Comparative kinetics of SARS-CoV-2 anti-spike protein RBD IgGs and neutralizing antibodies in convalescent and naïve recipients of the BNT162b2 mRNA vaccine versus COVID-19 patients.

BACKGROUND: Coronavirus SARS-CoV-2, the causative agent of COVID-19, has caused a still evolving global pandemic. Given the worldwide vaccination campaign, the understanding of the vaccine-induced versus COVID-19-induced immunity will contribute to adjusting vaccine dosing strategies and speeding-up vaccination efforts. METHODS: Anti-spike-RBD IgGs and neutralizing antibodies (NAbs) titers were measured in BNT162b2 mRNA vaccinated participants (n = 250); we also investigated humoral and cellular immune responses in vaccinated individuals (n = 21) of this cohort 5 months post-vaccination and assayed NAbs levels in COVID-19 hospitalized patients (n = 60) with moderate or severe disease, as well as in COVID-19 recovered patients (n = 34). RESULTS: We found that one (boosting) dose of the BNT162b2 vaccine triggers robust immune (i.e., anti-spike-RBD IgGs and NAbs) responses in COVID-19 convalescent healthy recipients, while naïve recipients require both priming and boosting shots to acquire high antibody titers. Severe COVID-19 triggers an earlier and more intense (versus moderate disease) immune response in hospitalized patients; in all cases, however, antibody titers remain at high levels in COVID-19 recovered patients. Although virus infection promotes an earlier and more intense, versus priming vaccination, immune response, boosting vaccination induces antibody titers significantly higher and likely more durable versus COVID-19. In support, high anti-spike-RBD IgGs/NAbs titers along with spike (vaccine encoded antigen) specific T cell clones were found in the serum and peripheral blood mononuclear cells, respectively, of vaccinated individuals 5 months post-vaccination. CONCLUSIONS: These findings support vaccination efficacy, also suggesting that vaccination likely offers more protection than natural infection.

Development of a novel risk score for the prediction of critical illness amongst COVID-19 patients.

OBJECTIVES: Coronavirus disease-19 (COVID-19) is associated with various clinical manifestations, ranging from asymptomatic infection to critical illness. The aim of this study is to evaluate the clinical and laboratory characteristics of hospitalised COVID-19 patients and construct a predictive model for the discrimination of patients at risk of disease progression. METHODS: A single-centre cohort study was conducted including consecutively patients with COVID-19. Demographic, clinical and laboratory findings were prospectively collected at admission. The primary outcome of interest was the intensive care unit admission. A risk model was constructed by applying a Cox's proportional hazard's model with elastic net penalty. Its diagnostic performance was assessed by receiver operating characteristic analysis and was compared with conventional pneumonia severity scores. RESULTS: From a total of 67 patients 15 progressed to critical illness. The risk score included patients' gender, presence of hypertension and diabetes mellitus, fever, shortness of breath, serum glucose, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein and fibrinogen. Its predictive accuracy was estimated to be high (area under the curve: 97.1%), performing better than CURB-65, CRB-65 and PSI/PORT scores. Its sensitivity and specificity were estimated to be 92.3% and 93.3%, respectively, at the optimal threshold of 1.6. CONCLUSIONS: A10-variable risk score was constructed based on clinical and laboratory characteristics in order to predict critical illness amongst hospitalised COVID-19 patients, achieving better discrimination compared with traditional pneumonia severity scores. The proposed risk model should be externally validated in independent cohorts in order to ensure its prognostic efficacy.

Longitudinal Analysis of Antibody Response Following SARS-CoV-2 Infection Depending on Disease Severity: A Prospective Cohort Study.

OBJECTIVE: Severe coronavirus disease 19 (COVID-19) is characterized by a dysregulated inflammatory response, with humoral immunity playing a central role in the disease course. The objective of this study was to assess the immune response and the effects of vaccination in recovered individuals with variable disease severity up to one year following natural infection. METHODS: A prospective cohort study was conducted including patients with laboratory-confirmed COVID-19. Disease severity was classified as mild, moderate, and severe based on clinical presentation and outcomes. Anti-RBD (receptor binding domain) and neutralizing antibodies were evaluated at multiple timepoints during the first year after COVID-19 diagnosis. RESULTS: A total of 106 patients were included; of them, 28 were diagnosed with mild, 38 with moderate, and 40 with severe disease. At least one vaccine dose was administered in 58 individuals during the follow-up. Participants with mild disease presented significantly lower anti-RBD and neutralizing antibodies compared to those with moderate and severe disease up to the 3rd and 6th months after the infection, respectively. After adjusting for covariates, in the third month, severe COVID-19 was associated with significantly higher anti-RBD (ß: 563.09; 95% confidence intervals (CI): 257.02 to 869.17) and neutralizing (ß: 21.47; 95% CI: 12.04 to 30.90) antibodies. Among vaccinated individuals, at the 12th month, a history of moderate disease was associated with significantly higher anti-RBD levels (ß: 5615.19; 95% CI: 657.92 to 10,572.46). CONCLUSIONS: Severe COVID-19 is associated with higher anti-RBD and neutralizing antibodies up to 6 months after the infection. Vaccination of recovered patients is associated with a remarkable augmentation of antibody titers up to one year after COVID-19 diagnosis, regardless of disease severity.