Severe acute respiratory syndrome-CoV-2 infection has been known to cause an array of chronic consequences, most of which are yet to be studied in detail. These presentations are due to direct invasion of the tissues by the virus or other factors such as immune response to the virus. These sequelae affect the patient's quality of life implicating the importance of follow-up care in all coronavirus disease-2019 (COVID-19) patients and changing the definition of “post-COVID-19 recovery.” Adequate preparedness for post-COVID consequences with adequate health care is need of the hour. This also warrants for the patients' awareness, stressing upon the importance of educating the general public about keeping a watch for certain symptoms. Regular screening procedures may also aid in timely prevention, recognition, and management hence reducing morbidity and mortality in the post-COVID phase.
Keywords: COVID-19, follow-up, sequelae
| Introduction|| |
Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome (SARS)-CoV-2, has affected every organ system in both acute and postacute phases. While initial public health responses focused on reducing the acute burden of COVID-19, a growing body of evidence indicates that SARS-CoV-2 infection can also result in long-term physical and mental health consequences, which are of increasing concern for health-care professionals. Such consequences last longer after infection and those lasting beyond 4 weeks from the onset of symptoms are currently referred to as “post-COVID-19 syndrome” or “Long COVID.”
This could either be subacute or ongoing symptomatic COVID-19 which comprises symptoms and abnormalities presenting 4–12 weeks beyond acute COVID-19 or chronic/post-COVID-19 syndrome which includes symptoms and abnormalities persisting beyond 12 weeks of the onset of acute COVID-19 and not attributable to alternative diagnoses.
| Pathophysiology|| |
The predominant pathophysiologic mechanisms include direct viral toxicity, endothelial damage, microvascular injury, immune system dysregulation, and stimulation of a hyperinflammatory state, thus leading to hypercoagulability with resultant in situ micro- and macrothrombosis. Another mechanism being proposed is maladaptation of the angiotensin-converting enzyme 2 (ACE2) pathway. The ACE2 receptor dysregulation leads to dysfunction of ACE2 containing sites and thus leads to organ-specific sequelae [Figure 1] and [Figure 2].
|Figure 1: Direct viral invasion – the image below shows binding of the severe acute respiratory syndrome CoV-2 spike protein to the angiotensin-converting enzyme 2 receptor, following which it is internalized into the host cell|
Click here to view
|Figure 2: Downregulation of angiotensin-converting enzyme 2 receptor – The attachment of the virus to the angiotensin-converting enzyme 2 receptor leads to its downregulation, hence resulting in decreased degradation of angiotensin I and angiotensin II. Consequently, there is increased action of angiotensin II on its receptors (the renin–angiotensin–aldosterone system)|
Click here to view
| Clinical Manifestations|| |
Pulmonary manifestations vary across a spectrum, ranging from dyspnea, chronic oxygen dependence, cough, chest pain, to difficult ventilator weaning and fibrotic lung damage. Dyspnea is the most common symptom, found in 42%–66% patients, at a 60–100 day follow-up. In several studies, 25% of patients were found to have a lower than normal 6-min walking distance at a 6-month follow-up. 6%–8% of cases had persistent hypoxemia with the need for supplemental oxygen, while a similar proportion of patients required breathing support while sleeping on 60-day follow-up.
The most common physiologic impairment reported was a reduction in diffusion capacity which is directly related to the severity of acute illness. Some COVID-19 survivors have been found to have restrictive pulmonary physiology at 3- and 6-month follow-ups. In around 50% of cases (25% of mild-to-moderate cases and 65% of severe cases), high-resolution computerized tomography (HRCT) on a 6-month follow-up has shown the presence of residual pulmonary changes, for example, ground-glass opacities, fibrotic changes, reticulations, or traction bronchiectasis.
