Complications table


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Data on the management of comorbidities in patients with COVID-19 is evolving rapidly. Tailor the management of critical illness to the patient’s comorbidities (e.g., decide which chronic therapies should be continued and which therapies should be temporarily stopped, monitor for drug-drug interactions).[2] For more information, see the Best Practice topic: Management of coexisting conditions in the context of COVID-19.

acute respiratory distress syndrome (ARDS)

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Reported in 15% to 33% of patients in case series.[27][28][252][253][309]

Children can quickly progress to ARDS.[8]

Factors that increase the risk of developing ARDS and death include older age, neutrophilia, elevated lactate dehydrogenase levels, and elevated D-dimer levels.[615]

Lung transplant has been reported in a small number of cases in China as the sole therapy for end-stage pulmonary fibrosis related to ARDS in COVID-19 patients.[616]

venous thromboembolism

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Coagulopathy in COVID-19 has a prothrombotic character, which may explain reports of thromboembolic complications.[617] Patients may be predisposed to venous thromboembolism due to the direct effects of COVID-19, or the indirect effects of infection (e.g., severe inflammatory response, critical illness, traditional risk factors).[399]

Venous thromboembolism (pulmonary embolism or deep vein thrombosis) has been reported in 20% to 31% of patients with severe COVID-19 in the intensive care unit (including some patients who were on thromboprophylaxis), and may be associated with poor prognosis.[618][619][620][621][622][623][624] Other studies have reported higher rates of 46% to 85%.[625][626][627]

Patients with very high D-dimer levels have the greatest risk of thrombosis and may benefit from active monitoring.[354][355] If venous thromboembolism is suspected, perform a computed tomographic angiography or ultrasound of the venous system of the lower extremities.[628]

Treat patients with a thromboembolic event (or who are highly suspected to have thromboembolic disease if imaging is not possible) with therapeutic doses of anticoagulant therapy as per the standard of care for patients without COVID-19. There are currently insufficient data to recommend either for or against using therapeutic doses of antithrombotic or thrombolytic agents for COVID-19. Patients who require extracorporeal membrane oxygenation or continuous renal replacement therapy, or who have thrombosis of catheters or extracorporeal filters, should be treated with antithrombotic therapy as per the standard institutional protocols for those without COVID-19.[3]

A high incidence (14.7%) of asymptomatic deep vein thrombosis was reported in a cohort of patients with COVID-19 pneumonia.[629] An autopsy study of 12 patients revealed deep vein thrombosis in 58% of patients in whom venous thromboembolism was not suspected before death.[630] These studies highlight the importance of having a high suspicion for venous thromboembolism in patients who have signs of coagulopathy, including elevated D-dimer level.

While these patients are at higher risk of thrombotic events, they may also be at an elevated risk for bleeding. In a small retrospective study, 11% of patients at high risk of venous thromboembolism also had a high risk of bleeding.[631]

Antiphospholipid antibodies and lupus anticoagulant have been detected in a small number of patients. The presence of these antibodies can rarely lead to thrombotic events that are difficult to differentiate from other causes of multifocal thrombosis. The significance of this finding is unknown, although it is thought that these antibodies may not be involved in the pathogenesis of venous thromboembolism in patients with severe COVID-19.[632][633][634]

It has been suggested that a new term (e.g., COVID-19-associated pulmonary thrombosis, diffuse pulmonary intravascular coagulopathy, or microvascular COVID-19 lung vessels obstructive thrombo-inflammatory syndrome [MicroCLOTS]) be used rather than the term pulmonary embolism as it has been hypothesised that the pathophysiology is different; local thrombi are formed in the lung vessels due to a local inflammatory process rather than the classical emboli coming from elsewhere in the body.[635][636][637]

Cases of arterial thrombosis, cerebral venous thrombosis, and acute limb ischaemia secondary to thrombosis have been reported.[638][639][640][641][642]

cardiovascular complications

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COVID-19 is associated with a high inflammatory burden that can result in cardiovascular complications with a variety of clinical presentations. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, arrhythmias, acute coronary syndrome, rapid deterioration, and sudden death.[643][644][645] These complications can present on presentation or develop as the severity of illness worsens.[646] It is uncertain to what extent acute systolic heart failure is mediated by myocarditis, cytokine storm, small vessel thrombotic complications, microvascular dysfunction, or a variant of stress-induced cardiomyopathy.[647]

Acute myocardial injury has been reported in 7% to 20% of patients in case series, and is indicated by elevated cardiac biomarkers.[27][252][309][648] Acute myocardial injury at admission has been associated with a higher risk of all-cause mortality in patients with COVID-19.[649]

