SARS-CoV-2-Omicron-variant Induced COVID-19-Infection in Unvaccinated and Vaccinated Patients: Impact on Immune Response, Symptomatology, and Risk of POST-COVID Syndrome

Abstract

Worldwide, the SARS-CoV-2-omicron-variant (B.1.1.529) is highly infectious, even in vaccinated patients. Little is known about the duration of acute SARS-CoV-2-omicron-infection, severity of symptoms, immunologic response and development of POST-COVID-syndrome in unvaccinated compared to vaccinated patients after acute SARS-CoV-2 omicron infection. Methods: In 24 patients suffered from acute SARS-CoV-2-omicron infection (10 unvaccinated participants, 5 participants twice vaccinated and 9 participants getting three mRNA vaccinations), symptoms and duration of disease, SARS-CoV-2-omicron immune response, 25(OH)-vitamineD3 and vitamine C were determined in blood 4 weeks after acute infection. In addition, POST-COVID-symptoms and autoantibodies against G protein-coupled receptors in blood were determined 16 weeks after acute infection. Pearson correlations and one-way ANOVA were used. p≤0.05 was assumed to be significant, and p≤0.01 was assumed to be highly significant, respectively. Results: All 24 patients (age: 54 ± 12 years; 16 females - 8 males) complained of mild symptoms during acute omicron-COVID-19 infection. In vaccinated versus (vs) unvaccinated patients the disease duration was significantly prolonged (3.4-times vs 3.8-times). POST-COVID symptoms were reported by 50% of unvaccinated patients, 60%, and 78% of vaccinated patients, respectively. Vaccinated vs unvaccinated patients showed significantly larger number of POST-COVID-symptoms. Vitamin C deficiency was detectable in all patients 4 weeks after acute COVID-19 infection. The 25(OH) Vitamin D3 concentration was within the normal range in all patients. In the SARS-CoV2-immunoblot, the unvaccinated patients showed the same antibody level against the virus core protein (NP) virus compared with the vaccinated patients, but no antibody level against the linking protein (RBD) or the spike protein (S1). Also, unvaccinated vs vaccinated patients showed no immunological response in building neutralizing antibody level IgG-S1 [neutralizing antibody IgG-S1 (norm < 34 BAU/ml) at 0-vaccination vs 2-vaccination vs 3-vaccination = <34 vs 14584 ± 12012.4 vs 15116.7 ± 10997.9 BAU/ml]. 4 weeks after omicron-COVID-19-infection, patients getting 2-vaccination vs 3-vaccination before infection showed a significant 5.4fold vs 14.9fold activation of neutralizing antibody level IgG-S1 (neutralizing antibody IgG-S1 (norm < 34 BAU/ml) in 2-vaccination vs 3-vaccination patients - before / after infection = 2678.5 ± 3454.1 / 14584 ± 12012.4 vs 1012.9 ± 918.5 vs 15116.7 ± 10997.9 BAU/ml). The level of neutralizing antibody IgG-S1 after acute Omicron-COVID-19 infection correlates significantly with the duration of disease. All patients showed a cellular immune response against the SARS-CoV-2-omicron variant in the immune tolerance test (ITT) being significantly more robust in vaccinated vs. unvaccinated patients (ITT-Omicron IL2 / IFN at 0-vaccination vs. 2-vaccination vs. 3- vaccination = 14.8 ± 23.4 / 4.0 ± 4.8 vs. 34.4 ± 28.8 / 21.2 ± 13.0 vs 59.9 ± 103.8 / 29.3 ± 40.0 pg/ml). Autoantibodies level against G-protein coupled receptors are twice as strong in 3-dose vaccinated vs unvaccinated patients. Autoantibody level of ß1-adrenergic receptor or M3-muscarinergic-choline-receptor and the level of cellular immune response ITT-omicron-IL2 significantly correlate with the risk of developing POST-COVID syndrome. Conclusion: Acute SARS-CoV-2-omicron infection causes mild disease in both unvaccinated and vaccinated patients. However, vaccinated patients experienced prolonged disease with each vaccination. Unvaccinated patients showed no level of neutralizing antibodies to IgG-S1 spike compared with vaccinated patients after acute Omicron-COVID-19 infection, which is led back to multiple mutations in the region of the spike genome in the Omicron variant. Acute Omicron-COVID-19 infection after mRNA vaccination increases the risk of a strong immune response (neutralizing antibodies IgG-S1 spike, antibodies IgG-RBD, T-cellular response in IL2 and IFN, Autoantibodies to G-protein coupled receptor ß1-ß2-M2-M3) which correlates with the risk of POST-COVID syndrome. A deficiency of immune modulating micronutrients (vitamin C, vitamin D3, selenium, zinc) might be responsible. Further studies treating POST-COVID patients with high-dose micronutrient infusion are necessary proving to reduce or eliminate the symptoms in POST-COVID patients