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We report anti-SARS-CoV-2 nucleocapsid IgG seroconversion rates from a population-based cohort in Manaus, between August and November 2020, before the COVID-19 second wave in Brazil. Among seronegative and uninfected participants, we observed an overall incidence of 13.06% (95%CI, 11.52-14.79) and 6.78% (95%CI, 5.61-8.10) for symptomatic seroconversion. Risk factors for seroconversion were: having a COVID-19 case in the household, not wearing a mask during contact, relaxation of protective measures, and non-remote work. We observed an intense infection transmission period that preceded the second wave of COVID-19 in Manaus, and identified several modifiable behaviors that increased the risk of seroconversion.

Numerous mechanisms have been proposed to explain why patients with malaria are more susceptible to bloodstream invasions by Salmonella spp., however there are still several unknown critical factors regarding the pathogenesis of coinfection. From a coinfection model, in which an S. enterica serovar Typhi (S_Typhi) was chosen to challenge mice that had been infected 24 h earlier with Plasmodium berghei ANKA (P.b_ANKA), we evaluated the influence of malaria on cytokine levels, the functional activity of femoral bone marrow-derived macrophages and neutrophils, and intestinal permeability. The cytokine profile over eight days of coinfection showed exacerbation in the cytokines MCP-1, IFNγ and TNFα in relation to the increase seen in animals with malaria. The cytokine profile was associated with a considerably reduced neutrophil and macrophage count and a prominent dysfunction, especially in ex vivo neutrophils in coinfected mice, though without bacterial modulation that could influence the invasion capacity of ex vivo S_Typhi obtained from liver macerate in non-phagocyte cells. Finally, irregularities in the integrity of intestinal tissue evidenced ruptures in the enterocyte layer, a presence of mononuclear leukocytes in the enterocyte layer, an increase of goblet cells in the enterocyte layer and a high volume of leukocyte infiltrate in the sub-mucosa were greatly increased in coinfected animals. Increases of mononuclear leukocytes in the enterocyte layer and volume of leukocyte infiltrate in the sub-mucosa were also seen in monoinfected animals with P. berghei ANKA. Our findings suggest malaria causes a disarrangement of intestinal homeostasis, exacerbation of proinflammatory cytokines and dysfunction in neutrophils that render the host susceptible to bacteremia by Salmonella spp.

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Background: Relapses of Plasmodium vivax (P. vivax) infections are major causes of malaria morbidity, and tools for distinguishing relapses from reinfections are needed in malaria endemic areas. Methods: Herein, a panel of plasmas of 72 P. vivax-infected pregnant women, of whom 31 had had at least a recurrence of P. vivax infection, was used in a serology for IgM and IgG against 6 P. vivax-merozoite surface protein-1 (P. vivax-MSP1-Block 2) haplotype-specific peptides, in order to identify re-expositions to same haplotypes in the recurrences during the pregnancy. In parallel, we used the amplicon deep sequencing (ADS) with P. vivax-MSP1-Block 2 amplicons of the in eight blood samples of non-pregnant P. vivax-infected patients to identify multi or monoclonal infections based on MSP1-Block-2 haplotypes, and to quantify the reads of different haplotypes between those with multiclonal infections. We synthetized a new panel of overlapping peptides mapping each one of the six P. vivax-MSP1-Block 2 haplotypes and we validated with new IgM and IgG serology. Results: Most pregnant women presented IgM that recognized more than one peptide, thus indicating multiple infections by P. vivax-MSP1-Block 2 haplotypes. The same IgM anti-peptides remained in several women in the recurrent episodes most likely indicates re-exposure to the same haplotype of MSP1 Block 2. The IgG reactivity the IgM to IgG switch were low. The ADS using next-generation sequencing (NGS) identified multi- and monoinfection by P. vivax-MSP1-Block 2 haplotypes. Of eight patients, two of them had had the first P. vivax-infection. Monoinfections with P. vivax-MSP1-Block 2 haplotypes were observed in two prime-infected patients and three of patients with previous malaria. In all P. vivax-MSP1-Block 2 haplotype-monoinfected patients, the reactivity of IgM was observed only against overlapped peptides of the same haplotype detected in ADS, while for IgG, no reactivity was observed for any of the peptides of the same haplotype or the others.We were able to identify multiclonal infections through three haplotypes of P. vivax MSP1 Block 2 in three remaining patients, among which, there was always one majority haplotype that predominated with more of 95% of high-quality reads. The levels of haplotype-specific IgM in the serology correlated with the read ratios of each haplotype, but IgG levels not, including in one of the multiclonal infections, a minority haplotype was recognized with higher levels of IgG than that of the majority one. Conclusion: Our findings suggest that the combination of ADS and serology for P. vivax-MSP1-Block 2 haplotypes may be used as a new tool for distinguishing reinfections from relapses in malaria.

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.