As of July 8, 2021, almost 186 million people have been infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with over 4 million people dying because of this virus. Approximately 80% of individuals who acquire the coronavirus disease 2019 (COVID-19), which is the disease caused by SARS-CoV-2, will experience mild to moderate symptoms, whereas about 5% will develop severe symptoms.
As more research is being conducted on those who have recovered from COVID-19, the development of persistent or new symptoms lasting weeks or months have become increasingly prevalent. This phenomenon has been referred to as “long COVID” or “Post COVID syndrome.”
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Acute COVID-19
Following infection by SARS-CoV-2, symptoms will often begin to develop 4 to 5 days after the initial exposure. The acute symptoms associated with COVID-19 can be divided into three categories including respiratory, musculoskeletal, and enteric symptoms.
The respiratory symptoms of COVID-19 can include cough, sputum, shortness of breath, and fever. Comparably, some of the musculoskeletal symptoms of COVID-19 include myalgia, joint pain, headache, and fatigue. Thirdly, the enter symptom cluster associated with this disease can include abdominal pain, vomiting, and diarrhea. Aside from those mentioned, some of the more severe symptoms that can arise during acute COVID-19 include chest pain, confusion, and shortness of breath.
Long COVID-19
The recovery from mild COVID-19 will typically occur between 7 and 10 days following the onset of symptoms. However, patients who have experienced more severe forms of this infection may find that their symptoms do not improve until 3 to 6 weeks after symptom onset. Continued follow-up of patients who have recovered from COVID-19 found that one or more symptoms appear to persist in a substantial percentage of these patients for several weeks to even months.
“Long COVID,” which is often used to describe the persistence of these various symptoms, can be continuous or relapsing and remitting in nature. Notably, microbiological recovery of these patients has been confirmed through negative polymerase chain reaction (PCR) tests coming back negative; therefore, long COVID is the time lag between this microbiological recovery and the clinical recovery of symptoms.
Symptoms
Interestingly, long COVID-19 can be associated with the persistence of one or more symptoms that patients experienced while infected with COVID-19, or it could also be associated with the development of entirely new symptoms. Typically, two main patterns of symptoms have been associated with long COVID and can be divided into two categories of general malaise symptoms and upper respiratory complaints or multi-system complaints.
The first category of long COVID symptoms includes fatigue, headache, shortness of breath, sore throat, persistent cough, and loss of smell. Profound fatigue, in particular, is a common symptom of long COVID that some studies have shown affects more than 50% of patients who have recovered from COVID-19. Comparatively, the multi-system complaints can range from ongoing fever to gastroenterological symptoms such as nausea, vomiting, and diarrhea.
Pathophysiology
Several different mechanisms have been proposed to be responsible for long COVID, some of which include:
- Persistence of chronic inflammation
- Immune response
- Persistence of virus in the body
- Nonspecific effect of hospitalization
- Sequelae of critical illness
- Post-intensive care syndrome
- Complications related to comorbidities
- Adverse effects of medications
- Persistent viremia in immunocompromised individuals
- Re-infection/relapse
- Psychological issues
Other viruses associated with persistent symptoms
Post-viral fatigue, which is one of the most commonly reported complaints associated with long COVID-19, has been reported in patients who have recovered from many other viral infections. More specifically, this persistent symptom has been reported following recovery from the Ebola virus, the severe acute respiratory syndrome (SARS) of the 2002 epidemic, the Middle East Respiratory Syndrome (MERS), as well as the Ebstein-Barr Virus (EBV).
In fact, it is estimated that up to 40% of patients who have recovered from SARS, which is a virus that exhibits several similarities to SARS-CoV-2, have chronic fatigue. Some of the different mechanisms that have been proposed to be responsible for the persistent muscle fatigue following recovery from these viruses include the presence of chronic oxidative and nitrosative stress, low-grade inflammation, and impaired production of the heat shock protein (HSP).
The long-haul symptoms of Ebola, in particular, have been frequently likened to those associated with long COVID-19. Aside from prolonged fatigue, survivors of Ebola have also reported pain and several neurological symptoms including headaches and dizziness.
Further research into the persistence of these symptoms has found that a high proportion of Ebola survivors will experience a resurgence in their antibody levels akin to that which was present while they were infected with the virus for up to 12 months after their recovery. The genetic material of the Ebola virus has been detected in the eyes, lymph nodes, breast milk, and semen for several months following their recovery.
Conclusion
Overall, scientists believe that the symptoms of both long COVID and long Ebola are due to the inability of the body to clear the virus. By remaining inside various reservoirs, these viruses can continue to induce local inflammation. As the viruses multiply in these areas, they periodically return to the bloodstream, where they can trigger more macroscopic immune reactions and accompanying symptoms.
Aside from this hypothesis, scientists have also suggested that SARS-CoV-2 may even trigger an autoimmune reaction to arise in some patients. This proposed mechanism may even be gender-specific. More specifically, women, who are already more vulnerable to developing autoimmune diseases, have been reported to be more likely affected by long COVID. To confirm the possible autoimmune mechanisms of COVID-19, researchers are currently looking to identify patients with circulating autoantibodies to identify whether these antibodies are causing these long symptoms.
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Further Reading
Phase 2 study evaluates safety and efficacy of asunercept in COVID-19 patients