Adaptive immunity to SARS-CoV-2 infection: A systematic review.

Background: There is evidence that the adaptive or acquired immune system is one of the crucial variables in differentiating the course of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work aimed to analyze the immunopathological aspects of adaptive immunity that are involved in the progression of this disease. Methods: This is a systematic review based on articles that included experimental evidence from in vitro assays, cohort studies, reviews, cross-sectional and case-control studies from PubMed, SciELO, MEDLINE, and Lilacs databases in English, Portuguese, or Spanish between January 2020 and July 2022. Results: Fifty-six articles were finalized for this review. CD4+ T cells were the most resolutive in the health-disease process compared with B cells and CD8+ T lymphocytes. The predominant subpopulations of T helper lymphocytes (Th) in critically ill patients are Th1, Th2, Th17 (without their main characteristics) and regulatory T cells (Treg), while in mild cases there is an influx of Th1, Th2, Th17 and follicular T helper cells (Tfh). These cells are responsible for the secretion of cytokines, including interleukin (IL) - 6, IL-4, IL-10, IL-7, IL-22, IL-21, IL-15, IL-1α, IL-23, IL-5, IL-13, IL-2, IL-17, tumor necrosis factor alpha (TNF-α), CXC motivating ligand (CXCL) 8, CXCL9 and tumor growth factor beta (TGF-ß), with the abovementioned first 8 inflammatory mediators related to clinical benefits, while the others to a poor prognosis. Some CD8+ T lymphocyte markers are associated with the severity of the disease, such as human leukocyte antigen (HLA-DR) and programmed cell death protein 1 (PD-1). Among the antibodies produced by SARS-CoV-2, Immunoglobulin (Ig) A stood out due to its potent release associated with a more severe clinical form. Conclusions: It is concluded that through this study it is possible to have a brief overview of the main immunological biomarkers and their function during SARS-CoV-2 infection in particular cell types. In critically ill individuals, adaptive immunity is varied, aberrantly compromised, and late. In particular, the T-cell response is also an essential and necessary component in immunological memory and therefore should be addressed in vaccine formulation strategies.

Clinical Characteristics and Outcomes among Vaccinated and Unvaccinated Patients with Cardiovascular Disease Who Were Hospitalized for COVID-19 in Brazil: Retrospective Cohort.

INTRODUCTION: COVID-19 in Brazil has already caused, and it still causes, several impacts on health, economy, and education. The risk factors for death involved those with cardiovascular diseases (CVD), which were prioritized for the vaccination of COVID-19. OBJECTIVE: To investigate the clinical characteristics and outcomes between vaccinated and unvaccinated patients with cardiovascular diseases hospitalized for COVID-19 in Brazil in the year 2022. METHODS: A retrospective cohort was analyzed from the year 2022, with cases being hospitalized by COVID-19 being drawn from SIVEP-GRIPE surveillance. We compared clinical characteristics, comorbidities, and outcomes between CVD carriers and non-carriers, and we also compared vaccinated with two doses vs. those that are unvaccinated in CVD carriers. We performed chi-square, odds ratio, logistic regression, and survival analysis. RESULTS: We included, in the cohort, 112,459 hospital inpatients. An amount of 71,661 (63.72%) of the hospitalized patients had CVD. Regarding deaths, 37,888 (33.69%) died. Regarding vaccination against COVID-19, 20,855 (18.54%) people were not vaccinated with any dose among those with CVD. Death p- < 0.001 (OR 1.307-CI 1.235-1.383) and fever p- < 0.001 (OR 1.156-CI 1.098-1.218) were associated with the unvaccinated CVD carriers, and diarrhea p-0.015 (OR 1.116-CI 1.022-1.218), dyspnea p-0.022 (OR 1.074-CI 1.011-1.142), and respiratory distress p-0.021 (OR 1.070-CI 1.011-1.134) were also recorded. Those patients who possessed predictors of death, including invasive ventilation (p- < 0.001 (OR 8.816-CI 8.313-9.350)), were admitted to the ICU p- < 0.001 (OR 1.754-CI 1.684-1.827), and some had respiratory distress p- < 0.001 (OR 1.367-CI 1.312-1.423), dyspnea p < 0.001 (OR 1.341-CI 1.284-1.400), O2 saturation < 95% p- < 0. 001 (OR 1.307-CI 1.254-1.363), they were unvaccinated against COVID-19 p- < 0.001 (OR 1.258-CI 1.200-1.319), they were of male sex p- < 0.001 (OR 1.179-CI 1.138-1.221), they had diarrhea p-0.018 (OR 1.081-CI 1.013-1.154), and they may have been old p < 0.001 (OR 1.034-CI 1.033-1.035). Survival was shorter for the unvaccinated p-0.003, and p- <0.001. CONCLUSIONS: We highlight the predictors of death for those unvaccinated against COVID-19 in this research, and we evidenced the benefits of the COVID-19 vaccine in reducing deaths in hospitalized CVD patients.