Prevalence of cardiac disease is high among patients who are severely or critically ill, and these patients usually require intensive care and have a poor prognosis and higher rate of in-hospital mortality. These patients are more likely to require non-invasive or invasive ventilation, and have a higher risk of thromboembolic events and septic shock compared with patients without a history of cardiac disease.[646][648][650][651][652] The mortality of patients with cardiovascular disease was 22% in one retrospective study, compared with the mortality of the overall population in the study, which was 9.8%.[653] Patients with underlying cardiovascular disease but without myocardial injury have a relatively favourable prognosis.[654]

Predictors for myocardial injury include older age, presence of cardiovascular-related comorbidities, and elevated C-reactive protein. Elevated myocardial markers predict risk for in-hospital mortality.[655]

Cases of fulminant myocarditis, cardiomyopathy, cardiac tamponade, myopericarditis with systolic dysfunction, pericarditis and pericardial effusion, ST-segment elevation (indicating potential acute myocardial infarction), cor pulmonale, and takotsubo syndrome have been reported.[9][585][588][656][657][658][659][660]

Perform an ECG and order high-sensitivity troponin I (hs-cTnI) or T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with symptoms or signs that suggest acute myocardial injury in order to make a diagnosis. Results should be considered in the clinical context.[661]

Monitor blood pressure, heart rate, and fluid balance, and perform continuous ECG monitoring in all patients with suspected or confirmed acute myocardial injury.[661]

There are limited data to recommend any specific drug treatments for these patients. Management should involve a multidisciplinary team including intensive care specialists, cardiologists, and infectious disease specialists.[647] It is important to consider that drugs such as hydroxychloroquine and azithromycin may prolong the QT interval and lead to arrhythmias.[661]

Guidelines for the management of COVID-19-related myocarditis are available.[662]

Infection may have longer-term implications for overall cardiovascular health; however, further research is required.[663]

acute kidney injury

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Overall risk in hospitalised patients is low, with a pooled incidence rate of 3%. This risk increases to 19% when patients are admitted to the intensive care unit.[664] In a retrospective study in New York, 36.6% of hospitalised patients went on to develop acute kidney injury, and of these 14.3% required renal replacement therapy. Nearly 90% of patients on mechanical ventilation developed acute kidney injury, and 97% of patients requiring renal replacement therapy were on ventilators.[665] Data from the UK indicate that approximately 31% of patients on ventilators (and 4% not on ventilators) require renal replacement therapy.[666] Similarly, 31% of critically ill patients in a New York study required dialysis.[143]

Can develop at any time before or during hospital admission. Risk factors include age ≥65 years, black ethnicity, history of acute kidney injury, chronic kidney disease, cardiovascular disease, hypertension, heart failure, hepatic disease, and diabetes.[665][666] Causes include haemodynamic changes, hypovolaemia, viral infection leading directly to kidney tubular injury, thrombotic vascular processes, glomerular pathology, or rhabdomyolysis.[666] Direct kidney infection has been confirmed in an autopsy study of a single patient.[667]

Patients should meet criteria for acute kidney injury for diagnosis. NHS England: acute kidney injury (AKI) algorithm external link opens in a new window Perform a urinalysis for blood, protein, and glucose to help identify the underlying cause. Imaging is recommended if urinary tract obstruction is suspected.[666]

Stop any drugs that can cause or worsen acute kidney injury, if possible. Aim to achieve optimal fluid status (euvolaemia) in all patients. Consider a loop diuretic for treating fluid overload only. Manage hyperkalaemia according to local protocols. See local protocols for guidance on renal replacement therapy.[666]

Specialist input may be required in some cases (e.g., uncertainty about cause, abnormal urinalysis results, complex fluid management needs, indications for renal replacement therapy), and some patients may require critical care admission.[666]

Monitor fluid status daily, as well as serum urea, creatinine, and electrolytes at least every 48 hours (or more often if clinically indicated). Monitor patients for the development of, or progression to, chronic kidney disease for at least 2 to 3 years after acute kidney injury.[666]

Acute kidney injury is associated with poor prognosis.[665]

Cases of nephritis and collapsing glomerulopathy have been reported.[668][669]

acute liver injury

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Abnormal liver function has been reported in 19% of patients. Patients in Hubei province were more likely to present with abnormal liver function compared with those outside of Hubei.[320]

Abnormal liver function (higher levels of aspartate aminotransferase, alanine aminotransferase, and total bilirubin, and lower levels of serum albumin) is associated with a significant increase in the severity of COVID-19 infection.[670] Although data support a higher prevalence of abnormal aminotransferase levels in patients with severe illness, evidence suggests that clinically significant liver injury is uncommon.[671]

Medications (e.g., lopinavir/ritonavir) may have a detrimental effect on liver injury.

neurological complications

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Patients with severe illness commonly have neurological complications, possibly due to viral invasion of the central nervous system (SARS-CoV-2 has been detected in the brain and cerebrospinal fluid) or systemic illness.

