Differences in clinical features and mortality in very old unvaccinated patients (≥ 80 years) hospitalized with COVID-19 during the first and successive waves from the multicenter SEMI-COVID-19 Registry (Spain)

Background: Old age is one of the most important risk factors for severe COVID-19. Few studies have analyzed changes in the clinical characteristics and prognosis of COVID-19 among older adults before the availability of vaccines. This work analyzes differences in clinical features and mortality in unvaccinated very old adults during the first and successive COVID-19 waves in Spain. Methods This nationwide, multicenter, retrospective cohort study analyzes unvaccinated patients >= 80 years hospitalized for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). Patients were classified according to whether they were admitted in the first wave (March 1-June 30, 2020) or successive waves (July 1-December 31, 2020). The endpoint was all-cause in-hospital mortality, expressed as the case fatality rate (CFR). Results Of the 21,461 patients hospitalized with COVID-19, 5,953 (27.7%) were >= 80 years (mean age [IQR]: 85.6 [82.3-89.2] years). Of them, 4,545 (76.3%) were admitted during the first wave and 1,408 (23.7%) during successive waves. Patients hospitalized in successive waves were older, had a greater Charlson Comorbidity Index and dependency, less cough and fever, and met fewer severity criteria at admission (qSOFA index, PO2/FiO2 ratio, inflammatory parameters). Significant differences were observed in treatments used in the first (greater use of antimalarials, lopinavir, and macrolides) and successive waves (greater use of corticosteroids, tocilizumab and remdesivir). In-hospital complications, especially acute respiratory distress syndrome and pneumonia, were less frequent in patients hospitalized in successive waves, except for heart failure. The CFR was significantly higher in the first wave (44.1% vs. 33.3%; -10.8%; p = 95 years (54.4% vs. 38.5%; -15.9%; p < 0.001). After adjustments to the model, the probability of death was 33% lower in successive waves (OR: 0.67; 95% CI: 0.57-0.79). Conclusions Mortality declined significantly between the first and successive waves in very old unvaccinated patients hospitalized with COVID-19 in Spain. This decline could be explained by a greater availability of hospital resources and more effective treatments as the pandemic progressed, although other factors such as changes in SARS-CoV-2 virulence cannot be ruled out

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio