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First Author:  Makoto Miyara et al. 

Journal/preprint name: medRxiv 

Tags: immunity, antibodies, cross-reactivity, coronaviruses 


Banalysing 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  

Research Highlights 

  1. A substantial percentage of the population has pre-existing antibodies against coronavirus  

  1. Pre-existing antibodies do not bind SARS-CoV-2 RBD  

  1. Pre-existing antibodies fail to neutralize SARS-Cov-2 in vitro 

  1. 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 patients 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 Typein 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 infectionalthough 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 (