In a case series of 214 patients, neurological symptoms were seen in 36% of patients, and were more common in patients with severe illness.[672] In a small retrospective study of patients in an intensive care unit, 44% of patients with neurological symptoms had abnormal findings on brain magnetic resonance imaging.[673]

Complications include acute cerebrovascular disease (including large-vessel stroke in younger patients), impairment of consciousness, ataxia, seizures, neuralgia, skeletal muscle injury, corticospinal tract signs, meningitis, encephalitis, encephalopathy, myoclonus, and Guillain-Barre syndrome. Patients may present with these signs/symptoms, or they may develop them during the course of the disease. These patients have a poor prognosis.[674][675][676][677]

Ischaemic stroke (confirmed on imaging) was reported in 0.9% of patients in a retrospective cohort study of hospitalised patients with COVID-19 in New York. Most strokes were cryptogenic.[678]

Guidelines for the management of acute ischaemic stroke in patients with COVID-19 infection have been published.[679]

cytokine release syndrome

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Cytokine release syndrome may cause ARDS or multiple-organ dysfunction, which may lead to death.[680] Elevated serum proinflammatory cytokines (e.g., tumour necrosis factor alpha, interleukin-2, interleukin-6, interleukin-8, interleukin-10, granulocyte-colony stimulating factor, monocyte chemoattractant protein 1) and inflammatory markers (e.g., C-reactive protein, serum ferritin) have been commonly reported in patients with severe COVID-19. This likely represents a type of virus-induced secondary haemophagocytic lymphohistiocytosis, which may be fatal.[27][364][593][681] Interleukin-6, in particular, has been associated with severe COVID-19 and increased mortality.[595]

One study found that patients who require admission to the intensive care unit have significantly higher levels of interleukin-6, interleukin-10, and tumour necrosis factor alpha, and fewer CD4+ and CD8+ T cells.[682]

Anti-inflammatory/immunosuppressive treatments (e.g., tocilizumab, hydroxychloroquine/chloroquine, Janus kinase inhibitors) are being trialled in COVID-19 patients.[683] See our Emerging section for more information.

Cytokine release syndrome has been reported in children, although cases appear to be rare.[684] See section below on paediatric multisystem inflammatory syndrome.

paediatric multisystem inflammatory syndrome

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Also known as multisystem inflammatory syndrome in children (MIS-C).

A small number of children and adolescents who develop a significant systemic inflammatory response have been identified in some locations including Europe and the US. A small number of deaths have been reported.[685]

The rare syndrome shares common features with Kawasaki disease, toxic shock syndrome, bacterial meningitis, and macrophage activation syndromes. Common features include abdominal pain, other gastrointestinal symptoms, and cardiac inflammation (elevated troponin and pro-B-type natriuretic peptide levels). This syndrome has been temporally associated with COVID-19 only, and patients may test positive or negative for SARS-CoV-2.[686][687][688][689]

A retrospective review at a centre in Bergamo province, Italy, reports a higher number of cases of Kawasaki-like disease during the COVID-19 epidemic, with a monthly incidence 30 times greater than the monthly incidence of the previous 5 years, and a clear starting point after the first case of COVID-19 was diagnosed. The clinical and biochemical features of these patients differ from the centre’s historical cohort of patients with Kawasaki disease. The authors conclude that there is a strong association between this syndrome and the COVID-19 epidemic.[690]

A retrospective study in France and Switzerland identified 35 children with fever and acute heart failure possibly associated with this syndrome. The median age at admission was 10 years, and comorbidities were present in 28% of children. Gastrointestinal symptoms were prominent. Inflammation markers were suggestive of cytokine release syndrome and macrophage activation. Left ventricular ejection fraction was <30% in one third of patients. Some 88% of patients tested positive for SARS-CoV-2. All patients were treated with immunoglobulin, and some received corticosteroids. All patients recovered.[691]

The Royal College of Paediatrics and Child Health in the UK has published a case definition, as well as guidance on how to manage these patients. Management is mainly supportive and involves a multidisciplinary team (paediatric infectious disease, cardiology, rheumatology, critical care).[692] The World Health Organization and the US Centers for Disease Control and Prevention have also published case definitions.[693][694]

While an association between this syndrome and COVID-19 seems plausible based on current evidence, the association is not definitive and further research is required. It is not clear yet whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or whether this is a different syndrome.

septic shock

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Reported in 4% to 8% of patients in case series.[27][28][252][309]

