Pre-COVID-19 humoral immunity to common coronaviruses does not confer cross-protection against SARS-CoV-2
First Author: Makoto Miyara et al.
Journal/preprint name: medRxiv
Paper DOI: https://doi.org/10.1101/2020.08.14.20173393
Tags: immunity, antibodies, cross-reactivity, coronaviruses
By analysing the serum of 76 healthy donors from 2015, Miyara et al., demonstrate the widespread presence (ca 8%) in the COVID19-naive population of cross-reactive antibodies against SARS-Cov-2. These antibodies were mainly against Spike, the spike S2 subunit, and nucleocapsid proteins, and no reactivity against the SARS-CoV-2 Receptor Binding Domain was detected in the healthy donors or in pooled intravenous immunoglobulins (IVIG). None of the pre-existing antisera had in vitro neutralizing activity against SARS-Cov-2, possibly because they fail to target RBD. Also, the serum of seven out of eight severe COVID19 patients analysed had pre-existing antibodies against other coronaviruses suggesting that these do not provide protection against severe SARS-Cov-2 infection
A substantial percentage of the population has pre-existing antibodies against coronavirus
Pre-existing antibodies do not bind SARS-CoV-2 RBD
Pre-existing antibodies fail to neutralize SARS-Cov-2 in vitro
Pre-existing antibodies do not protect against severe COVID19 infection
Impact for COVID-19 research:
This study shows how IVIG prepared before the SARS-Cov-2 pandemic would not be useful to fight the disease but, in pooled IVIG, even a small amount of convalescent patient’s serum is enough to neutralize the virus in vitro.
The study indicates how the serological tests that look at previous SARS-Cov-2 infection should focus on the anti-RBD antibodies to avoid false positives
Study Type: in vitro, patient samples
Important cell lines/viral models used:
Key Techniques: neutralisation assay
The study fails to identify which are exactly the antibodies found in the population that are cross-reactive for SARS-Cov-2. This could be done by isolation of individual B cell clones reactive with SARS-CoV-2 antigens. Because of this they cannot exclude that specific clones found in the healthy population could neutralize SARS-CoV-2 and help fight the infection, although they show that none of the pooled healthy donor samples can neutralize the virus in vitro.
They fail to acknowledge that cross-reactive antibodies from a different coronavirus had been found to be neutralizing (https://www.biorxiv.org/content/10.1101/2020.05.14.095414v1)