Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period.

BACKGROUND: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination. METHODS: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants' SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression. RESULTS: During September 22, 2020 - February 13, 2021, 2712 eligible adults were enrolled, 1541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model. CONCLUSION: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset.

Effectiveness of Bivalent mRNA COVID-19 Vaccines in Preventing SARS-CoV-2 Infection in Children and Adolescents Aged 5 to 17 Years.

Importance: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. Objective: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. Design, Setting, and Participants: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. Exposure: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. Main Outcome and Measures: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. Results: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. Conclusion and Relevance: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

Work Attendance with Acute Respiratory Illness Before and During COVID-19 Pandemic, United States, 2018-2022.

Both SARS-CoV-2 and influenza virus can be transmitted by asymptomatic, presymptomatic, or symptomatic infected persons. We assessed effects on work attendance while ill before and during the COVID-19 pandemic in the United States by analyzing data collected prospectively from persons with acute respiratory illnesses enrolled in a multistate study during 2018-2022. Persons with previous hybrid work experience were significantly less likely to work onsite on the day before through the first 3 days of illness than those without that experience, an effect more pronounced during the COVID-19 pandemic than during prepandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other acute respiratory illnesses. Among persons with positive COVID-19 test results available by the second or third day of illness, few worked onsite. Hybrid and remote work policies might reduce workplace exposures and help reduce spread of respiratory viruses.

A rapid and flexible microneutralization assay for serological assessment of influenza viruses.

BACKGROUND: Serological responses from influenza vaccination or infection are typically measured by hemagglutinin inhibition (HAI) or microneutralization (MN). Both methods are limited in feasibility, standardization, and generalizability to recent strains. We developed a luciferase MN (LMN) assay that combines the advantages of the conventional MN assay with the ease of the HAI assay. METHODS: Sera were obtained from the HIVE study, a Michigan household cohort. Reverse genetics was used to generate recombinant influenza viruses expressing the hemagglutinin and neuraminidase of test strains, all other viral proteins from an A/WSN/1933 backbone, and a NanoLuc reporter. Serum neutralization of luciferase-expressing targets was quantified as a reduction in light emission from infected cells. Neutralization titers were measured for cell- and egg-adapted versions of A/Hong Kong/4801/2014 and A/Singapore/INFIMH-16-0019/2016 and compared to HAI titers against egg-grown antigens. RESULTS: Three hundred thirty-three sera were collected from 259 participants between May 2016 and July 2018. Sampled participants were 7-68 years of age, and >80% were vaccinated against influenza. HAI and LMN titers were correlated for A/Hong Kong/4801/2014 (ρ = 0.52, p ≤ 0.01) and A/Singapore/INFIMH-16-0019/2016 (ρ = 0.79, p ≤ 0.01). LMN titers were lower for cell strains compared to egg strains (A/Hong Kong/4801/2014 mean log2 fold change = -2.66, p ≤ 0.01 and A/Singapore/INFIMH-16-0019/2016 mean log2 fold change = -3.15, p ≤ 0.01). CONCLUSIONS: The LMN assay was feasible using limited sample volumes and able to differentiate small antigenic differences between egg-adapted and cell-derived strains. The correspondence of these results with the commonly used HAI confirms the utility of this assay for high-throughput studies of correlates of protection and vaccine response.

Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 U.S. States, February 1, 2022-January 31, 2023.

As of April 2023, the COVID-19 pandemic has resulted in 1.1 million deaths in the United States, with approximately 75% of deaths occurring among adults aged ≥65 years (1). Data on the durability of protection provided by monovalent mRNA COVID-19 vaccination against critical outcomes of COVID-19 are limited beyond the Omicron BA.1 lineage period (December 26, 2021-March 26, 2022). In this case-control analysis, the effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses was evaluated against COVID-19-associated invasive mechanical ventilation (IMV) and in-hospital death among immunocompetent adults aged ≥18 years during February 1, 2022-January 31, 2023. Vaccine effectiveness (VE) against IMV and in-hospital death was 62% among adults aged ≥18 years and 69% among those aged ≥65 years. When stratified by time since last dose, VE was 76% at 7-179 days, 54% at 180-364 days, and 56% at ≥365 days. Monovalent mRNA COVID-19 vaccination provided substantial, durable protection against IMV and in-hospital death among adults during the Omicron variant period. All adults should remain up to date with recommended COVID-19 vaccination to prevent critical COVID-19-associated outcomes.

