RESUMEN
We evaluated the clinical and socioeconomic burdens of respiratory disease in a cohort of Guatemalan banana plantation workers. All eligible workers were offered enrollment from June 15-December 30, 2020, and annually, then followed for influenza-like illnesses (ILI) through: 1) self-reporting to study nurses, 2) sentinel surveillance at health posts, and 3) absenteeism. Workers with ILI submitted nasopharyngeal swabs for influenza, RSV, and SARS-CoV-2 testing, then completed surveys at days 0, 7, and 28. Through October 10, 2021, 1,833 workers developed 169 ILIs (12.0/100 person-years) and 43 (25.4%) of these ILIs were laboratory-confirmed SARS-CoV-2 (3.1/100 person-years). Workers with SARS-CoV-2-positive ILI reported more anosmia (p<0.01), dysgeusia (p<0.01), difficulty concentrating (p=0.01), and irritability (p=0.01), and greater clinical and well-being severity scores (Flu-iiQ) than test-negative ILIs; they also had greater absenteeism (p<0.01) and lost income (median US$127.1, p<0.01). These results support the prioritization of Guatemalan farm workers for COVID-19 vaccination.
RESUMEN
We used the dried tube specimen (DTS) procedure to develop the COVID-19 Serology Control Panel (CSCP). The CSCP contains five well-characterized SARS-CoV-2 pooled plasma samples made available for labs around the world to compare test kits, use for external quality assurance, harmonize laboratory testing, and train laboratory workers. Article Summary LineThe dried tube specimen system is a highly effective and resilient way to provide laboratories with well-characterized serology materials. The CSCP can help clinical laboratories inform their choice of diagnostic test to supplement clinical diagnoses of SARS-CoV-2 infection.
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Severe COVID-19 has been associated with T cell lymphopenia 1,2, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from SARS-CoV-2 infections we studied rhesus macaques that were depleted of either CD4+, CD8+ or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to controls. The T cell-depleted groups developed virus-neutralizing antibody responses and also class-switched to IgG. When re-infected six weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Neither primed CD4+ or CD8+ T cells appeared critical for immunoglobulin class switching, the development of immunological memory or protection from a second infection.
RESUMEN
The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and four major variants of concern. Our data reveal increased interferon resistance in emerging SARS-CoV-2 variants, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections. Author SummaryIn less than 2 years since its spillover into humans, SARS-CoV-2 has infected over 220 million people, causing over 4.5 million COVID-19 deaths. High infection rates provided substantial opportunities for the virus to evolve, as variants with enhanced transmissibility, pathogenesis, and resistance to vaccine-elicited neutralizing antibodies have emerged. While much focus has centered on the Spike protein which the virus uses to infect target cells, mutations were also found in other viral proteins that might inhibit innate immune responses. Specifically, viruses encounter a potent innate immune response mediated by the interferons, two of which, IFN2 and IFN{beta}, are being repurposed for COVID-19 treatment. Here, we compared the potency of human interferons against ancestral and emerging variants of SARS-CoV-2. Our data revealed increased interferon resistance in emerging SARS-CoV-2 strains that included the alpha, beta, gamma and delta variants of concern, suggesting a significant, but underappreciated role for innate immunity in driving the next phase of the COVID-19 pandemic.