Viral-dependent and viral-independent mechanisms are the two major factors attributing to the residual pulmonary deficits in patients with postacute COVID illness. The former is secondary to the invasion of alveolar epithelial and endothelial cells, while the latter is secondary to immunological damage, including perivascular inflammation, thus contributing to the breakdown of the endothelial–epithelial barrier with invasion of monocytes and neutrophils and extravasation of a protein-rich exudate into the alveolar space, consistent with other forms of acute respiratory distress syndrome (ARDS) ultimately leading to fibrosis on recovery. Other mechanisms include pulmonary vascular (micro and macro) thrombosis with widespread microangiopathy and severe endothelial injury which is higher in comparison with other forms of ARDS.,
For those with persistent symptoms, like dyspnea at 6 and 12 months, home pulse-oximetry devices have been suggested as a useful tool for monitoring along with pulmonary function tests, 6-min walk test, and HRCT chest.
Treatment with corticosteroids may be beneficial in patients with post-COVID. Steroid use during acute COVID-19 was not associated with diffusion impairment and radiographic abnormalities at 6-month follow-up in the postacute COVID-19 study.
Antifibrotic therapies may be needed to prevent pulmonary fibrosis and lung transplantation in fibroproliferative lung disease after ARDS due to COVID-19.
| Hematologic Sequelae|| |
COVID-19-associated coagulopathy is consistent with a hyperinflammatory and hypercoagulable state. This explains the disproportionately high rates of thrombotic complications rather than bleeding complications in acute COVID-19. A recent study concluded that patients discharged without thromboprophylaxis had a 2%–4% cumulative incidence of thrombosis (pulmonary embolism, intracardiac thrombus, thrombosed arteriovenous fistula, ischemic stroke) and a 3.7% cumulative incidence of bleeding (mostly related to mechanical falls) at 30 days postdischarge.,
Mechanisms of thromboinflammation
Mechanisms including endothelial injury, complement activation, platelet activation and platelet–leukocyte interactions, neutrophil extracellular traps, and release of pro-inflammatory cytokines with disruption of normal coagulant pathways and hypoxia are also postulated contributing factors for thromboinflammation. Patients with elevated D-dimer levels, in addition to comorbidities such as cancer and prolonged immobility, are at high risk for thrombosis. The risk of thrombotic complications in postacute COVID-19 is directly proportional to the duration and severity of the hyperinflammatory state.
Extending hospital stay (up to 6 weeks) and prolonged primary thromboprophylaxis (up to 45 days) in those managed as outpatients have been proven to be beneficial. Direct oral anticoagulants and low-molecular-weight heparin are preferred over warfarin due to lower risk of drug–drug interactions and lack of need to frequently monitor coagulation profile and therapeutic levels., The role of antiplatelet agents such as aspirin as an alternative (or in conjunction with anticoagulation agents) for thromboprophylaxis in COVID-19 is not yet clear. Physical activity and ambulation should be recommended to all patients when appropriate.
| Cardiovascular Sequelae|| |
Cardiovascular manifestations include persistent tachycardia, pulmonary embolism, vasculitis, increased risk of arrhythmias, new-onset cardiac injury (evidenced by increased circulating troponin), or worsening of underlying heart disease. An increased incidence of stress cardiomyopathy has also been reported. Chest pain was reported in approximately 20% of COVID-19 survivors at a 60-day follow-up in a study.
Pathophysiologic mechanisms postulated include direct viral invasion, downregulation of ACE2, inflammation, and the immunologic response affecting the structural integrity of the myocardium, pericardium, and conduction system. COVID-19 increases risk of arrhythmias due to a high catecholaminergic state and cytokines such as interleukin-6 (IL-6), IL-1, and tumor necrosis factor-α, which can prolong ventricular action potentials by modulating cardiac myocyte ion channel expression. Myocardial fibrosis and cardiomyopathy may also occur due to viral infection, leading to re-entrant arrhythmias. Autonomic dysfunction, such as postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia, has also been reported.,
Serial electrocardiography and echocardiogram at 4–12 weeks are recommended in patients with cardiovascular complications during acute infection, or persistent cardiac symptoms, but routine utilization of advanced cardiac imaging is not recommended. Athletes with cardiovascular complications related to COVID-19 are advised abstinence from strenuous sports or aerobic activity for 3–6 months or until cardiac MRI or normalization of troponin confirms the resolution of myocardial inflammation., Despite initial concerns with the use of renin–angiotensin aldosterone system (RAAS) inhibitors, they have been shown to be safe and should be continued in those with stable cardiovascular disease if recommended. Abrupt cessation of RAAS inhibitors could actually be potentially harmful. Low-dose beta-blocker is recommended for patients with postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. Use of anti-arrhythmic agents such as amiodarone in patients with fibrotic pulmonary changes is not recommended due to the increased risk of pulmonary fibrosis.
