoviruses, endemic coronaviruses (OC43, 229E, NL63, HKU1), influenza A (subtypes H3, H1, H1N1pdm), influenza B, metapneumovirus (MPV), parainfluenza viruses 1-4 (PIV), rhinovirus and/or enterovirus (RhV/EV), and respiratory syncytial virus (RSV). Two molecular tests were used to detect norovirus. We calculated point prevalence rates with 95% confidence intervals to assess statistical differences in percent positivity.
Results. There was a statistically significant decline in percent positivity for endemic coronaviruses, influenza, MPV, PIV, RSV and norovirus during the time-periods after March 2020 when compared to all other time-periods ( Figure). RhV/EV, followed by adenovirus were the most prevalent types of respiratory viruses circulating during height of COVID-19. There was a statistically significant decline seen in RhV/ EV in April-Dec 2020, but activity increased in 2021. There was no difference seen in adenovirus activity across time-periods.

Percent Positivity of Respiratory Viral Pathogens and Norovirus by Time Period
Conclusion. Our study demonstrated statistically significant decreases in the percent positivity of several respiratory viral pathogens, as well as norovirus, during the time-period of high community prevalence of SARS-CoV-2. Strategies put in place to mitigate SARS-CoV-2 transmission likely contributed to these differences. Non-enveloped viruses like rhinovirus and adenoviruses may have been less impacted by these strategies since they are more resistant to disinfection.  The burden of rhinovirus among adults hospitalized with ARI is less well known. We compared the burden of influenza and rhinovirus from 2 consecutive winter respiratory viral seasons in hospitalized adults and healthy controls pre-COVID-19 and one season mid-COVID-19 to determine the impact of rhinovirus as a pathogen.

The Burden of Influenza and Rhinovirus Among Hospitalized Adults Post the COVID-19 Pandemic
Methods. From Oct 2018 to Apr 2021, prospective surveillance of adults ≥50 years old admitted with ARI or COPD/CHF exacerbations at any age was conducted at two Atlanta hospitals. Adults were eligible if they lived within an eightcounty region around Atlanta and if their symptom duration was < 14 days. In the seasons from Oct 2018 to Mar 2020, asymptomatic adults ≥50 years old were enrolled as controls. Standard of care test results were included and those enrolled contributed nasopharyngeal swabs that were tested for respiratory pathogens using BioFire® FilmArray® Respiratory Viral Panel (RVP).
Results. During the first two seasons, 1566 hospitalized adults were enrolled. Rhinovirus was detected in 7.5% (118) and influenza was detected in 7.7% (121). Rhinovirus was also detected in 2.2% of 466 healthy adult controls while influenza was detected in 0%. During Season 3, the peak of the COVID-19 pandemic, influenza declined to 0% of ARI hospitalizations. Rhinovirus also declined (p=0.01) but still accounted for 5.1% of all ARIs screened (Figure 1). Rhinovirus was detected at a greater rate in Season 3 than in asymptomatic controls in the first 2 seasons (p=0.008). In the first two seasons, Influenza was detected in 8.6% (24/276) of those admitted to the ICU. Rhinovirus was detected in 6.1% (17/276) of those admitted to the ICU but declined to 3.1% (8/258) in Season 3.

Figure 1. Percent Positive Cases of Influenza and Rhinovirus between Season 1&2 (hospitalized and healthy controls) vs Season 3 (hospitalized)
Conclusion. Dramatic declines occurred in influenza in adults hospitalized with ARI, CHF, or COPD in Atlanta during the COVID-19 pandemic and with enhanced public health measures. Although rhinovirus declined during the COVID-19 pandemic, it continued to be identified at a rate higher than in historical controls. Additional data are needed to understand the role of rhinovirus in adult ARI, CHF, and COPD exacerbations. Background. Non-egg-based influenza vaccine manufacturing reduces egg adaptation and therefore has the potential to increase vaccine effectiveness. This study evaluated whether the cell-based quadrivalent influenza vaccine (QIVc) improved relative vaccine effectiveness (rVE) compared to standard-dose egg-based quadrivalent influenza vaccine (QIVe-SD) in the reduction of influenza-related and respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season.
Methods. A retrospective analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the United States of America (U.S.) (IQVIA PharMetrics ® Plus). Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders. Post-IPTW, the number of events and rates (per 1,000 vaccinated subject-seasons) of influenza-related hospitalizations/ER visits, respiratory-related hospitalizations/ ER visits and all-cause hospitalizations were assessed. Poisson regression was used to estimate adjusted rVE. To avoid any influenza outcome misclassification with COVID-19 infection, the study period ended March 7,2020. A sub-analysis for a high-risk subgroup was conducted. Urinary tract infection (UTI) hospitalization was assessed as a negative control endpoint.
Conclusion. QIVc was significantly more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits, as well as all-cause hospitalizations, compared to QIVe-SD.