Direct Observation of Repeated Infections With Endemic Coronaviruses

Abstract

Background: Although the mechanisms of adaptive immunity to pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still unknown, the immune response to the widespread endemic coronaviruses HKU1, 229E, NL63, and OC43 provide a useful reference for understanding repeat infection risk.

Methods: Here we used data from proactive sampling carried out in New York City from fall 2016 to spring 2018. We combined weekly nasal swab collection with self-reports of respiratory symptoms from 191 participants to investigate the profile of recurring infections with endemic coronaviruses.

Results: During the study, 12 individuals tested positive multiple times for the same coronavirus. We found no significant difference between the probability of testing positive at least once and the probability of a recurrence for the betacoronaviruses HKU1 and OC43 at 34 weeks after enrollment/first infection. We also found no significant association between repeat infections and symptom severity, but found strong association between symptom severity and belonging to the same family.

Conclusions: This study provides evidence that reinfections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection.

Keywords: endemic coronaviruses; repeated endemic coronavirus infection; waning immunity to endemic coronavirus.

Figure 1.

Kaplan–Meier plots showing the probability of testing positive within x weeks after enrollment for each of the 4 types of seasonal coronavirus. The shaded area is the 95% confidence interval. In the case of individuals testing positive multiple times for the same coronavirus type, we only considered the time to the first occurrence in this plot. Abbreviation: P(infection), probability of testing positive.

Figure 2.

Probability of becoming reinfected with the same betacoronavirus type (OC43 in red crossed line and HKU1 in black straight line) within x weeks after a first documented infection. Dashed lines show the 95% confidence interval. Here, only individuals testing positive multiple times for the same coronavirus type are considered. For each occurrence, we calculated the time distance from the previous infection. Abbreviation: P(reinfection), probability of testing positive again after a previous documented infection with the same coronavirus type.

Figure 3.

Total symptom score associated with infections by any coronavirus type. The score is calculated as the sum of daily symptom scores for the –3/+7 day window around the test date, as indicated for definition 3 in Table 1. Each point represents an infection event, and each cluster represents a family group. Each family group 1 to 9 is composed of a parent and 1–4 children. For each box, the red line indicates the median, and the bottom and top edges of the blue box are the 25th and 75th percentiles. The dashed lines extend to the most extreme data points that are not outliers, whereas the outliers are indicated by the red “+” symbol.