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Objectives: To assess the benefits of remdesivir in hospitalized COVID-19 patients receiving combined immunomodulatory therapy (CIT) with dexamethasone and tocilizumab., Methods: This was a cohort study of microbiologically confirmed COVID-19 hospitalized patients. The primary outcome was all-cause 28 day mortality. Secondary outcomes were need for invasive mechanical ventilation (IMV) and IMV/death. Subgroup analyses according to SARS-CoV-2 cycle threshold (Ct) values and inflammation biomarkers were performed. Multivariable marginal structural Cox proportional hazards regression models were used to analyse the association between remdesivir therapy and the risk of outcomes of interest., Results: Of 1368 hospitalized patients treated with corticosteroids, 1014 (74%) also received tocilizumab, 866 (63%) remdesivir and 767 (56%) tocilizumab + remdesivir. The 28 day mortality was 9% in the overall cohort, with an adjusted HR (aHR) of 0.32 (95% CI = 0.17-0.59) for patients receiving CIT. In the latter group, the 28 day mortality was 6.5%, with an aHR of 1.11 (95% CI = 0.57-2.16) for remdesivir use and there were no differences in secondary outcomes. The risk of primary and secondary outcomes with remdesivir differed by Ct and C-reactive protein (CRP) levels in patients receiving CIT: for 28 day mortality, the aHR was 0.48 (95% CI = 0.21-1.11) for Ct <25, 0.12 (95% CI = 0.02-0.66) for Ct <25 and <5 day symptom duration and 0.13 (95% CI = 0.03-0.50) for CRP <38 mg/L; for IMV and IMV/death, the aHR was 0.32 (95% CI = 0.13-0.77) and 0.33 (95% CI = 0.17-0.63), respectively, in patients with Ct <25., Conclusions: The benefits of remdesivir administered with dexamethasone and tocilizumab in hospitalized COVID-19 patients differ depending on Ct and CRP. Remdesivir decreases the risk of mortality and need for IMV in patients with high viral loads and low-grade systemic inflammation., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (R e  < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: Durability of the humoral immune response to SARS-CoV-2 has yet to be defined. We longitudinally evaluated during a 12-month period the antibody responses to SARS-CoV-2, and analysed predictors of antibody titres decline and seroreversion., Methods: Prospective study conducted in a cohort of patients hospitalized for microbiologically-confirmed COVID-19. Blood and nasopharyngeal samples were sequentially obtained during hospital stay and at 1, 2, 6 and 12 months after patients' discharge for measuring anti-spike (S) and anti-nucleocapsid (N) IgG antibody levels and SARS-CoV-2 RNA, respectively., Results: 80 non-vaccinated patients were analysed. At month 12 after discharge, 73 (91.2%) patients exhibited detectable S-IgG and 35 (43.8%) N-IgG antibody titres. A gradual wane was observed in S-IgG and N-IgG antibody titres. Linear regression showed that S-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.059 [0.05-0.067], p < 0.001), inversely with WHO severity score (coefficient [95% CI] -0.042 [-0.079/-0.004], p = 0.033), and there was a trivial positive association with age (coefficient [95% CI] 0.002 [0-0.005], p = 0.10); N-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.091 [0.078-0.105], p < 0.001). Logistic regression showed that seroreversion for S-IgG was inversely associated with peak S-IgG (OR 0.19; 95% CI, 0.04-0.45; p = 0.004); seroreversion for N-IgG was inversely associated with peak N-IgG (OR 0.71; 95% 0.53-0.90; p = 0.009) and positively with cycle threshold of RT-PCR (OR 1.14; 95% CI, 1.00-1.33; p = 0.062)., Conclusion: Anti-spike IgG antibodies remain detectable one year after hospitalization for COVID-19. Higher peak antibody titres and disease severity were associated with increased durability of detectable antibodies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Data on the performance of saliva specimens for diagnosing coronavirus disease 2019 (COVID-19) in ambulatory patients are scarce and inconsistent. We assessed saliva-based specimens for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase PCR (RT-PCR) in the community setting and compared three different collection methods. This prospective study was conducted in three primary care centers. RT-PCR was performed on paired nasopharyngeal swabs (NPS) and saliva samples collected from outpatients with a broad clinical spectrum of illness. To assess differences in collection methods, saliva specimens were obtained in a different way in each of the participating centers: supervised collection (SVC), oropharyngeal washing (OPW), and self-collection (SC). Pairs of NPS and saliva samples from 577 patients (median age, 39 years; 44% men; 42% asymptomatic) were collected and tested, and 120 (20.8%) gave positive results. The overall agreement with NPS results and kappa coefficients (κ) for saliva samples obtained by SVC, OPW, and SC were 95% (κ = 0.85), 93.4% (κ = 0.76), and 93.3% (κ = 0.76), respectively. The sensitivities (95% confidence intervals [95% CI]) of the saliva specimens ranged from 86% (72.6% to 93.7%) for SVC to 66.7% (50.4% to 80%) for SC samples. Sensitivity was higher for samples with lower cycle threshold ( C T ) values. The best RT-PCR performance was observed for SVC, with sensitivities (95% CI) of 100% (85.9% to 100%) in symptomatic individuals and 88.9% (50.7% to 99.4%) in asymptomatic individuals at C T values of ≤30. We conclude that saliva is an acceptable specimen for the detection of SARS-CoV-2 in the community setting. Specimens collected under supervision perform comparably to NPS and can effectively identify individuals at higher risk of transmission under real-life conditions., (Copyright © 2021 American Society for Microbiology.)

The clinical presentation of COVID-19 is very heterogeneous, ranging from asymptomatic to severe, which could lead to the need for mechanical ventilation or even death.We analyzed the serum levels of IL-6 in patients with COVID-19 diagnosis and its relationship with the severity of the disease, the need for mechanical ventilation and with patient mortality. We assessed IL-6 in a cohort of 50 patients diagnosed with COVID-19 pneumonia with different degrees of disease severity, and compared it with clinical and laboratory findings. We found higher levels of IL-6 in patients with more severe pneumonia according to CURB-65 scale (p = 0.001), with ICU mechanical ventilation requirements (p = 0.02), and who subsequently died (p = 0.003). Of the clinical and analytical parameters analyzed in the current study, the serum levels of IL-6 was the most effective predictor of disease severity. From the data obtained in ROC curve analysis, we defined a cut-off point for serum IL-6 levels of 35 pg/mL above which both the risk of mortality (OR = 20.00, 95 % CI 4.214-94-912, p = 0.0001) and ICU admission (OR = 12.750, 95 % CI 2,159-75,3,3, p = 0.005) were increased. Starting from blood IL-6 levels 27 out of 50 patients, with high levels and more severe symptoms, were treated with the IL-6 receptor antagonist Tocilizumab. IL-6 serum levels appear to be a useful prognostic biomarker in patients with a diagnosis of COVID-19 pneumonia. A cut-off point of 35 pg/mL could clearly differentiate patients a with more severe disease., (Copyright © 2020 Elsevier Ltd. All rights reserved.)