By Maggie Chen and Kimmy Ye
As of August 15, 2020, there are close to 3 million recovered COVID-19 patients across the US. The symptoms during the infection have been gaining attention, as symptoms are the first way to self-identify SARS-CoV-2 infection. However, few studies on sequelae were done previously, as clinicians and scientists were trying to decipher the infection, transmission, and prevention of COVID-19 instead. Now, the growing number of recovered patients provides public health specialists, researchers, and scientists with a larger sample size to study the physiological and psychological effects post-COVID-19. Investigating the post-recovery life can greatly aid researchers in better understanding the disease, as well as ensure that those who recover receive the necessary support. According to the WHO, patients who are 10 days beyond symptom onset, with an additional three days of no fever and other respiratory symptoms, can be discharged. Sequelae, by definition, is a residual effect after the termination of the acute phase of an illness or discharge from the hospital.
As a consequence of any severe viral pneumonia (including flu, MERS, SARS, and COVID-19), patients can develop prolonged inflammation, which, in combination with underlying chronic diseases, can increase the risk of heart attack, stroke, and kidney disease post-recovery. Studies conducted in Italy have shown that 87.4% of previously hospitalized COVID-19 patients experienced at least one sequelae for more than a month post-discharge. Reported sequelae include fatigue, shortness of breath, impairment of renal and cardiovascular function, ongoing hypercoagulability, myalgia, etc. Patients who recovered from severe COVID-19 are more susceptible to experience physiological or psychological sequelae. For many of them, beating the virus is just the beginning.
Long-term pulmonary function is another critical factor for patients’ post-recovery quality of life. Researchers found radiological and physiological lung abnormalities in COVID-19 survivors three months after discharge, and oxygen therapy is needed in these patients. Lung function impairment secondary to infection includes chronic cough, fibrotic lung disease, bronchiectasis, and pulmonary vascular disease. Such conditions may increase the individual’s risk of getting other respiratory diseases as common as bacterial/viral infections, as well as asthma, chronic obstructive pulmonary disorders (COPD), and idiopathic pulmonary fibrosis; of these conditions, some can be fatal.
Extrapulmonary (outside of the lung) complications are not as intuitive as their counterparts in the lung, but they are just as important and deserve more investigation. Neurological disorders, long term or short term, can be observed in recovered patients, as they experience various sensory symptoms. Headache, temporary loss of smell or taste are some common early indicators of COVID-19. However, some patients may continue to experience these symptoms post-recovery of COVID-19. Studies have shown that infection in the central nervous system may lead to neural injury, causing prolonged headaches and vertigo. Infection in olfactory sensory neurons and cells within the nose’s lining can lead to continued loss of taste or smell.
Endotheliitis (inflammation in endothelial cells found in blood vessels) is another proposed sequelae found in non-pulmonary organs. Symptoms such as deep-vein thrombosis (DVT), pulmonary embolism (PE), disseminated intravascular coagulation (DIC), cerebrovascular accident (CVA, stroke) were found in very rare, severe cases. Moreover, individuals with predisposing conditions such as hypertension, diabetes, and chronic kidney diseases were experiencing more severe symptoms and higher mortality, suggesting that SARS-CoV-2 can target the blood vessels. Direct viral infection of the endothelial cell and diffuse endothelial inflammation was found to be present during and after COVID-19.
Autoimmunity and inflammatory diseases are also one of the potential post-infection complications. COVID-19 could be a triggering factor for various autoimmune diseases due to possible shared pathological mechanisms. Reported autoimmune diseases in children following COVID-19 include multi-system inflammatory syndrome (MIS-C), also known as pediatric inflammatory multi-systemic syndrome (PIMS). In adults, the inflammatory complications are broader, idiopathic thrombocytopenic purpura (low platelet count due to self-antibody attacking platelets), Guillain-Barré syndrome (immune system attacking nervous system) and autoimmune hemolytic anaemia (immune system attacking red blood cells) have been recorded in patients 4–13 days following the onset of COVID-19 symptoms.
The reproductive and sexual health of both males and females can also be affected by SARS-CoV-2 infection. One study indicates that many factors affected by COVID-19 contribute to the potential onset of erectile dysfunction (ED) in males. Persistent endothelial dysfunction post-recovery from COVID-19 can cause vascular damage in suggested sites and thus lead to ED. Pulmonary fibrosis in recovered patients can cause impaired oxygen saturation, which could impair erectile function as well. For both male and female patients, COVID-19 can damage the central nervous system and cardiovascular system, which results in reduced blood supply to genitalia and causes impotency. Patients who experienced severe COVID-19 are more susceptible to strokes and other severe neurological damages that can negatively affect sexual function and desire. Sexual activity is also closely associated with mental and psychological health; post-traumatic stress disorder (PTSD), depression, and anxiety have been reported in COVID-19 survivors. In addition to prolonged physiological conditions, psychiatric health could be another hurdle COVID-19 survivors need to overcome. A study conducted in the United Kingdom found more than a quarter of patients who wind up in the intensive care unit (ICU) suffer cognitive impairment, psychological distress, or other associated ailments, which is approximately 1 to 2 % of total infected cases. This phenomenon is called "post-intensive care syndrome" (PICS). In addition to battling with the disease, the absence of friends and families in ICU or in quarantine and the PPE-wearing healthcare professionals could exacerbate the anxiety patients experience. Adult patients may experience difficulties resuming the activities of daily life or struggle to return to work. Physically, patients may suffer from muscle weakness and chronic pain. Cognitively, these individuals may struggle with concentration and memory. People suffering from PICS may experience anxiety, sleep difficulties, depression, or PTSD. One study found 33% of patients with COVID-19 (15 of 45) had a dysexecutive syndrome and delirium upon discharge.
Many questions regarding the sequelae of COVID-19 remain to be answered: how long do each of the sequelae last? What are some predictors? Taking the experience from SARS and MERS, patient rehabilitation is and will be in critical demand to help patients restore the usual quality of life. Most of the post-infection experience is still anecdotal; hopefully, as longitudinal studies are underway, more supporting data will elucidate the complications and provide explanations of these patients’ personal anecdotes. More details about the sequelae can direct healthcare providers to find solutions to mitigate the lingering symptoms, guide scientists to better understand the virus-host interaction, and prompt policymakers to determine the next step for building infrastructure and resources for supporting the recovered patients.
Your healthcare providers, as well as counselors and therapists, continue to be major liaisons for personalized recovery; thus, they are the reliable point of contact when you are in doubt. We would like to end with highlighting some current resources recovered-COVID19 individuals can use for wellness and support.
Maryland Department of Health has an ongoing initiative on connecting recovered patients called CovidCONNECT.
Results from ongoing research and the current understanding of COVID-19 are continually evolving. This post contains information that was last updated on August 15, 2020.