Inflammatory pathways in patients with post-acute sequelae of COVID-19: The role of the clinical immunologist
Elliott, MR; O'Connor, AE; Marshall, GD, Annals of Allergy, Asthma, and Immunology, November 2024
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Short Summary
This RECOVER literature review paper summarizes what scientists currently know about the relationship between inflammation (the body’s response to an infection or injury) and Long COVID. Researchers reviewed past studies about how different parts of the body work together (biological pathways) and how those pathways can be related to Long COVID. They found that ongoing (chronic) inflammation—inflammation that does not stop when it should—may play an important role in Long COVID. Chronic inflammation can happen for many reasons. One reason is that viruses that were inactive, or “asleep,” in the body may become active again. Another reason is that SARS-CoV-2, the virus that causes COVID-19, may also stay in the body longer than expected. Another reason is that Long COVID may be related to changes in the immune system, which fights against infections. In some cases, the immune system may attack the body’s own healthy tissues by mistake, causing inflammation. Problems with mast cells, which help control allergic reactions and inflammation, may also play a role. Doctors can look for signs of inflammation using common tests, like bloodwork, but these tests by themselves cannot show that a person has Long COVID. The authors found that some early studies suggest that certain treatments for chronic inflammation may lower the risk of developing Long COVID or help manage its symptoms. However, there is no approved or proven treatment for Long COVID yet. This literature review is important because it shows that more research is needed to understand the links between inflammation and Long COVID. Establishing these links could help doctors more easily identify Long COVID and treat its symptoms.
This summary was prepared by the RECOVER Initiative.
Publication Details
DOI: 10.1016/j.anai.2024.08.021
Abstract
As the SARS-CoV-2 pandemic progressed, some survivors noted prolonged symptoms after acute infection, termed post-acute sequelae of COVID-19 (PASC) or "long COVID." PASC is a significant clinical and public health concern that adversely affects patients' quality of life, income, and health care expenses. Moreover, PASC symptoms are highly heterogeneous, the most common being fatigue and cognitive impairment, and they likely reflect a spectrum of clinical phenotypes. The proposed role of persistent inflammation is one of leading pathophysiological theories. This review article addresses these proposed mechanisms of persistent and aberrant inflammation, their clinical evaluation, and theoretical approaches to management. A review of public databases was used to collect literature for the review. The literature supports a prominent role of persistent and aberrant inflammation as a major contributor to the symptoms of PASC. Proposed mechanisms for persistent inflammation include reactivation of latent viruses, viral persistence, loss of immunoregulatory pathways, autoimmune mechanisms, and/or mast cell dysregulation. Persistent inflammation may result in constitutional symptoms such as fatigue, brain fog, body aches, and/or organ-specific dysfunction, such as gastrointestinal dysregulation and myocardial inflammation. There are no approved or even proven therapies for PASC at this time, but some studies have identified therapeutic options that may either reduce the risk for progression to PASC or decrease symptom burden. Laboratory evaluation and therapeutic options are limited and require further investigation to establish their clinical value. A more refined definition of PASC is needed to address the wide variety of clinical presentations, pathophysiology, and therapeutic options.Authors
Matthew R Elliott, Anna E O'Connor, Gailen D Marshall
Keywords
Humans; COVID-19/immunology/complications; SARS-CoV-2/immunology; Post-Acute COVID-19 Syndrome; Inflammation/immunology