People with long-term after-effects of COVID-19 infection have been referred to colloquially as “long-haulers,” a reference to individuals who experience one or more long-term effects following an initial improvement or recovery from a serious illness.1 Today, primary care providers (PCPs) are encountering patients who suffer from post-COVID conditions. A baseline definition of post-COVID conditions or long COVID consists of symptoms present 4 or more weeks after an acute COVID-19 infection.2 These conditions may result directly from the SARS-CoV-2 infection, may be the effects of prolonged illness and hospitalization, or may be preexisting conditions unmasked by the infection.2 A wide variety of sequelae is possible. This article will review select considerations of post-COVID conditions in adults.
The science is emerging about what constitutes long COVID and how to manage “long-haulers.” New science is emerging as we gain more experience with COVID-19 infection and its after-effects. Despite continued vaccinations to counter the pandemic, there is still much to be learned about SARS-CoV-2 and its effects. The potential variants make it difficult to determine if herd immunity is the answer. The number of patients suffering with post-COVID conditions is poorly defined, with estimates ranging from 5% to 80%.2 Many patients will have long-term adverse reactions and continue to present with long-term complications.
The virus that causes COVID-19, SARS-CoV-2, is not the first coronavirus to cause widespread illness. SARS-CoV-1 caused an epidemic in 2002 that spread to 30 countries prior to containment. The Middle East respiratory syndrome coronavirus (MERS-CoV) infected persons residing in the Middle East in 2012. Neither of these coronaviruses reached the proportion of COVID-19 (SARS-CoV-2) in terms of the numbers of infections and deaths, but they caused similar respiratory infections and fatalities. Pulmonary fibrosis was a common after-effect of SARS-CoV-1 and MERS.3 In addition to persistent respiratory symptoms, reduced exercise capacity and mental health disorders such as anxiety, depression, and decreased quality of life were found post illness.4
Most healthy persons infected with COVID-19 recover in 2 weeks with symptoms persisting for up to 4 weeks. For others, it takes 4-12 weeks before they feel better, and others have symptoms lasting more than 12 weeks. The symptoms experienced may be varied and individualized. A variety of symptoms have been reported post-COVID-19 infection according to the National Institute for Health and Care Excellence (NICE) guidelines (see Potential symptoms of long COVID).
One study by Huang et al. followed over 1,700 patients for 6 months post-hospital discharge after acute COVID-19 infections.5 The patients were interviewed, underwent physical exams and lab work, and categorized into three groups based on disease severity during hospitalization: 1) patients not requiring supplemental oxygen, 2) patients requiring supplemental oxygen, and 3) patients requiring high-flow nasal cannula/ventilators.5 Specific symptoms were commonly reported, with over three quarters experiencing at least one symptom, such as fatigue or muscle weakness (63%), insomnia (26%), hair loss (22%), smell disorder (11%), taste disorder (7%), and mobility issues (7%).
Pulmonary symptoms such as dyspnea and lung abnormalities such as pulmonary fibrosis have been reported following COVID-19 infection.6 In the study by Huang et al., lung abnormalities were observed 6 months after acute infection in many patients, but it was unclear whether this was due to COVID-19 infection or comorbidities. Renal dysfunction, diabetes, and venous thromboembolic disease were found in some of the participants following COVID-19 infection, but their association was unclear. One weakness in this study was that baseline data were not available for comparison in areas of functional and mental health status.5
Postural orthostatic tachycardia syndrome
Autonomic nervous system disorders including postural orthostatic tachycardia syndrome (POTS) can occur after COVID-19 infections in previously healthy patients. Signs and symptoms of POTS include dizziness, postural tachycardia, presyncope, orthostatic intolerance, and activity intolerance. POTS is diagnosed with a rise in heart rate of 30 beats/minute within 10 minutes of standing, or on a tilt-table test, without orthostatic hypotension. PCPs should be aware that sudden onset of POTS may occur post COVID-19 infection. In one small study, 60% of patients suffering with post-COVID-19 POTS were unable to return to work within 8 months after having COVID-19.7 Antibodies produced by viruses may damage the autonomic nervous system. Young women are disproportionately affected by POTS with autoimmunity as a key factor. This is a very disturbing and disabling condition that is hard to treat and could be mistaken for a mental versus physiologic disorder.
