Morbidity of SARS-CoV-2 in the evolution to endemicity and in comparison with influenza

Introduction

Infection with SARS-CoV-2 can result in a broad range of health consequences, from asymptomatic infection to respiratory insufficiency, hospitalization, and death. Additionally, severe cases of SARS-CoV-2 infection can lead to manifestations in various organs, herein referred to as morbidity/excess morbity, which can encompass pulmonary, cardiovascular, hematological, metabolic, gastrointestinal, kidney, mental health, musculoskeletal, and neurological disorders¹. These organ-related manifestations can present months after the acute infection and are also referred to as sequelae^1,2. In contrast, the morbidity and sequelae of influenza virus infection have received less attention³. Although the pulmonary complications of influenza are well-understood, influenza virus infection can involve numerous organ systems, as described in an extensive review by Sellers et al.⁴ in 2017. That review highlighted that the recognition of these extra-pulmonary complications is crucial in determining the actual health consequences of influenza infection. Empirical estimates of the full global influenza disease burden are complicated by challenges of associating non-respiratory outcomes with influenza: only patients with respiratory illness may be tested for influenza, and presentations that do not conform to strict case definitions are likely missed⁵. Therefore, quantifying the impact of disease beyond the acute infection episode is critical for establishing the full burden of SARS-CoV-2 and influenza infections on patients and on the health system. Two modalities of health data are now facilitating the study of epidemic and pandemic infections at the population level: large scale access to medical records⁶, and wastewater surveillance data^7,8.

Effective treatments for SARS-CoV-2 are now available, and randomized clinical trials have demonstrated their ability to reduce hospitalization, severe disease, and death rates. Recent publications have shed light on the SARS-CoV-2 morbidity and time profile after acute infection^1,2 and the impact of Nirmatrelvir/Ritonavir treatment on post-acute sequelae of COVID-19⁹. Vaccination for infuenza is also associated with measurable diminution of the global organ disease burden⁵. However, there has been considerable debate regarding the benefits of antiviral treatment against acute influenza infection¹⁰. We have recently participated in a challenge competition to create computational models using the National Covid Cohort Collaborative¹¹. Here, we direct our analyses to compare two viral infections – SARS-CoV-2 and influenza in terms of acute...