| Neuropsychiatric Sequelae|| |
The neuropsychiatric sequelae include chronic malaise, diffuse myalgia, depressive symptoms, nonrestorative sleep, migraine-like headache (often refractory to traditional analgesics), and late-onset headaches. In a study of 100 patients with a 6-week follow-up, approximately 38% had ongoing headache. Loss of taste or smell still persisted after resolution of other symptoms in approximately one-tenth of patients at 6-month follow-up. Cognitive impairment (brain fog) which manifests as difficulties with concentration, memory, receptive language, and/or executive function is also seen. In a cohort of 402 COVID-19 survivors, after 1 month of hospitalization, approximately 56% screened positive in at least one of the following including posttraumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive–compulsive symptomatology.
Other neurologic complications of acute COVID-19 include ischemic or hemorrhagic stroke, hypoxic–anoxic damage, posterior reversible encephalopathy syndrome, and acute disseminated myelitis, which may lead to lingering or permanent neurological deficits requiring extensive rehabilitation.
The mechanisms contributing to neuropathology in COVID-19 include direct viral infection, increase in cytokines including severe systemic inflammation and neuro-inflammation, microvascular thrombosis, and neurodegeneration. There is no evidence yet of SARS-CoV-2 directly infecting neurons, but it may cause changes in brain parenchyma and vessels, possibly by effects on blood–brain barriers, which drive inflammation in neurons, supportive cells, and brain vasculature. Levels of immune activation directly correlate with cognitive–behavioral changes. Other possible mechanisms include dysfunctional lymphatic drainage from circumventricular organs and viral invasion in the extracellular spaces of olfactory epithelium with passive diffusion and axonal transport through the olfactory complex.,
Neurofilament light chains (biomarkers of cerebral injury) have been found in peripheral blood of patients with COVID-19, with a more sustained increase in severe infection.
Thorough neuropsychological evaluation should be considered in patients with cognitive impairment, along with a standard protocol for screening patients with anxiety, depression, sleep disturbances, PTSD, dysautonomia, and fatigue. Proper therapies should be implemented for neurologic complications, and referral to a neurologist is required in cases like refractory headache.
| Renal Sequelae|| |
Five percent of all hospitalized patients and 20%–30% of critically ill patients present with severe acute kidney injury (AKI) requiring renal replacement therapy. Around 35% of patients have decreased estimated glomerular filtration rate (eGFR; defined as <90 ml/min per 1.73 m2) at 6 months. New-onset reduction of eGFR after documented normal renal function has been reported in 13% of patients during acute COVID-19.,,,
Acute tubular necrosis is the primary finding noted from renal biopsies. COVID-19-associated nephropathy, which is characterized by collapsing variant of focal segmental glomerulosclerosis with acute tubular injury, is thought to develop in response to interferon and chemokine activation. Thrombi in the renal microcirculation may also occur, potentially contributing to the development of renal injury. Patients with apolipoprotein L1 (APOL1) high-risk alleles are found to be more susceptible to renal injury.,
While the need for dialysis-dependent AKI at the time of discharge is low, the extent of the recovery remains unclear. As a result, these patients will require a close follow-up with a nephrologist.,
| Endocrine Sequelae|| |
Endocrine associations include increased risk of diabetes mellitus and its complications, and thyroid disorders. Diabetic ketoacidosis occurs even in patients without known diabetes mellitus, weeks to months following resolution of COVID-19 symptoms. Furthermore, weeks after the resolution of respiratory symptoms, patients report with subacute thyroiditis and clinical thyrotoxicosis.,,,
Endocrine manifestations may be consequences of direct viral injury, immunological and inflammatory damage, as well as iatrogenic complications. However, there is no evidence of permanent damage to pancreatic beta-cells. The primary deficit in insulin production is probably mediated by factors such as inflammation or the infection stress response, along with peripheral insulin resistance, whereas new-onset Hashimoto's thyroiditis or Graves' disease following COVID-19 may be potentiated by latent thyroid autoimmunity.