Post-COVID-19 neuropsychiatric effects
Cognitive impairment or “brain fog” is a common complaint after COVID-19 infection.5 Patients may have difficulty concentrating and complain about issues with memory. Headaches, dizziness, and peripheral neuropathy are also possible after-effects.8 For older adults and patients requiring mechanical ventilation and extended hospital stays, delirium, severe functional decline, and postintensive care syndrome may have lasting detrimental effects on physical and mental health.9
COVID-19 can potentially enter the central nervous system by way of the nose.10 Patients critically ill with COVID-19 show leukoencephalopathy and microbleeds on imaging, and patients deceased from COVID-19 have been found to have inflammation in the brain on autopsy. A breakdown of the blood-brain barrier is also thought to occur.10
The COVID-19 pandemic has caused an increase in psychological stress and mental health disorders among the general population. This may be particularly true of people on the precipice of mental illness. After being hospitalized with COVID-19, increases in depression, anxiety, and posttraumatic stress disorder are reported.10 Psychiatric complications may relate in part to the social stress of the illness and bereavement of those lost. Anxiety may persist after the acute infection and may cause physiologic responses. Among the participants in the study by Huang et al., nearly one quarter of study participants were experiencing anxiety or depression at 6 months after acute COVID-19 infection.5 Female gender and increased disease severity heightened the risk of persistent mental health problems.5 The full list of mental health sequelae remains to be seen.10
Post-COVID-19 cardiac effects
Following acute infection with COVID-19, up to 30% of patients reported chest pain and nearly 10% experience palpitations.11 Postexertional malaise has also been reported. Cardiac complications can consist of arrhythmias, myocarditis, pericarditis, heart failure, and thrombosis.2,12 Myocarditis may persist after acute COVID-19 infection and is possible after even asymptomatic cases.7,12 Viral carditis can occur after infections with coxsackievirus, enterovirus, Epstein-Barr virus, parvovirus, and mumps.13 Etiology of post-COVID-19 cardiac effects may include direct viral effects and damage to the heart from the inflammatory cascade secondary to the viral infection and from the immunologic response.6,12 Multisystem inflammatory syndrome (MIS), a rare condition associated with COVID-19 which causes inflammation in different areas of the body including the heart and muscles and is thought to involve autoimmune responses, is another potential etiology of cardiac complications related to COVID-19 infection.12,14 Further study regarding cardiac sequelae of COVID-19 infection is required.6,12
Diagnosis, care plan, and treatment approach
A thorough history and physical exam should be completed. The patient's disease course should be reviewed, and preexisting comorbidities and baseline functional status should be taken into consideration.2 The impact of the patient's symptoms on quality of life and function should be assessed. The CDC suggests that although a positive SARS-CoV-2 test can help document a past/present infection, these tests are not necessary to diagnose a post-COVID condition.2 Some patients who were infected by COVID-19 will not test positive for the antibody.2 Rather, post-COVID conditions can be diagnosed by patient history and physical exam in many cases. Of note, the risk of reinfection is a possibility and should be considered.2,5
Patients presenting with signs or symptoms of potentially life-threatening conditions should be referred to the ED for immediate evaluation and treatment.2 For a patient presenting with vague symptoms after COVID-19 infection, some differential diagnoses to be considered include anemia, heart disease, lung disease, chronic fatigue syndrome, diabetes, hypothyroidism, and inflammatory conditions. Basic lab studies should include complete blood cell count, basic metabolic panel, liver function studies, inflammatory markers, thyroid hormones, and vitamin levels such as D and B12.2
The CDC suggests expanded testing for patients experiencing symptoms for longer than 12 weeks.2 For patients experiencing arthralgia and/or myalgia, antinuclear antibody, rheumatoid factor, anticyclic citrullinated peptide, anticardiolipin, and creatine phosphokinase tests may be diagnostic and/or help rule out coexisting illnesses. For possible coagulation disorders, D-dimer, fibrinogen, and prothrombin time and international normalized ratio testing may be appropriate. For cardiac complications or symptoms, a troponin level is appropriate, and for symptoms that could be cardiac or pulmonary, a B-type natriuretic peptide may be indicated.2 Other testing for pulmonary or cardiac signs or symptoms may include chest X-ray, echocardiography, and ECG. Further testing should be guided by history, physical exam, and previous test results.2 Certain specific screening tools and functional assessments may also be appropriate (see Select assessments post-COVID-19). Of note, when considering what tests are appropriate, the NP must consider that tests ordered may not be diagnostic.
After the PCP establishes that serious and life-threatening conditions or comorbidities are not present, a holistic and supportive approach is recommended by NICE for patients presenting with these varied and vague symptoms.5 Comprehensive primary care services can help to guide patients toward total recovery. The goal of treatment of post-COVID conditions is often to improve function and quality of life.2 The NP must consider the various potential etiologies such as inflammatory cascades that have occurred and their long-term effects. Healthcare providers should not wait for positive diagnostic testing to help patients with residual, life-altering symptoms post COVID-19 infection. General recommendations for healthy diet, adequate rest, exercise, and stress reduction can be helpful. Treatment plans should be individualized based on the patient's unique situation. The PCP can refer to guidance from the CDC and other professional organizations when developing a treatment plan, with the understanding that guidance is likely to evolve as new information is discovered.2 Specialty consultation is important for many patients with post-COVID conditions, including those experiencing pulmonary or cardiac symptoms. Referral for rehabilitation services such as physical and occupational therapy may be important for certain patients.2
There may also be an increased need for referral to mental health counseling and medical treatment of depression and anxiety. Community services and resources must be accessed for patients undergoing financial devastation from an inability to work. Support groups, whether virtual or in-person, can be invaluable. The NP can also direct patients to online resources containing accurate information, such as the CDC or “Your COVID Recovery” from the National Health Service England (www.yourcovidrecovery.nhs.uk/).
There is some evidence that after COVID-19 infection, patients who were treated with monoclonal antibodies or convalescent plasma must be advised to wait 90 days after acute infection to receive COVID-19 vaccination.15 Those with a history of MIS are recommended to wait until they have recovered and for 90 days after the MIS diagnosis for vaccination.14
Patients with post-COVID conditions, or long-haulers, may present with a wide range of symptoms that can come and go. The symptoms are vague, and treatment is ill defined. Each practitioner must use their training and experience to treat post-COVID conditions to the best of their ability until we gather more evidence and establish best practices for the treatment of these conditions. This represents a gray area without much evidence-based guidance yet available. Before we diagnose a patient with a post-COVID condition, we must use due diligence to make sure there is not an underlying or undiagnosed condition present. Once those are ruled out, we can begin treating our patients symptomatically and providing them with the necessary referrals and encouragement. Validating that these symptoms are not “all in the patient's head” can help the patient start the recovery process. Presenting case studies, participating in research studies, and encouraging our patients to enroll in clinical trials are ways that we can contribute to this growing field of knowledge.
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14. Centers for Disease Control and Prevention. Multisystem inflammatory syndrome. 2021. www.cdc.gov/mis/index.html
15. Centers for Disease Control and Prevention. COVID-19 frequently asked questions. 2021. www.cdc.gov/coronavirus/2019-ncov/vaccines/faq.html