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Cell Studies on MIS-C, Acute SARS-CoV-2 Adaptive Immunity, Maternal Microbe Transplant

Researchers from the Icahn School of Medicine at Mount Sinai describe cytokine shifts and other inflammation and immune features found in SARS-CoV-2-infected children who develop multisystem inflammatory syndrome (MIS-C). Using mass cytometry, antibody-based cytokine assays, enzyme-linked immunosorbent assays, phage immunoprecipitation sequencing, and other approaches, the team characterized peripheral blood immune cell features in nine children or young adults from the New York City area with documented SARS-CoV-2 exposures and compared them with four pediatric controls with other types of infection. "While the immune signature of MIS-C partially overlapped with that of COVID-19, it could ultimately be distinguished as a distinct immune pathology," the authors report, noting that "definitive conclusions were limited by the absence of acute COVID-19 samples from age-matched, otherwise healthy children — a population which goes clinically undetected."

A La Jolla Institute for Immunology- and University of California, San Diego-led team takes a look at antigen-specific adaptive immune features in individuals with acute SARS-CoV-2 infections. The researchers relied on flow cytometry, immune cell assays, and other methods to assess CD4+ and CD8+ T cells and neutralizing antibody features in dozens of individuals with acute, prior, or unrelated infections and in uninfected control individuals. Their findings pointed to T cell features with ties to milder disease, along with altered, "uncoordinated" CD4+ and CD8+ T cell responses in individuals over 65 years old or with particularly poor SARS-CoV-2 outcomes. From these and other findings, the authors argue that "vaccine approaches that elicit antiviral SARS-CoV-2-specific CD4+ and CD8+ T cells in coordination with neutralizing antibodies will generate protective immunity that [is] most closely analogous to the coordinated adaptive antiviral immune response seen in most cases of COVID-19 following natural SARS-CoV-2 infection."

Finally, investigators in Finland and the Netherlands identify potentially beneficial microbes in fecal samples from new mothers that are proposed to boost gut microbiome development in infants born by caesarean section. For their small proof-of-principle analysis, the researchers used 16S ribosomal rRNA gene sequencing to characterize fecal microbiome representatives in seven mothers and cesarean section-born infants who received diluted fecal microbiota transplants (FMT) from their mothers that were delivered via milk. Over the first few months of life, the results hint that the FMT approach may push infant fecal microbiomes closer to those found in babies born vaginally, the authors report, though they caution that "this should only be done after careful clinical and microbiological screening."