SARS-CoV-2 infection induces cross-reactive autoantibodies against angiotensin II, Quote: “These results demonstrate that anti-AngII autoantibodies can be induced in mice by vaccination against Spike or RBD in the absence of SARS-CoV-2 infection” ( lower blood oxygenation, blood pressure dysregulation )

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Abstract

Patients infected with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV- 2) can experience life-threatening respiratory distress, blood pressure dysregulation and thrombosis. This is thought to be associated with an impaired activity of angiotensin- converting enzyme-2 (ACE-2), which is the main entry receptor of SARS-CoV-2 and which also tightly regulates blood pressure by converting the vasoconstrictive peptide angiotensin II (AngII) to a vasopressor peptide. Here, we show that a significant proportion of hospitalized COVID-19 patients developed autoantibodies against AngII, whose presence correlates with lower blood oxygenation, blood pressure dysregulation, and overall higher disease severity. Anti-AngII antibodies can develop upon specific immune reaction to the SARS-CoV-2 proteins Spike or RBD, to which they can cross- bind, suggesting some epitope mimicry between AngII and Spike/RBD. These results provide important insights on how an immune reaction against SARS-CoV-2 can impair blood pressure regulation.

Competing Interest Statement

P.S.B., J.A.H. and M.A.S. are named as inventors on US Provisional Patent 63/123,199, filed December 9, 2020, relating to measurement of anti-AngII in immune response. The University of Chicago has filed a patent application relating to anti-SARS-CoV-2 antibodies generated by P.C.W., H.L.D., and C.T.S. as co-inventors.

Funding Statement

This study was funded by the University of Chicago, through the Chicago Immunoengineering Innovation Center, the Chicago Biomedical Consortium and the University of Chicago Big Ideas Generator for COVID research. S.R.J. was supported by the T32 CA009566.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The IRB of the University of Chicago, Department of Medicine gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv



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