![]() In total, 1004 ARIs associated with coronavirus infection were identified. Between 8.3% and 16.3% of the cohort had an ARI associated with seasonal HCoV infection each year. There were 1378 (40%) individuals who were under study for ≥3 years. In total, 3418 individuals participated for 1–8 study years (median, 2 years) contributing a total of 9378 person-years of observation ( Figure 1). ![]() RESULTS RT-PCR–Confirmed HCoV Coinfections and Reinfections Over Time Odds ratios (ORs) estimated from these models were interpreted as the reduction in odds of infection associated with a 2-fold increase in AUC. Inclusion of study year in adjusted models did not substantially change point estimates. Log 2 AUC was compared between cases of single infection with a specific HCoV type and controls that were singly infected with the other 3 HCoV types in logistic generalized estimating equation regression models with exchangeable correlation structure clustered on the individual and adjusted for age, influenza vaccination, and high-risk health status. The association between antibody binding levels and subsequent infection risk was estimated using a case test-negative design analysis. Pearson correlation coefficients were calculated comparing multiplex and singleplex AUC at each time point ( Supplementary Tables 1 and 2). The rate of antibody waning and half-life was estimated in linear generalized estimating equation models predicting log 2 AUC by time. Participants with ARI attended an illness visit within 7 days of symptom onset where study staff collected nasal and throat swabs (nasal only in children 1 infection per year were excluded. Although year-round surveillance did not begin until the fall of 2014, complete coronavirus epidemics were likely captured in each study year because of their sharp seasonality. Participants were also actively questioned regarding their illness status via weekly calls or emails. Seasonal Coronavirus SurveillanceĮach study year, participants were asked to report all acute respiratory illnesses (ARIs) defined by ≥2 symptoms as soon as they occurred. ![]() This study was reviewed and approved by the University of Michigan Medical School Institutional Review Board. Adult participants provided informed consent for themselves and their children, and children ≥7 years of age provided verbal assent prior to participating. ![]() Households were retained as long as possible with replacement households enrolled and returning households reengaged in the spring or summer of each year participant and household characteristics were recorded at this time. Households with children receiving primary care from Michigan Medicine were recruited from Ann Arbor, Michigan and surrounding communities beginning in the summer of 2010. The complete methods of the HIVE cohort have been published previously. In this report, we characterize RT-PCR–documented, symptomatic reinfections with these viruses and investigate antibody response to infection, including cross-reactivity and persistence. This, and past studies of HCoVs suggested that these agents, like most respiratory viruses, reinfect through life. The infections were most frequent in children, but substantial numbers of infections were identified in adults. Over that period, 2010–2018, 1004 infections were detected by reverse-transcription polymerase chain reaction (RT-PCR). We have previously reported on 8 years of seasonal HCoV infection among persons in the continuing Household Influenza Vaccine Evaluation (HIVE) study being conducted in Michigan. Few have examined antibody response to seasonal infection, antibody waning, or cross-response between the 4 seasonal HCoVs or with SARS-CoV-2 in large prospective cohort studies. Of particular importance are questions around possible cross-protection or enhancement of COVID-19 disease from prior seasonal virus infection and duration of infection following SARS-CoV-2 infection. The current coronavirus disease 2019 (COVID-19) pandemic, the first recognized to be caused by an HCoV, has focused attention on the seasonal coronaviruses in comparison to SARS-CoV-2. Prior to the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it was recognized that coronaviruses that infect humans (HCoVs) could be separated into the 4 seasonal, or common, coronaviruses (229E, OC43, NL53, and HKU1), which regularly cause mainly mild respiratory illnesses, and severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), which have caused epidemics of severe lower respiratory disease. Seasonal coronavirus, SARS-CoV-2, COVID-19, reinfection, antibody, waning, household cohort, serology, correlates of protection, immunity
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