In the absence of traditional risk factors for type 2 diabetes, serologic testing for type 1 diabetes for associated autoantibodies and repeat postprandial c-peptide measurements should be obtained at follow-up in patients with newly diagnosed diabetes mellitus, whereas in patients with thyrotoxicosis, new-onset Graves' disease should also be ruled out.
| Gastrointestinal and Hepatobiliary Sequelae|| |
Prolonged viral fecal shedding with viral ribonucleic acid detectable for up to 4 weeks after the onset of COVID-19 infection symptoms and persistence for about 11 days after negative respiratory samples has been demonstrated. COVID-19 has also been known to cause alterations in the gut microbiome, depleting the beneficial commensals and supporting growth of opportunistic organisms. For instance, a butyrate-producing anaerobe Faecalibacterium prausnitzii, associated with good health, was found to inversely correlate with disease severity, leading to irritable bowel syndrome and dyspepsia. Dysbiosis and gut microbial metabolites influence immune responses, inflammation, and disease development in the lungs. This cross-talk between gut microbiota and lungs is referred to as the “gut-lung axis” and seems to be bidirectional: gut microbial metabolites can impact the lung through blood and when inflammation occurs in the lung, it can affect the gut microbiota as well. Although still underscored, these conditions might count in large amounts with regard to COVID-19 severity. Gut microorganisms are able to regulate mucosal sites distal from the intestine through their metabolites such as short chain fatty acids that can reach other organs via the bloodstream to exert immune regulation and induction of immunoglobulins, and anti-inflammatory effects. A healthy microbiota can counteract respiratory tract infection including the influenza A virus (IAV) and Streptococcus pneumonia, modulating the functions of effector immune cells, including alveolar macrophages and neutrophils through nucleotide-binding oligomerization domain-like receptor agonists. The novel SARS-CoV-2 might also have an impact on the gut microorganisms.,,,
| Dermatologic Sequelae|| |
In addition to all the above manifestations, postacute COVID-19 has been shown to have effects on the skin and its appendages, the predominant dermatologic complaint being hair loss-in 20% of patients, followed by a skin rash in 3% of patients at 6-month follow-up. Hair loss could be attributed to telogen effluvium as a result of viral infection or stress response.
All clinical manifestations of post COVID-19 illness are summarized in [Table 1].
|Table 1: Summary of clinical manifestations of postcoronavirus disease-2019 illness|
Click here to view
Multisystem inflammatory syndrome in adults
Multisystem inflammatory syndrome in adults (MIS-A) can present with cardiac, gastrointestinal, dermatological, and neurological symptoms without severe respiratory system involvement. In a study of 51 cases with MIS-A, cardiovascular system was affected the most (82.4%), followed by the gastrointestinal system (72.5%).
The underlying etiopathogenesis remains unknown, MIS-A is proposed to be a postinfectious phase with dysregulated immune complex activation, causing direct endothelial damage and associated thromboinflammation and dysregulation of the renin–angiotensin–aldosterone system.
Intravenous immunoglobulin (IVIG) is considered a first-line therapy (at a dose of 2 g/kg) and steroids can be used as adjunctive. IVIG influences the regulatory T-cells and controls inflammation. Other drugs include anakinra, a recombinant IL-1 receptor antagonist (dose of 4 mg/kg/day IV) which is shown to be effective and is preferred over tocilizumab, due to better safety profile, and lesser myelosuppressive and hepatotoxic effects.,
| Conclusion|| |
Post-COVID-19 “recovery” cannot be gauged solely on a negative polymerase chain reaction or hospital discharge. There is remarkable variation in the duration, severity, and fluctuation of symptoms, which can affect survivors' quality of life, functional status, cognition, and mood, and lead to severe disability. Given the global scale of this pandemic, it is apparent that the health-care needs for patients with sequelae of COVID-19 will continue to increase for the foreseeable future.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Greenhalgh T, Knight M, A'Court C, Buxton M, Husain L. Management of post-acute COVID-19 in primary care. BMJ 2020;370:m3026.
Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, et al.
Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine 2020;25:100463.
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al.
Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med 2020;383:120-8.
Lang M, Som A, Mendoza DP, Flores EJ, Reid N, Carey D, et al.
Hypoxaemia related to COVID-19: Vascular and perfusion abnormalities on dual-energy CT. Lancet Infect Dis 2020;20:1365-6.
Raghu G, Wilson KC. COVID-19 interstitial pneumonia: Monitoring the clinical course in survivors. Lancet Respir Med 2020;8:839-42.
Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al.
6-month consequences of COVID-19 in patients discharged from hospital: A cohort study. Lancet 2021;397:220-32.
Chang Y, Lee SO, Shim TS, Choi SH, Kim HR, Kim YH, et al.
Lung transplantation as a therapeutic option in acute respiratory distress syndrome. Transplantation 2018;102:829-37.
Alarcón-Rodríguez J, Fernández-Velilla M, Ureña-Vacas A, Martín-Pinacho JJ, Rigual-Bobillo JA, Jaureguízar-Oriol A, et al.
Radiological management and follow-up of post-COVID-19 patients. Radiologia (Engl Ed) 2021;63:258-69.
Patell R, Bogue T, Koshy A, Bindal P, Merrill M, Aird WC, et al
. Post discharge thrombosis and haemorrhage in patients with COVID-19. Blood 2020;136:1342-6.
Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020;135:2033-40.
Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al.
COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020;75:2950-73.
Barnes GD, Burnett A, Allen A, Blumenstein M, Clark NP, Cuker A, et al.
Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: Interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis 2020;50:72-81.
Bikdeli B, Madhavan MV, Gupta A, Jimenez D, Burton JR, Der Nigoghossian C, et al.
Pharmacological agents targeting thromboinflammation in COVID-19: Review and implications for future research. Thromb Haemost 2020;120:1004-24.
Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al.
Post-acute COVID-19 syndrome. Nat Med 2021;27:601-15.
Lau ST, Yu WC, Mok NS, Tsui PT, Tong WL, Cheng SW. Tachycardia amongst subjects recovering from severe acute respiratory syndrome (SARS). Int J Cardiol 2005;100:167-9.
Hendren NS, Drazner MH, Bozkurt B, Cooper LT Jr. Description and proposed management of the acute COVID-19 cardiovascular syndrome. Circulation 2020;141:1903-14.
Maron BJ, Udelson JE, Bonow RO, Nishimura RA, Ackerman MJ, Estes NM, et al
. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task force 3: Hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: A scientific statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015;66:2362-71.
Vaduganathan M, Vardeny O, Michel T, McMurray JJ, Pfeffer MA, Solomon SD. Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N Engl J Med 2020;382:1653-9.
Raj SR, Black BK, Biaggioni I, Paranjape SY, Ramirez M, Dupont WD, et al.
Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: Less is more. Circulation 2009;120:725-34.
Kociol RD, Cooper LT, Fang JC, Moslehi JJ, Pang PS, Sabe MA, et al.
Recognition and initial management of fulminant myocarditis: A scientific statement from the American Heart Association. Circulation 2020;141:e69-92.
Mazza MG, De Lorenzo R, Conte C, Poletti S, Vai B, Bollettini I, et al.
Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors. Brain Behav Immun 2020;89:594-600.
Perrin R, Riste L, Hann M, Walther A, Mukherjee A, Heald A. Into the looking glass: Post-viral syndrome post COVID-19. Med Hypotheses 2020;144:110055.
Morbini P, Benazzo M, Verga L, Pagella FG, Mojoli F, Bruno R, et al.
Ultrastructural evidence of direct viral damage to the olfactory complex in patients testing positive for SARS-CoV-2. JAMA Otolaryngol Head Neck Surg 2020;146:972-3.
Kanberg N, Ashton NJ, Andersson LM, Yilmaz A, Lindh M, Nilsson S, et al.
Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. Neurology 2020;95:e1754-9.
Kaseda ET, Levine AJ. Post-traumatic stress disorder: A differential diagnostic consideration for COVID-19 survivors. Clin Neuropsychol 2020;34:1498-514.
