Outpatients prescribed with fluvoxamine around the time of COVID-19 diagnosis are not at a reduced risk of unfavorable COVID-19 course compared to their non-prescribed peers: population-based matched cohort study (preprint)

Purpose: To assess the effect of exposure to fluvoxamine around the COVID-19 diagnosis on subsequent hospitalizations and mortality in COVID-19 outpatients in a real-life setting. Methods. Using nationwide administrative data, we identified adult COVID-19 outpatients diagnosed up to August 15, 2021 and conducted two cohort studies. Study 1 included subjects prescribed fluvoxamine around the index COVID-19 diagnosis (Cohort A), their peers suffering similar psychiatric difficulties but not prescribed fluvoxamine (Cohort B) and those free of psychiatric difficulties/treatments (Cohort C). Study 2 included subjects prescribed fluvoxamine (Cohort Fluvoxamine) and their peers prescribed paroxetine (Cohort Paroxetine). Cohorts were mutually exactly matched and incidence of COVID-19-related hospitalization, 30-day all-cause hospitalization and of COVID-19-related mortality was estimated. Results. Of the 416030 first-episode outpatients, Study 1 included 1016 Cohort A, 95984 Cohort B and 275804 Cohort C patients. Matched Cohort A (n=749) vs. Cohort B (n=31336) relative risks (95%CI/CrI), frequentist and Bayes with skeptical, otpimistic and pesimistic priors, were: COVID-related hospitalization 1.37 (0.56-3.33), 1.15 (0.55-2.11), 1.03 (0.56.1.96) and 1.43 (0.63-2.94), respectively; 30-day all-cause hospitalization 1.88 (0.76-4.67), 1.76 (1.39-2.25), 1.76 (1.39-2.24) and 1.86 (1.43-2.38), respectively; COVID-19 related mortality 0.73 (0.35-1.55), 0.93 (0.53-1.76), 0.79 (0.40-1.54) and 0.88 (0.37-2.11), respectively. Matched Cohort A vs. C (866 vs. 222792) comparison yielded similar estimates, as did the matched Cohort Fluvoxamine vs. Paroxetine comparison in Study 2 (344 of 994 matched to 535 of 1796 patients). Conslusion. Outpatients prescribed fluvoxamine around the time of COVID-19 diagnosis were not at a reduced risk of hospitalizations and mortality compared to their non-prescribed peers.

Outpatients prescribed with fluvoxamine around the time of COVID-19 diagnosis are not at a reduced risk of subsequent hospitalization and death compared to their non-prescribed peers: population- based matched cohort study (preprint)

Purpose. To assess the effect of exposure to fluvoxamine around the COVID-19 diagnosis on subsequent hospitalizations and mortality in COVID-19 outpatients in a real-life setting. Methods. Using nationwide administrative data, we identified adult COVID-19 outpatients diagnosed up to August 15, 2021 and conducted two cohort studies. Study 1 included subjects prescribed fluvoxamine around the index COVID-19 diagnosis (Cohort A), their peers suffering similar psychiatric difficulties but not prescribed fluvoxamine (Cohort B) and those free of psychiatric difficulties/treatments (Cohort C). Study 2 included subjects prescribed fluvoxamine (Cohort Fluvoxamine) and their peers prescribed paroxetine (Cohort Paroxetine). Cohorts were mutually exactly matched and incidence of COVID-19-related hospitalization, 30-day all-cause hospitalization and of COVID-19-related mortality was estimated. Results. Of the 416030 first-episode outpatients, Study 1 included 1016 Cohort A, 95984 Cohort B and 275804 Cohort C patients. Matched Cohort A (n=749) vs. Cohort B (n=31336) relative risks (95%CI/CrI), frequentist and Bayes with skeptical, otpimistic and pesimistic priors, were: COVID-related hospitalization 1.37 (0.56-3.33), 1.15 (0.55-2.11), 1.03 (0.56.1.96) and 1.43 (0.63-2.94), respectively; 30-day all-cause hospitalization 1.88 (0.76-4.67), 1.76 (1.39-2.25), 1.76 (1.39-2.24) and 1.86 (1.43-2.38), respectively; COVID-19 related mortality 0.73 (0.35-1.55), 0.93 (0.53-1.76), 0.79 (0.40-1.54) and 0.88 (0.37-2.11), respectively. Matched Cohort A vs. C (866 vs. 222792) comparison yielded similar estimates, as did the matched Cohort Fluvoxamine vs. Paroxetine comparison in Study 2 (344 of 994 matched to 535 of 1796 patients). Conslusion. Outpatients prescribed fluvoxamine around the time of COVID-19 diagnosis were not at a reduced risk of hospitalizations and mortality compared to their non-prescribed peers.

