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• Improvement at 14 days occurs in 63.3% of severe COVID-19 treated with tocilizumab. • Early administration of tocilizumab is associated with better clinical response. • A recruitment window of 48 hours from admission in tocilizumab randomized clinical trials is advisable. Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients. We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital "12 de Octubre" until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models. Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1–3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3–8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively). TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission. [ABSTRACT FROM AUTHOR]

The individual influence of a variety of comorbidities on COVID-19 patient outcomes has already been analyzed in previous works in an isolated way. We aim to determine if different associations of diseases influence the outcomes of inpatients with COVID-19. Retrospective cohort multicenter study based on clinical practice. Data were taken from the SEMI-COVID-19 Registry, which includes most consecutive patients with confirmed COVID-19 hospitalized and discharged in Spain. Two machine learning algorithms were applied in order to classify comorbidities and patients (Random Forest -RF algorithm, and Gaussian mixed model by clustering -GMM-). The primary endpoint was a composite of either, all-cause death or intensive care unit admission during the period of hospitalization. The sample was randomly divided into training and test sets to determine the most important comorbidities related to the primary endpoint, grow several clusters with these comorbidities based on discriminant analysis and GMM, and compare these clusters. A total of 16,455 inpatients (57.4% women and 42.6% men) were analyzed. According to the RF algorithm, the most important comorbidities were heart failure/atrial fibrillation (HF/AF), vascular diseases, and neurodegenerative diseases. There were six clusters: three included patients who met the primary endpoint (clusters 4, 5, and 6) and three included patients who did not (clusters 1, 2, and 3). Patients with HF/AF, vascular diseases, and neurodegenerative diseases were distributed among clusters 3, 4 and 5. Patients in cluster 5 also had kidney, liver, and acid peptic diseases as well as a chronic obstructive pulmonary disease; it was the cluster with the worst prognosis. The interplay of several comorbidities may affect the outcome and complications of inpatients with COVID-19. [ABSTRACT FROM AUTHOR]

The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations. Author summary: In this work we describe the prognostic value of early detection of SARS-CoV-2-specific T cell response in acute COVID-19, as patients without a prompt SARS-CoV-2-specific T cell response progress to severe COVID-19. We also show that the presence of specific T cells against SARS-CoV-2 when patients arrive to the emergency room is a protective factor against developing severe COVID-19, independently of the age and gender of the patient, which are two major known contributors to disease outcome. In addition, we show robust cellular and humoral immune responses persist 3 months after real-world vaccination. [ABSTRACT FROM AUTHOR]

The aim of our study was to elucidate if SARS-CoV-2 viral load on admission, measured by real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on nasopharyngeal samples, was a marker of disease severity. All hospitalized adult patients with a diagnosis of SARS-CoV-2 infection by rRT-PCR performed on a nasopharingeal sample from March 1 to March 18 in our institution were included. The study population was divided according to the Ct value obtained upon admission in patients with high viral load (Ct < 25), intermediate viral load (Ct: 25–30) and low viral load (Ct > 30). Demographic, clinical and laboratory variables of the different groups were analyzed to assess the influence of viral load on the development of respiratory failure during admission. Overall, 455 sequential patients were included. The median Ct value was 28 (IQR: 24–32). One hundred and thirty patients (28.6%) had a high viral load, 175 (38.5%) an intermediate viral load and 150 (33%) a low viral load. Advanced age, male sex, presence of cardiovascular disease and laboratory markers such as lactate dehydrogenase, lymphocyte count and C-reactive protein, as well as a high viral load on admission, were predictive of respiratory failure. A Ct value < 25 was associated with a higher risk of respiratory failure during admission (OR: 2.99, 95%IC: 1.57–5.69). SARS-CoV-2 viral load, measured through the Ct value on admission, is a valuable tool to predict the development of respiratory failure in COVID-19 inpatients. [ABSTRACT FROM AUTHOR]

• An increasing number of immunomodulatory therapies are being tested for COVID-19. • A survival benefit has been shown with the use of corticosteroids. • The role of combination therapy with corticosteroids and tocilizumab is unclear. • This study analyzed a single-center cohort of patients aged ≥65 years with severe COVID-19. • The sequential use of corticosteroids and tocilizumab was associated with better outcomes. The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. A retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5 mg/kg/12 h to 250 mg/24 h), either alone (CS group) or associated with intravenous tocilizumab (400–600 mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. Totals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17–0.68; P = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21–0.68; P = 0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21–0.72; P = 0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49–3.41; P < 0.001). The occurrence of secondary infection was similar between both groups. The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19. [ABSTRACT FROM AUTHOR]

• Immunomodulatory treatment could improve the prognosis of COVID-19. • Patients who received anakinra as rescue therapy were compared with controls. • Anakinra did not improve in-hospital prognosis of patients after tocilizumab failure. A subgroup of patients with SARS-CoV-2 infection was thought to have developed cytokine release syndrome and were treated with tocilizumab; however, a significant percentage of patients evolved. This study aimed to determine the usefulness of anakinra as a rescue treatment for patients with tocilizumab-refractory COVID-19 disease. A prospective cohort of patients with COVID-19 pneumonia who received anakinra as salvage therapy after failure of tocilizumab were compared (1:1) with selected controls in a historical cohort of patients treated with tocilizumab. Cases and controls were matched by age, comorbidities, pulse oximetry oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at baseline, and time elapsed since the initiation of treatment with tocilizumab. The primary outcome was the improvement in clinical status measured by a 6-point ordinal scale, from baseline to day 21. The study included 20 cases and 20 controls (mean age 65.3 ± 12.8 years, 65% males). No differences were found in the clinical improvement rates at 7, 14 and 21 days of follow-up. The in-hospital mortality rate for patients receiving anakinra was 55% vs. 45% in the control group (P = 0.527). Treatment with anakinra was not useful in improving the prognosis of patients with tocilizumab-refractory severe COVID-19. [ABSTRACT FROM AUTHOR]