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Review 1: "Development of antibodies to pan-coronavirus spike peptides in convalescent COVID-19 patients"

This study investigates whether antibodies present in COVID19 patients cross-react with spike proteins from other coronaviruses and demonstrates activity against MERS-CoV. Implications of these findings are narrow due to limited testing and poorly described methods.

Published onOct 02, 2020
Review 1: "Development of antibodies to pan-coronavirus spike peptides in convalescent COVID-19 patients"
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key-enterThis Pub is a Review of
Development of antibodies to pan-coronavirus spike peptides in convalescent COVID-19 patients

Coronaviruses are sharing several protein regions notable the spike protein (S) on their enveloped membrane surface, with the S1 subunit recognizing and binding to the cellular receptor, while the S2 subunit mediates viral and cellular membrane fusion. This similarity opens the question whether infection with one coronavirus will confer resistance to other coronaviruses? Investigating patient serum samples after SARS-CoV-2 infection in cross-reactivity studies of immunogenic peptides from Middle East respiratory syndrome coronavirus (MERS-CoV), we were able to detect the production of antibodies also recognizing MERS virus antigens. The cross-reactive peptide comes from the heptad repeat 2 (HR2) domain of the MERS virus spike protein. Indeed, the peptide of the HR2 domain of the MERS spike protein, previously proven to induce antibodies against MERS-CoV is sharing 74% homology with the corresponding sequence of SARS-CoV-19 virus. Sera samples of 47 convalescent SARS-CoV-2 patients, validated by RT-PCR-negative testes 30 days post-infection, and samples of 40 sera of control patients (not infected with SARS-CoV-2 previously) were used to establish eventual cross-bind reactivity with the MERS peptide antigen. Significantly stronger binding (p<0.0001) was observed for IgG antibodies in convalescent SARS-CoV-2 patients compared to the control group. If used as an antigen, the peptide of the HR2 domain of the MERS spike protein allows discrimination between post-Covid populations from non-infected ones by the presence of antibodies in blood samples. This suggests that polyclonal antibodies established during SARS-CoV-2 infection has the ability to recognize and probably decrease infectiveness of MERS-CoV infections as well as other coronaviruses. The high homology of the spike protein domain suggests in addition that the opposite effect can also be true: coronaviral infections producing cross-reactive antibodies affective against SARS-CoV-19. The collected data prove in addition that despite the core HR2 region being hidden in the native viral conformation, its exposure during cell entry makes it highly immunogenic. Since inhibitory peptides to this region were previously described, this opens new possibilities in fighting coronaviral infections.

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.



- I think the English grammar should be slightly improved at some points, for better clarity in the exposed concepts.

- The beginning of the abstract is a bit confusing. You can say that “Protein regions like that of the spike protein in corona viruses are conserved among their member species like SARS-CoV, SARS-CoV-2 and MERS.”

- Instead of writing that consent was taken for every person, you can write that written consent was taken for the patients considered for the study.

- In the methodology section the bioinformatics can be replaced by in-silico approaches or computational methods."

- In the reference section, inconsistencies are found like Science (80-.)

- The discussion section seems incomplete.

- No conclusion is present.

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