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.

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.

A First Plasmodium vivax Natural Infection Induces Increased Activity of the Interferon Gamma-Driven Tryptophan Catabolism Pathway.

The human immune response that controls Plasmodium infection in the liver and blood stages of the parasite life cycle is composed by both pro- and anti-inflammatory programs. Pro-inflammatory responses primarily mediated by IFN-γ controls the infection, but also induce tolerogenic mechanisms to limit host damage, including the tryptophan (TRP) catabolism pathway mediated by the enzyme Indoleamine 2,3-Dioxygenase (IDO1), an enzyme that catalyzes the degradation of TRP to kynurenines (KYN). Here we assessed total serum kynurenines and cytokine dynamics in a cohort of natural Plasmodium vivax human infection and compared them to those of endemic healthy controls and other febrile diseases. In acute malaria, the absolute free kynurenine (KYN) serum levels and the KYN to TRP (KYN/TRP) ratio were significantly elevated in patients compared to healthy controls. Individuals with a diagnosis of a first malaria episode had higher serum KYN levels than individuals with a previous malaria episode. We observed an inverse relationship between the serum levels of IFN-γ and IL-10 in patients with a first malaria episode compared to those of subjects with previous history of malaria. Kynurenine elevation was positively correlated with serum IFN-γ levels in acute infection, whereas, it was negatively correlated with parasite load and P. vivax LDH levels. Overall, the differences observed between infected individuals depended on the number of Plasmodium infections. The decrease in the KYN/TRP ratio in malaria-experienced subjects coincided with the onset of anti-P. vivax IgG. These results suggest that P. vivax infection induces a strong anti-inflammatory program in individuals with first time malaria, which fades with ensuing protective immunity after subsequent episodes. Understanding the tolerance mechanisms involved in the initial exposure would help in defining the balance between protective and pathogenic immune responses necessary to control infection and to improve vaccination strategies.

Kynurenine elevation correlates with T regulatory cells increase in acute Plasmodium vivax infection: A pilot study.

BACKGROUND: Disease-tolerance mechanisms limit infection severity by preventing tissue damage; however, the underlying mechanisms in human malaria are still unclear. Tryptophan (TRP), an essential amino acid, is catabolized into tolerogenic metabolites, kynurenines (KYN), by indoleamine 2,3-dioxygenase 1 (IDO1), which can induce Foxp3+ T regulatory cells (Tregs). In this study, we evaluated the relationship of these metabolites with Treg-mediated tolerance induction in acute malaria infections. METHODS: We performed a cross-sectional study that evaluated asymptomatic, symptomatic malaria patients and endemic control patient groups. We assessed plasmatic concentration of cytokines by ELISA. Plasmatic TRP and KYN levels were measured by HPLC. Peripheral T regulatory cells were measured and phenotyped by flow cytometry. RESULTS: The KYN/TRP ratio was significantly elevated in asymptomatic and symptomatic Plasmodium infection, compared to healthy controls. Also, Th1 and Th2 cytokines were elevated in the acute phase of malaria disease. IFN-γ increase in acute phase was positively correlated with the KYN/TRP ratio and KYN elevation was positively correlated with the increase of peripheral FoxP3+ T regulatory cells. CONCLUSIONS: Additional studies are needed not only to identify innate mechanisms that increase tryptophan catabolism but also the role of Tregs in controlling malaria-induced pathology and malaria tolerance by the host.