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      Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment

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          Abstract

          Tocilizumab (TCZ) has been administered in SARS-CoV-2 pneumonia but the factors associated with mortality before and after treatment remain unclear. Cox regression models were used to estimate the predictors of time to death in a cohort of hospitalized patients with COVID-19 receiving TCZ. In addition, the mean differences between discharged and deceased patients in laboratory parameters measured before and 3, 6 and 9 days after TCZ administration were estimated with weighted generalized estimation equations. The variables associated with time to death were immunosuppression (Hazard Ratio-HR 3.15; 95% confidence interval-CI 1.17, 8.51), diabetes mellitus (HR 2.63; 95% CI 1.23–5.64), age (HR 1.05; 95% CI 1.02–1.09), days since diagnosis until TCZ administration (HR 1.05, 95% CI 1.00–1.09), and platelets (HR 0.27; 95% CI: 0.11, 0.69). In the post-TCZ analysis and compared to discharged patients, deceased patients had more lactate dehydrogenase ( p = 0.013), troponin I ( p = 0.013), C-reactive protein ( p = 0.013), neutrophils ( p = 0.024), and fewer platelets ( p = 0.013) and lymphocytes ( p = 0.013) as well as a lower average PaO 2/FiO 2 ratio. In conclusion, in COVID-19 diagnosed patients receiving TCZ, early treatment decreased the risk of death, while age, some comorbidities and baseline lower platelet counts increased that risk. After TCZ administration, lower platelet levels were again associated with mortality, together with other laboratory parameters.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

            Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
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              Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

              Abstract Background In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives To describe the coagulation feature of patients with NCP. Methods Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed. Results The overall mortality was 11.5%, the non‐survivors revealed significantly higher D‐dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non‐survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. Conclusions The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                01 July 2021
                2021
                01 July 2021
                : 12
                Affiliations
                [ 1 ]Departamento de Reumatología, Hospital Universitario Virgen de las Nieves, Granada, Spain
                [ 2 ]Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, España
                [ 3 ]Instituto de Investigación Biosanitaria (ibs.Granada), Granada, Spain
                [ 4 ]Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
                Author notes

                Edited by: Rafael Maldonado, Pompeu Fabra University, Spain

                Reviewed by: Eliseo Albert, Hospital Clínico Universitario de Valencia, Spain

                Cristian Deana, Azienda Sanitaria Universitaria Integrata di Udine, Italy

                Yojana Gokhale, Lokmanya Tilak Municipal General Hospital, India

                *Correspondence: Inmaculada Salcedo-Bellido, isalcedo@ 123456ugr.es ; Rocío Barrios-Rodríguez, rbarrios@ 123456ugr.es
                [†]

                These authors share senior authorship

                This article was submitted to Drugs Outcomes Research and Policies, a section of the journal Frontiers in Pharmacology

                Article
                620187
                10.3389/fphar.2021.620187
                8281134
                34276355
                b94d84fa-292c-40bc-bda0-7e08ea4147bf
                Copyright © 2021 Sarabia De Ardanaz, Andreu-Ubero, Navidad-Fuentes, Ferrer-González, Ruíz del Valle, Salcedo-Bellido, Barrios-Rodríguez, Cáliz-Cáliz and Requena.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                covid-19,immunosupression,tocilizumab,mortality,risk factor,platelet

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