Coronavirus Occurrence in the Household Influenza Vaccine Evaluation (HIVE) Cohort of Michigan Households: Reinfection Frequency and Serologic Responses to Seasonal and Severe Acute Respiratory Syndrome Coronaviruses

Abstract

Background: We investigated frequency of reinfection with seasonal human coronaviruses (HCoVs) and serum antibody response following infection over 8 years in the Household Influenza Vaccine Evaluation (HIVE) cohort.

Methods: Households were followed annually for identification of acute respiratory illness with reverse-transcription polymerase chain reaction-confirmed HCoV infection. Serum collected before and at 2 time points postinfection were tested using a multiplex binding assay to quantify antibody to seasonal, severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins and SARS-CoV-2 spike subdomains and N protein.

Results: Of 3418 participants, 40% were followed for ≥3 years. A total of 1004 HCoV infections were documented; 303 (30%) were reinfections of any HCoV type. The number of HCoV infections ranged from 1 to 13 per individual. The mean time to reinfection with the same type was estimated at 983 days for 229E, 578 days for HKU1, 615 days for OC43, and 711 days for NL63. Binding antibody levels to seasonal HCoVs were high, with little increase postinfection, and were maintained over time. Homologous, preinfection antibody levels did not significantly correlate with odds of infection, and there was little cross-response to SARS-CoV-2 proteins.

Conclusions: Reinfection with seasonal HCoVs is frequent. Binding anti-spike protein antibodies do not correlate with protection from seasonal HCoV infection.

Keywords: COVID-19; SARS-CoV-2; antibody; correlates of protection; household cohort; immunity; reinfection; seasonal coronavirus; serology; waning.

Figure 1.

Distributions of follow-up time (A) and observed acute respiratory illnesses (B) associated with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed seasonal coronavirus infection, Household Influenza Vaccine Evaluation (HIVE) cohort, 2010–2018. The number of observed acute respiratory illnesses associated with RT-PCR–confirmed seasonal coronavirus infection per individual ranged from 1 to 13.

Figure 2.

Frequency of seasonal human coronavirus (HCoV) pairings in coinfections by type (A) and genus (B), and frequency of seasonal HCoV pairings in consecutive reinfections by type (C) and genus (D).

Figure 3.

Kaplan–Meier curves of time to reinfection following a prior seasonal human coronavirus (HCoV) infection for any seasonal HCoV reinfection (A), and for same-genus alpha (B) and beta (C) coronavirus reinfections.

Figure 4.

Infection-homologous log₂ area under the curve (AUC) values preinfection and at 2 postinfection time points for individuals infected with human coronaviruses 229E (A), HKU1 (B), NL63 (C), and OC43 (D).