key: cord-0927893-n9sb3x0m
authors: Ringlander, Johan; Martner, Anna; Nilsson, Staffan; Westin, Johan; Lindh, Magnus; Hellstrand, Kristoffer
title: Verified infections with endemic common cold coronaviruses do not entail significant protection against SARS-CoV-2
date: 2021-03-29
journal: J Infect Dis
DOI: 10.1093/infdis/jiab089
sha: c20ba6215fe9f4efb6e3811b498aa1beba5dbee0
doc_id: 927893
cord_uid: n9sb3x0m

nan

Several recent studies have proposed the existence of immune cross-reactivity between human common cold coronaviruses (CCCoV) and SARS-CoV-2. Humans unexposed to SARS-CoV-2 may harbor antibodies that neutralize SARS-CoV-2 in cell culture (1) along with T-cells that recognize epitopes shared between SARS-CoV-2 and CCCoVs (2, 3) . Henns et al. (4) detected neutralizing antibodies against the NL63 CCCoV in serum from subjects with mild COVID-19, but not in those with severe disease. On the other hand, Schwaiger et al. (5) reported that antibodies against CCCoVs had low functional avidity for SARS-CoV-2, which argues against clinically relevant cross-reactivity. These and other recent reports (6) emphasize that additional studies are required to determine whether or not cross-reactivity translates into clinically relevant cross-immunity.

Previous studies suggest that prior verified human respiratory infections with any of the four endemic CCCoV (HKU1, OC43, NL63 and 229E) induce long-term protection against infection with the same (homologous) strain of CCCoV (7, 8) . In accordance, we reported that homologous infections of humans with CCCoV are approximately 10 times less common than heterologous infections (9), thus implying that infection with CCCoV entails significant protective immunity against the homologous virus. Analysis of the risk and severity of SARS-CoV-2 infection in patients with verified previous CCCoV infections might, therefore, inform the degree of clinically relevant cross-immunity.

We interrogated a database of >75,000 respiratory samples from >50,000 patients with respiratory tract infection diagnosed during 2013-2020. The database contains results from analyses of 18 respiratory pathogens using real-time PCR (rtPCR), including the four A c c e p t e d M a n u s c r i p t endemic CCCoV described elsewhere (10) . Among patients in the database, we assessed the risk of subsequent SARS-CoV-2 infection, as determined by rtPCR detection of SARS-CoV-2 RNA in respiratory specimens or by the presence of IgG antibodies in blood against the nucleocapsid (Architect, Abbott, Abbott Park, IL, USA) and the nucleocapsid/spike protein (iFlash, YHLO, Shenzhen, China) of SARS-CoV-2. More than 100,000 patients were tested for SARS-CoV-2 at our department during February to November 2020 and of those, 8, 298 had at least one previous result in the above-referenced respiratory tract infection database prior to the COVID-19 pandemic. We also utilized hospital records to determine the severity of COVID-19 disease (hospitalization/intensive care unit referral or not). The proportion of SARS-CoV-2 positivity among patients with previous respiratory infections was compared against patients with no previously verified infection using chi2-tests. The study was approved by the Swedish Ethical Review Board (application no. 2020-03276).

As shown in Table 1 (Table 1) .

Additionally, the amount of SARS-CoV-2 in respiratory samples of patients with previously confirmed CCCoV infections [7.2  2.07 log 10 viral particles/swab (mean  standard error of the mean, range 2.9-9.6)] did not differ significantly from that of patients with previous A c c e p t e d M a n u s c r i p t M a n u s c r i p t Hospitalized after at least one positive respiratory sample of SARS-CoV-2 (RT-PCR). Forty-five patients were SARS-CoV-2-positive but had no information regarding hospitalization. g OR and 95% CI for hospitalization after diagnosis of SARS-CoV-2 where the OR for patients with no previous infections was set to 1.

Preexisting and de novo humoral immunity to SARS-CoV-2 in humans

Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

Low avidity CD4+ T cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19

Analysis of Humoral Immune Responses in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Neutralization by Intravenous Immunoglobulins Produced From Plasma Collected Before the 2020 Pandemic

Recent endemic coronavirus infection is associated with less-severe COVID-19

The time course of the immune response to experimental coronavirus infection of man

Seasonality and immunity to laboratory-confirmed seasonal coronaviruses (HCoV-NL63, HCoV-OC43, and HCoV-229E): results from the Flu Watch cohort study

Low Incidence of Reinfection With Endemic Coronaviruses Diagnosed by Real-Time PCR

Multiplex real-time PCR for detection of respiratory tract infections