1333. A National Outbreak of Respiratory Syncytial Virus Associated with Emergence of a Genetically Distinct ON1 variant

Abstract Background A national outbreak of respiratory syncytial virus (RSV) has been observed in the community since Fall 2020 in Taiwan. Methods We reviewed a national laboratory-based surveillance network established over 20 years by Taiwan Centers for Disease Control (TCDC) for respiratory viral positivity rate and viral pathogen in outpatient department and hospitalized patients. A retrospective study of children younger than 5 years old hospitalized with RSV infections at Chang Gung Memorial Hospital (CGMH) including Lin Kou and Kaohsiung branch between 2018 and 2020 was conducted. Samples positive for RSV A were sequenced. Patients’ clinical data was obtained from medical files and stratified by genotype and year. Results 2020 showed a 4-fold surge in RSV cases in Taiwan, in which surpassed both 2011 (the appearance of ON1 strain in Taiwan) and 2013 (ON1 strain predominates in Taiwan)(Figure1,Table1). Phylogenetic analysis of G protein sequences showed that most strains in 2020 were clustered apart from 2018, 2019 seasons and other ON1 reference strains between 2011 and 2016, indicating a novel ON1 variant had been circulating in the community(Figure2). The novel ON1 variants carried six amino acid changes, of which T113I,V131D, H258Q,H266L,Y304H located in the mucin domains and N178G in central conserved domain. These changes emerged gradually in 2019 and showed a high consistency in 2020. The unique amino acid substitution E257K in the second mucin domain was noticed in 2020 exclusively. Besides, 10 substitutes in F protein were appeared between 2018 and 2020, of which R213S and N276S were in antigenic sites. Furthermore, substitutes T12I and H514N in F protein were first emerged since 2020. On multivariate analysis, age (OR 0.97; 95% CI 0.94-0.99; p 0.02) and ON1 variant in 2020 (OR 2.52; 95% CI 1.13-5.63; p 0.025) were independently associated with oxygen saturation < 94% during hospitalization (Table 2). Figure 2. The phylogenetic tree of G protein sequences including ON1 strains in our study from 2018 to 2020 and reference strains from 2011 to 2016 The phylogenetic tree showed that most strains of the 2020 season clustered apart from those of the previous seasons, which indicated there was a novel ON1 variant circulating in the community associated with 2020 RSV epidemic. Variables with p<0.1 in the univariate analysis were included in the multivariate analysis. Conclusion An unprecedented RSV epidemic within the last 10 years caused by a novel ON1 variant has occurred in 2020 (Figure 1), suggesting the sets of mutations may confer fitness advantage. Further studies on viral replication, infectivity and virulence is needed to understand the evolution and spread of RSV. Disclosures All Authors: No reported disclosures

