CD4 + T cells are central to long-term immunity against viruses through the functions of T helper-1 (Th1) and T follicular helper (Tfh) cell subsets. To better understand the role of these subsets in COVID-19 immunity, we conducted a longitudinal study of SARS-CoV-2-specific CD4 + T cell and antibody responses in convalescent subjects who seroconverted during the first wave of the pandemic in Boston, Massachusetts, United States, across a range of COVID-19 disease severities. Analyses of spike (S) and nucleocapsid (N) epitope-specific CD4 + T cells using peptide and major histocompatibility complex class II (peptide:MHCII) tetramers demonstrated expanded populations of T cells recognizing the different SARS-CoV-2 epitopes in most subjects compared to pre-pandemic controls. Individuals who experienced a milder disease course not requiring hospitalization had a greater percentage of circulating Tfh (cTfh) and Th1 cells among SARS-CoV-2-specific cells. Analysis of SARS-CoV-2-specific CD4 + T cells responses in a subset of individuals with sustained anti-S antibody responses following viral clearance also revealed an increased proportion of memory cTfh cells. Our findings indicate efficient early disease control also predicts favorable long-term adaptive immunity.

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Since phase-out of highly persistent perfluorosulfonates in the U.S. from non-stick and stain-resistant products in the early 2000s, perfluorobutanesulfonic acid (PFBS) has replaced these compounds as a primary surfactant. Measurements of PFBS in environmental and human samples have been rising in recent years, raising concerns about potential negative health effects. We previously found that embryonic exposures to a related compound, perfluorooctanesulfonic acid (PFOS), decreased pancreas length and insulin-producing islet area in zebrafish embryos (Danio rerio). The objective of this study was to compare the effects of PFBS exposures on pancreatic organogenesis with our previous PFOS findings. Dechorionated zebrafish embryos from two different transgenic fish lines (Tg(insulin:GFP), Tg(ptf1a:GFP)) were exposed to 0 (0.01% DMSO), 16, or 32 µM PFBS daily beginning at 1 day post fertilization (dpf) until 4 and 7 dpf when they were examined using fluorescent microscopy for islet area and morphology, and exocrine pancreas length. PFBS-exposed embryos had significantly increased caudal fin deformities, delayed swim bladder inflation, and impaired yolk utilization. Incidence of fish with significantly stunted growth and truncated exocrine pancreas length was significantly increased, although these two effects occurred independently. Islet morphology revealed an increased incidence of severely hypomorphic islets (areas lower than the 1st percentile of controls) and an elevated occurrence of fragmented islets. RNA Seq data (4 dpf) also identify disruptions in regulation of lipid homeostasis. Overall, this work demonstrates that PFBS exposure can perturb embryonic development, energy homeostasis, and pancreatic organogenesis.