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medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.03.02.23286693


COVID-19 has challenged the scientific community in the search for biological markers and information that can contribute to the early management of the severe disease. Given the global scale of COVID-19, including reports of reinfection even in the presence of effective vaccines, we have not yet been able to eradicate the disease. This factor implies the emergence of new waves and an increasing number of hospitalizations. This study aimed to characterize the neutralizing antibody (Nab) geometric mean titers (GMTs) in hospitalized patients with COVID-19 and to evaluate the association with length of stay, comorbidities, and patient outcome. Among the 103 participants, 84 (81.5%) had some previous condition associated with worsening health, and 31 (30%) died. We found that neutralization potency varied greatly across individuals and was significantly higher in patients discharged before 14 days than in patients who stayed longer in the hospital. During the study period, 15 people living with HIV (PLWH) were hospitalized, and no significant difference in clinical characteristics or anti-SARS-CoV-2 Nabs was observed. However, PLWH with severe COVID-19 were younger (41.7, IQR=17.5) than other hospitalized COVID-19 patients (59.3, IQR=22, P <0.01). A high anti-HIV-1 antibody GMT of 583.9 (95% CI: 344-990) was detected, demonstrating maintenance of anti-HIV-1 Nab production among PLWH coinfected with SARS-CoV-2. Therefore, these results indicate that neutralizing antibodies are not the only immunological response capable of controlling disease progression. Nevertheless, these data highlight the importance of more Nab screening studies to predict shorter hospital stays.

HIV Infections , COVID-19
researchsquare; 2021.


Background: COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic to mild or moderate symptoms, reaching the most severe forms and death. The mechanisms underlying the SARS-CoV-2 infection and its clinical evolution are still unclear. Once SARS-CoV-2 infects individuals, host factors are activated by the presence of the virus inside the cells, such as the inflammasome system. The search of risk factors for COVID-19 is of relevance for clinical management. In this study, we investigated the impact of 11 single-base polymorphisms (SNPs) in the NLRP3, CARD8, AIM2, CASP-1, IFI16, and IL-1β inflammasome genes in SARS-CoV-2 infected individuals with distinct disease outcomes. Methods Patients were divided into two groups: (1) inpatients, with severe/critical disease (Hospitalized group, n=451), and (2) convalescent volunteers with prior SARS-CoV-2 infection and a history of asymptomatic to mild symptoms (Mild group, n=43). Patients hospitalized were followed up at a Hospital Center for COVID-19 Pandemic – National Institute of Infectology (INI)/FIOCRUZ, Rio de Janeiro, Brazil, from June 2020 to March 2021. The Mild group was recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, Rio de Janeiro, Brazil, in 2020. Genotyping of the SNPs was determined by Real-Time PCR. Protection and risk estimations were performed by unconditional logistic regression models. Results Among the genotyped SNPs, significant differences in the NLRP3 rs1539019 and rs10754558 frequencies were observed between the groups. The C/C genotype (OR adj =6.31; P adj =0.026) or allele C (OR adj =1.05; P adj =0.002) in rs1539019 polymorphism were associated with the risk for hospitalization, while the C/G genotype (OR adj =0.16; P adj =0.016) or carrier-G (OR adj =0.2; P adj =0.028) in rs10754558 polymorphism were associated with protection for hospitalization. Regarding the NLRP3 genetic variants, the A-C-G-C-G haplotype (OR adj =0.14; P adj = 0.030) was associated with protection for hospitalization. No significant association was observed for the other polymorphisms. Conclusions As of our knowledge, this is the first study demonstrating the association of inflammasome NLRP3 variants with risk and/or protection for hospitalization in COVID-19. Studies linking the NLRP3 inflammasome and SARS-CoV-2 infection are still scarce due to the recent emergence of this pathogen. Our results contribute to the discussion of the impact of inflammasomes in the clinical evolution of COVID-19.

ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3886418


Background: Due to the slow vaccination and limited resources in Brazil, a risk assessment in hospital screening becomes imperative to improve efficiency and ensure universal access to the health system. This study aimed to evaluate the association between pre-screening clinical characteristics (age, symptoms, and comorbidities) and healthcare resource demand (ventilatory support or intensive care units) and COVID-19-related deaths.Methods: We included patients from the SIVEP-Gripe database with a confirmatory diagnosis of COVID-19, aged 21-80 years, admitted and discharged from February 20th to December 31st, 2020. We used binomial models adjusted for confounders with second-order interactions between the effects of interest.Findings: Of 430,723 symptomatic patients diagnosed with COVID-19 admitted to hospitals, and registered in the SIVEP-Gripe, 258,564 (70·6%) required some ventilatory support, 127,663 (29·6%) required intensive care, and 112,569 (26·1%) had COVID-19-related deaths. Diabetes (27-65%), obesity (53-129%), and smoking (68-130%) increased the chance of ventilatory support in almost all age strata and symptom groups. Obesity (45-124%) was a major risk factor for ICU admission, while immunosuppression (54-235%) and renal disease (89-189%) increased the risk of COVID-19-related deaths. Unexpectedly, Patients who had mild symptoms were often more associated with an unfavorable clinical course than other symptoms considered more severe.Interpretation: Our results revealed the complex distribution of risks considering the interaction between age, group of symptoms, and comorbidities for increased demand for healthcare resources and deaths. Early identification of high-risk patients may improve the efficiency of the health system.Funding Information: Inova Fiocruz/Fundação Oswaldo Cruz.Declaration of Interests: We declare no competing interests.

Kidney Diseases , COVID-19 , Obesity
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.01.22.21250346


Background COVID 19 has been alarmingly spreading worldwide, with Brazil ranking third in total number of cases and second in deaths. Being a continental country, which comprises many ethnic groups and an engrained social inequality, the pandemic evidenced this heterogeneous discrepancy. We aimed to estimate the impact of associated risk factors, isolated or combined, on COVID 19 severeness, detecting specific epidemiological profiles for multiple age ranges in hospitalized Brazilians. Methods In this large retrospective cohort study, we used open-access data from the Ministry of Health of Brazil with COVID 19 confirmed hospitalized patients annotated in SRAG system between February and August 2020, a total of 235555 entries. The association of COVID 19 death with socio-demographic and clinical characteristics was analysed and presented as odds ratios adjusted by confounding co-variables. We also presented marginal mean aOR values for high-order interactions either by or not another fixed level or condition. We kept all other variables in the multivariate logistic models in their mean values or equal proportions. Findings Younger individuals with one or more comorbidities had an adjusted odds ratio up to four-fold compared to those without it, in the same age interval. Younger diabetic patients either self-declared as brown ethnicity (aOR 5,58, 95% CI 4,97-6,25; p < 0,0001) or with some other associated comorbidities, mainly chronic hematologic disease (21,09, 13,64-32,6; p < 0,0001) and obesity (aOR 21,7, 95% CI not calculated; p < 0,0001), resulted in outstanding death risk. Age over 60, particularly over 90 (28,91, 24,5-34,11; p < 0,001), usage of invasive ventilatory support (16,23, 14,05-18,75; p < 0,001), admission to intensive care units (3,14, 2,82-3,48; p < 0,001), multiple respiratory symptoms (3,24, 2,79-3,75; p < 0,0001), black ethnicity (1,78, 1,52-2,07; p < 0,05), and diagnosis previous to hospitalization (1,32, 1,19-1,47; p < 0,05) were associated with higher death odds. As protective factors, with roughly one third less death risk, we found hospitalization duration of (4, 7] days and illness onset to hospitalization over 6 days. Interpretation We found evidence for increased COVID 19 risk in two distinct groups: younger patients with prevalent comorbidities, especially in brown ethnicity, and patients with black ethnicity. We speculate that the pro-inflammatory synergism of COVID 19 and comorbidities, promoting an overproduction of cytokines, is partially the cause of higher mortality in this young group. Brazilian black and brown are underprivileged populations, with structural social inequality, limited healthcare access and, thus, remarkable disease vulnerability. Our study supplies essential data to patient stratification upon admission, optimizing hospital management, and to guide public policy determinations, including group prioritization for COVID 19 vaccination in Brazil.

Diabetes Mellitus , Obesity , Hematologic Diseases , Death , COVID-19