Pre-morbid use of proton pump inhibitors has no effect on the risk of death or hospitalization in COVID-19 patients: a matched cohort study (preprint)

Background. Several studies assessed the effect of pre-morbid exposure to proton pump inhibitors (PPIs) on disease course in adult COVID-19 patients with somewhat inconsistent results. Methods. This population-based matched cohort study embraced first COVID-19 episodes in adults diagnosed up to August 15 2021 in Croatia. Considering over-the-counter (OTC) availability of PPIs, patients were classified based on exposure to PPIs and burden of PPI-requiring conditions as "non-users" (no issued prescriptions, no recorded treatment-requiring conditions between January 1 2019 and COVID-19 diagnosis), "possible users" (no issued prescriptions, recorded treatment-requiring conditions; OTC use possible) and "users" (different intensity of issued prescriptions over 12 months prior to diagnosis, at least one within 3 months). Subsets were mutually exactly matched in respect to a range of pre-COVID-19 characteristics. The contrast between "users" and "possible users" was considered the most informative for the effect of PPIs that is separate of the effect of PPI-requiring conditions. Results. Among 433609 COVID-19 patients, 332389 were PPI "non-users", 18170 were "possible users", and 55098 were "users". Users and possible users were matched 41195 to 17334 and 33272 to 16434 in the primary and sensitivity analyses. There was no relevant difference between "users" and "possible users" regarding COVID-19-related mortality [RR=0.93 (95%CI 0.85-1.02; RD= -0.34% (-0.73, 0.03) in primary and RR=0.88 (0.78-0.98); RD=-0.45 (-0.80, -0.11) in sensitivity analysis] or COVID-19-related hospitalizations [RR=1.04 (0.97-1.13); RD=0.29% (-0.16, 0.73) in primary and RR=1.05 (0.97-1.15); RD=0.32% (-0.12, 0.75) in sensitivity analysis]. Conclusions. Pre-morbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID-19 patients.

Publishing of COVID-19 Preprints in Peer-reviewed Journals, Preprinting Trends, Public Discussion and Quality Issues (preprint)

IntroductionCOVID-19-related (vs. non-related) articles appear to be more expeditiously processed and published in peer-reviewed journals. We aimed to evaluate: (i) whether COVID-19-related preprints were favoured for publication, (ii) preprinting trends and public discussion of the preprints and (iii) relationship between the publication topic (COVID-19-related or not) and quality issues. MethodsManuscripts deposited at bioRxiv and medRxiv between January 1 and October 21 were assessed for the probability of publishing in peer-reviewed journals, and those published were evaluated for submission-to-acceptance time. The extent of public discussion was assessed based on Altmetric and Disqus data. The Retraction Watch database and PubMed were used to explore the retraction of COVID-19 and non-COVID-19 articles and preprints. ResultsWith adjustment for the preprinting server and number of deposited versions, COVID-19-related preprints were more likely to be published within 120 days since the deposition of the first version (OR=1.99, 95%CI 1.76-2.25) as well as over the entire observed period (OR=1.49, 95%CI 1.36-1.62). Submission-to-acceptance was by 41.69 days (95%CI 46.56-36.80) shorter for COVID-19 articles. Public discussion of preprints was modest and COVID-19 articles were overrepresented in the pool of retracted articles in 2020. ConclusionCurrent data suggest a preference for publication of COVID-19-related preprints over the observed period.

World Health Organization (WHO) COVID-19 Database: Who Needs It? (preprint)

Introduction: A large number of COVID-19 publications has created a need to collect all research-related material in practical and reliable centralized databases. The aim of this study was to evaluate the functionality and quality of the compiled World Health Organisation COVID-19 database and compare it to Pubmed and Scopus. Methods: Article metadata for COVID-19 articles and articles on 8 specific topics related to COVID-19 was exported from the WHO global research database, Scopus and Pubmed. The analysis was conducted in R to investigate the number and overlapping of the articles between the databases and the missingness of values in the metadata. Results: The WHO database contains the largest number of COVID-19 related articles overall but retrieved the same number of articles on 8 specific topics as Scopus and Pubmed. Despite having the smallest number of exclusive articles overall, the highest number of exclusive articles on specific COVID-19 related topics was retrieved from the Scopus database. Further investigation revealed that PubMed and Scopus have more comprehensive structure than the WHO database, and less missing values in the categories searched by the information retrieval systems. Discussion: This study suggests that the WHO COVID-19 database, even though it is compiled from multiple databases, has a very simple and limited structure, and significant problems with data quality. As a consequence, relying on this database as a source of articles for systematic reviews or bibliometric analyses is undesirable.