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Long-Haul COVID-19

The pandemic that has gripped the entire world for over a year was caused by a novel coronavirus strain, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) leading to coronavirus disease 2019 (COVID-19).

Manifestations of COVID-19

One of the main effects of COVID-19 includes pneumonia and a life-threatening condition called acute respiratory distress syndrome (ARDS). Though typically a virus that affects the respiratory system, SARS-CoV-2 also affects multiple organ systems, including thrombotic complications, myocardial dysfunction, cardiac arrhythmias, acute coronary syndromes, acute renal injury, gastrointestinal dysfunction, hepatocellular injury, endocrine abnormalities, neurologic illnesses, ocular symptoms, and dermatologic complications.

Harmful effects of the body’s COVID-19

In addition to the harmful effects of SARS-CoV-2 acting on human cells, another aspect of COVID-19 pathophysiology is the abnormal inflammatory response of the host, which is the patient’s own immune system mounting an “over-enthusiastic” response against the virus that causes more harm than good. This aberrant immune response and its accompanying release of chemicals called cytokines (the so-called cytokine-release syndrome, or cytokine “storm”) plays a key role in many of the signs and symptoms associated with severe COVID-19.

Long-Haul COVID-19 or Post-Acute COVID-19

As we are learning more about COVID-19, physicians have been able to better treat the patients. As more patients recover from this disease, there is a new emerging problem. Many recent studies have shed light on a plethora of persistent symptoms that linger after acute infection with COVID-19. This has been described by various names, such as post-acute COVID-19, long-haul COVID-19, or long COVID-19. This syndrome is characterized by persistent symptoms and complications that remain 4 weeks after initial COVID-19 disease.

The most common symptoms of post-acute COVID-19 are fatigue, brain fog, and breathlessness. The exact reason behind long-haul COVID-19 or which patients show this type of prolonged disease is not known. Furthermore, there is no consensus on what percent of patients show these symptoms. In fact, some physicians and scientists regard this as a purely psychological problem. However, there are sufficient number of documented cases of COVID long-haulers to warrant further investigation.

A review article published in the most recent issue of Nature Medicine suggests that organ damage due to either the infection or immune effects and inflammation are responsible for some or all of the effects of long COVID-19. In this article, scientists at New York-Presbyterian/Columbia University Irving Medical Center categorized these long-term effects into two:

  1. Subacute or ongoing COVID-19: Symptoms within 4-12 weeks after acute COVID-19

  2. Chronic or post-COVID-19: Symptoms beyond 12 weeks after acute COVID-19

Post-acute COVID-19 syndrome (Image Credit: Reprinted from – Nalbandian, A., Sehgal, K., Gupta, A. et al. Post-acute COVID-19 syndrome. Nat Med (2021).

Specifically, these scientists demonstrate in this article specific effects on the cells of COVID long-haulers, including signs of cell damage, abnormal clotting, and hyperactive immune responses. The scientists hypothesize that these molecular abnormalities are responsible for long-haul COVID-19.

A similar study from Northwestern Memorial Hospital in Chicago tested 100 patients and showed many long-term effects on the nervous system of patients who recovered from COVID-19. In this study, scientists found symptoms such as brain fog, headache, tingling and numbness, loss of taste, muscle pain, dizziness, blurred vision, and ringing sensation in the ear. This study was not able to identify any reason for development of these symptoms.

In contrast, a third study from the United Kingdom showed that patients who recovered from acute COVID-19 suffered from persistent symptoms, such as breathlessness and chronic fatigue. In this study, researchers found that post-acute COVID-19 patients had abnormalities in lymphocytes and think that this likely contributes to some of these long-term effects in COVID-19 patients.


Further research is required to identify and characterize the nature of long-haul COVID-19. While basic research to identify the cellular mechanisms that lead to these symptoms is important, it is also necessary to run clinical studies to identify ways to target and treat these symptoms. Recently, the National Institutes of Health has earmarked $1.15B over the next four years to study long-haul COVID-19 and design effective treatment measures that can treat it. Considering how many people worldwide are affected by this pandemic, this is an important and urgent healthcare need for patients everywhere over the next few years.

Written by: Sandeep Pingle, MD PhD

Keywords: long covid, long-haul covid, long-term covid effects, COVID-19, SARS-CoV-2


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