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      No time for complacency on COVID-19 in Europe

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          A paradigm shift to combat indoor respiratory infection

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            Therapeutic strategies for COVID-19: progress and lessons learned

            The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic strategies that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or human proteins to control viral infection, encompassing hundreds of potential drugs and thousands of patients in clinical trials. So far, a few small-molecule antiviral drugs (nirmatrelvir–ritonavir, remdesivir and molnupiravir) and 11 monoclonal antibodies have been marketed for the treatment of COVID-19, mostly requiring administration within 10 days of symptom onset. In addition, hospitalized patients with severe or critical COVID-19 may benefit from treatment with previously approved immunomodulatory drugs, including glucocorticoids such as dexamethasone, cytokine antagonists such as tocilizumab and Janus kinase inhibitors such as baricitinib. Here, we summarize progress with COVID-19 drug discovery, based on accumulated findings since the pandemic began and a comprehensive list of clinical and preclinical inhibitors with anti-coronavirus activities. We also discuss the lessons learned from COVID-19 and other infectious diseases with regard to drug repurposing strategies, pan-coronavirus drug targets, in vitro assays and animal models, and platform trial design for the development of therapeutics to tackle COVID-19, long COVID and pathogenic coronaviruses in future outbreaks.
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              Effectiveness of a bivalent mRNA vaccine booster dose to prevent severe COVID-19 outcomes: a retrospective cohort study

              Background In late 2022, the SARS-CoV-2 omicron (B.1.1.529) BA.5 sublineage accounted for most of the sequenced viral genomes worldwide. Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the omicron BA.4 and BA.5 sublineages. Since September, 2022, a single bivalent mRNA vaccine booster dose has been recommended for adults who have completed a primary SARS-CoV-2 vaccination series and are at high risk of severe COVID-19. We aimed to evaluate the effectiveness of a bivalent mRNA vaccine booster dose to reduce hospitalisations and deaths due to COVID-19. Methods We did a retrospective, population-based, cohort study in Israel, using data from electronic medical records in Clalit Health Services (CHS). We included all members of CHS who were aged 65 years or older and eligible for a bivalent mRNA COVID-19 booster vaccination. We used hospital records to identify COVID-19-related hospitalisations and deaths. The primary endpoint was hospitalisation due to COVID-19, which we compared between participants who received a bivalent mRNA booster vaccination and those who did not. A Cox proportional hazards regression model with time-dependent covariates was used to estimate the association between the bivalent vaccine and hospitalisation due to COVID-19 while adjusting for demographic factors and coexisting illnesses. Findings Between Sept 27, 2022, and Jan 25, 2023, 569 519 eligible participants were identified. Of those, 134 215 (24%) participants received a bivalent mRNA booster vaccination during the study period. Hospitalisation due to COVID-19 occurred in 32 participants who received a bivalent mRNA booster vaccination and 541 who did not receive a bivalent booster vaccination (adjusted hazard ratio 0·28, 95% CI 0·19–0·40). The absolute risk reduction for hospitalisations due to COVID-19 in bivalent mRNA booster recipients versus non-recipients was 0·089% (95% CI 0·075–0·101), and the number needed to vaccinate to prevent one hospitalisation due to COVID-19 was 1118 people (95% CI 993–1341). Interpretation Participants who received a bivalent mRNA booster vaccine dose had lower rates of hospitalisation due to COVID-19 than participants who did not receive a bivalent booster vaccination, for up to 120 days after vaccination. These findings highlight the importance of bivalent mRNA booster vaccination in populations at high risk of severe COVID-19. Further studies with longer observation times are warranted. Funding None.
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                Author and article information

                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Published by Elsevier Ltd.
                0140-6736
                1474-547X
                22 May 2023
                22 May 2023
                Affiliations
                [a ]Institute of Global Health, Faculty of Medicine, University of Geneva, CH-1202, Geneva, Switzerland
                [b ]HIV/AIDS Unit, Division of Infectious Diseases, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland
                [c ]Geneva Centre for Emerging Viral Diseases, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland
                [d ]University Hospitals of Geneva and University of Geneva, Geneva, Switzerland
                [e ]French Academy of Sciences and Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, INSERM Paris, France
                [f ]National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Health of the Russian Federation, Moscow, Russia
                [g ]Department of Anthropology and The Vaccine Confidence Project, London School of Hygiene & Tropical Medicine, London, UK
                [h ]University of Antwerp, Antwerp, and KULeuven, Leuven, Belgium
                [i ]Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
                [j ]Imperial College London, London, UK
                [k ]George Institute for Global Health UK, London, UK
                [l ]School of Civil Engineering, University of Leeds, Leeds, UK
                [m ]Global Health Center, Graduate Institute for International Affairs and Development, Geneva, Switzerland
                [n ]WHO Regional Office for Europe, UN City, Copenhagen, Denmark
                Article
                S0140-6736(23)01012-7
                10.1016/S0140-6736(23)01012-7
                10202416
                37230103
                02ea946e-9626-4624-8e65-c579f0d762ca
                © 2023 Published by Elsevier Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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