How Much Has Science Learned About Long COVID?

After the first wave of COVID-19, people began describing signs of “long COVID” – a chronic cluster of symptoms with causes that were difficult to pinpoint. Early research showed that long-term complications of the virus could wreak havoc on the heart and lungs. More than two years into the pandemic, studies indicate that long COVID is a systemic issue triggering a myriad of problems throughout the body.

The term “long COVID” was coined by a patient on social media in the first months of the pandemic to describe the lingering and complex course of her illness.¹ Today, it’s an all-too-common experience. It is estimated that anywhere between 30% and 80% of people who recover from COVID-19 may endure  new, returning, or ongoing health problems such as fatigue, shortness of breath, chest pain, and “brain fog” in the months following an acute infection.^2,3 The projections (and official definitions) for long COVID continue to evolve as global researchers seek clues to its underlying causes and prolonged effects. 

Prior to the emergence of COVID-19, it was known that human “common cold” coronaviruses can cause mild to moderate respiratory illness. But a distinction of COVID-19 was the severity of this respiratory attack in many patients (called a “cytokine storm” in the lungs), and the virus’s potential to damage the heart directly or indirectly – this also being the case in asymptomatic patients, young and previously healthy patients, and even athletes. Early studies provided evidence that a COVID-19 infection could cause arrythmias (abnormal heart rhythm), myocarditis (inflammation of the heart), cardiac arrest, and sudden death.^4,5

More recent data shed light on long COVID as an independent risk factor for circulatory damage leading to blood clots. Research is demonstrating that COVID-19 patients may have a significantly higher risk of deep vein thrombosis, or DVT, (a blood clot in the leg), pulmonary embolism (a blood clot in the lung), and bleeding events in the months after their illness. This increased risk of events could be attributed to several alterations caused by the infection, such as inflammation and activation of the body’s natural process of blood-clotting after an injury.⁶

For many who contract COVID-19, the virus wages a war on their immune systems that ends with the production of antibodies, and seemingly, a symptom “cease-fire”. However, among those experiencing long COVID, the jarring immune attack may cause inflammation that reactivates dormant viruses in the body (such as Epstein-Barr)¹¹ or triggers an excessive production of autoantibodies that attack the body itself.¹² This can cause a heightened reaction to allergies, new anaphylaxis reactions, shingles, and other serious conditions.⁷ 

Existing vaccines are effectively lowering the risk of severe infection, hospitalization, and death due to COVID-19; however, transmission is still spreading across the globe. As the scientific community races to keep up with new variants and clinical research data, the debate continues about who and how many will likely experience long COVID.    

Current research shows that people with a history of hospitalization, Type 2 diabetes, and higher body mass index are more likely to suffer from lingering problems.² The symptoms of long COVID are numerous and can disguise as a variety of conditions that cause fatigue, exercise intolerance, chest pain, shortness of breath, cognitive changes, and much more. This means that misdiagnosed or downplayed signals are bound to occur. Especially in cases of cardiovascular and respiratory abnormalities, early diagnosis is critical to prevent irreversible damage.

Experts advise that people who experience serious symptoms – or even a cluster of milder symptoms –seek medical care. Many hospital systems are setting up multidisciplinary post-COVID clinics to deal with the growing number of patients with persistent health issues.^13,14

Currently there is no cure or go to treatment.  The current approach for treating Long COVID revolves around addressing specific symptoms and conditions. The consensus is that it is important not to rush your recovery and to gradually resume activity. It will take many years for the full long-term impact of the pandemic to be fully understood. Therefore, staying up to date with vaccines and boosters as well as practicing coronavirus mitigation measures like vigilant hygiene continue to be essential.

_{References:
¹Callard F., Perego E. How and why patients made Long Covid. Soc Sci Med (2021). doi:10.1016/j.socscimed.2020.113426  
²Yoo, S.M., Liu, T.C., Motwani, Y. et al. Factors Associated with Post-Acute Sequelae of SARS-CoV-2 (PASC) After Diagnosis of Symptomatic COVID-19 in the Inpatient and Outpatient Setting in a Diverse Cohort. J Gen Intern Med (2022). https://doi.org/10.1007/s11606-022-07523-3 
³Cabrera Martimbianco A.L., Pacheco R.L., Bagattini Â.M., Riera R. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract (2021) doi: 10.1111/ijcp.14357. Epub 2021 Jun 2. PMID: 33977626; PMCID: PMC8236920
⁴Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021 Jan;93(1):250-256. doi: 10.1002/jmv.26232. Epub 2020 Sep 30. PMID: 32592501; PMCID: PMC7361342.
⁵Topol EJ. COVID-19 can affect the heart. Science. 2020; 370: 408– 9. https://doi.org/10.1126/science.abe2813.
⁶ Fors Connolly, A.M. et al. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study, BMJ (2022); 377:e069590 doi: https://doi.org/10.1136/bmj-2021-069590 
⁷Davis, H.E., Assafa, G.S., McCorkella, L. et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. Lancet (2021). https://www.thelancet.com/action/showPdf?pii=S2589-5370%2821%2900299-6 
⁸Quarleri J., Delpino M.V. SARS-CoV-2 interacts with renin-angiotensin system: impact on the central nervous system in elderly patients. Geroscience (2022). https://www.ncbi.nlm.nih.gov/pubmed/35157210
⁹Fernández-Castañeda, A., Lu, P., Geraghty, A.C. et al. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain. bioRxiv (2022). doi: https://doi.org/10.1101/2022.01.07.475453
¹⁰Novak, P., Mukerji, S.S., Alabsi, H.S., et al. Multisystem Involvement in Post-Acute Sequelae of Coronavirus Disease 19. Ann Neurol (2022). https://doi.org/10.1002/ana.26286
¹¹Su, J., Yuan, D., Chen, D.G., et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell (2022).  https://doi.org/10.1016/j.cell.2022.01.014
¹²Bastard, P., Rosen, L., Zhang, Q., et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science (2020). doi: 10.1126/science.abd4585
¹³Baraniuk, C. Covid-19: How Europe is approaching long covid. BMJ (2022). doi:10.1136/bmj.o158 
¹⁴Carbajal, E., Gleeson, C. 66 hospitals, health systems that have launched post-COVID-19 clinics. Becker’s Hospital Review (2022). https://www.beckershospitalreview.com/patient-safety-outcomes/13-hospitals-health-systems-that-have-launched-post-covid-19-clinics.html}