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Review
. 2024 Nov 13;16(773):eado2106.
doi: 10.1126/scitranslmed.ado2106. Epub 2024 Nov 13.

Translating insights into therapies for Long Covid

Annukka A R Antar  1 , Andrea L Cox  1
Affiliations
Review

Translating insights into therapies for Long Covid

Annukka A R Antar et al. Sci Transl Med. .

Abstract

Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis. Potential mechanisms of Long Covid are diverse, including persistence of viral reservoirs, dysregulated immune responses, direct viral damage of tissues targeted by SARS-CoV-2, inflammation driven by reactivation of latent viral infections, vascular endothelium activation or dysfunction, and subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, and microbiota dysbiosis. The heterogeneity of symptoms and baseline characteristics of people with Long Covid, as well as the varying states of immunity and therapies given at the time of acute infection, have made etiologies of Long Covid difficult to determine. Here, we examine progress on preclinical models for Long Covid and review progress being made in clinical trials, highlighting the need for large human studies and further development of models to better understand Long Covid. Such studies will inform clinical trials that will define treatments to benefit those living with this condition.

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Conflict of interest statement

Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1.
Fig. 1.. Several factors modulate long Covid progression.
Increased acute disease severity, elevated BMI, female sex, and concomitant comorbidities increase the risk of long Covid, whereas vaccination prior to infection decreases the risk. Treatments in the acute phase and age may also influence risk. CREDIT: A. MASTIN/SCIENCE TRANSLATIONAL MEDICINE
Fig. 2.
Fig. 2.. Translational research is required to identify effective therapies.
The diverse etiologies of long Covid and patient input define research and clinical trial goals. The potential causes of long Covid need to be characterized to identify the most promising treatments. Current clinical trials are detailed in the text. CREDIT: A. MASTIN/SCIENCE TRANSLATIONAL MEDICINE
See this image and copyright information in PMC

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