Table 1.

Symptomatic management of PASC

PASC symptoms that may be managed by primary care providers and generally do not require referral
Constitutional	• 80–90% of hospitalized with COVID-19 are successfully discharged • Management of patients with mild PASC should focus on functional status • There can be light aerobic exercise such as walking or Pilates, with a gradually increased intensity over a 4-to-6 week period, and with a phased return to work [10] • Fever can be treated with antipyretics such as acetaminophen or NSAIDs • Patients should be encouraged to monitor their general health and nutrition, get adequate sleep, and limit substances such as tobacco, alcohol, and caffeine • Patients should check daily pulse oximetry if indicated • Set SMART goals to manage activities of daily living -Specific, Measurable, Attainable, Realistic and Timely goals [32]
Gastrointestinal	• Symptomatic management includes that for nausea, vomiting, anorexia, diarrhea, GERD, and loss of appetite
Olfactory	• For patients with persistent anosmia, olfactory training has been proposed as a self-management strategy by using essential oils or other strong odors on a regular basis for several weeks • Patients should minimize external distractions and focus at least 20 s on a single scent, and then move on to another to amplify the body’s natural mechanism of recovery by altering neural pathways [33] • Intranasal steroids (Mometasone furoate as example) have also been used in patients with loss of smell for more than 2 weeks associated with nasal symptoms [34] • Omega 3 fatty acids (no specific dose recommendation) shown to be beneficial in patients with isolated anosmia > 2 weeks, with resolution of other symptoms [34]
Ocular	• Symptomatic management of conjunctivitis, keratoconjunctivitis, or ocular irritation
Skin	• Non-specific erythematous rash, maculopapular rash, urticaria, vesicles, and chilblain-like lesions on extremities, sometimes called “COVID toe” are all managed per standard of care
Ability to exercise	• The Stanford Hall consensus for returning to exercise recommends [35]: 1. Mild disease-One week of low grade stretching and strengthening before cardiovascular sessions 2. Mild disease-Limited activity such as slow walking, increased rest periods if symptoms worsen 3. If persistence of fatigue, breathlessness, cough, fever-limited activity to 60% maximum heart rate, until 2–3 weeks after symptoms resolve 4. If lymphopenia or oxygen requirement-requires respiratory assessment before resuming exercise 5. If cardiac involvement-requires cardiac assessment before resuming exercise
PASC symptoms that may require referral to subspecialties
Chronic fatigue	• There is a potential role for Cognitive Behavioral Therapy (CBT) and Health & Wellness Coaching (HWC) programs focused nutritional status, graded exercise, mindfulness, and sleep hygiene, with the goal of improved quality of life
Respiratory complications	• Chest imaging is necessary in patients with current respiratory symptoms and previous abnormal imaging • For most patients, a chest radiography is sufficient • Chest computed tomography (CT), if needed, should be based upon concern for underlying pathology, such as contrast-enhanced CT if malignancy is suspected, non-contrast high resolution CT for concern of interstitial lung disease, especially in patients who had ARDS • A chest radiograph is recommended at 12 weeks in patients who have had COVID pneumonia, as patients may have persistence of signs of lung damage, including ground-glass opacities, consolidation, and interlobular septal thickening • If the chest radiograph is abnormal, then a CT chest and consultation with pulmonologist is recommended • Lung abnormalities have been noted to persist on chest CT for > 6 months in 50% of previously hospitalized patients, even those with non-severe respiratory disease [36] • For patients with a normal chest radiograph, unexplained respiratory symptoms, and hypoxia, there should be a high index of suspicion for venous thromboembolism. These patients should be evaluated with CT-chest angiogram • Rarely, chest or neck discomfort related to venous stenosis from previous central venous catheterization is present and an ultrasound or phlebography may be needed [37] • Patients with persistent, progressive, new respiratory symptoms, or those who were hospitalized for respiratory symptoms, including COVID-19-related ARDS, may benefit from treatment for restrictive or obstructive disorders if uncovered after pulmonary function testing is completed. Pulmonary fibrosis noted on CT chest of patients after hospitalization, may be treated with oral steroid therapy and antifibrotic drugs (pirfenidone and nintedanib are currently being evaluated for use) [38] • This testing may include spirometry, lung volumes, and diffusion capacity • Patients recovering from severe lung infection, such as those requiring oxygen by high flow nasal canula or mechanical ventilation have been found to have impaired diffusing capacity for carbon monoxide in up to 56% of cases, and impaired exercise capacity during the first 6 months after discharge [15] • Referral to pulmonology for persistent abnormal chest x-ray, abnormal oximetry, or unexplained dyspnea is appropriate, as complete cardiopulmonary exercise testing may identify those who would benefit from pulmonary or physical rehabilitation; however, more data about appropriate timing of pulmonary function tests (PFTs) and follow-up PFTs is needed • For patients with chronic cough, if all other causes of cough have been ruled out, the treatment is supportive. Patients may also experience breathlessness after infection. In the absence of other underlying complications such as pleuritis or infection, patients should be instructed on breathing techniques to control or manage their symptoms • Breathing techniques include diaphragmatic breathing, slow deep breathing, yoga breathing, pursed lip breathing, or breathing through the nose and out through the mouth, slowly, aiming for a ratio of 1:2, in 5–10-min bursts throughout the day [10]
Hypoxia	• Hypoxia associated with decreased diffusion capacity may occur as a sequela of COVID-19. It may be silent, which is to say asymptomatic, or be associated with increased work of breathing • Patients with hypoxia during the subacute phase of COVID-19 do not necessarily require pulmonary rehabilitation but should be monitored closely and supported with supplemental oxygen if necessary [39] • Monitoring oxygen saturation in post COVID-19 patients without “red flags” can be reassuring in those experiencing persistent breathlessness • Oxygen saturations of 96% or above in patients without chronic lung disease are expected. For those with chronic lung disease, saturations in the 88 to 92% range may be acceptable