Respiratory virus circulation during the first year of the COVID-19 pandemic in the Household Influenza Vaccine Evaluation (HIVE) cohort.

Background: The annual reappearance of respiratory viruses has been recognized for decades. COVID-19 mitigation measures taken during the pandemic were targeted at respiratory transmission and broadly impacted the burden of acute respiratory illnesses (ARIs). Methods: We used the longitudinal Household Influenza Vaccine Evaluation (HIVE) cohort in southeast Michigan to characterize the circulation of respiratory viruses from March 1, 2020, to June 30, 2021, using RT-PCR of respiratory specimens collected at illness onset. Participants were surveyed twice during the study period, and SARS-CoV-2 antibodies were measured in serum by electrochemiluminescence immunoassay. Incidence rates of ARI reports and virus detections were compared between the study period and a preceding pre-pandemic period of similar duration. Results: Overall, 437 participants reported a total of 772 ARIs; 42.6% had respiratory viruses detected. Rhinoviruses were the most frequent virus, but seasonal coronaviruses, excluding SARS-CoV-2, were also common. Illness reports and percent positivity were lowest from May to August 2020, when mitigation measures were most stringent. Seropositivity for SARS-CoV-2 was 5.3% in summer 2020 and increased to 11.3% in spring 2021. The incidence rate of total reported ARIs for the study period was 50% lower (95% CI: 0.5, 0.6; p < 0.001) than the incidence rate from a pre-pandemic comparison period (March 1, 2016, to June 30, 2017). Conclusions: The burden of ARI in the HIVE cohort during the COVID-19 pandemic fluctuated, with declines occurring concurrently with the widespread use of public health measures. Rhinovirus and seasonal coronaviruses continued to circulate even when influenza and SARS-CoV-2 circulation was low.

Influenza Vaccine Effectiveness Among Children: 2011-2020.

BACKGROUND AND OBJECTIVES: Infants and children are at increased risk of severe influenza virus infection and its complications. Influenza vaccine effectiveness (VE) varies by age, influenza season, and influenza virus type/subtype. This study's objective was to examine the effectiveness of inactivated influenza vaccine against outpatient influenza illness in the pediatric population over 9 influenza seasons after the 2009 A(H1N1) pandemic. METHODS: During the 2011-2012 through the 2019-2020 influenza seasons at outpatient clinics at 5 sites of the US Influenza Vaccine Effectiveness Network, children aged 6 months to 17 years with an acute respiratory illness were tested for influenza using real-time, reverse-transcriptase polymerase chain reaction. Vaccine effectiveness was estimated using a test-negative design. RESULTS: Among 24 148 enrolled children, 28% overall tested positive for influenza, 3017 tested positive for influenza A(H3N2), 1459 for influenza A(H1N1)pdm09, and 2178 for influenza B. Among all enrollees, 39% overall were vaccinated, with 29% of influenza cases and 43% of influenza-negative controls vaccinated. Across all influenza seasons, the pooled VE for any influenza was 46% (95% confidence interval, 43-50). Overall and by type/subtype, VE against influenza illness was highest among children in the 6- to 59-month age group compared with older pediatric age groups. VE was lowest for influenza A(H3N2) virus infection. CONCLUSIONS: Analysis of multiple seasons suggested substantial benefit against outpatient illness. Investigation of host-specific or virus-related mechanisms that may result in differences by age and virus type/subtype may help further efforts to promote increased vaccination coverage and other influenza-related preventative measures.

Comparing the Etiology of Viral Acute Respiratory Illnesses Between Children Who Do and Do Not Attend Childcare.

BACKGROUND AND OBJECTIVE: Childcare attendance is a common risk factor for acute respiratory illness (ARI) in young children. Our goal was to better understand the specific respiratory viruses that predominate in childcare, which may support the development of tailored illness prevention and intervention strategies in childcare settings. METHODS: Using data from a prospective household cohort of ARI surveillance, we assessed specimen from 1418 ARIs reported by 359 childcare-aged children over 6 study seasons (2012/2013 through 2017/2018). Respiratory swabs were tested by polymerase chain reaction for 9 respiratory viruses. A mixed-effect logistic regression model was used to compare odds of various viral detection outcomes. The Shannon's Diversity index was used to compare the richness (ie, number of species) and diversity (ie, relative species abundance) associated with respiratory viruses detected in both groups. RESULTS: At least 1 virus was detected in 75.5% of childcare-associated ARIs and in 80.1% of homecare ARIs. Compared with illnesses among homecare children, childcare illnesses were associated with significantly higher odds of detected adenovirus (odds ratio = 1.86, 95% confidence interval = 1.05-3.28) and human metapneumovirus (odds ratio = 1.76, 95% confidence interval = 1.03-3.0). The pool of viruses associated with childcare ARI was found to be significantly richer and more diverse than that of viruses associated with homecare ARI ( P < 0.0001). CONCLUSIONS: Children attending childcare experience a higher risk of adenovirus and human metapneumovirus infection and are regularly exposed to a rich and diverse pool of respiratory viruses in childcare environments. Our results underscore the necessity of thorough and multifaceted viral prevention strategies in childcare settings.

