COVID-19 – Immune defense and antiviral strategies for prevention and treatment

The SARS-CoV-2 pandemic is of historic proportions and associated with exceptional morbidity and mortality. To effectively contain and minimize an outbreak of a novel virus, it is important to study intervention strategies from different angles. Within the scope of the present work, we conducted studies investigating COVID-19 on the level of prevention, therapy, and immunity.

SARS-CoV-2 can be transmitted through aerosols containing viral particles and through virus-contaminated surfaces. We tested two commercially available UVC-LED disinfection boxes for their ability to inactivate high viral loads of SARS‑CoV‑2 on materials representative of personal item surfaces. The UVC-LED boxes effectively inactivated SARS-CoV-2 on glass, metal, and plastic surfaces after 3 minutes of irradiation. Our results showed that UVC-LED boxes can be an affordable and environmentally friendly option for disinfecting personal items.

Next, we tested the antiviral activity of curcumin from turmeric root and glycyrrhizin from licorice root against SARS-CoV-2. We showed that curcumin and glycyrrhizin effectively neutralized SARS-CoV-2 with a half-maximal effective concentration (EC50) of 7.9 µg/mL (21.5 µM) and an EC50 of 440 µg/mL (534.7 µM), respectively. Both natural products effectively reduced SARS-CoV-2 RNA levels in cell culture. Furthermore, we discovered glycyrrhizin as an inhibitor of the SARS-CoV-2 main protease (Mpro). We identified curcumin and glycyrrhizin as promising compounds for complementary treatment of COVID-19 that require further investigation in large-scale randomized controlled trials.

The reduced neutralization activity of sera from vaccinated individuals against newly emerging SARS-CoV-2 variants of concern (VOCs) led to an increase in vaccine breakthrough infections. We showed strongly reduced neutralizing activity of sera from vaccinated people and patients with SARS-CoV-2 breakthrough infection against the Omicron sub-variants BA.1 and BA.5. Furthermore, vaccine breakthrough infections with Delta and BA.1, but not BA.5, boosted immunity against SARS-CoV-2 in a variant specific manner. In addition, we showed that kidney transplant (KTX) patients might be partly protected against SARS-CoV-2 after booster vaccination by IL-2 producing T cells or neutralizing antibodies. After treatment with convalescent plasma, we found an increase of antibodies and IFN‐γ secreting T cells against SARS-CoV-2 in KTX and hemodialysis patients. In summary, we showed that vaccine breakthrough infections can enhance vaccination-acquired immunity against SARS-CoV-2 in immunocompetent individuals. Immunocompromised patients might benefit from booster vaccination and treatment with convalescent plasma.


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