Guidelines for the management of shock in critically ill patients with COVID-19 recommend a conservative fluid strategy (crystalloids preferred over colloids) and a vasoactive agent. Noradrenaline (norepinephrine) is the preferred first-line agent, with vasopressin or adrenaline (epinephrine) considered suitable alternatives. Vasopressin can be added to noradrenaline if target mean arterial pressure cannot be achieved with noradrenaline alone.[391][3] Dopamine is only recommended as an alternative vasopressor in certain patients (e.g., those with a low risk of bradycardia or tachyarrhythmias). Dobutamine is recommended in patients who show evidence of persistent hypoperfusion despite adequate fluid loading and the use of vasopressors. Low-dose corticosteroid therapy is recommended for refractory shock.[3]

disseminated intravascular coagulation

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Reported in 71% of non-survivors.[695] Disseminated intravascular coagulation (DIC) is a manifestation of coagulation failure, and an intermediate link in the development of multi-organ failure. Patients may be at high risk of bleeding/haemorrhage or venous thromboembolism.[696]

Coagulopathy manifests as elevated fibrinogen, elevated D-dimer, and minimal change in prothrombin time, partial thromboplastin time, and platelet count in the early stages of infection. Increasing interleukin-6 levels correlate with increasing fibrinogen levels. Coagulopathy appears to be related to severity of illness and the resultant thromboinflammation. Monitor D-dimer level closely.[697]

Prophylactic-dose low molecular weight heparin should be considered in all hospitalised patients with COVID-19 (including those who are not critically ill), unless there are contraindications. This will also protect against venous thromboembolism.[698] Anticoagulant therapy with a low molecular weight heparin or unfractionated heparin has been associated with a better prognosis in patients with severe COVID-19 who have a sepsis-induced coagulopathy (SIC) score of ≥4 or a markedly elevated D-dimer level.[699] In patients with heparin-induced thrombocytopenia (or a history of it), argatroban or bivalirudin are recommended.[696]

Standard guidance for the management of bleeding manifestations associated with DIC or septic coagulopathy should be followed if bleeding occurs; however, bleeding manifestations without other associated factors is rare.[697][698]

acute respiratory failure

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Reported in 8% of patients in case series.[28]

Leading cause of mortality in patients with COVID-19.[588]

Children can quickly progress to respiratory failure.[8]

pregnancy-related complications

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Retrospective reviews of pregnant women with COVID-19 found that women appeared to have fewer adverse maternal and neonatal complications and outcomes than would be expected for those with severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). Adverse effects on the newborn including fetal distress, premature labour, respiratory distress, thrombocytopenia, and abnormal liver function have been reported; however, it is unclear whether these effects are related to maternal SARS-CoV-2 infection. Maternal deaths have been reported, as well as miscarriage (including a case in the second trimester), ectopic pregnancy, intrauterine growth restriction, oligohydramnios, perinatal death, preterm birth, and neonatal death. It is unclear whether this is related to COVID-19.[100][700][446][701][702][703][704][705][706][707][708]

secondary infection

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Reported in 6% to 10% of patients in case series.[27][309]

Cases of Staphylococcus aureus superinfection and Mycoplasma pneumoniae have been reported.[709][710]


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Invasive pulmonary aspergillosis has been reported in critically ill patients with moderate to severe ARDS.[711][712][713] A prospective observational study found that one third of mechanically ventilated patients with COVID-19 had putative invasive pulmonary aspergillosis.[714]

Intubation for more than 7 days may be a risk factor. Potential contributing factors include immunosuppression, critical illness, or use of high-dose corticosteroids. Consider aspergillosis in patients who deteriorate despite optimal supportive care or have other suspicious radiological or clinical features.[430]

Prescribe appropriate antifungal therapy according to local guidelines.[715]

pancreatic injury

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Mild pancreatic injury (defined as elevated serum amylase or lipase levels) has been reported in 17% of patients in one case series. It is unknown whether this is a direct viral effect or due to the harmful immune response that occurs in some patients. Further research is required.[716]


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There have been case reports of rhabdomyolysis in adults and children.[717][718]

autoimmune haemolytic anaemia

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Warm or cold autoimmune haemolytic anaemia (first episode) has been reported in 7 patients after the onset of COVID-19 symptoms and within the timeframe compatible with cytokine release syndrome. Four patients had indolent B lymphoid malignancy. It is unknown whether the haemolytic anaemia is related to COVID-19 infection.[719]

immune thrombocytopenia

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A small number of cases of immune thrombocytopenia have been reported in patients with COVID-19, including one case report in a 10-year-old child and another in a pregnant woman.[720][721][722]

subacute thyroiditis

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The first known case of subacute thyroiditis has been reported in an 18-year-old woman after SARS-CoV-2 infection. Subacute thyroiditis is a thyroid disease of viral or post-viral origin.[723]

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