An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients (preprint)

BackgroundWhilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. MethodsHere, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. ResultsOur analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61 - 0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. ConclusionsAlthough clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome.

Cellular and Humoral Functional Responses After BNT162b2 SARS-CoV-2 mRNA Vaccination Differ Between Naïve and COVID-19-Recovered Individuals (preprint)

Medical history of COVID-19 was an exclusion criterion in the clinical trial that led to the vaccination regimen of two-doses for the BNT162b2 SARS-CoV-2 mRNA vaccine. Herein, we have analyzed a wide panel of immune responses triggered by this immunization in a cohort of naïve and COVID-19-recovered individuals. Plasma levels of S-specific immunoglobulins peaked after one vaccine shot in COVID-19-recovered individuals, while a second dose was needed in naïve subjects to achieve similar levels. However, naïve individuals did not reach as much neutralizing titers as COVID-19-recovered participants did after a complete vaccination regimen. At that point, after T cell stimulation with S-protein antigens from SARS-CoV-2, naïve individuals exhibited higher cytokine production levels, CD4+ T cells activation and proliferation than COVID-19-recovered individuals. Moreover, patent inverse correlations were observed between humoral and cellular immune variables, discriminating naïve from COVID-19-recovered subjects. Our data indicate that a previous history of COVID-19 determines the functional T and B cell-mediated responses to BNT162b2 vaccination and, consequently, individual’s history should be considered prior to the vaccination regime.Funding Information: CdF, JGP and JA are supported by Instituto de Salud Carlos III (ISCII). Research in ELC’s lab is supported by Fundación Familia Alonso, Santander Bank, Real Seguros, Fundación Mutua Madrileña, Fundación Uria, Fundación Caixa and Ayuntamiento de Madrid. Declaration of Interests: The authors declare that no conflict of interest exists.Ethics Approval Statement: Informed consent was obtained from all volunteers in accordance with the ethical standards and following the ethical guidelines of the 1975 Declaration of Helsinki. All healthy health personnel data were anonymized before study inclusion

A cohort of patients with COVID-19 in a major teaching hospital in Europe (preprint)

BACKGROUND Since the confirmation of the first patient infected with SARS-CoV-2 in Spain in January 2020, the epidemic has grown rapidly, with the greatest impact on the Madrid region. This article describes the first 2226 consecutive adult patients with COVID-19 admitted to the La Paz University Hospital in Madrid. METHODS Our cohort included all consecutively admitted patients who were hospitalized and who had a final outcome (death or discharge) in a 1286-bed hospital of Madrid (Spain) from February 25th (first case admitted) to April 19th, 2020. Data was entered manually into an electronic case report form, which was monitored prior to the analysis. RESULTS We consecutively included 2226 adult patients admitted to the hospital who either died (460) or were discharged (1766). The patients median age was 61 years; 51.8% were women. The most common comorbidity was arterial hypertension (41.3%). The most common symptoms on admission were fever (71.2%). The median time from disease onset to hospital admission was 6 days. Overall mortality was 20.7% and was higher in men (26.6% vs 15.1%). Seventy-five patients with a final outcome were transferred to the ICU (3.4%). Most patients admitted to the ICU were men, and the median age was 64 years. Baseline laboratory values on admission were consistent with an impaired immune-inflammatory profile. CONCLUSIONS We provide a description of the first large cohort of hospitalized patients with COVID-19 in Europe. Advanced age, male gender, the presence of comorbidities and abnormal laboratory values were more common among the patients with fatal outcomes.