SARS-CoV-2 infection produces covid-19 symptoms in up to 80% of cases during the first two weeks, according to a recent meta-analysis that examined more than 21,000 infected. People who are asymptomatic or with mild symptoms may be less contagious, apparently because their viral load in the respiratory tract is lower.
In any case, with or without symptoms, all those infected can transmit the coronavirus for between 10 and 14 days. Most importantly, they can be contagious during the incubation period, that is, during the 2 to 3 days that precede the onset of cough, fever, and the sensation of suffocation (dyspnea). In most patients, after two weeks the immune system stops viral replication and eliminates the coronavirus.
The Centers for Disease Control and Prevention in the United States, better known by the acronym CDC, have recently proposed three stages in the natural history of SARS-CoV-2 infection, as shown in the following table:
In phase 1 (acute infection) there is viral replication and predominant respiratory manifestations (cough, dyspnea, etc.), although there may also be digestive manifestations such as diarrhea, nausea and vomiting, as well as fever and headache.
Although many patients recover after this stage, some progress to phase 2 after two weeks. This point coincides with the appearance of the immune response and antibodies, with a hyperinflammatory condition associated with a cytokine storm, which causes a clinical worsening. They develop bilateral pneumonia, bleeding disorders, and damage to other organs such as the heart, kidney, and brain. These patients require hospitalization and some require transfer to intensive care units.
A phase 3 has been added to the two clinical phases of COVID-19 described above. This includes late complications and a residual condition known as postcovid syndrome after one month of suffering from the acute infection.
Late complications after covid-19
Although SARS-CoV-2 infection, with or without symptoms, clears up naturally within a couple of weeks, some patients do not fully recover and have late complications. These occur because the damage that SARS-CoV-2 infection can cause is not only limited to the lungs , but the heart (myocarditis), blood vessels (embolisms), kidneys (renal failure), the nervous system (neuropathies, stroke, etc.) and liver (hepatitis), among others. Similarly, some patients with severe bilateral pneumonia recover with significant residual pulmonary fibrosis.
It is convenient to collect a good medical history from these patients and differentiate at least three situations that explain their post-coronavirus pathology:
- After prolonged stays in intensive care, with mechanical ventilation and bedridden for several weeks, with muscle atrophy due to little mobilization.
- For permanent damage to affected organs in acute infection. This is the case of pulmonary fibrosis after severe pneumonias, or of heart failure secondary to myocarditis or pulmonary embolisms.
- Due to persistence of viral replication for several months together with symptoms in patients with severe immunosuppression, well demonstrated in at least two patients.
- The last situation, with sustained viral replication, is reminiscent of that described more than a decade ago with the hepatitis E virus, another RNA virus that typically produces a self-limited infection. However, unexpected cases of chronic hepatitis and cirrhosis due to the E virus began to be described in transplant patients, in direct relation to the use of immunosuppressive treatment.
Prolonged covid-19 syndrome
Around 5% of patients suffering from covid-19 report persistence of symptoms months after the cure. The most frequent clinical manifestations in these patients are: fatigue, dyspnea, cough, changes in smell and taste, joint and muscle pain (arthralgia). It is the prolonged covid-19 syndrome ( long covid in the Anglo-Saxon medical literature).
They are patients with acute coronavirus infection in the previous months, who report not having recovered normality. They manifest sleep disorders, memory loss, disorientation, difficulty concentrating, tiredness, depression, muscle and joint pain, headache, palpitations, alopecia, and intermittent low-grade fever or fever. Many say they have experienced accelerated aging.
A recent pre-publication from King’s College London, pending peer review, examined 4,182 patients who had had a positive PCR for SARS-CoV-2. The results showed that 13.3% said they had not recovered after four weeks, 4.5% after eight weeks and 2.3% even after 12 weeks.
Chronic Fatigue Syndrome
Postviral fatigue in these patients with residual COVID-19 is reminiscent of chronic fatigue syndrome, also known as myalgic encephalomyelitis.
Myalgic encephalomyelitis is a poorly defined entity, like a catch-all for a heterogeneous group of patients who report intense or strenuous fatigue, often after having suffered a viral infection.
It has been associated occasionally with infections by viruses of the herpes family, such as the Epstein-Barr virus, which can cause chronic infections and episodes of reactivation after being latent. It is more frequent in women in the middle age of life.
Of other viruses that cause chronic infections in humans, such as HIV, hepatitis B virus and hepatitis C virus, we know that processes of chronic inflammation and persistent immune activation have been associated with an increase in cellular metabolism and phenomena of early aging, both in certain organs and systemically. It is difficult to accept this hypothesis for a coronavirus, which only produces self-limited infections that remit naturally, unlike HIV or hepatitis B or C viruses.
However, the cytokine storm that can be unleashed after several days of SARS-CoV-2 infection could lead to immune dysregulation and lead to clinical worsening and complications throughout the body. This could lead to an activation of endogenous virus expression and epigenetic changes that would increase cellular metabolism. This appears to be the pathogenesis of post-coronavirus syndrome.
Outpatient follow-up of patients who have had a confirmed SARS-CoV-2 infection will help to better understand the frequency and characteristics of the prolonged COVID-19 syndrome. Identifying its causes will provide guidance on possible treatment strategies.
Vicente Soriano, Faculty of Health Sciences & Medical Center, UNIR – International University of La Rioja
This article was originally published on The Conversation. Read the original.
