ABSTRACT
Background: T-cell response against SARS-CoV-2 is essential for disease control and to understand correlates of protection against various disease outcomes in COVID-19. This makes T-cell measurement an important tool for clinical management. Aim(s): To evaluate the IFN-gamma-releasing T-cell response against spike (S), nucleocapsid (N) and membrane (M) SARS-CoV-2 antigens using an ELISPOT-based assay in acute, convalescent, and vaccinated individuals. Method(s): Blood samples were collected from acute (n=71) and convalescent (n=59) individuals classified according to severity;and from vaccinated (n=48) and non-vaccinated (n=80) controls. After stimulating with S, N and M antigens overnight, T-cell response was measured (T-SPOT Discovery SARS-CoV-2. Oxford Immunotec, UK). IgG against S and N were also measured. Result(s): S antigen triggered the highest number of T-cell responses (46%), although responses against N and M were in a large percentage of individuals. The majority of convalescent individuals (93%) had a reactive T-cell response more than 200 days after diagnosis. Such response increased with severity. Acute patients had fewer positive responses (68%). S antigen triggered most responses in vaccinated controls, but only in half of them T-cell response was observed after the second dose. A higher percentage of individuals showed IgG response compared to IFN-gamma-releasing T-cell responses, and moderate correlations between both quantitative responses were seen. Conclusion(s): T-cell response against SARS-CoV-2 is low during acute phase but may increase over time, as seen in convalescent individuals. Regarding vaccinated individuals, half had a positive test result after the second dose.
ABSTRACT
OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.
ABSTRACT
Objective To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design A secondary analysis derived from multicenter, observational study. Setting Critical Care Units. Patients Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions Corticosteroids vs. no corticosteroids. Main variables of interest Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0;95% CI: 0.98–1.15). Corticosteroids were administered in 298/537 (55.5%) patients of “A” phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55–1.33]). A total of 338/623 (54.2%) patients in “B” phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49–1.05]). Finally, 535/857 (62.4%) patients in “C” phenotype received corticosteroids. In this phenotype HR (0.75 [0.58–0.98]) and sHR (0.79 [0.63–0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.