Impact of the COVID-19 pandemic on the mental health of frontline healthcare workers in a highly affected region in Brazil.

BACKGROUND: The COVID-19 pandemic had a major impact on the mental health of healthcare workers (HCWs), especially in low and middle-income countries, which had to face additional political, social, and economic challenges. We thus aimed to assess the prevalence of mental health outcomes and the associated factors in HCWs treating COVID-19 patients in one of the most affected regions in Brazil. METHODS: We used the Respondent-Driven Sampling method to assess the risks of COVID-19 infection and symptoms of mental disorders in nurses, nursing technicians, and physicians who worked on the frontline in the metropolitan region of Recife. 865 healthcare workers completed a survey regarding sociodemographic data, work-related risks, and symptoms of mental disorders - SRQ-20 for common mental disorders (CMD); AUDIT-C for problematic alcohol use; GAD-7 for anxiety; PHQ-9 for depression; PCL-5 for post-traumatic stress disorder (PTSD). Gile's successive sampling estimator was used to produce the weighted estimates by professional category. A Poisson regression model with robust variance was used to analyze factors associated with a positive screening for CMD. We will present the results of a cross-sectional analysis of the mental health outcomes after the first peak of COVID-19 - from August 2020 to February 2021. RESULTS: The prevalence ratios for a positive screening for CMD were 34.9% (95% CI: 27.8-41.9) in nurses, 28.6% (95% CI: 21.3-36.0) in physicians, and 26.6% (95% CI: 16.8-36.5) in nursing technicians. Nurses presented a higher prevalence of depressive symptoms (23%). Positive screening for problematic alcohol use (10.5 to14.0%), anxiety (10.4 to 13.3%), and PTSD (3.3 to 4.4%) were similar between the professional categories. The main factors associated with CMD in nurses and physicians were related to an intrinsic susceptibility to mental illness, such as previous or family history of psychiatric disorder, and female sex. Among nurse technicians, work-related factors, such as accidents with biological material, presented the strongest association with CMD. CONCLUSION: The mental health of HCWs fighting COVID-19 in Recife was severely affected. It is crucial that healthcare services provide adequate working conditions and psychological support, investing in programs to promote and protect HCWs mental health.

Reports from the frontline: health workers describe COVID-19 risks and fears in five cities in Brazil.

BACKGROUND: Health providers are under unprecedented pressures to perform in the COVID-19 health crisis and under unprecedented risks. We initiated a large mixed-method survey of health professionals in five large metropolitan areas in Brazil to document the risks and needs of health professionals. To initiate the study, we conducted formative research. METHODS: We conducted 77 open-ended semi-structured interviews online in a convenience sample of physicians, nurses, nurse technicians, and physiotherapists in Belem, Fortaleza, Porto Alegre, Recife, and São Paulo, Brazil. Design, data collection, and analysis were informed by Rapid Ethnographic Analysis (REA). RESULTS: Responses are organized into three themes that emerged in the interviews: the lack of preparation - both locally and nationally-for the pandemic and its effects on staffing and training; the overlap of personal, family, and professional risk and consequences; and inadequately addressed anxiety and suffering among health staff. CONCLUSIONS: Our respondents were unprepared for the epidemic, especially the institutional sequelae and psychological cost. These consequences were exacerbated by both lack of leadership and sweeping changes undercutting the Brazilian health system noted by almost all participants.

Hyperinflammatory Response in COVID-19: A Systematic Review.

