Authors: Devaraju Kanmaniraja,a,⁎ Jessica Kurian,a Justin Holder,a Molly Somberg Gunther,a Victoria Chernyak,b Kevin Hsu,a Jimmy Lee,a Andrew Mcclelland,a Shira E. Slasky,a Jenna Le,a and Zina J. Riccia
The coronavirus disease 2019 (COVID -19) pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected almost every country in the world, resulting in severe morbidity, mortality and economic hardship, and altering the landscape of healthcare forever. Although primarily a pulmonary illness, it can affect multiple organ systems throughout the body, sometimes with devastating complications and long-term sequelae. As we move into the second year of this pandemic, a better understanding of the pathophysiology of the virus and the varied imaging findings of COVID-19 in the involved organs is crucial to better manage this complex multi-organ disease and to help improve overall survival. This manuscript provides a comprehensive overview of the pathophysiology of the virus along with a detailed and systematic imaging review of the extra-thoracic manifestation of COVID-19 with the exception of unique cardiothoracic features associated with multisystem inflammatory syndrome in children (MIS-C). In Part I, extra-thoracic manifestations of COVID-19 in the abdomen in adults and features of MIS-C will be reviewed. In Part II, manifestations of COVID-19 in the musculoskeletal, central nervous and vascular systems will be reviewed.
Keywords: Abdominal imaging, COVID-19, Multisystem inflammatory syndrome
1. Abdominal findings of COVID019 in adults
The coronavirus 2019 disease (COVID-19), which originated in Wuhan, China, has quickly become a global pandemic, bringing normal life to a standstill in almost all countries around the world. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a novel virus preceded by two other recent coronavirus infections, the severe acute respiratory syndrome coronavirus (SARS-CoV-1) and the Middle Eastern respiratory syndrome coronavirus (MERS–CoV), but it has more far-reaching and devastating consequences. As of March 2021, the COVID-19 pandemic has resulted in over 29 million cases in the United States and over 121 million cases globally. As of April 2021, it is responsible for the deaths of over half a million people in the United States and more than 2 ½ million worldwide . As the disease has evolved over the past year, so has our understanding of the virus, including its pathophysiology, clinical presentation and imaging manifestations. Although COVID-19 is predominately a pulmonary illness, it is now established to have widespread extra-pulmonary involvement affecting multiple organ systems. The SARS-CoV-2 has a highly virulent spike protein which binds efficiently to the angiotensin converting enzyme 2 (ACE2) receptors which are expressed in many organs, including the airways, lung parenchyma, several organs in the abdomen, particularly the kidneys and GI system, central nervous system and the smooth and skeletal muscles of the body . The virus initially induces a specific adaptive immune response, and when this response is ineffective, it results in uncontrolled inflammation, which ultimately results in tissue injury .
This article provides a comprehensive review of the pathophysiology and imaging findings of the extra-thoracic manifestations of COVID-19 with the exception of unique cardiothoracic features associated with multisystem inflammatory syndrome in children (MIS-C). In Part I, extra-thoracic manifestations of COVID-19 in the abdomen in adults and the varying features of multisystem inflammatory syndrome in children will be reviewed, with imaging findings summarized in Table 1, Table 2 . In Part II, manifestations of COVID-19 in the musculoskeletal system, the central nervous system and central and peripheral vascular systems will be reviewed.
Summary of abdominal imaging findings in COVID-19 in adults.
|• Increased or coarsened echogenicity on US|
|• Hypoattenuation on non-contrast or contrast enhanced CT|
|• Periportal edema and heterogeneous enhancement on CT|
|• Loss of signal on opposed-phase sequences on MRI|
|• Portal vein thrombus|
|Pancreas||• Features of acute interstitial pancreatitis|
|Biliary Tree||• Biliary ductal dilatation|
|Kidney||• Increased or heterogeneous parenchymal echogenicity on US|
|• Loss of corticomedullary differentiation on US|
|• Preserved cortical thickness|
|• Perinephric fat stranding and thickening of Gerota’s fascia on CT|
|• Wedge shaped perfusion defects on CT or MRI|
|• Thrombus in the renal artery or vein|
|• Mural edema|
|• Acalculous cholecystitis|
|Urinary Bladder||• Bladder wall thickening|
|• Mural hyperenhancement|
|• Perivesicular stranding|
|Bowel||• Mural thickening|
|• Fluid-filled colon|
|• Pneumatosis intestinalis|
|• Portal vein gas|
|• Acute mesenteric ischemia|
|• Vascular occlusion (superior mesenteric artery, superior mesenteric vein, or portal vein)|
|• Mesenteric fat stranding, ascites|
|• Active gastrointestinal bleeding (duodenal or gastric ulcer) on CTA|
|• Clostridium difficile colitis|
|• Ischemic colitis|
|Spleen||• Wedge shaped perfusion defects on CT or MRI|
|• Thrombus in the splenic artery or vein|
Summary of imaging findings in Multisystem Inflammatory Syndrome in Children.
