Comparative Organ Disease Burden and Sequelae of Influenza and SARS-CoV-2 Infection: An Observational Study Using Real-World Data

Infections with SARS-CoV-2 and influenza are associated with acute and post-acute complications and sequelae of many organ systems (i.e., disease burden). It is important to understand the global disease burden that associates with and follows acute infection in order to establish preventive and therapeutic strategies and to reduce the use of health resources and improve patient health outcomes. To address these questions, we utilized the National Covid Cohort Collaborative, which is an integrated and harmonized data repository of electronic health record data in the USA. From this database, we included in analysis 346,648 eligible SARS-CoV-2-infected patients, 78,086 eligible influenza infected patients, and 146,635 uninfected controls. We describe the disease burden that extends over 2-3 months following infection, and we quantify the reduction of disease burden by treatment. We identify a burden of disease following medically attended influenza that is comparable to that of medically attended SARS-CoV-2 infection. However, in contrast to SARS-CoV-2, influenza acute infection and disease burden are not responsive to antiviral treatment and thus remain as an unmet medical need. Focusing therapeutic strategies solely on the short-term management of acute infection may also underestimate the extended health benefits of antiviral treatment. ### Competing Interest Statement Authors are employees or contractors of Vir Biotechnology Inc., San Francisco, CA, USA ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Chute CG. National COVID Cohort Collaborative (N3C) institutional review board protocol. Zenodo 2020 Apr 22. doi: 10.5281/zenodo.3902948 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Access to data through the NCATS N3C Data Enclave covid.cd2h.org/enclave