COVID-19 is a multisystemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The immunopathogenic conditions of the hyperinflammatory response that cause systemic inflammation are extremely linked to its severity. This research sought to review the immunopathological elements that contribute to its progression. This is a systematic review using the PUBMED, LILACS, MEDLINE, and SCIELO databases using articles between May 2020 and July 2022 with the following search terms in conjunction with "AND": "SARS-CoV-2"; "COVID-19"; "ARDS" and "Cytokine Storm". The quality appraisal and risk of bias were assessed by the JBI checklists and the Cochrane Collaboration's RoB 2.0 and ROBINS-I tools, respectively, and the risk of bias for in vitro studies by a pre-defined standard in the literature. The search resulted in 39 articles. The main actors in this response denote SARS-CoV-2 Spike proteins, cellular proteases, leukocytes, cytokines, and proteolytic cascades. The "cytokine storm" itself brings several complications to the host through cytokines such as IL-6 and chemokines (such as CCL2), which influence tissue inflammation through apoptosis and pyroptosis. The hyperinflammatory response causes several unfavorable outcomes in patients, and systemic inflammation caused largely by the dysregulation of the immune response should be controlled for their recovery.

Characteristics and outcomes of severe COVID-19 in hospitalized patients with cardiovascular diseases in the Amazonian region of Brazil: a retrospective cohort.

The northern region of Brazil is already vulnerable to other infectious diseases and it was no different in COVID-19. However, cardiovascular diseases still lead the causes of death. Thus, the objective of this study is to identify the clinical predictors and outcome of severe COVID-19 in hospitalized patients with and without CVD in this region of the Amazon. A retrospective cohort, referring to the notifications from January 1 to December 31, 2020, including cases confirmed by molecular testing. The study consisted of 9223 confirmed cases for COVID-19. Of these, 6011 (65.17%) did not have cardiovascular disease and 3212 (34.83%) had some cardiovascular disease. The significance of deaths was in the age group of < 1 to 59 CVD carriers (< 0.001). Predictor of mortality were invasive ventilation for patients with CVD, (OR 23,688 CI 18,180-30,866), followed by chronic kidney disease (OR 2442 CI 1568-3740), dyspnea (OR 2312 CI 1817-3941), respiratory distress (OR 1523 CI 1210-2919), cough (OR 1268 CI 1005-1599), Lower oxygen saturation 95% (OR 1281 CI 1039-1579), diabetes mellitus (OR 1267 CI 1050-1528) and age (OR 1051 CI 1044-1058). Carriers of CVD had a lower survival rate (< 0.0001). The order of the predictors of death differed among the non-carriers, as well as the high odds ratio in the predictors of CVD, only cough was an independent predictor. The age group under 59 years was associated with deaths. We also show the shorter survival in CVD carriers, as well as the higher cardiovascular morbidity rate than other studies in the literature.

Adaptive immunity to SARS-CoV-2 infection: A systematic review

Background There is evidence that the adaptive or acquired immune system is one of the crucial variables in differentiating the course of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work aimed to analyze the immunopathological aspects of adaptive immunity that are involved in the progression of this disease. Methods This is a systematic review based on articles that included experimental evidence from in vitro assays, cohort studies, reviews, cross-sectional and case-control studies from PubMed, SciELO, MEDLINE, and Lilacs databases in English, Portuguese, or Spanish between January 2020 and July 2022. Results Fifty-six articles were finalized for this review. CD4+ T cells were the most resolutive in the health-disease process compared with B cells and CD8+ T lymphocytes. The predominant subpopulations of T helper lymphocytes (Th) in critically ill patients are Th1, Th2, Th17 (without their main characteristics) and regulatory T cells (Treg), while in mild cases there is an influx of Th1, Th2, Th17 and follicular T helper cells (Tfh). These cells are responsible for the secretion of cytokines, including interleukin (IL) - 6, IL-4, IL-10, IL-7, IL-22, IL-21, IL-15, IL-1α, IL-23, IL-5, IL-13, IL-2, IL-17, tumor necrosis factor alpha (TNF-α), CXC motivating ligand (CXCL) 8, CXCL9 and tumor growth factor beta (TGF-β), with the abovementioned first 8 inflammatory mediators related to clinical benefits, while the others to a poor prognosis. Some CD8+ T lymphocyte markers are associated with the severity of the disease, such as human leukocyte antigen (HLA-DR) and programmed cell death protein 1 (PD-1). Among the antibodies produced by SARS-CoV-2, Immunoglobulin (Ig) A stood out due to its potent release associated with a more severe clinical form. Conclusions It is concluded that through this study it is possible to have a brief overview of the main immunological biomarkers and their function during SARS-CoV-2 infection in particular cell types. In critically ill individuals, adaptive immunity is varied, aberrantly compromised, and late. In particular, the T-cell response is also an essential and necessary component in immunological memory and therefore should be addressed in vaccine formulation strategies.

