Mitigation of Socio-Economical Inequalities on the Profile of Healthcare Workers Infected with SARS-CoV-2 upon Vaccination: The Experience of a Brazilian Public Healthcare Institution during the Omicron Wave

Background: COVID-19 increased health inequalities worldwide. Even among healthcare workers, social-economical features enhanced the risk of infection (having positive serology) during the first outbreak. The Omicron variant changed the pandemic course and differs from previous variants in many aspects (molecular, clinical, and epidemiological). Herein, we investigated if the profile of our hospital SARS-CoV-2-positive workers during the Omicron outbreak was the same as the first COVID-19 wave. Methods: Socio-demographics, previous infection, and vaccine status of 351 healthcare workers from our institution during the Omicron outbreak were compared between SARS-CoV-2-negative and -positive workers, using chi-square tests. These data were confronted with the profile observed at the beginning of the pandemic. Results: Compared to the original COVID-19 wave, higher odds of SARS-CoV-2 positivity in highly exposed workers in our hospital and a loss of impact of public transportation and other socio-demographic features in SARS-CoV-2 transmission were observed. Conclusions: Our data suggest the current phase of the pandemic is associated with a reduction of social inequalities among healthcare workers in Rio de Janeiro, possibly due to vaccine-associated protection. Therefore, a worldwide effort to advance vaccination coverage, especially for healthcare workers in developing countries, should be reinforced.

Critically Ill Coronavirus Disease 2019 Patients Exhibit Hyperactive Cytokine Responses Associated With Effector Exhausted Senescent T Cells in Acute Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can progress to severe pneumonia with respiratory failure and is aggravated by the deregulation of the immune system causing an excessive inflammation including the cytokine storm. METHODS: In this study, we report that severe acutely infected patients have high levels of both type-1 and type-2 cytokines. RESULTS: Our results show abnormal cytokine levels upon T-cell stimulation, in a nonpolarized profile. Furthermore, our findings indicate that this hyperactive cytokine response is associated with a significantly increased frequency of late-differentiated T cells with particular phenotype of effector exhausted/senescent CD28-CD57+ cells. Of note, we demonstrated for the first time an increased frequency of CD3+CD4+CD28-CD57+ T cells with expression of programmed death 1, one of the hallmarks of T-cell exhaustion. CONCLUSIONS: These findings reveal that COVID-19 is associated with acute immunodeficiency, especially within the CD4+ T-cell compartment, and points to possible mechanisms of loss of clonal repertoire and susceptibility to viral relapse and reinfection events.

SARS-CoV-2 seroprevalence and social inequalities in different subgroups of healthcare workers in Rio de Janeiro, Brazil.

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 Cramer's V. FINDINGS: Overall, the serum prevalence for the virus in the healthcare workers was 30% (342/1141). Non-white workers (208/561) with lower income (169/396) and schooling (150/353), as well as users of the mass transportation system (157/246) showed the highest infection rates. Importantly they mostly corresponded to hospital support workers (131/324), in particular the cleaning personnel (42/70). 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.

Gut Microbiota Dysbiosis Is a Crucial Player for the Poor Outcomes for COVID-19 in Elderly, Diabetic and Hypertensive Patients.

A new infectious disease, named COVID-19, caused by the coronavirus associated to severe acute respiratory syndrome (SARS-CoV-2) has become pandemic in 2020. The three most common pre-existing comorbidities associated with COVID-19-related death are elderly, diabetic, and hypertensive people. A common factor among these risk groups for the outcome of death in patients infected with SARS-CoV-2 is dysbiosis, with an increase in the proportion of bacteria with a pro-inflammatory profile. Due to this dysbiosis, elderly, diabetic, and hypertensive people present a higher propensity to mount an inflammatory environment in the gut with poor immune editing, culminating in a weakness of the intestinal permeability barrier and high bacterial product translocation to the bloodstream. This scenario culminates in a low-grade, persistent, and systemic inflammation. In this context, we propose here that high circulating levels of bacterial products, like lipopolysaccharide (LPS), can potentiate the SARS-CoV-2-induced cytokines, including IL-6, being crucial for development of the cytokine storm in the severe form of the disease. A better understanding on the possible correlation between gut dysbiosis and poor outcomes observed in elderly, diabetic, and hypertensive people can be useful for the development of new therapeutic strategies based on modulation of the gut microbiota.

The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19).

The novel coronavirus SARS-CoV-2 causes COVID-19, a highly pathogenic viral infection threatening millions. The majority of the individuals 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), evolving to 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-CoV-2 can stimulate extracellular neutrophils traps (NETs) in a process called NETosis. We demonstrated for the first time that SARS-CoV-2 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.

Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health.

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The impacts of the disease may be beyond the respiratory system, also affecting mental health. Several factors may be involved in the association between COVID-19 and psychiatric outcomes, such as fear inherent in the pandemic, adverse effects of treatments, as well as financial stress, and social isolation. Herein we discuss the growing evidence suggesting that the relationship between SARS-CoV-2 and host may also trigger changes in brain and behavior. Based on the similarity of SARS-CoV-2 with other coronaviruses, it is conceivable that changes in endocrine and immune response in the periphery or in the central nervous system may be involved in the association between SARS-CoV-2 infection and impaired mental health. This is likely to be further enhanced, since millions of people worldwide are isolated in quarantine to minimize the transmission of SARS-CoV-2 and social isolation can also lead to neuroendocrine-immune changes. Accordingly, we highlight here the hypothesis that neuroendocrine-immune interactions may be involved in negative impacts of SARS-CoV-2 infection and social isolation on psychiatric issues.