Robbins-Juarez SY, Qian L, King KL, Stevens JS, Husain SA, Radhakrishnan J, et al.
Outcomes for patients with COVID-19 and acute kidney injury: A systematic review and meta-analysis. Kidney Int Rep 2020;5:1149-60.
Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, et al.
Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York city: A prospective cohort study. Lancet 2020;395:1763-70.
Gupta S, Hayek SS, Wang W, Chan L, Mathews KS, Melamed ML, et al.
Factors associated with death in critically ill patients with coronavirus disease 2019 in the US. JAMA Intern Med 2020;180:1436-47.
Stevens JS, King KL, Robbins-Juarez SY, Khairallah P, Toma K, Alvarado Verduzco H, et al.
High rate of renal recovery in survivors of COVID-19 associated acute renal failure requiring renal replacement therapy. PLoS One 2020;15:e0244131.
Velez JC, Caza T, Larsen CP. COVAN is the new HIVAN: The re-emergence of collapsing glomerulopathy with COVID-19. Nat Rev Nephrol 2020;16:565-7.
Peleg Y, Kudose S, D'Agati V, Siddall E, Ahmad S, Nickolas T, et al.
Acute kidney injury due to collapsing glomerulopathy following COVID-19 infection. Kidney Int Rep 2020;5:940-5.
Meier P, Bonfils RM, Vogt B, Burnand B, Burnier M. Referral patterns and outcomes in noncritically ill patients with hospital-acquired acute kidney injury. Clin J Am Soc Nephrol 2011;6:2215-25.
Harel Z, Wald R, Bargman JM, Mamdani M, Etchells E, Garg AX, et al.
Nephrologist follow-up improves all-cause mortality of severe acute kidney injury survivors. Kidney Int 2013;83:901-8.
Ruggeri RM, Campennì A, Siracusa M, Frazzetto G, Gullo D. Subacute thyroiditis in a patient infected with SARS-COV-2: An endocrine complication linked to the COVID-19 pandemic. Hormones (Athens) 2021;20:219-21.
Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F. Subacute thyroiditis after Sars-COV-2 infection. J Clin Endocrinol Metab 2020;105:2367-70.
Chng CL, Tan HC, Too CW, Lim WY, Chiam PP, Zhu L, et al.
Diagnostic performance of ATA, BTA and TIRADS sonographic patterns in the prediction of malignancy in histologically proven thyroid nodules. Singapore Med J 2018;59:578-83.
Mateu-Salat M, Urgell E, Chico A. SARS-COV-2 as a trigger for autoimmune disease: Report of two cases of Graves' disease after COVID-19. J Endocrinol Invest 2020;43:1527-8.
Cheung KS, Hung IF, Chan PP, Lung KC, Tso E, Liu R, et al.
Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from a Hong Kong cohort: Systematic review and meta-analysis. Gastroenterology 2020;159:81-95.
Zuo T, Zhang F, Lui GC, Yeoh YK, Li AY, Zhan H, et al.
Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020;159:944-55.e8.
Donati Zeppa S, Agostini D, Piccoli G, Stocchi V, Sestili P. Gut microbiota status in COVID-19: An unrecognized player? Front Cell Infect Microbiol 2020;10:576551.
Bradley KC, Finsterbusch K, Schnepf D, Crotta S, Llorian M, Davidson S, et al.
Microbiota-driven tonic interferon signals in lung stromal cells protect from influenza virus infection. Cell Rep 2019;28:245-56.e4.
Miquel S, Martin R, Rossi O, Bermúdez-Humarán LG, Chatel JM, Sokol H, et al
. Faecalibacteriumprausnitzii and human intestinal health. Curr Opin Microbiol 2013;16:255-61.
Genovese G, Moltrasio C, Berti E, Marzano AV. Skin manifestations associated with COVID-19: Current knowledge and future perspectives. Dermatology 2021;237:1-12.
Tenforde MW, Morris SB. Multisystem inflammatory syndrome in adults: Coming into focus. Chest 2021;159:471-2.
Department of General Medicine, MVJMC and RH, Hoskote, Bengaluru - 562 114, Karnataka
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]