Neurological	• Patients should be evaluated for focal symptoms and sensory deficits • Unexplained muscle weakness may indicate the need for neurologic consult with electromyography and nerve conduction studies. Neurologic imaging is necessary only in the face of a neurologic deficit • Headache management includes amitriptyline, venlafaxine, and mirtazapine for tension-type headaches [40] • Migraine-like headaches may benefit from beta-blockers, neuromodulators, antidepressants, calcium channel blockers, or ACE inhibitors/angiotensin II receptor blockers [40] • Address mood, sleep, and stress disorders [40]
Dysautonomia and orthostatic intolerance	Patient education regarding physiologic changes associated with orthostatic intolerance syndrome, and management may provide reassurance [41–43]. This includes: • Structured non-upright exercise such as swimming, or recumbent exercise bicycle should be encouraged • Fluid and salt repletion with 2–3 L of water daily, one to two teaspoons of salt daily, and limiting alcohol and caffeine are recommended • Avoiding exacerbating factors such as prolonged standing, warm environments, dehydration, and sudden changes in position. Consume small and frequent meals to avoid splanchnic vasodilatation • Compression garments extending to waist, or abdominal binders • Isometric exercises with sustained tensing of muscles to improve venous return to the heart and raise blood pressure may be beneficial. Counter-pressure maneuvers include tensing thigh, buttock muscles, crossing arms and legs, folding arms and leaning forward, squatting, or raising a leg and putting foot on a stool • Patients with POTS symptomology may benefit from pharmacological therapy such as Fludrocortisone, a fluid expander; Midodrine, a sympathomimetic alpha-1-agonist that increases vasoconstriction and venous return to heart; and Clonidine and Methyldopa, which improve hyperadrenergic symptoms caused by catecholamine surge on standing
Cardiovascular complications	• Patients should be questioned about ongoing or intermittent dyspnea occurring with both rest and exertion; fatigue, cough, chest pain or discomfort experienced at rest, with exertion, or positionally; orthopnea, peripheral edema, palpitations, dizziness, orthostasis, syncope or presyncope; as well as any supplemental oxygen needs • It is important to determine if the symptoms are worsening, persistent, or new as late complications such as secondary bacterial pneumonia, empyema, pulmonary embolism, myocardial inflammation, and injury may occur • A 12-lead ECG is recommended to evaluate patients with cardiac symptoms, and if unremarkable, in the setting of persistent palpitations or dysautonomia symptoms, Holter monitoring is recommended • Patients with orthostatic symptoms may benefit from tilt table testing • An echocardiogram, chest CT, or CMR is recommended in patients with history of myocardial injury, myocarditis, dyspnea, or cardiac symptoms and signs such as chest pain not typical for pleuritic or musculoskeletal conditions, edema, and new murmurs • Left ventricular systolic function and heart failure should be managed according to standards of care • If echocardiography is normal, patients may need cardiopulmonary exercise testing • Patients should avoid intense cardiovascular exercise for three months after myocarditis or pericarditis; athletes should rest from cardiovascular training and competitive sports for 3–6 months until resolution of myocardial inflammation by CMR or troponin normalization and be followed by a cardiologist to guide them in their return to exercise [44] • Patients with significant cardiac injury and functional limitations would benefit from cardiac rehabilitation • Training and high-level sport may resume following myocarditis if left ventricular systolic function is normal, serum biomarkers of myocardial injury are normal, and if relevant arrhythmias are ruled out on 24-h ECG monitoring and exercise testing [42] • If returning to high–level sport or physically demanding occupation following myocarditis, patients are required to undergo periodic reassessment, in particular during the first 2 years [44] • There is insufficient evidence of long-term cardiac function after patients seems to have recovered, or for how long patients remain in a hypercoagulable state after acute infection [45]
Thromboembolic complications	• Patients hospitalized typically receive prophylactic anticoagulation • Higher-risk patients may be discharged with 10 additional days of thromboprophylaxis [46], but there is no consensus on the benefit, or duration of prolonged prophylaxis with low molecular weight heparin after hospital discharge • If a patient has a thrombotic event, standard guidelines for anticoagulation should be followed • No data are available on the duration of hypercoagulability post-acute COVID-19
Multisystem Inflammatory Syndrome (MIS)	• Intravenous immunoglobulins, adjunctive glucocorticoids, and low dose aspirin until coronary arteries are confirmed normal at least 4 weeks after diagnosis [47]
Post-Intensive Care Syndrome	• Patients with protracted mental health disorders, should be referred for psychiatric care if experiencing moderate to severe symptoms • Therapy for PTSD may focus on trauma-based CBT, cognitive processing therapy, and/or eye movement desensitization and reprocessing [48]
Additional considerations	• There are currently no studies showing any definite benefit of vitamin and mineral supplementation in the management of acute, subacute, or chronic COVID-19 symptoms • A healthy diet including vegetables, fruits, whole grains, legumes, nuts, and moderate amounts of fish, dairy, and poultry is recommended to aid in recovery • Patients should limit red and processed meats, as well as refined carbohydrates and sugar • Many supplements have been recommended for managing acute symptoms of COVID-19, such as vitamins A, C, D, and E, along with zinc, omega-3 fatty acids, and probiotics. Modest results have been noted with supplements, except vitamin C and zinc which showed no benefit [49]; these may be especially beneficial in older patients who often do not ingest enough of these nutrients due to changes in appetite, limited access to healthy foods, cost of groceries, and chronic health conditions • Bone density studies to evaluate for osteopenia and osteoporosis may be indicated in patients with prolonged illness and immobilization