|Cardiothoracic||• Bilateral symmetric diffuse airspace opacities with lower lobe predominance on CXR|
|• Diffuse ground glass opacity, septal thickening, and mild hilar lymphadenopathy on CT|
|• Bilateral pleural effusions|
|• Pericardial effusion|
|• Myocarditis pattern on cardiac MRI|
|Abdominal||• Mesenteric lymphadenopathy, most common in right lower quadrant|
|• Mesenteric edema|
|• Bowel wall thickening|
|• Gallbladder wall thickening|
2. Abdominal findings of COVID-19 in adults
2.1. Hepatobiliary derangement
Varying derangements of the liver, biliary system, gallbladder, portal vein and pancreas may occur in COVID-19 with hepatic parenchymal injury and biliary stasis reported with highest frequency. The mechanism of involvement of these structures appears to be multifactorial. The most direct form of injury results from SARS CoV-2 entry into host cells by binding to ACE2 receptors detected in several locations in the hepatobiliary system, including biliary epithelial cells (cholangiocytes), gallbladder endothelial cells and both pancreatic islet cells and exocrine glands [, , , ].
2.1.1. Hepatic injury
Direct SARS CoV-2 entry into cholangiocytes may cause liver damage by disrupting bile acid transportation or by triggering acid accumulation resulting in liver injury . Systemic inflammation, hypoxia inducing hepatitis and adverse drug reactions may incite liver injury . Several drugs commonly used to treat COVID-19 patients, including acetaminophen, lopinavir and ritonavir can be hepatotoxic . One study excluding COVID-19 patients receiving hepatotoxic drugs, still found patients with liver injury. Therefore, liver damage in COVID-19 patients is likely not entirely drug-induced but may also be due to acute infection [8,9]. Furthermore, since patients with chronic liver disease such as cirrhosis, autoimmune liver disease and prior liver transplantation are more susceptible to COVID-19 infection , underlying conditions may also contribute to liver injury.
The most frequent hepatic derangement is abnormal liver function tests reported in 16–53% of patients [10,11] and including raised levels of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase with mild elevation of bilirubin. The majority of cases are mild and self-limited, with severe liver damage rare . Liver injury is most prevalent in the second week of COVID-19 infection, and has a higher incidence in those with gastrointestinal symptoms and more severe infection . Based on a meta-analysis of hepatic autopsy findings of deceased COVID-19 patients in 7 countries, hepatic steatosis (55%), hepatic sinus congestion (35%) and vascular thrombosis (29%) were the most common . In a retrospective study of abdominal imaging findings of 37 COVID-19 patients, 27% who underwent ultrasound had increased hepatic echogenicity considered to represent fatty liver with elevated liver enzymes being the most frequent indication for ultrasound . It should be noted that since obesity is a major risk factor for severe COVID-19 infection, it might contribute to the frequency of steatosis identified on imaging. In another retrospective abdominal sonographic study of 30 ICU patients with COVID-19, the most common finding was hepatomegaly (56%), with most cases having increased hepatic echogenicity and elevated liver function tests . In the only retrospective case-control study of 204 COVID-19 patients who underwent non-contrast chest CT scan, steatosis was found in 31.9% of cases and only 7.1% of controls . Steatosis was based on a single ROI measurement in the right lobe with an attenuation value ≤ 40 HU. However, underlying risk factors for steatosis such as diabetes, obesity, hypertension and abnormal lipid profile, were not available to exclude preexisting conditions leading to steatosis. Finally, unlike in the spleen and kidney where infarcts are reported in COVID-19, hepatic infarction is not a distinct feature. This is likely due to the liver’s unique dual blood supply.
On imaging the liver may be enlarged. On ultrasound, the liver of patients with abnormal liver function tests may be coarsened and/or increased in echogenicity (Fig. 1, Fig. 2 ). On CT scan, the liver may be hypoattenuated on non-contrast or contrast-enhanced exam due to steatosis (Fig. 3 ). Periportal edema and heterogeneity of hepatic enhancement may be seen on contrast-enhanced CT or MRI due to parenchymal inflammation. On MRI, loss of signal on opposed-phase sequences (Fig. 4 ) may be seen due to steatosis and periportal edema may be conspicuous on T2-weighted images or on contrast-enhanced images [7,8,14]. Periportal lymphadenopathy, typical of chronic liver disease, is not reported in COVID-19 . In patients with severe COVID-19 infection, ancillary manifestations of hepatic inflammation and injury, such as parenchymal attenuation changes and abscesses may be seen (Fig. 5 ).
This Article Presents a Detailed Overview with Imaging. To View the Rest of This Analysis Click Here: