key: cord-0832814-90lqqwer
authors: Ma, Zhongren; Li, Pengfei; Ikram, Aqsa; Pan, Qiuwei
title: Does Cross-Neutralization of SARS-CoV-2 Only Relate to High Pathogenic Coronaviruses?
date: 2020-08-08
journal: Trends Immunol
DOI: 10.1016/j.it.2020.08.002
sha: 20b5e3463bb4e0818c8952167f30ca95b8d70618
doc_id: 832814
cord_uid: 90lqqwer

nan

Production of antibodies in response to viral infections constitutes an essential feature of adaptive immunity. Great efforts have been dedicated to characterize antibody responses in patients with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A recent article by Jiang et al, published in Trends in Immunology discussed the state of research and development of neutralizing antibodies for the prevention and treatment of COVID-19, with a specific emphasis on cross-reactivity with other two highly pathogenic human coronaviruses, SARS-CoV and MERS-CoV [1] . However, the authors of this article largely disregarded the potential cross-reactive immunity triggered by the prevalence of low pathogenic human coronaviruses (LPH-CoV).

Coronaviruses are a large family of RNA viruses circulating among a wide range of animal species. Seven types of coronaviruses naturally infect humans, although all of them were thought to originate from animals [2] . The three highly pathogenic coronaviruses including MERS-CoV, SARS-CoV and SARS-CoV-2 can cause severe acute respiratory diseases in humans. In contrast, the four genotypes of LPH-CoV, including OC43, HKU1, 229E and NL63, usually only cause mild and self-limiting respiratory tract Letter relevant especially in regions where the number of SARS-CoV-2 cases are low (e.g.

outside of an epicenter), and where false-positivity can be caused by cross-reactivity to anti-LPH-CoV antibodies, likely drastically overestimating the real prevalence rates [9] .

It remains unproven whether such cross-reactivity could functionally neutralize SARS-CoV-2 infection. If it does provide cross-protective effects against SARS-CoV-2 to some extent --either by preventing infection or by mitigating pathogenesis --this would have a fundamental impact on the COVID-19 pandemic because LPH-CoV infection is extremely common in humans. The global incidence of upper respiratory infections is several billion episodes per year, and among these, over 5% are LPH-CoV infections [3] .

In addition, viral antigen triggered antibodies are usually long-lived and infection with OC43 or 229E effectively triggers IgG antibody production, which peaks two weeks postinfection [10] . And, although the antibody titers appear to wane gradually, they persist for at least one year [10] . Therefore, a large proportion of the global population should be seropositive to LPH-CoV.

LPH-CoV have a clear seasonal feature, in that they are more prevalent in the winter time based on studies from countries in the northern hemisphere [3] . It would be interesting to monitor whether this seasonal frequency might have an impact on the possible seasonality of SARS-CoV-2. It is also intriguing that LPH-CoV appear to be highly prevalent in young children. Thus, it will be relevant to investigate whether this prevalence can influence in any way the clinical features of COVID-19, whereby most children appear to be hardly affected by SARS-CoV-2 infection [3, 11] . In the clinic, intravenous immunoglobulin (IVIG) has been explored to treat COVID-19 patients, showing some evidence of clinical benefits [12] . Because IVIG is a pool of 

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