Surveillance Quality Indicators Highlight the Need for Improving Tuberculosis Diagnostics and Monitoring in a Hyperendemic Area of the Brazilian Amazon Region.

The city of Ananindeua, State of Pará, Brazil, is a hyperendemic area for tuberculosis (TB). The present study describes the population characteristics and epidemiological indicators of TB cases from Ananindeua, from 2018 to 2020. The TB cases were screened from the Municipal Health Department of Ananindeua database, and the secondary data were obtained from the Brazilian Notifiable Diseases Information System (SINAN). A high percentage of cases did not undergo a rapid molecular test (74.9%) or culture (84.8%) for diagnosis of TB; a chest X-ray examination for diagnosis of TB was performed in 74.47% of new cases. The SINAN form data was incomplete on susceptibility test results (<0.01-92.7). Sputum smear microscopy for monitoring treatment was recorded in the follow-up form in 34.3% and after the 6th month in 61.1% of cases. The cure rate (60.31%) was below the recommendation by the Brazilian Ministry of Health. The quality indicators showed many weaknesses: (I) lack of availability of smear microscopy as a diagnostic test in a hyper-endemic area; (II) low availability of specific exams such as culture and rapid molecular test (RMT); (III) low adherence to smear microscopy to monitor the evolution of cases during treatment; (IV) absence of drug susceptibility test data; (V) failure to fill in essential variables for TB surveillance.

Innate immunity to SARS-CoV-2 infection: a review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, first notified in China, has spread around the world causing high morbidity and mortality, which is due to factors such as the subversion of the immune response. The aims of the study are to summarise and present the immunopathological relationship of COVID-19 with innate immunity. This is a systematic review conducted by the National Library of Medicine - National Institutes of Health, USA (PUBMED), Latin American and Caribbean Literature on Health Sciences (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Scientific Electronic Library Online (SCIELO) databases with clinical trials, in vitro assays, case-controls, cohort studies, systematic reviews and meta-analyses between February 2020 and July 2021. The version 2 of the Cochrane risk-of-bias tool for RCTs (RoB 2), Joana Briggs Institute (JBI) Critical Appraisal (for the review articles) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tools were used to evaluate the quality and the risk of bias of the studies included in this review. The innate immune response through the generation of interferons, alternative pathways and complement system lectins and the joint action of innate immune cells and cytokines and chemokines lead to different clinical outcomes, taking into account the exacerbated inflammatory response and pathogenesis. Then, in addition to interacting as a bridge for adaptive immunity, the innate immune response plays an essential role in primary defense and is one of the starting points for immune evasion by SARS-CoV-2.

Risk of SARS-CoV-2 infection among front-line healthcare workers in Northeast Brazil: a respondent-driven sampling approach.

OBJECTIVES: We assessed the prevalence of SARS-CoV-2 infection, personal protective equipment (PPE) shortages and occurrence of biological accidents among front-line healthcare workers (HCW). DESIGN, SETTING AND PARTICIPANTS: Using respondent-driven sampling, the study recruited distinct categories of HCW attending suspected or confirmed patients with COVID-19 from May 2020 to February 2021, in the Recife metropolitan area, Northeast Brazil. OUTCOME MEASURES: The criterion to assess SARS-CoV-2 infection among HCW was a positive self-reported PCR test. RESULTS: We analysed 1525 HCW: 527 physicians, 471 registered nurses, 263 nursing assistants and 264 physical therapists. Women predominated in all categories (81.1%; 95% CI: 77.8% to 84.1%). Nurses were older with more comorbidities (hypertension and overweight/obesity) than the other staff. The overall prevalence of SARS-CoV-2 infection was 61.8% (95% CI: 55.7% to 67.5%) after adjustment for the cluster random effect, weighted by network, and the reference population size. Risk factors for a positive RT-PCR test were being a nursing assistant (OR adjusted: 2.56; 95% CI: 1.42 to 4.61), not always using all recommended PPE while assisting patients with COVID-19 (OR adj: 2.15; 95% CI: 1.02 to 4.53) and reporting a splash of biological fluid/respiratory secretion in the eyes (OR adj: 3.37; 95% CI: 1.10 to 10.34). CONCLUSIONS: This study shows the high frequency of SARS-CoV2 infection among HCW presumably due to workplace exposures. In our setting, nursing assistant comprised the most vulnerable category. Our findings highlight the need for improving healthcare facility environments, specific training and supervision to cope with public health emergencies.

