The effect of the immune response to SARS-CoV-2 S protein on angiotensin II levels in rats

Autoantibodies against key molecules of the renin-angiotensin system (RAS) are found in some patients infected with SARS-CoV-2. These autoantibodies include antibodies against angiotensin II and angiotensin converting enzyme 2 (ACE2). The presence of antibodies to the RAS-related molecules is associated with episodes of hypotension or hypertension. The aim of this work was to study the effect of antibodies to SARS-CoV-2 S protein and autoantibodies to ACE2 on angiotensin II levels in a model of induced multiple organ damage caused in rats by immunization with SARS-CoV-2 S protein. The effect of pre-existing autoimmune encephalomyelitis on change in angiotensin II level caused by immunization with S protein is also was studied. Wistar rats were immunized with S protein of SARS-CoV-2 emulsified in incomplete Freund’s adjuvant (IFA). At the time of injection of S protein 6 of the rats were intact (S group), in 4 of the rat experimental autoimmune encephalomyelitis was previously induced by immunization with guinea pig myelin basic protein (EAE + S group). The control group of rats was injected with IFA. Antibodies to S protein, autoantibodies to ACE2, and angiotensin II level were determined in blood plasma by enzyme linked immunosorbent assay. It was found that immunization with S protein leads to a transient decrease in the blood level of angiotensin II. The blood angiotensin II level was lower than normal in 3 out of 6 rats (50%) in group S, and in 3 out of 4 (75%) in the EAE + S group at week 6 after immunization. The decrease in angiotensin II level was significant in the EAE + S group relative to the control group (ANOVA, p = 0.0423). A deeper decrease in the angiotensin II level in the blood of EAE + S group than in S group was associated with a higher level of antibodies to S protein: the level of antibodies to S protein was significantly higher in the EAE + S group for 1-6 weeks after immunization with S protein compared to the S group of rats. Immunization of rats with S protein did not cause the production of anti-ACE2 autoantibodies in the EAE + S group, and in the S group it was weak and was not accompanied by an increase in angiotensin II levels. Thus, in rats immunized with S protein, a transient decrease in the level of angiotensin II was detected at the peak of production of antibodies to S protein, which may indicate that antibodies to S protein may contribute to a decrease in angiotensin II level in SARS-CoV-2 infection. In addition, pre-existing autoimmune disease leads to a stronger response to S protein, accompanied by a stronger decrease in angiotensin II level.