Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Authors: Amy D. Proal1 and Michael B. VanElzakker1,2*

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.

Introduction

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic of coronavirus disease 2019 (COVID-19) (Hiscott et al., 2020). Classic cases of acute COVID-19 are characterized by respiratory symptoms, fever, and gastrointestinal problems (Larsen et al., 2020). However, patients can present with a wide range of other symptoms, including neurological issues suggesting central nervous system (CNS) involvement (Harapan and Yoo, 2021). Acute COVID-19 cases range in length and severity. Many patients are asymptomatic, while others require hospitalization and ventilation (Cunningham et al., 2021). Overall, an average case of COVID-19 lasts between 1 and 4 weeks. However, across the globe, a subset of patients who sustain an acute SARS CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months (Carfì et al., 2020Davis et al., 2020Huang C. et al., 2021) (Figure 1). One study of COVID-19 patients who were followed for up to 9 months after illness found that approximately 30% reported persistent symptoms (Logue et al., 2021). These patients are being given the diagnosis Long COVID, post-acute COVID-19 syndrome (PACS), or post-acute sequelae of COVID-19.

For More Information: https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full