Risk factors associated with the severity of COVID-19 in a region of the Brazilian Amazon.

The Brazilian Northern region registered a high incidence of COVID-19 cases, particularly in the state of Pará. The present study investigated the risk factors associated with the severity of COVID-19 in a Brazilian Amazon region of 100,819 cases. An epidemiological, cross-sectional, analytical and demographic study, analyzing data on confirmed cases for COVID-19 available at the Brazilian Ministry of Health's surveillance platform, was conducted. Variables such as, municipalities of residence, age, gender, signs and symptoms, comorbidities were included and associated with COVID-19 cases and outcomes. The spatial distribution was performed using the ArcGIS program. A total of 100,819 cases were evaluated. Overall, patients had the mean age of 42.3 years, were female (51.2%) and with lethality reaching 4.79% of cases. Main symptoms included fever (66.5%), cough (61.9%) and sore throat (39.8%). Regarding comorbidities, most of the patients presented cardiovascular disease (5.1%) and diabetes (4.2%). Neurological disease increased risk of death by nearly 15 times, followed by obesity (5.16 times) and immunodeficiency (5.09 time). The municipalities with the highest incidence rate were Parauapebas, Canaã dos Carajás and Jacareacanga. Similarity between the Lower Amazon, Marajó and Southwest mesoregions of Pará state were observed concerning the highest morbidity rates. The obtained data demonstrated that the majority of cases occurred among young adults, females, with the classic influenza symptoms and chronic diseases. Finally, data suggest that the highest incidences were no longer in the metropolitan region of the state. The higher lethality rate than in Brazil may be associated with the greater impacts of the disease in this Amazonian population, or factors associated with fragile epidemiological surveillance in the notification of cases of cure.

As descobertas genômicas do SARS-CoV-2 e suas implicações na pandemia de COVID-19

Objetivo: Auxiliar no entendimento da COVID-19 em relação à origem do SARS-CoV-2, suas descobertas genômicas, patogenia, possíveis hospedeiros primários e intermediários, além da comparação com outros coronavírus. Metodos: foram utilizadas as bases de dados Scientific Eletronic Library Online e PubMed, com artigos de revisão e originais, em língua portuguesa e inglesa, pesquisados no período de 05 de março a 10 de abril de 2020, adotando os seguintes descritores: SARS-CoV, COVID-19, coronavirus, Wuhan, genome, structure, origin, transmission, evolution, zoonotic. Os artigos originais identificados foram incluídos nesta revisão, juntamente com artigos de suporte referenciados por estes. Resultados: As características genômicas descritas até o momento podem explicar, em parte, a infectividade e a transmissibilidade do SARS-CoV-2 em humanos. Devido aos notáveis recursos de SARS-CoV-2, incluindo o local otimizado do domínio de ligação ao receptor (RBD) e de clivagem polibásica, é pouco provável um cenário laboratorial para a origem do SARS-CoV-2. Conclusão: Para o presente, é de extrema importância obter mais dados genéticos e funcionais sobre o SARS-CoV-2, incluindo estudos em animais, sequenciamento do vírus em casos muito precoces e identificação dos parentes virais mais próximos do SARS-CoV-2 que circulam em animais.(AU)Objective: To assist in the understanding of COVID-19 in relation to the origin of SARS-CoV-2, its genomic discoveries, pathogenesis, possible primary and intermediate hosts, in addition to comparison with other coronaviruses. Methods: the Scientific Electronic Library Online and PubMed databases were used, with review articles and originals, in Portuguese and English, researched from March 5 to April 10, 2020, adopting the following descriptors: SARS-CoV , COVID-19, coronavirus, Wuhan, genome, structure, origin, transmission, evolution, zoonotic. The original articles identified were included in this review, along with supporting articles referenced by them. Results: The genomic characteristics described so far may partly explain the infectivity and transmissibility of SARS-CoV-2 in humans. Due to the remarkable resources of SARS-CoV-2, including the optimized site of the receptor binding domain (RBD) and polybasic cleavage, a laboratory scenario for the origin of SARS-CoV-2 is unlikely. Conclusion: For the present, it is extremely important to obtain more genetic and functional data on SARS-CoV-2, including studies on animals, sequencing of the virus in very early cases and identification of the closest viral relatives of SARS-CoV-2 that circulate in animals.(AU)