Prevalence and Clinical Outcomes of Respiratory Syncytial Virus vs Influenza in Adults Hospitalized With Acute Respiratory Illness From a Prospective Multicenter Study.

BACKGROUND: Current understanding of severe respiratory syncytial virus (RSV) infections in adults is limited by clinical underrecognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses (ARIs) in a prospective national surveillance network. METHODS: Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across 3 respiratory seasons from hospitals participating across all sites of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (2016-2019). All participants were tested for RSV and influenza using real-time reverse-transcription polymerase chain reaction assay. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. RESULTS: Among 10 311 hospitalized adults, 6% tested positive for RSV (n = 622), 18.8% for influenza (n = 1940), and 75.1% negative for RSV and influenza (n = 7749). Congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) was more frequent with RSV than influenza (CHF: 37.3% vs 28.8%, P < .0001; COPD: 47.6% vs 35.8%, P < .0001). Patients with RSV more frequently had longer admissions (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.06-1.80) for stays >1 week) and mechanical ventilation (OR, 1.45; 95% CI, 1.09-1.93) compared with influenza but not compared with the influenza-negative group (OR, 1.03; 95% CI, .82-1.28 and OR, 1.17; 95% CI, .91-1.49, respectively). CONCLUSIONS: The prevalence of RSV across 3 seasons was considerable. Our findings suggest that those with RSV have worse outcomes compared with influenza and frequently have cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults with severe ARI.

Absolute and Relative Vaccine Effectiveness of Primary and Booster Series of COVID-19 Vaccines (mRNA and Adenovirus Vector) Against COVID-19 Hospitalizations in the United States, December 2021-April 2022.

Background: Coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines. Methods: Booster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE. Results: A total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary. Conclusions: Vaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.

Relationship between Telework Experience and Presenteeism during COVID-19 Pandemic, United States, March-November 2020.

Persons with COVID-19-like illnesses are advised to stay home to reduce the spread of SARS-CoV-2. We assessed relationships between telework experience and COVID-19 illness with work attendance when ill. Adults experiencing fever, cough, or loss of taste or smell who sought healthcare or COVID-19 testing in the United States during March-November 2020 were enrolled. Adults with telework experience before illness were more likely to work at all (onsite or remotely) during illness (87.8%) than those with no telework experience (49.9%) (adjusted odds ratio 5.48, 95% CI 3.40-8.83). COVID-19 case-patients were less likely to work onsite (22.1%) than were persons with other acute respiratory illnesses (37.3%) (adjusted odds ratio 0.36, 95% CI 0.24-0.53). Among COVID-19 case-patients with telework experience, only 6.5% worked onsite during illness. Telework experience before illness gave mildly ill workers the option to work and improved compliance with public health recommendations to stay home during illness.

Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants.

Transmission bottlenecks limit the spread of novel mutations and reduce the efficiency of selection along a transmission chain. While increased force of infection, receptor binding, or immune evasion may influence bottleneck size, the relationship between transmissibility and the transmission bottleneck is unclear. Here we compare the transmission bottleneck of non-VOC SARS-CoV-2 lineages to those of Alpha, Delta, and Omicron. We sequenced viruses from 168 individuals in 65 households. Most virus populations had 0-1 single nucleotide variants (iSNV). From 64 transmission pairs with detectable iSNV, we identify a per clade bottleneck of 1 (95% CI 1-1) for Alpha, Delta, and Omicron and 2 (95% CI 2-2) for non-VOC. These tight bottlenecks reflect the low diversity at the time of transmission, which may be more pronounced in rapidly transmissible variants. Tight bottlenecks will limit the development of highly mutated VOC in transmission chains, adding to the evidence that selection over prolonged infections may drive their evolution.

Protection of Messenger RNA Vaccines Against Hospitalized Coronavirus Disease 2019 in Adults Over the First Year Following Authorization in the United States.

