COVID-19, G protein-coupled receptor, and renin-angiotensin system autoantibodies: Systematic review and meta-analysis.

INTRODUCTION

There are an increasing number of reports of autoantibodies (AAbs) against host proteins such as G-protein coupled receptors (GPCRs) and the renin-angiotensin system (RAS) in COVID-19 disease. Here we have undertaken a systematic review and meta-analysis of all reports of AAbs against GPCRs and RAS in COVID-19 patients including those with long-COVID or post-COVID symptoms.

METHODS

PubMed, Embase, Web of Science, and Scopus databases were searched to find papers on the role of GPCR and RAS AAbs in the presence and severity of COVID-19 or post- COVID symptoms available through March 21, 2023. Data on the prevalence of AngII or ACE, comparing AngII or ACE between COVID-19 and non-COVID-19, or comparing AngII or ACE between COVID-19 patients with different disease stages were pooled and a meta-analysed using random- or fixed-effects models were undertaken.

RESULTS

The search yielded a total of 1042 articles, of which 68 studies were included in this systematic review and nine in the meta-analysis. Among 18 studies that investigated GPCRs and COVID-19 severity, 18 distinct AAbs were detected. In addition, nine AAbs were found in case reports that assessed post- COVID, and 19 AAbs were found in other studies that assessed post- COVID or long- COVID symptoms. Meta-analysis revealed a significantly higher number of seropositive ACE2 AAbs in COVID-19 patients (odds ratio = 7.766 [2.056, 29.208], p = 0.002) and particularly in severe disease (odds ratio = 11.49 [1.04, 126.86], p = 0.046), whereas AngII-AAbs seropositivity was no different between COVID-19 and control subjects (odds ratio = 2.890 [0.546-15.283], p = 0.21).

CONCLUSIONS

GPCR and RAS AAbs may play an important role in COVID-19 severity, the development of disease progression, long-term symptoms COVID and post- COVID symptoms.