ABSTRACT
Clinical and experimental data indicate that severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection is associated with significant changes in the composition and function of intestinal microbiota. However, the relevance of these effects for SARS-CoV-2 pathophysiology is unknown. In this study, we analyzed the impact of microbiota depletion after antibiotic treatment on the clinical and immunological responses of K18-hACE2 mice to SARS-CoV-2 infection. Mice were treated with a combination of antibiotics (kanamycin, gentamicin, metronidazole, vancomycin, and colistin, Abx) for 3 days, and 24 h later, they were infected with SARS-CoV-2 B lineage. Here, we show that more than 80% of mice succumbed to infection by day 11 post-infection. Treatment with Abx had no impact on mortality. However, Abx-treated mice presented better clinical symptoms, with similar weight loss between infected-treated and non-treated groups. We observed no differences in lung and colon histopathological scores or lung, colon, heart, brain and kidney viral load between groups on day 5 of infection. Despite some minor differences in the expression of antiviral and inflammatory markers in the lungs and colon, no robust change was observed in Abx-treated mice. Together, these findings indicate that microbiota depletion has no impact on SARS-CoV-2 infection in mice.
Subject(s)
COVID-19 Drug Treatment , Microbiota , Angiotensin-Converting Enzyme 2 , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Disease Models, Animal , Melphalan , Mice , Mice, Transgenic , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , gamma-GlobulinsABSTRACT
The persistent circulation of SARS-CoV-2 represents an ongoing global threat due to the emergence of new viral variants that can sometimes evade the immune system of previously exposed or vaccinated individuals. We conducted a follow-up study of adult individuals that had received an inactivated SARS-CoV-2 vaccine, evaluating antibody production and neutralizing activity over a period of 6 months. In addition, we performed mice immunization with inactivated SARS-CoV-2, and evaluated the immune response and pathological outcomes against Gamma and Zeta variant infection. Vaccinated individuals produced high levels of antibodies with robust neutralizing activity, which was significantly reduced against Gamma and Zeta variants. Production of IgG anti-S antibodies and neutralizing activity robustly reduced after 6 months of vaccination. Immunized mice demonstrated cellular response against Gamma and Zeta variants, and after viral infection, reduced viral loads, IL-6 expression, and histopathological outcome in the lungs. TNF levels were unchanged in immunized or not immunized mice after infection with the Gamma variant. Furthermore, serum neutralization activity rapidly increases after infection with the Gamma and Zeta variants. Our data suggest that immunization with inactivated WT SARS-CoV-2 induces a promptly responsive cross-reactive immunity response against the Gamma and Zeta variants, reducing COVID-19 pathological outcomes.
Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccines, Inactivated/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Cross Protection , Cytokines/metabolism , Follow-Up Studies , Humans , Immunization , Lung/metabolism , Lung/pathology , Mice , Vaccines, Inactivated/administration & dosage , Viral LoadABSTRACT
At some point in history, medicine was integrated with pathology, more precisely, with pathological anatomy [...].
