The terms “Long COVID” and “post COVID Condition” refer to a wide range of new, returning, or ongoing health issues that people experience following infection with the COVID-19 virus. The good news is that most people will fully recover within a few days to a few weeks after infection. However, anyone who has been infected can develop post-COVID conditions that can last for weeks, months or even years. Post-COVID conditions could first be identified after at least four weeks had passed since contracting the COVID infection. Symptoms of Long COVID may be the same or different than symptoms following COVID-19 infection .
What are the Symptoms of Long COVID?
About 200 different symptoms have been connected to Long-COVID, and the condition has yet to be fully defined. Here is the list of the most common ones:
General symptoms
- Tiredness that interferes with daily life
- Symptoms that get worse after physical or mental effort (also known as “post-exertional malaise”)
Respiratory and heart symptoms
- Difficulty breathing or shortness of breath
- Cough
- Chest pain
- Fast-beating or pounding heart
Neurological symptoms
- Difficulty thinking or concentrating (sometimes referred to as “brain fog”)
- Headache
- Sleep problems
- Dizziness when you stand up (lightheadedness)
- Pins-and-needles feelings
- Loss of smell or taste
- Depression
- Anxiety
Digestive symptoms
- Diarrhea
- Stomach pain
Other symptoms
- Joint or muscle pain
- Rash
- Changes in menstrual cycles
What Causes Long COVID?
- Persistent Virus SARS-CoV-2 virus particles may become active again, causing the virus and/or symptoms to reappear. Several recent studies suggest that it is surprisingly common for SARS-CoV-2 to return in people who did not receive COVID-19 treatment. In a study to assess the incidence of COVID-19 viral and symptom rebound, 12% of 568 participants experienced viral rebound, while 27% experienced a rebound in symptoms that appeared several days after they had recovered. Another study looking at incidence of COVID-19 viral rebound involving COVID-19 vaccinated individuals who were treated with Paxlovid found that the virus resurfaced more fiercely and that it was more common for the virus to rebound following Paxlovid treatment compared to no treatment.There is also evidence that SARS-CoV-2 infects multiple tissues throughout the body and that the infection can persist long after the respiratory symptoms have subsided. A Stanford University study found that 4% of recovered COVID-19 patients were shedding the virus and experiencing gastrointestinal symptoms 7 months after infection.
- Autoimmune Response
The infection may trigger the immune system to produce autoantibodies that attack the body’s own organs and tissues.Autoantibodies are immune system proteins that target the body’s own tissues. Autoantibodies are found in a wide range of autoimmune diseases, such as lupus and rheumatoid arthritis.Autoantibody activity is typically associated with chronic inflammation and injury involving specific organ systems and tissues such as the joints, skin, and nervous system.A study published in the Journal of Translational Medicine found autoantibody activity in individuals with asymptomatic to mildly symptomatic SARS-CoV-2 infection. Interestingly, the autoantibody response was more prominent in women with asymptomatic COVID-19 disease, while the extent of autoantibody reactivity was more prominent in men following at least mildly symptomatic illness.The mechanisms underlying the production of such autoantibodies are still unclear. Widespread and long-term inflammation caused by severe COVID-19 may cause the immune system to produce antibodies to virus fragments it would not normally recognize. Some of those fragments may be similar enough to human proteins to induce the production of autoantibodies. - Prolonged Inflammation
Several studies have demonstrated that inflammation is a hallmark of long COVID. A recent study compared the effects of COVID infection in hamsters to flu virus and found that only the SARS-CoV-2 infection caused lasting inflammation, permanent damage to lungs, kidneys, and uniquely affected the olfactory bulb, and olfactory epithelium. The olfactory epithelium and the olfactory bulb demonstrated myeloid and T cell activation, pro inflammatory cytokine production, and interferon response. - Microclots
Lingering virus fragments may cause inflammation in blood vessels, resulting in the formation of microclots. Microclots can cause fatigue, breathlessness, decreased exercise tolerance as a result of muscles not receiving enough oxygen. The royal College of Surgeons in Dublin studied the clotting problem in both hospitalized and nonhospitalized COVID-19 patients. The study demonstrated that individuals with a mild illness still had elevated levels of protein fragments left over from clots, along with high levels of factor VIII, a clotting protein. Levels of the protein markers were highest in people who had severe illness.Taken together, several studies suggest that long COVID and its symptoms may have more than one cause. Multiple mechanisms responsible for long COVID could be present in some people at the same time with one being more dominant than the other.
Prevalence
Post-COVID-19 conditions prevalence is substantial. A meta-analysis of 41 studies on global and regional ( US, Europe and Asia) prevalence of post COVID Conditions showed that pooled global prevalence of long COVID was estimated to be 43%. The studies that included only hospitalized individuals tended to show higher post-COVID-19 condition prevalence (54%) than non-hospitalized patients (34%).
Fatigue was the most common symptom reported (with a prevalence of 23%), followed by memory problems (14%), respiratory problems/difficulty breathing (13%), sleep problems (11%), and joint pain (10%).
Long-COVID was found in 25.24% of children and adolescents, with mood symptoms (16.50%), fatigue (9.66%), and sleep disorders (8.42%) being the most common symptoms.
Treatment Options
Efforts to identify and treat long COVID have been ongoing almost since the outbreak began. Since long COVID is a relatively new condition, treatment will entail determining the best combination of drugs and/or therapy to help the body to return to homeostasis.
Several drugs and drug combination studies are already being undertaken to treat the condition. A recent Veterans Affairs study, for example, found that Paxlovid, an antiviral medication used to treat mild to moderate COVID disease, can also reduce the risk of long-COVID symptoms.
A major new consortium of researchers at STIMULATE-ICP also launched a study on test therapies and progression of long COVID. Some of the drug therapies that will be studied are Rivaroxaban, Colchicine, and Famotidine/Loratidine.
Rivaroxaban is an anticoagulant drug that is currently used for stroke prophylaxis, reduction of thrombotic and cardiovascular events, and treatment of deep vein thrombosis and pulmonary embolism. According to reports from healthcare professionals and some early study data, Rivaroxaban have been successfully used for treating long COVID such as fatigue, post exertion malaise and pain that might stem from muscles being deprived of oxygen by microclots. Colchicine is another drug that is being studied for its anti-inflammatory properties and for a potential benefit in treatment of the heart (pericarditis) and lungs (pleuritis) inflammation. Famotidine/Loratidine might be also aid in treating inflammation, which is related to “mast cell activation” and release of histamine.
A study using systemic corticosteroids (Deflazacort) in tapering doses for 8-10 weeks for treating long COVID patients have found improvement in occurrence of breathlessness. Patients who had low oxygen saturation levels and rapid breathing at rest also showed improvement.
To target the micro clots formation, the researchers at the University of South Africa have applied an existing blood thinner regimen for atherosclerosis treatment to treat long COVID symptoms. A dual therapy of antiplatelet drugs Clopidogrel 75 mg/ Aspirin 75 mg once a day, along with an anticoagulant drug Apixiban 5 mg once a day was given to 24 patients enrolled in the study. All of the treated participants reported that their main symptoms were resolved and fatigue as the main symptom was relieved. In addition, their activity had returned to pre-COVID levels and that their symptoms of exhaustion and brain fog had resolved. According to the study authors, the findings supported the hypothesis that microclots deprive tissue, including the brain, of oxygen.
