Author(s): Erpenbach K*, Erpenbach AS, Mayer W and Seidl H
ABSTRACT
Background/Introduction: The SARS-CoV-2 B.1.1.529 variant (Omicron) has shown high infectivity worldwide, even in vaccinated patients. Little is known about how well naturally acquired immunity protect against further COVID-19 infections in unvaccinated or vaccinated patients. We investigated whether vaccination is still warranted, and if so, what type of vaccine should be used.
Methods: 36 patients with previous PCR-confirmed SARS-CoV-2-omicron infection (10 unvaccinated, 10 with Valneva booster vaccination and 16 triple vaccinated with mRNA), were included in this six-month prospective observational study from Oct2022 to Mar2023. SARS-CoV-2-Omicron immune status (SARS-CoV-2 immunoblot nucleoprotein IgG (BLOT-NP)) was analyzed four weeks after acute illness or Valneva booster vaccination, along with neutralizing antibodies IgG-S1 spike (NAB-S1) and T-cell response interleukin2 (ITT-BA5-IL2) or interferon (ITT-BA5-IFN) against Omicron-BA5 in blood samples. Endpoint at follow-up was PCR-confirmed reinfection with a SARS-CoV-2 variant. Wilcoxon-, Pearson-Chi-Square- and Whitney-U-tests were used for statistical analysis. p≤0.05 was assumed to be significant and p≤0.01 highly significant.
Results: The ten patients in the Valneva group, all older than 60 years (75.4 ± 13.3 y) showed no persisting humoral or cellular immunity to SARS-CoV-2-Omicon in their blood at baseline. These patients were boosted with inactivated whole virus vaccine VLA2001 against SARS-CoV-2. Immunity was fully restored within 4 weeks (BLOT-NP before 0 vs. after 1.2 ± 1.2 [p=0.026], ITT-BA5-IL2 before 5.7 ± 7.5 pg./mL vs. after 11.2 ± 9.9 pg./mL [p=0.063], ITT-BA5-IFN before 1.7 ± 2.6 pg./mL vs. after 5.5 ± 4.5 pg./mL
[p=0.011]). There were no side effects of vaccination. Compared to the group of unvaccinated patients (N=10) or the triple mRNA-vaccinated patients (N=16), patients in the Valneva group suffered fewer reinfections with a SARS-CoV-2 variant during follow-up (40% vs. 25% vs. 20% [p=0.575]). All patients reinfected with SARS-CoV-2 (N=10) had either a metabolic syndrome (N=5: diabetes mellitus and obesity) or a neuro-degenerative-psychiatric disease [N=5: dementia (2), anxiety disorder (2), depression (1)]. In the BLOT-NP, patients with reinfection showed a significantly poorer immune response compared to patients without reinfection, both in the group of unvaccinated patients and in the group of Valneva-vaccinated patients, but not in the group of mRNA-vaccinated patients (BLOT-NP reinfection yes vs. no unvaccinated: 0.5 ± 0.7 vs. 1.38 ± 1.30 [p=0.041] / Valneva-vaccinated: 1.0 ± 0.82 vs 2.32 ± 0.82 [p=0.046] / mRNA-vaccinated: 2.0 ± 0.82 vs 2.42 ± 0.79 [p=n’s.]). In ITT-BA5-IL2 and ITT-BA5-IFN, patients with reinfection showed significantly poorer cellular immunity to SARS-CoV-2-Omicron compared with patients without reinfection, not only within the Valneva-vaccinated group, but also in the groups of unvaccinated and mRNA-vaccinated patients (ITT-BA5-IL2 reinfection yes vs. no with Valneva vaccination vs. 0 vaccination vs. 3 vaccination: 0 vs. 14 ± 8.99 pg./ mL [p=0.036] / 4.75 ± 5.5 vs. 17.5 ± 26.82 pg./mL [p=n’s.] / 40.5 ± 31.98 vs. 47.25 ± 91.14 pg./mL [p=n’s.] - ITT-BA5-IFN reinfection yes vs. no with Valneva vaccination vs. 0 vaccination vs. 3 vaccination: 0 vs. 6.88 ± 3.83 pg./mL [p=0.034] / 2.5 ± 4.36 vs. 4.83 ± 4.88 pg./ml [p=n’s.] / 10.25 ± 8.18 vs. 30.17 ± 34.07 pg./mL [p=n’s.]).
Conclusion: Recurrent mutations of the SARS-CoV2 virus continue to cause acute infection, the current variant EG5 triggering significantly more severe COVID-19 symptoms than the previous variant Omicron BA5. Patients over 65 years of age with high-risk underlying illnesses and a lack of humoral protection (SARS-CoV-2 nucleoprotein IgG antibodies) as well as limited or no cellular protection (ITT-BA5-IFN) are highly likely to experience reinfection. In this prospective study the whole virus vaccination VLA2001 was found to be effective in restoring humoral or cellular immune protection. mRNA vaccination, on the other hand, failed to restore humoral immune protection (SARS-CoV-2 nucleoprotein IgG antibodies) and can therefore no longer be recommended for immune boosting.
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