To the Editor—Monto et al recently reported results on the seasonal variation and transmission of the endemic (common) human coronaviruses (HCoV) HKU1, OC43, NL63, and 229E [1]. However, their study design did not allow for assessment of reinfection with the same HCoV. Knowledge about reinfections with common HCoV might inform the risk of recurrent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and may shed light on the efficiency of protective immunity. We interrogated a database of >75 000 clinical samples from >50 000 patients with respiratory tract infection to determine the rate of reinfection with the same HCoV (eg, NL63 followed by NL63) or a new HCoV (eg, NL63 followed by OC43).
Data were retrieved from the routine diagnostics unit at the Department of Clinical Microbiology, Sahlgrenska University Hospital with a catchment area of approximately 700 000 inhabitants. Both hospitals and primary care centers refer to this laboratory. We used a database of results obtained using an in-house real time polymerase chain reaction (PCR) panel targeting 18 respiratory pathogens [2] analyzed in 78 135 nasopharyngeal or oropharyngeal samples from 53 447 patients, mean age 47 years, between January 2013 and February 2020. We applied a lag period of >50 days from the first infection to distinguish recurrent from protracted infections. All patients with a positive initial test results for HCoV (HKU1, OC43, NL63, or 229E) and at least one additional sample analyzed >50 days later were thus included for assessment of reinfection. Ethical approval was granted by the Swedish Ethical Review Authority in Gothenburg.
The HCoV strains HKU1, OC43, NL63, or 229E were detected in 2162/78 135 (3%) samples from 1982 unique patients. HCoV accounted for 7% of samples positive for any virus. In agreement with the report by Monto et al [1], OC43 was the most prevalent HCoV (40%). Of the patients with an initial HCoV-positive test result, 470 had at least 1 additional sample taken >50 days later. In 47 samples, from 40 patients, HCoV was detected in these later samples. Six of the 40 patients tested positive for the same type of HCoV (NL63 n = 3, HKU1 n = 2, and OC43 n = 1). The mean times from first to recurrent infection with the same HCoV or a new HCoV were 676 and 566 days, respectively. One case of reinfection with the same HCoV and 18 reinfections with another HCoV were diagnosed within 1 year after the first infection.
Five of the 6 patients who were reinfected with the same HCoV were children or adolescents (mean age, 14 years; range, 2–17) and 4 of those had 1 or several comorbidities such as chronic lung disease (n = 3), cancer (n = 1), and/or compromised immunity caused by disease or therapy (n = 4). Patients who were reinfected by a new species of HCoV were older (mean age, 32 years; range, 1–82; P = .037). We did not observe a significant difference in the frequency of severe comorbidity between reinfected patients carrying the same versus a new HCoV.
Reinfection was significantly more likely to occur with a new rather than the same HCoV species (χ 2 goodness-of-fit P = .012; Table 1). While 9% of follow-up samples showed reinfection with a new HCoV, only 1% indicated reinfection with the same HCoV. These results imply that strain-specific protective immunity is achieved after HCoV infection. Notably, however, our results also suggest that recurrent infections with the same HCoV strain occur [3] and that these infections may be more common in younger immunocompromised patients.
Table 1.
Recurrent Human Coronaviruses (HCoV) Infections of the Respiratory Tract
| HCoV | Reinfection With the Same HCoV | Reinfection With a New HCoVa | P Value | ||
|---|---|---|---|---|---|
| Observed | Expected | Observed | Expected | ||
| OC43 | 1 | 4.5 | … | … | |
| NL63 | 3 | 5.6 | … | … | |
| HKU1 | 2 | 3.0 | … | … | |
| 229E | 0 | 0.4 | … | … | |
| All | 6 | 13.5 | 41 | 33.5 | P = .012b |
aOne patient tested positive for the same HCoV in a second sample and another HCoV in a third sample.
bThe χ 2 test was used to calculate the difference between observed and expected numbers of reinfections with the same or a new HCoV.
A limitation to this study was that it did not allow for systematic long-term follow-up. Our results suggest that reinfection with the same species of HCoV is infrequent and usually does not occur until >1 year after the first infection.
Notes
Financial support. This work was supported by the Swedish Cancer Society and the Swedish State through an agreement with Sahlgrenska University Hospital.
Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References
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