Table 2.

Summary of Important Findings in the Systemic Sequelae of Post-Acute COVID-19^a,b

System	Clinical findings or diagnostic criteria 17,19	Risk factors 27, 28, 29	Management recommendations 30, 31, 32, 33, 34, 35, 36, 37	Clinical trial based pharmacology 30,38, 39, 40, 41, 42, 43, 44
Pulmonary	Fatigue, dyspnea CT: ground-glass opacities and fibrotic changes	Severe disease, ICU admission, or severe hospital stay Lower limit 6MWT, higher CT severity score, increased D-dimer or urea nitrogen Advanced age, male, history of cigarette smoking	Initial evaluation 4-6 weeks with pulmonary function testing and 6MWT Follow-up imaging at 12 wks Dyspnea: pulmonary and cardiac workup	Maximum initial dose 0.5 mg/kg oral prednisolone: FVC, radiological and symptomatic improvement 2403 mg daily pirfenidone: FVC, 6WMT, and disease progression improvement 150 mg of twice daily nintedanib: FVC improvement Pulmonary rehabilitation: pulmonary function improvements Ongoing clinical trials to determine potential pharmacological candidates, use current recommended guidelines for most likely differential diagnosis
Cardiovascular	Chest pain, heart palpitations CMR: myocardial inflammation, myocarditis, pericarditis, cardiac fibrosis Echocardiogram: impaired LVEF, pericarditis, myocarditis, other cardiac anomalies Increased troponin level	Severe disease, high viral load, pneumonia during hospitalization Increased troponin levels, decrease in LVEF Hydroxychloroquine with or without ritonavir/lopinavir and azithromycin use in acute COVID-19	Initial evaluation with noninvasive technology (point-of-care ECG, transthoracic echocardiogram, laboratory tests for CRP, and troponin-T) Escalate to invasive testing and referral if abnormalities are detected in the initial evaluation	Ongoing clinical trials to determine potential pharmacological candidates, use current recommended guidelines for most likely differential diagnosis Continue RAAS modifying drug use (ACE-inhibitors, ARBs, etc) Avoid amiodarone as it may exacerbate pulmonary fibrosis
Neurological	Neuropsychiatric: anxiety, depression, PTSD, OCD, insomnia Cognitive: headaches, brain fog, memory loss, nonrestorative sleep Peripheral: anosmia, ageusia, fatigue, malaise, POTS	Severity of illness, ICU admission, MIS-C Medications such as lopinavir-ritonavir and corticosteroid use (rare)	Standard screening tools be used for neuropsychiatric conditions by primary care providers to evaluate for disorders such as anxiety, depression, PTSD, and OCD No specific published guidelines on screening protocols for neurological disorders	Standard therapies with referral to neurological specialists for refractory conditions or imaging abnormalities Beta-blockers, diet, and exercise: beneficial in reducing POTS symptoms
Hematological	Pulmonary embolism, VTE, ATE	Disease severity, length of acute infection, and ICU admission Low fibrinogen and higher D-dimer on admission, and DI ≥1.5-fold Increased age, cancer, and corticosteroid use (critically ill)	In-patient (all): CBC, coagulation studies PT and aPTT, fibrinogen and D-Dimer Outpatient (symptomatic or at-risk): same as in-patient Proceed to further invasive testing and imaging studies under standard protocols recommended for the suspected differential diagnosis if abnormalities are present	Thromboprophylaxis in those with high clot burden or at risk of thromboembolic events if there is no bleeding risk Ongoing clinical trials to determine potential pharmacological candidates, use current recommended guidelines for most likely differential diagnosis
Renal	AKI, wide spectrum of glomerular and tubular diseases	Same as hematological system High-risk APOL1 variant (collapsed glomerulopathy)	Refer to a nephrologist if AKI is persistent or there is severe dysfunction	Standard therapies with referral to specialists as needed
Endocrine	New-onset diabetes, worsening pre-existing diabetes, DKA, subacute thyroiditis, Graves thyrotoxicosis	High viral loads, severe disease	Initial evaluation for new-onset diabetes should include testing for antibodies to beta-islet cells and CRP and rule out risk factors for type 2 diabetes Monitor labs to rule out new-onset thyroid autoimmune diseases (Graves and Hashimoto thyroiditis) vs COVID-19 thyroiditis Refer to an endocrine specialist as necessary	Standard therapies with referral to specialists as needed
Gastrointestinal	Loss of appetite, nausea, acid reflux, diarrhea, abdominal distension, belching, vomiting, and bloody stools	High viral loads, severe disease	Fecal cultures to check for gut dysbiosis, refer to a gastrointestinal specialist as necessary	Dietary changes or fecal transplantation Standard therapies with referral to specialists as needed
Integumentary	Hair loss, skin rash, urticarial lesions, angioedema	Unknown	Standard protocols with referral to specialists as needed	Standard therapies with referral to specialists as needed
MIS-C	(Age ≤ 21 y): fever ≥ 38.0°C or subjective fever for ≥24 h, laboratory inflammation evidence, severe illness requiring hospitalization with ≥ 2 organ involvement	Presenting to the emergency department or admitted to the general ward Increased D-dimer, troponin, BNP, pro-BNP,CRP, and ferritin In patients ≥5 y old, identify as Black	Tier 1: CBC, CMP, ESR, CRP and SARS-CoV-2 PCR/serology If tier 1 results reach the diagnostic threshold then tier 2: cardiac enzymes (BNP, troponin T, etc), hematological/coagulation factors (D-dimer, fibrinogen, PTT, blood smear, etc), cardiac studies (ECG and echocardiogram), LDH, triglycerides, urinalysis, and cytokine panel In shock without clear etiology: tiers 1 and 2	1st line in shock: IVIG 2 gm/kg and MPIV at 1-2 mg/kg per day Refractory disease with shock: MPIV 10-30 mg/kg per day or high dose anakinra No shock: IVIG 2 gm/kg per day Refractory Disease, No shock: MPIV 1-2 mg/kg per day or high-dose anakinra

^a6MWT, 6-minute walk test; ACE, angiotensin-converting enzyme; AKI, acute kidney injury; APOL1, apolipoprotein L1; aPTT, activated partial prothrombin time; ARB, angiotensin receptor blocker; ATE, arterial thromboembolism; BNP, brain natriuretic peptide; CBC, complete blood count; CMP, complete metabolic panel; CMR, cardiac magnetic resonance; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; CT, computed tomography; DI, D-dimer increment; DKA, diabetic ketoacidosis; ECG, electrocardiogram; ESR, erythrocyte sedimentation rate; FVC, forced vital capacity; ICU, intensive care unit; IVIG, intravenous immunoglobulin; LDH, lactate dehydrogenase; LVEF, left ventricular ejection fraction; MIS-C, multisystem inflammatory syndrome in children; MPIV, methylprednisone intravenous; OCD, obsessive compulsive disorder; PCR, polymerase chain reaction; POTS, postural orthostatic tachycardia syndrome; PT, prothrombin time; PTSD, post-traumatic stress disorder; RAAS, renin angiotensin-aldosterone system; SARS-CoV-2, severe acute respiratory syndrome; VTE, venous thromboembolism.

^bHigh-risk or symptomatic individuals are the priority for screening.