Understanding Long-Haul COVID

The COVID-19 pandemic has now affected >204 million people and resulted in the deaths of >4.3 million since its recognition in late 2019. The unprecedented medical, research and public health response to this crisis fostered optimism during 2020 that control was within reach. However, the SARS-CoV-2 virus has continued to evolve and mutate, and new variants have taken hold that could challenge the effectiveness of vaccines and other countermeasures intended to limit its spread.

The spectrum of clinical disease following infection with the SARS-CoV-2 virus ranges from asymptomatic to severe and critical. While the vast majority of those affected fortunately recover from the acute illness, 10-30% have been found to suffer COVID 19 symptoms, oftentimes debilitating, months after recovery. The syndrome experienced by these individuals has been characterized as “long-haul COVID”, or simply “long COVID.”

What is Long COVID?

Long COVID is a complex, multifaceted disorder with an ambiguous clinical presentation and natural history. There is, as yet, no consensus definition for the disorder, and there are no currently accepted objective diagnostic tests or biomarkers. The Centers for Disease Control (CDC) and The National Institute for Health and Care Excellence (NICE) describe long COVID as having a range of long-haul symptoms that can last weeks or months that are present 4 or more weeks after SARS-CoV-2 infection, and which can affect anyone who has had COVID-19 (including those with mild or asymptomatic infections). Females and individuals with underlying asthma appear more frequently affected post-COVID-19 infection as are those with more severe acute COVID-19 clinical illnesses. Persistent fatigue; myasthenia; olfactory, gustatory, and sleep disorders; and anxiety are common among COVID long-haulers. Multiple organs can be affected including the pulmonary, cardiovascular, and gastrointestinal systems, as well as the brain.

The pathophysiology underlying long COVID and its various phenotypes are currently unknown. Hypotheses under study include the persistence of the virus in selected organs or tissues, a triggered autoimmune or autoinflammatory response, and other considerations. A recent comprehensive assessment of transcriptional, cellular, and humoral immune responses in a cohort of individuals with long COVID following mild, moderate, severe, and critical COVID-19 demonstrated significant abnormalities in innate and cellular immune cell populations in these individuals, suggesting variable and ongoing immune and metabolic dysregulation as an important underlying feature.

Interventions to Prevent Long Covid

Long COVID is a frequent and often debilitating consequence of COVID-19, that can affect anyone infected with the SARS-CoV-2 virus. The magnitude of the COVID-19 global pandemic coupled with the frequency of this post-infectious disorder point to long COVID as a significant clinical disorder as well as an emerging public health crisis, the societal impact of which is only just now beginning to be recognized. Until further clarity and understanding of the underlying pathophysiology emerge, the most effective intervention remains vaccination to reduce the risk of SARS-CoV-2 infection and to prevent the development of symptomatic COVID-19.

Allucent is actively providing CRO services in support of COVID-19 clinical trials. As an Infectious Disease and Vaccine-focused CRO, we are an experienced and trusted partner to industry and government sponsors in their quest to rapidly develop and test vaccines and therapeutics for drug approval and market readiness. Allucent has directly supported clinical trials under Operation Warp Speed (OWS) and continues these efforts through ongoing activities in support of its successor, the Countermeasures Acceleration Group (CAG). At the same time, we have been successfully servicing our other government and industry sponsors by supporting other vaccines and therapeutics undergoing clinical trials.

References:

• Johns Hopkins University, COVID-19 Map - Johns Hopkins Coronavirus Resource Center (jhu.edu), accessed 11 August 2021.
• Phillips S, Williams MA. Confronting our next national health disaster-long-haul COVID. 374 N Engl J Med 2021; DOI: 10.1056/NEJMp2109285
• Centers for Disease Control and Prevention. Post-COVID conditions: information for healthcare providers. 9 July 2021. Post-COVID Conditions: Information for Healthcare Providers (cdc.gov)
• National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing the long-term effects of COVID-19. NICE guideline [NG188] Published: 18 December 2020. https://www.nice.org.uk/guidance/ng188/chapter/1-Identifying-people-with-ongoing-symptomatic-COVID-19-or-post-COVID-19-syndrome
• Sudre CH, Murray B, Varsavky T, et al. Attributes and predictors of long COVID. Nature Medicine 2021; 27: 626-631.
• Crook H, Raza S, Nowell J, et al. Long covid-mechanisms, risk factors, and management. BMJ 2021; 374; n1648.doi: 10.1136/bmj.n1648.
• Ryan FJ, Hope CM, Masavuli MG, et al. Long term perturbation of the peripheral immune system months after SARS-CoV-2 infection. medRxiv preprint doi: 3 Aug 2021; https://doi.org/10.1101/2021.07.30.21261234