In December 2019, a novel β-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in Wuhan, China, and soon spread worldwide . By 11 March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic and a public health emergency of international concern . As of 16 June, > 8 million people were confirmed infected and > 400,000 had died globally . As there were initially no authorized treatments for COVID-19, any drug used in the treatment of the disease could be considered off-label use. Numerous drugs are being repurposed and investigated for therapeutic efficacy. A notable effort launched by the WHO is the international “Solidarity” trial, which is evaluating the efficacy of azithromycin, chloroquine, hydroxychloroquine, the fixed-combination lopinavir/ritonavir, and remdesivir in COVID-19 compared with standard of care. As of 3 June 2020, more than 3500 patients from 400 hospitals in 35 countries had been recruited into the trial . The initial protocol included both hydroxychloroquine and chloroquine; however, the WHO announced on 25 May 2020 that the trial had only pursued hydroxychloroquine and on 6 July 2020 that the hydroxychloroquine and lopinavir/ritonavir arms were being discontinued .
The impact of patient sex on COVID-19 outcomes has previously been described [5,6,7]. An early study investigated the influence of patient sex on morbidity and mortality in both COVID-19 and the earlier severe acute respiratory syndrome (SARS-CoV-1) epidemic in 2002 [6, 8]. The authors concluded that men and women had a similar incidence of the diseases, but that men with COVID-19 or SARS-CoV-1 infection were at higher risk of worse outcomes and death, independent of age . A review of 48 articles representing multiple countries and databases confirmed this finding , reporting that males accounted for 55–62% of hospitalized patients. The sex imbalance was even more pronounced for admissions to intensive care units (ICUs), with a male proportion of 65–74%. Throughout Europe, 73% of admissions to ICUs were men. Deaths were more common among men than among women in all countries except India and Pakistan .
During the initial part of the pandemic, the > 130 countries within the WHO Programme for International Drug Monitoring (PIDM) began reporting side effects from drugs used to treat COVID-19 into VigiBase, the WHO global database for individual case safety reports. The database contains nearly 23 million reports of suspected adverse drug reactions (ADRs), including reports via the US FDA and EU-wide ADR collecting systems. Methods to monitor and communicate reviews of the COVID-19 reporting were rapidly developed within the Uppsala Monitoring Centre, which harbours the database.
When studying sex-related differences related to drug treatment in COVID-19, spontaneous reports of suspected ADRs may complement other data sources, and our study used data retrieved for general monitoring. The vast majority of the reports contain data on age and sex. In VigiBase, reporting rates are higher for women than for men, whereas men have a higher proportion of serious and fatal reports .