Antigen-Specific Antibody Signature Is Associated with COVID-19 Outcome.

Numerous studies have focused on inflammation-related markers to understand COVID-19. In this study, we performed a comparative analysis of spike (S) and nucleocapsid (N) protein-specific IgA, total IgG and IgG subclass response in COVID-19 patients and compared this to their disease outcome. We observed that the SARS-CoV-2 infection elicits a robust IgA and IgG response against the N-terminal (N1) and C-terminal (N3) region of the N protein, whereas we failed to detect IgA antibodies and observed a weak IgG response against the disordered linker region (N2) in COVID-19 patients. N and S protein-specific IgG1, IgG2 and IgG3 response was significantly elevated in hospitalized patients with severe disease compared to outpatients with non-severe disease. IgA and total IgG antibody reactivity gradually increased after the first week of symptoms. Magnitude of RBD-ACE2 blocking antibodies identified in a competitive assay and neutralizing antibodies detected by PRNT assay correlated with disease severity. Generally, the IgA and total IgG response between the discharged and deceased COVID-19 patients was similar. However, significant differences in the ratio of IgG subclass antibodies were observed between discharged and deceased patients, especially towards the disordered linker region of the N protein. Overall, SARS-CoV-2 infection is linked to an elevated blood antibody response in severe patients compared to non-severe patients. Monitoring of antigen-specific serological response could be an important tool to accompany disease progression and improve outcomes.

Inhibition of extracellular traps by spores of Trichoderma stromaticum on neutrophils obtained from human peripheral blood.

Although the genus Trichoderma is widely used as a biocontrol agent in crops, little is known about its potential impact on the human immune system. In mice, our group has shown that exposition to T. asperelloides spores lead to reduced neutrophil counts in the peripheral blood and in the peritoneal cavity. In addition, T. stromaticum spores produced an inflammatory infiltrate on mice lungs, reducing the levels of IFN-γ and IL-10 cytokines, reactive oxygen species, and receptors of microbial patterns. Here we demonstrate that the interaction of human peripheral neutrophils with T. stromaticum spores also leads to a reduced release of neutrophil extracellular traps (NETs) after induction with the NET-inducer agent phorbol 12-myristate 13-acetate. This interaction also reduced the expression levels of multiple microRNAs, such as miR-221, miR-222, miR-223 and miR-27a, as well as genes related to NETs, such as ELANE, MPO and PADI4. Furthermore, T. stromaticum spores affected the expression of the genes SOCS3, TLR4, CSNK2A1, GSDMD, and NFFKBIA, related to the activation of inflammatory immune responses in neutrophils. Overall, our results suggest T. stromaticum as a potential NET inhibitor and as an immunomodulatory agent. Since this fungus is used as biocontrol in crops, our findings point to the importance of advancing our knowledge on the effects of this bioagent on the human immune system. Finally, the study of the active compounds produced by the fungus is also important for the prospection of new drugs that could be used to block the exacerbation of inflammatory immune responses present in several human diseases.

SARS-CoV-2 seroprevalence and associated factors in Manaus, Brazil: baseline results from the DETECTCoV-19 cohort study.

BACKGROUND: Manaus, located in the Brazilian rainforest, has experienced two health system collapses due to the coronavirus disease 2019 (COVID-19) pandemic. However, little is known about which groups among the general population have been most affected. METHODS: A convenience sampling strategy via online advertising recruited 3046 adults between 19 August 2020 and 2 October 2020. Sociodemographic characteristics, COVID-19-related symptoms, COVID-19 testing, self-medication and prescribed medications were recorded. Serum anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid immunoglobulin G antibodies were measured with an enzyme-linked immunosorbent assay. Prevalence ratios (PR) were obtained using cluster-corrected and adjusted Poisson's regression models. RESULTS: A crude positivity rate among asymptomatic and symptomatic individuals was estimated at 29.10%, with maximum possible seroprevalence of 44.82% corrected by test characteristics and an antibody decay rate of 32.31%. Regression models demonstrated a strong association towards marginalized low-income and vulnerable residents with limited access to health care. The presence of a COVID-19 case [PR 1.39, 95% confidence interval (CI) 1.24-1.57] or death (PR 2.14, 95% CI 1.74-2.62) in a household greatly increased the risk of other household members acquiring infection. The seroprevalence of SARS-CoV-2 was higher among those who self-medicated to prevent infection (PR 1.36, 95% CI 1.27-1.46). CONCLUSIONS: Disproportionate socio-economic disparity was observed among the study participants. The syndemic nature of COVID-19 in the Amazon region needs differential policies and urgent solutions to control the ongoing pandemic.