Table 1.

Summary of systemic manifestations and possible pathological mechanisms

Body systems	Clinical manifestations	Imaging/Electrocardiogram (ECG) findings	Blood test anomalies	Pathological mechanisms/findings
Respiratory system	• Cough • Sputum production • Shortness of breath • Respiratory distress and failure (acute respiratory distress syndrome)	• Ground-glass opacities and pulmonary consolidation or exudation (thoracic CT-scan)		• Hyaline membrane formation at the alveolar level (acute stage) • Interstitial edema • Fibroblast proliferation • Altered alveolar-capillary exchange • Pulmonary thrombosis
Cardiovascular system	• Acute coronary syndrome • Acute heart failure • Myocarditis • Cardiac arrhythmias • Thromboembolic events	• QT prolongation • Torsades de pointes (TdP); seen on ECG		• Infection and acute respiratory distress (for acute heart failure) • Inflammation (for myocarditis and thromboembolism) • Hypoxia, immobilization, disseminated intravascular coagulation (for thromboembolic events) • Myocardial injury, renal failure, liver failure, hypokalemia (for TdP)
Urinary system	• Acute kidney injury • Isolated urine abnormalities (proteinuria, hematuria)	• Kidney inflammatory signs (CT-scan)		• Viral-induced kidney inflammation
Hematopoietic system	• Signs of anemia.		• Low hemoglobin levels • Leukocytosis • Neutrophilia • Increased neutrophils/lymphocytes ratio • Low eosinophil, monocytes, lymphocytes, and platelet counts • Raised erythrocyte sedimentation rate • Increased C-reactive protein • High ferritin • High procalcitonin levels • “Cytokine storm” with high levels of interleukins 1, 2R, 6, 7, and 17; tumor necrosis factor alpha; monocyte chemoattractant protein 1; macrophage inflammatory protein 1α; and interferon-γ inducible protein 10 • Increase of prothrombotic markers: D-dimers, fibrinogen and prothrombin levels and partial activated thromboplastin time	• Viral-induced hyperinflammation • Spleen enlargement/atrophy • Diffused lymphoid tissue atrophy • Immune reaction in response to the infectious process (for leukocytosis and neutrophilia) • Virus-induced apoptosis, increased lymphocyte activation, and inhibition of lymphocyte proliferation (for lymphopenia) • Platelet consumption (for thrombocytopenia)
Gastrointestinal tract system plus hepatic and pancreatic involvement	• Diarrhea • Vomiting • Abdominal pain	• Focal enlargement of the pancreas or dilatation of the pancreatic duct, without acute necrosis	• Raised transaminases levels • Increased total bilirubin • Low albumin levels • Increased levels of pancreatic enzymes	• Alteration of intestinal permeability with resultant malabsorption, gut microbiome alterations, intestinal inflammation mediated by ACE2 receptors (for diarrhea) • Viral binding on ACE2 cholangiocytes (for liver dysfunction) • Microvascular steatosis, mild lobular and portal activity • Drug-induced liver injury by lopinavir/ritonavir combination, hydroxychloroquine, through reactive metabolites or idiosyncrasy • Direct effect of the virus on pancreatic tissues, systemic inflammatory response and drug-related pancreatic injury
Nervous system	• Headaches • Impaired consciousness (and other encephalitis signs such as seizures) • Motor deficit (if stroke) • Smell and taste alterations • Visual impairment • Neuralgia • Agitation • Mental ill health (stress, anxiety, depression, suicidal intentions, isolation, social exclusion and stigma)	• CT-scan signs of cerebrovascular lesions		• Direct infection injury demonstrated by the presence of the virus in the cerebrospinal fluid • Cytokine dysregulation • Demyelinating reactions (mainly for peripheral nervous system signs) • Brain hypoxia • Peripheral immune cells transmigration • Post-infectious autoimmunity • Microbial translocation through the gut-brain axis • Drug adverse effects (i.e., chloroquine and agitation)
Musculoskeletal system	• Muscle pain • Muscle weakness • Joint pain			• Cytokine-mediated sensitization of sensitive receptors on the muscular fibers (for muscle weakness and pain) • Articular deposit of cytokines (for joint pain)

ACE 2 angiotensin-converting enzyme 2, CT-scan computed tomography scan, ECG electrocardiogram, TdP Torsades de pointes