BACKGROUND: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization. METHODS: Case-control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states 11 March-15 December 2021, including COVID-19 case patients and reverse transcriptase-polymerase chain reaction-negative controls. We included adults who were unvaccinated or vaccinated with 2 doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing odds of vaccination in cases versus controls, adjusting for confounders. Models included dichotomous time (<180 vs ≥180 days since dose 2) and continuous time modeled using restricted cubic splines. RESULTS: A total of 10 078 patients were included, 4906 cases (23% vaccinated) and 5172 controls (62% vaccinated). Median age was 60 years (interquartile range, 46-70), 56% were non-Hispanic White, and 81% had ≥1 medical condition. Among immunocompetent adults, VE <180 days was 90% (95% confidence interval [CI], 88-91) versus 82% (95% CI, 79-85) at ≥180 days (P < .001). VE declined for Pfizer-BioNTech (88% to 79%, P < .001) and Moderna (93% to 87%, P < .001) products, for younger adults (18-64 years) (91% to 87%, P = .005), and for adults ≥65 years of age (87% to 78%, P < .001). In models using restricted cubic splines, similar changes were observed. CONCLUSIONS: In a period largely predating Omicron variant circulation, effectiveness of 2 mRNA doses against COVID-19-associated hospitalization was largely sustained through 9 months.

Influenza Vaccine Effectiveness Against Influenza A(H3N2)-Related Illness in the United States During the 2021-2022 Influenza Season.

BACKGROUND: In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness (VE) for the first time since the beginning of the coronavirus disease 2019 pandemic. We estimated influenza VE against laboratory-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. METHODS: Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, participants who tested positive for SARS-CoV-2 were excluded from VE estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity, and general health status. RESULTS: Among 6260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1948 SARS-CoV-2-positive patients, 4312 patients were included in analyses of influenza VE; 2463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95% confidence interval, 20%-49%) overall. CONCLUSIONS: Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons.

Influenza During the 2010-2020 Decade in the United States: Seasonal Outbreaks and Vaccine Interventions.

The 10 years between the last influenza pandemic and start of the severe acute respiratory syndrome coronavirus 2 pandemic have been marked by great advances in our ability to follow influenza occurrence and determine vaccine effectiveness (VE), largely based on widespread use of the polymerase chain reaction assay. We examine the results, focusing mainly on data from the United States and inactivated vaccines. Surveillance has expanded, resulting in increased ability to characterize circulating viruses and their impact. The surveillance has often confirmed previous observations on timing of outbreaks and age groups affected, which can now be examined in greater detail. Selection of strains for vaccines is now based on enhanced viral characterization using immunologic, virologic, and computational techniques not previously available. Vaccine coverage has been largely stable, but VE has remained modest and, in some years, very low. We discuss ways to improve VE based on existing technology while we work toward supraseasonal vaccines.

Respiratory Virus Circulation during the First Year of the COVID-19 Pandemic in the Household Influenza Vaccine Evaluation (HIVE) Cohort.

Background: The annual reappearance of respiratory viruses has been recognized for decades. The onset of the COVID-19 pandemic altered typical respiratory virus transmission patterns. COVID-19 mitigation measures taken during the pandemic were targeted at SARS-CoV-2 respiratory transmission and thus broadly impacted the burden of acute respiratory illnesses (ARIs), in general. Methods: We used the longitudinal Household Influenza Vaccine Evaluation (HIVE) cohort of households in southeast Michigan to characterize mitigation strategy adherence, respiratory illness burden, and the circulation of 15 respiratory viruses during the COVID-19 pandemic determined by RT-PCR of respiratory specimens collected at illness onset. Study participants were surveyed twice during the study period (March 1, 2020, to June 30, 2021), and serologic specimens were collected for antibody measurement by electrochemiluminescence immunoassay. Incidence rates of ARI reports and virus detections were calculated and compared using incidence rate ratios for the study period and a pre-pandemic period of similar length. Results: Overall, 437 participants reported a total of 772 ARIs and 329 specimens (42.6%) had respiratory viruses detected. Rhinoviruses were the most frequently detected organism, but seasonal coronaviruses-excluding SARS-CoV-2-were also common. Illness reports and percent positivity were lowest from May to August 2020, when mitigation measures were most stringent. Study participants were more adherent to mitigation measures in the first survey compared with the second survey. Supplemental serology surveillance identified 5.3% seropositivity for SARS-CoV-2 in summer 2020; 3.0% between fall 2020 and winter 2021; and 11.3% in spring 2021. Compared to a pre-pandemic period of similar length, the incidence rate of total reported ARIs for the study period was 50% lower (95% CI: 0.5, 0.6; p<0.001) than the incidence rate from March 1, 2016, to June 30, 2017. Conclusions: The burden of ARI in the HIVE cohort during the COVID-19 pandemic fluctuated, with declines occurring concurrently with the widespread use of public health measures. It is notable, however, that rhinovirus and seasonal coronaviruses continued to circulate even as influenza and SARS-CoV-2 circulation was low.

