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      Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID‐19

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          Abstract

          Objective

          To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID‐19) compared to the use of other common analgesics.

          Methods

          We performed a propensity score–matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co‐codamol (paracetamol and codeine) or co‐dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID‐19, and the secondary outcome measure was all‐cause mortality.

          Results

          During follow‐up, the incidence rates of suspected/confirmed COVID‐19 were 15.4 and 19.9 per 1,000 person‐years in the NSAID‐exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID‐19 among the unmatched and propensity score–matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62–1.10) and 0.79 (95% CI 0.57–1.11), respectively, and adjusted hazard ratios for the risk of all‐cause mortality were 0.97 (95% CI 0.75–1.27) and 0.85 (95% CI 0.61–1.20), respectively. There was no effect modification by age or sex.

          Conclusion

          No increase in the risk of suspected or confirmed COVID‐19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.

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          Most cited references27

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              OpenSAFELY: factors associated with COVID-19 death in 17 million patients

              COVID-19 has rapidly impacted on mortality worldwide. 1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths. COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively). We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.
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                Author and article information

                Contributors
                k.raza@bham.ac.uk
                k.nirantharan@bham.ac.uk
                Journal
                Arthritis Rheumatol
                Arthritis Rheumatol
                10.1002/(ISSN)2326-5205
                ART
                Arthritis & Rheumatology (Hoboken, N.j.)
                John Wiley and Sons Inc. (Hoboken )
                2326-5191
                2326-5205
                29 April 2021
                May 2021
                : 73
                : 5 ( doiID: 10.1002/art.v73.5 )
                : 731-739
                Affiliations
                [ 1 ] Institute of Applied Health Research University of Birmingham, Birmingham, UK, and Warwick Medical School University of Warwick Coventry UK
                [ 2 ] Institute of Applied Health Research University of Birmingham Birmingham UK
                [ 3 ] Cegedim Rx London UK
                [ 4 ] Kennedy Institute of Rheumatology University of Oxford Oxford UK
                [ 5 ] Institute of Inflammation and Ageing University of Birmingham Queen Elizabeth Hospital Birmingham University Hospitals Birmingham NHS Foundation Trust Birmingham UK
                [ 6 ] Institute of Inflammation and Ageing University of Birmingham MRC Versus Arthritis Centre for Musculoskeletal Ageing Research University of Birmingham Birmingham UK
                [ 7 ] Kennedy Institute of Rheumatology University of Oxford, Oxford, UK, and Institute of Inflammation and Ageing MRC Versus Arthritis Centre for Musculoskeletal Ageing Research University of Birmingham Birmingham UK
                [ 8 ] Institute of Inflammation and Ageing MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, Sandwell and West Birmingham NHS Hospitals Trust Birmingham UK
                [ 9 ] Institute of Applied Health Research University of Birmingham Queen Elizabeth Hospital Birmingham University Hospitals Birmingham NHS Foundation Trust Birmingham UK
                [ 10 ] Institute of Applied Health Research University of Birmingham Health Data Research UK Midlands Birmingham UK
                Author notes
                [*] [* ] Address correspondence to Krishnarajah Nirantharakumar, MD, IOEM Building, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK ( k.nirantharan@ 123456bham.ac.uk ) or to Karim Raza, PhD, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, B15 2WB, UK ( k.raza@ 123456bham.ac.uk ).

                Author information
                https://orcid.org/0000-0002-9561-5141
                https://orcid.org/0000-0002-2188-3784
                Article
                ART41593
                10.1002/art.41593
                8252419
                33185016
                069cd70c-217b-49ec-a4ff-b40e39860b6d
                © 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 13 September 2020
                : 10 November 2020
                Page count
                Figures: 2, Tables: 2, Pages: 9, Words: 7001
                Categories
                Full Length
                Covid‐19
                Custom metadata
                2.0
                May 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.4 mode:remove_FC converted:02.07.2021

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