‘When will I feel normal again?’ This is a question every clinician gets asked daily. In most instances, historical narratives, research studies, guidelines and personal experiences equip us to provide an informed answer. Most research on COVID-19, however, has so far focused on reducing deaths, shortening hospital stays, and arresting the spread of the disease. With the cohort of COVID survivors getting larger, we are now cognisant of the fact that a significant proportion of patients who survive the illness suffer from sequelae that may not be short-lived. Support groups have mushroomed online of thousands of individuals reporting persistent symptoms months after recovering from the illness. A recent study from Italy reported that at an average of two months post-hospitalisation, only 12.6% individuals were free of any symptoms. The most common symptom reported in over half of all patients was fatigue. Unexpectedly, a significant proportion of individuals with ‘mild’ illness are also reporting long-standing symptoms.
Effects of COVID-19
SARS-CoV-2 belongs to a family of single-stranded RNA viruses called coronaviruses. Viruses in this family have been known for their far-reaching effects, affecting the respiratory, neurological, cardiovascular (heart and blood vessels), hepatic (liver), and enteric (gut) systems. The focus of the present pandemic has been on the respiratory effects of the virus, which have been the most common manifestation and cause of morbidity and mortality. As many as 97% of all individuals with symptomatic disease have been reported to demonstrate abnormalities on a CT scan of the chest. In addition to the viral infection and the immune response to it, the use of oxygen and being on a ventilator can also cause injury to the lungs. Corticosteroids, the only drugs with a proven mortality benefit in COVID-19, have the potential to help reduce lung injury. However, their prolonged use can have ill-effects affecting multiple systems in the body. In the study mentioned above, 43% individuals reported shortness of breath two months after discharge.
The involvement of the cardiovascular system has been a prominent feature of this pandemic, as reflected both by clinical and autopsy studies. Individuals have gone to hospital with inflammation of the muscle fibres of the heart, limiting the functioning of the heart and mimicking heart attacks, and clots in the blood vessels of the lungs, brain and veins. These have been attributed to the direct effects of the virus (the heart muscle has an abundance of the same receptors that the virus binds to in the lungs, the ACE2 receptors) as well as abnormalities in the clotting pathways secondary to a dysfunctional and exuberant immune response to the virus. A fifth of all hospitalised patients have blood markers that reflect dying heart muscle cells. A subset of individuals report persistent palpitations and have an elevated resting heart rate, chest pain and exercise intolerance months after the illness. Structural damage to the heart and damage to the nerve transmission that regulates the functioning of the heart and the tone of blood vessels have been hypothesised to cause these effects.
The myelin sheath is a layer that covers nerves, facilitating transmission of signals along nerve fibres. Loss of this sheath, seen in demyelinating illnesses such as multiple sclerosis, is associated with severe fatigue and loss of muscle strength. Coronaviruses have been postulated to cause demyelinating disease through the direct effect on oligodendrocytes (cells in the nervous system), and through immune mechanisms in which similarities between the virus and myelin lead to T-cells attacking the body’s own myelin. The loss of smell that has been reported in COVID-19 is believed to be a result of the virus entering the brain through the olfactory bulb, and the presence of the virus has been demonstrated in the fluid surrounding the brain. The persistence of fatigue, ‘brain fog’, short-term memory loss, loss of smell and taste, and headaches are all being reported for months following the illness. These are possibly sequelae of the virus invading the nervous system. SARS-CoV-2 may have the potential for resulting in a cohort of individuals with progressive neurological disease, and long-haulers with such symptoms need to be followed-up closely.
Survivors of SARS infection reported post-traumatic stress disorder, and a range of mental illnesses including increased suicidality in the months’ post-infection. In the three years following the SARS epidemic, 59% survivors reported a psychiatric disorder at some point. A study published in Sleep Medicine revealed very high rates of clinically significant insomnia (20%), acute stress (15.8%), anxiety (18.5%), and depression (24.5%). The isolation from family and friends during the period of hospitalisation, stigma associated with the disease, and anxiety because of lockdowns are all likely to contribute to mental illness after being infected. Especially in those admitted with the illness, it would be naïve to assume that a discharge from the hospital would lead to a return to normalcy. Whether the effects of the virus on the brain are responsible for the psychiatric long-term effects, or these are a consequence of the mileu in which we live, is unknown, but needs close monitoring.
What can be done?
So, what do we tell patients who ask us the question? What we know is that other viral illnesses have been known to cause a post-viral fatigue syndrome too. Persistent viral fragments leading to a constant immune response have been thought to play a role. What makes COVID-19 relatively unique though is that these symptoms are being reported in individuals who have had a mild illness and are often young and had been healthy prior to the illness. What is reassuring is that our experience with other viral illnesses suggests that most individuals return to a normal life, and only a small fraction have symptoms which persist. For long-haulers, the limited experience that present survivors offer is that rest helps; trying to push through the pain can be counter-productive, especially if one attempts vigorous exercise too soon. A recent guideline published in the British Journal of Sports Medicine has warned against exercising during the illness (might increase viral replication within the heart, causing long-term damage, and can also cause sudden cardiac death), and has suggested a detailed assessment before return to sport in individuals with symptoms. Close monitoring is key, as is the control of co-morbidities, nutritional deficiencies and illnesses such as endocrine disorders. A graded rehabilitation which includes building physical endurance and addressing mental health issues is crucial to a holistic recovery.
Empathy is key, and research is needed to codify the illness and prevent the stigma that such individuals report having to face from their peers. It is becoming evident that post-COVID effects are real. We owe it to our patients to help them understand it better, and study ways in which we can alter its course.
Dr. Lancelot Pinto is a Consultant Pulmonologist and Epidemiologist at P.D. Hinduja National Hospital, Mumbai. Dr. Nikita Mehra is an Assistant Professor of Medical Oncology and Researcher in Molecular Oncology at Adyar Cancer Institute, Chennai. Views are personal