Durability of anti-spike antibodies after vaccination with mRNA SARS-CoV-2 vaccine is longer in subjects with previous infection: could the booster dose be delayed?

PURPOSE: The long-term effectiveness of BNT162b2/Pfizer vaccine remains undetermined. This observational prospective study was designed to verify durability of antibodies against the viral receptor-binding domain (RBD) spike (S)-protein (RBD S-Protein IgG) after the second-dose administration of the vaccine among Health Care Workers (HCWs). METHODS: In all HCWs at the Poliambulanza Foundation Hospital Brescia (Italy) were quantified the levels of RBD S-Protein IgG (Abbott Diagnostics) at 45 and 240 days after the second-dose vaccine. Previous infection was defined as antibodies against SARS-CoV-2 nucleocapsid positivity (Abbott Diagnostics) before vaccination. The Mann-Whitney U test was used to compare mean levels of RBD S-Protein IgG among previously infected and uninfected HCWs. RESULTS: The mean level of the RBD S-protein IgG detected 45 days after the second dose of the vaccine was 30,041 AU/mL (95% CI 145-80,000) for the 250 previously infected HCWs and it was significantly higher (p < 0.001) than that observed in the 1121 previously uninfected subject with the mean level of 10,604 AU/mL (95% CI 165-62,241). Similarly, at 240 days in previously infected subjects the antibody titer was of 8145 AU/mL (95% CI 347-80,000) and significantly higher (p < 0.001) than that observed in the 1121 previously uninfected HCWs with a mean antibody level of 1271 AU/mL (95% CI 50-80,000). When comparing the change in mean antibody levels overtime, the previously infected HCWs presented a 72.9% reduction in RBD S-protein IgG while in the previously uninfected HCWs the reduction was 88.0%. In addition, in the HCWs group without previous infection we reported 53 new SARS-CoV-2 infections and they had a mean level of RBD S-protein IgG antibodies of 1039 AU/mL (95% CI 157-4237) at 240 days. No new infections were found in previously SARS-CoV-2 infected subjects. CONCLUSIONS: We report that the mean level of post vaccinal RBD S-protein IgG was significantly higher in the previously infected HCWs than in previously uninfected subjects at 45 and 240 days after the second-dose vaccine. Moreover, our data suggest that the risk of a new SARS-CoV-2 infection was higher in the previously uninfected HCWs than in those who had already contracted natural viral infection. The limitations of this study prevent us to draw definitive conclusions on the antibody titers and on the role of a previous SARS-CoV-2 infection in influencing the levels of post-vaccine RBD S-protein IgG. The booster dose of the vaccine could be delayed after the second dose in previously naturally infected subject and it could have an important strategic impact on the organization of the future COVID-19 vaccination campaign.

Effect of Corticosteroids on Mortality in Hospitalized COVID-19 Patients Not Receiving Invasive Mechanical Ventilation.

The most beneficial effect of corticosteroid therapy in COVID-19 patients has been shown in subjects receiving invasive mechanical ventilation (IMV), corresponding to a score of 6 on the World Health Organization (WHO) COVID-19 Ordinal Scale for Clinical Improvement (OSCI). The aim of this observational, single-center, prospective study was to assess the association between corticosteroids and hospital mortality in coronavirus disease 2019 (COVID-19) patients who did not receive IMV (OSCI 3-5). Included were 1,311 COVID-19 patients admitted to nonintensive care wards, and they were divided in two cohorts: (i) 480 patients who received corticosteroid therapy and (ii) 831 patients who did not. The median daily dose was of 8 mg of dexamethasone or equivalent, with a mean therapy duration of 5 (3-9) days. The indication to administer or withhold corticosteroids was given by the treating physician. In-hospital mortality was similar between the two cohorts after adjusting for possible confounders (adjusted odds ratio (ORadj) 1.04, 95% confidence interval (CI), 0.81-1.34, P = 0.74). There was also no difference in Intensive Care Unit (ICU) admission (ORadj 0.81, 95% CI, 0.56-1.17, P = 0.26). COVID-19 patients with noninvasive mechanical ventilation (NIMV) had a lower risk for ICU admission if they received steroid therapy (ORadj 0.58, 95% CI, 0.35-0.94, P = 0.03). In conclusion, corticosteroids were overall not associated with a difference in hospital mortality for patients with COVID-19 with OSCI 3-5. In the subgroup of patients with NIMV (OSCI 5), corticosteroids reduced ICU admission, whereas the effect on mortality requires further studies.

Pulmonary thromboembolism in hospitalised COVID-19 patients at moderate to high risk by Wells score: a report from Lombardy, Italy.

OBJECTIVES: To present a single-centre experience on CT pulmonary angiography (CTPA) for the assessment of hospitalised COVID-19 patients with moderate-to-high risk of pulmonary thromboembolism (PTE). METHODS: We analysed consecutive COVID-19 patients (RT-PCR confirmed) undergoing CTPA in March 2020 for PTE clinical suspicion. Clinical data were retrieved. Two experienced radiologists reviewed CTPAs to assess pulmonary parenchyma and vascular findings. RESULTS: Among 34 patients who underwent CTPA, 26 had PTE (76%, 20 males, median age 61 years, interquartile range 54-70), 20/26 (77%) with comorbidities (mainly hypertension, 44%), and 8 (31%) subsequently dying. Eight PTE patients were under thromboprophylaxis with low-molecular-weight heparin, four PTE patients had lower-limbs deep vein thrombosis at ultrasound examination (performed in 33/34 patients). Bilateral PTE characterised 19/26 cases, with main branches involved in 10/26 cases. Twelve patients had a parenchymal involvement >75%, the predominant pneumonia pattern being consolidation in 10/26 patients, ground glass opacities in 9/26, crazy paving in 5/26, and both ground glass opacities and consolidation in 2/26. CONCLUSION: COVID-19 patients are prone to PTE. ADVANCES IN KNOWLEDGE: PTE, potentially attributable to an underlying thrombophilic status, may be more frequent than expected in COVID-19 patients. Extension of prophylaxis and adaptation of diagnostic criteria should be considered.