Department of Health, Research and Diagnostic Center, Centers for Disease Control, Taiwan, Guishan, Taoyuan, Taiwan; 3 Linkou Chang Gung Memorial Hospital, Taoyuan City, Taoyuan, Taiwan (Republic of China) ; 4 Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan, Guishan, Taoyuan, Taiwan Session: P-74. Respiratory Infections -Viral Background. A national outbreak of respiratory syncytial virus (RSV) has been observed in the community since Fall 2020 in Taiwan.
Methods. We reviewed a national laboratory-based surveillance network established over 20 years by Taiwan Centers for Disease Control (TCDC) for respiratory viral positivity rate and viral pathogen in outpatient department and hospitalized patients. A retrospective study of children younger than 5 years old hospitalized with RSV infections at Chang Gung Memorial Hospital (CGMH) including Lin Kou and Kaohsiung branch between 2018 and 2020 was conducted. Samples positive for RSV A were sequenced. Patients' clinical data was obtained from medical files and stratified by genotype and year.
Results. 2020 showed a 4-fold surge in RSV cases in Taiwan, in which surpassed both 2011 (the appearance of ON1 strain in Taiwan) and 2013 (ON1 strain predominates in Taiwan) (Figure1,Table1). Phylogenetic analysis of G protein sequences showed that most strains in 2020 were clustered apart from 2018, 2019 seasons and other ON1 reference strains between 2011 and 2016, indicating a novel ON1 variant had been circulating in the community(Figure2). The novel ON1 variants carried six amino acid changes, of which T113I,V131D, H258Q,H266L,Y304H located in the mucin domains and N178G in central conserved domain. These changes emerged gradually in 2019 and showed a high consistency in 2020. The unique amino acid substitution E257K in the second mucin domain was noticed in 2020 exclusively. Besides, 10 substitutes in F protein were appeared between 2018 and 2020, of which R213S and N276S were in antigenic sites. Furthermore, substitutes T12I and H514N in F protein were first emerged since 2020. On multivariate analysis, age (OR 0.97; 95% CI 0.94-0.99; p 0.02) and ON1 variant in 2020 (OR 2.52; 95% CI 1.13-5.63; p 0.025) were independently associated with oxygen saturation < 94% during hospitalization (Table 2). The phylogenetic tree showed that most strains of the 2020 season clustered apart from those of the previous seasons, which indicated there was a novel ON1 variant circulating in the community associated with 2020 RSV epidemic.
Variables with p<0.1 in the univariate analysis were included in the multivariate analysis.
Conclusion. An unprecedented RSV epidemic within the last 10 years caused by a novel ON1 variant has occurred in 2020 (Figure 1), suggesting the sets of mutations may confer fitness advantage. Further studies on viral replication, infectivity and virulence is needed to understand the evolution and spread of RSV. Background. A significant burden of disease exists for adults infected with influenza (flu) and SARS-CoV-2, which causes COVID-19. However, data are limited comparing outcomes between hospitalized adults infected with these viruses.

Outcomes Among Influenza and SARS-CoV-2 Infection in Hospitalized
Methods. Over the course of 3 consecutive winter respiratory viral seasons, adults ≥ 50 years of age admitted with acute respiratory tract infections (ARI) and adults of any age with COPD or CHF-related admissions were enrolled from 2 Atlanta area hospitals. For the 2018-19 and 2019-20 seasons, participants were approached in the hospital. If the participant enrolled, nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected and tested using BioFire® FilmArray® respiratory panel. Due to the COVID-19 pandemic in 2020-21 and limitations involving participant contact, only NP standard of care (SOC) swabs were collected. A comprehensive medical chart review was completed for each subject which encompassed data on their hospitalization, past medical history, and vaccination history. Co-infected patients were excluded from the analyses.
Results. Of the eligible participants, 118 were flu positive (three RSV-influenza co-infections were excluded) and 527 were COVID-19 positive. Median age was lower for the flu cohort at 62 (IQR 56-71) than those with COVID-19 (67, IQR 59-77) (p < 0.0001). Length of stay (LOS) was shorter in flu-infected patients (median 3 d, IQR 2-6), but was longer for COVID-19 patients (median 5 d, IQR 3-10). ICU admission occurred in 20% of those with flu, and among those admitted to the ICU mechanical ventilation (MV) occurred in 12.5%. ICU admission and MV was significantly higher for those with COVID-19, with 28% of patients admitted to the ICU and 47% of those requiring MV. Among patients with COVID-19, 8.9% died. This was significantly higher than that of flu (3.4%) (p=0.008). Hospital discharge occurred more frequently to a nursing home or LTCF with COVID-19 (10.3%) than with flu (0%) (p< 0.0001). Table 1. Breakdown of age, hospitalization course, and discharge disposition for participants diagnosed with influenza or COVID-19 during hospitalization.
Conclusion. COVID-19 resulted in a longer hospital admission, a greater chance of ICU admission and MV as compared to flu. Additionally, COVID-19 participants had a high rate of discharge to a nursing home/LTCF and a significantly higher risk of death. While the clinical course was not as severe as COVID-19, influenza contributed a significant burden.