Human seasonal coronavirus neutralization and COVID‐19 severity

The virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), responsible for the global coronavirus disease‐2019 (COVID‐19) pandemic, spread rapidly around the world causing high morbidity and mortality. However, there are four known, endemic seasonal coronaviruses in humans (HCoVs), and whether antibodies for these HCoVs play a role in severity of COVID‐19 disease has generated a lot of interest. Of these seasonal viruses NL63 is of particular interest as it uses the same cell entry receptor as SARS‐CoV‐2. We use functional, neutralizing assays to investigate cross‐reactive antibodies and their relationship with COVID‐19 severity. We analyzed the neutralization of SARS‐CoV‐2, NL63, HKU1, and 229E in 38 COVID‐19 patients and 62 healthcare workers, and a further 182 samples to specifically study the relationship between SARS‐CoV‐2 and NL63. We found that although HCoV neutralization was very common there was little evidence that these antibodies neutralized SARS‐CoV‐2. Despite no evidence in cross‐neutralization, levels of NL63 neutralizing antibodies become elevated after exposure to SARS‐CoV‐2 through infection or following vaccination.