SARS-CoV-2 Vaccine Strain Selection: Guidance From Influenza.

When first approved, many hoped that the SARS-CoV-2 vaccine would provide long-term protection after a primary series. Waning of immunity and continued appearance of new variants has made booster inoculations necessary. The process is becoming increasingly similar to that used for annual updating of the influenza vaccine. The similarity has become even more apparent with selection of BA.4/BA.5 as the Omicron strain of the updated bivalent (Original + Omicron) COVID-19 vaccines. It is hoped that, if COVID-19 develops winter seasonality, SARS-CoV-2 vaccines will require only annual review to determine if updates are necessary. Recommendations on whom should receive the booster would be based on conditions at that time.

Burden of medically attended influenza infection and cases averted by vaccination - United States, 2016/17 through 2018/19 influenza seasons.

BACKGROUND: Epidemics of seasonal influenza vary in intensity annually, and influenza vaccine effectiveness (VE) fluctuates based in part on antigenic match to circulating viruses. We estimated the incidence of influenza and influenza cases averted by vaccination in four ambulatory care sites in the United States, during seasons when overall influenza VE ranged from 29% to 40%. METHODS: We conducted active surveillance for influenza at ambulatory care settings at four sites within the United States Influenza Vaccine Effectiveness Network. We extrapolated the total number of influenza cases in the source populations served by these organizations based on incidence of medically attended acute respiratory illness in the source population and influenza test results in those actively tested for influenza. We estimated the number of medically attended influenza cases averted based on incidence, vaccine coverage, and VE. RESULTS: From 2016/17 through 2018/19, incidence of ambulatory visits for laboratory-confirmed influenza ranged from 31 to 51 per 1,000 population. Incidence was highest in children aged 9-17 years (range, 56 to 81 per 1,000) and lowest in adults aged 18-49 years (range, 23-32 per 1,000). Medically attended cases averted by vaccination ranged from a high of 46.6 (95 % CI, 12.1- 91.9) per 1,000 vaccinees in children aged 6 months to 8 years, to a low of 6.9 (95 % CI, -5.1- 27.3) per 1,000 vaccinees in adults aged ≥ 65 years. DISCUSSION: Even in seasons with low vaccine effectiveness for a particular virus subtype, influenza vaccines can still lead to clinically meaningful reductions in ambulatory care visits for influenza.

Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants.

Transmission bottlenecks limit the spread of novel mutations and reduce the efficiency of natural selection along a transmission chain. Many viruses exhibit tight bottlenecks, and studies of early SARS-CoV-2 lineages identified a bottleneck of 1-3 infectious virions. While increased force of infection, host receptor binding, or immune evasion may influence bottleneck size, the relationship between transmissibility and the transmission bottleneck is unclear. Here, we compare the transmission bottleneck of non-variant-of-concern (non-VOC) SARS-CoV-2 lineages to those of the Alpha, Delta, and Omicron variants. We sequenced viruses from 168 individuals in 65 multiply infected households in duplicate to high depth of coverage. In 110 specimens collected close to the time of transmission, within-host diversity was extremely low. At a 2% frequency threshold, 51% had no intrahost single nucleotide variants (iSNV), and 42% had 1-2 iSNV. In 64 possible transmission pairs with detectable iSNV, we identified a bottleneck of 1 infectious virion (95% CI 1-1) for Alpha, Delta, and Omicron lineages and 2 (95% CI 2-2) in non-VOC lineages. The latter was driven by a single iSNV shared in one non-VOC household. The tight transmission bottleneck in SARS-CoV-2 is due to low genetic diversity at the time of transmission, a relationship that may be more pronounced in rapidly transmissible variants. The tight bottlenecks identified here will limit the development of highly mutated VOC in typical transmission chains, adding to the evidence that selection over prolonged infections in immunocompromised patients may drive their evolution.