Social Inequalities Negatively Impact SARS-CoV-2 Seroprevalence in Different Subgroups of Healthcare Workers in Rio De Janeiro (preprint)

Background: COVID-19 has exacerbated health inequalities worldwide. Yet, such a perspective has not been investigated in specific healthcare workers and their resulting inclusion as a priority group for vaccination have been an important focus of political and social discussion. This study aimed at investigating whether SARS-CoV-2-seropositivity in healthcare workers in a public hospital in Rio de Janeiro, Brazil, was influenced by social determinants of health and the social vulnerability in subgroups of workers. Methods: A serological survey was conducted in 1,154 healthcare workers in June and July 2020. The association between the serological test results for detection of IgG antibodies to SARS-CoV-2 and socioeconomic, occupational characteristics and transportation used by the workers to commute was assessed using the Pearson´s chi-square test and Carmer’s V. Findings: Overall, the serum prevalence for the virus in the healthcare workers was 30%. Non-white workers with lower income and schooling, as well as users of the mass transportation system showed the highest infection rates. Importantly they mostly corresponded to hospital support workers, in particular the cleaning personnel. Accordingly, income, schooling and work modality appeared as negative predictors, as ascertained by forest plot analysis. Interpretations: The data clearly illustrate the inequality in SARS-CoV-2 infection in the Brazilian population, comprising even healthcare workers of the Brazilian unified health system.Funding Information: This study was financed by Fiocruz, CNPq, Faperj, Capes, FOCEM/Mercosur and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.Declaration of Interests: The authors declare no competing financial interests.Ethics Approval Statement: “Clinical and immunological characteristics of children, adolescents, and adults with COVID-19 diagnosis: COVID-19 Kids Project” was submitted to the Institutional Review Board of IFF (CEP/IFF) under identification number 30487120.2.0000.0008 and approved under review number 4.100.148. There was no discrimination in the selection of research subjects or exposure to unnecessary risks.

Hyperactive cytokine T-cell response is associated with immunosenescence in severe acute COVID-19 infection (preprint)

COVID-19 is a disease caused by the novel SARS-CoV-2 coronavirus, originally classified as a severe acute respiratory syndrome coronavirus (SARS-CoV). The most severe cases of COVID-19 can progress to severe pneumonia with respiratory failure, septicemia, multiple organ failure and death. The severity of the disease is aggravated by the deregulation of the immune system causing an excessive initial inflammation including the cytokine storm, compring interleukins characteristic of the T-dependent adaptive response. In the present study we show that severe patients have high levels of T helper type-1 and type-2 cytokines, as well as VGEF. Furthermore, our show abnormal cytokine levels upon T-cell mitogen stimulation, in a non-polarized response profile. This response is not specific, given that the stimulus with the heterologous tuberculin antigen was able to induce high levels of cytokines compared to healthy controls, including the vascular endothelial growth factor VEGF, which promotes neoangiogenesis in physiological and pathophysiological conditions, caused by tissue hypoxia, and involved in a clonal exhaustion program in T cells. This can be decisive given our findings demonstrating for the first time a significantly increased frequency of late-differentiated CD8+ T cells characterized by critically shortened telomeres with particular phenotype (CD57+CD28-) in severe acute COVID-19 infection. These findings reveal that severe COVID-19 is associated with senescence of T cells, especially within the CD8+ T cell compartment and points to possible mechanisms of loss of clonal repertoire and susceptibility to recurrences of COVID-19 symptoms, due to viral relapse and reinfection events.

The Emerging Role of Neutrophil Extracellular Traps in Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19) (preprint)

The novel coronavirus SARS-CoV2 causes COVID-19, a highly pathogenic viral infection threatening millions. The majority of those infected are asymptomatic or mildly symptomatic showing typical clinical signs of common cold. However approximately 20% of the patients can progress to acute respiratory distress syndrome (ARDS) and eventually death in about 5% of cases. Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for virus entry into host target cells. The upregulation of ACE2 in patients with comorbidities may represent a propensity for increased viral load and spreading of infection to extrapulmonary tissues. This systemic infection is associated with higher neutrophil to lymphocyte ratio in infected tissues and high levels of pro-inflammatory cytokines leading to an extensive microthrombus formation with multiorgan failure. Herein we investigated whether SARS-CoV2 can stimulate extracellular neutrophils traps (NETs) in a process called NETosis. We demonstrated for the first time that SARS-CoV2 in fact is able to activate NETosis in human neutrophils. Our findings indicated that this process is associated with increased levels of intracellular Reactive Oxygen Species (ROS) in neutrophils. The ROS-NET pathway plays a role in thrombosis formation and our study suggest the importance of this target for therapy approaches against disease.