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The gut, liver and COVID-19

Coronaviruses such as SARS-CoV-2, the cause of COVID-19, can cause serious disease in some people, usually affecting the lungs. However, other coronaviruses that also cause serious disease, SARS-CoV and MERS-CoV, can cause intestinal and liver injury. Therefore, it is possible that SARS-CoV-2 can cause similar problems.

In general, studies done in people with SARS in 2002-03 found that elevated levels of liver enzymes (AST and ALT) could occur in the early stages of this disease. In more severe cases of SARS, a greater degree of liver injury was found. In some cases, people with SARS-associated liver injury also had increased concentrations of the waste product bilirubin and the protein albumin in their blood. Biopsies of liver tissue from people who had SARS suggested that liver injury, caused by SARS-CoV, occurred.

COVID-19

A review of studies with people who have been diagnosed with COVID-19 has found that between 15% and 53% of such people can have some degree of liver injury. This injury is revealed by the presence of elevated levels of liver enzymes and sometimes bilirubin in their blood samples.

Cells of the liver and bile duct have the protein ACE2 on their surface. This protein serves as a receptor for SARS-CoV-2, allowing the virus entry into cells. Whether this virus directly or indirectly infects the liver remains unclear.

So far, there are no published reports in peer-reviewed journals of large numbers of people with chronic viral hepatitis caused by hepatitis B virus or hepatitis C virus who have also developed COVID-19. However, some doctors are concerned that people with chronic viral hepatitis may experience additional liver injury if they develop serious symptoms of COVID-19.

The role that medicines commonly used in managing complications of COVID-19 have on the liver needs to be investigated. Such medicines include antibiotics and steroids such as prednisolone.

A team of doctors at the Shanghai Public Health Clinical Center reviewed medical records of 148 people (75 men, 73 women) who sought help because of COVID-19. All patients were positive for SARS-CoV-2 RNA. The doctors found that about 37% of patients had elevated levels of liver enzymes in their blood. People with elevated levels of liver enzymes also had proteins in their blood suggestive of generalized inflammation, such as C-reactive protein. However, what is noteworthy is that the doctors found an association between the use of Kaletra (lopinavir-ritonavir) and an increased level of liver enzymes.

Kaletra was approved almost 20 years ago as part of combination therapy for HIV. Due to the crisis nature of the COIVID-19 pandemic, doctors in many countries have used drugs that are approved for another use, usually against another virus, in people infected with SARS-CoV-2 in the hope that it might save their lives. In the early days of the COVID-19 pandemic, Kaletra was widely used in Chinese hospitals for this purpose. As the analysis from Shanghai is retrospective in nature, it is not possible to be certain if the elevated levels of liver enzymes were caused by Kaletra exposure or were simply a natural part of the evolution of SARS-CoV-2 disease process. However, the Shanghai doctors urge caution when prescribing Kaletra for use as a potential treatment for COVID-19.

Diarrhea and other symptoms

Doctors in Guangdong, China, reported details on 95 people with acute SARS-CoV-2 and gastrointestinal issues. Sixty-five percent of these people developed GI symptoms, most of which occurred after hospitalization. Symptoms included the following:

  • diarrhea
  • loss of appetite
  • nausea

It is noteworthy that 12% of patients also had gastrointestinal symptoms prior to hospitalization.

The doctors suspect that diarrhea that occurred during hospitalization was likely due to the use of antibiotics (prescribed to treat lung infection).

Analysis of stool samples found that SARS-CoV-2 could be detected in 22 out of 42 people with gastrointestinal symptoms and in nine out of 23 people without gastrointestinal symptoms.

Additional investigation found that SARS-CoV-2 was detected in swabs or fluid samples from the throat, stomach, duodenum and rectum from two people with severe symptoms. In only one person with non-severe symptoms was SARS-CoV-2 found and only in the duodenum.

The doctors found that the presence of gastrointestinal symptoms did not seem to affect survival with COVID-19.

Other scientists in China have investigated databases that have information on different types of cells. Their research has confirmed that some cells from the digestive tract have the protein ACE2 on their surface. This protein serves as a way for SARS-CoV-2 to gain entry to cells.

There are at least two theories that may explain why some people with acute SARS-CoV-2 experience gastrointestinal symptoms:

  • The virus can infect cells of the gastrointestinal tract, which injures it.
  • When cells of the gastrointestinal tract are infected, inflammation occurs there, which allows the passage of bacteria and fungi that may be present in the digestive tract to enter the circulation.

As with nearly all studies of SARS-CoV-2, these findings should be viewed as preliminary.

—Sean R. Hosein

REFERENCES:

  1. Lin L, Jiang X, Zhang Z, et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020; in press.
  2. Xu L, Liu J, Lu M, Yang D, Zheng X. Liver injury during highly pathogenic human coronavirus infections. Liver International. 2020; in press.
  3. Zhang H AND Kang Z, Gong H, et al. Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process. Gut. 2020; in press.
  4. Fan Z, Chen L, Li J, et al. Clinical features of COVID-19-related liver damage. Clinical Gastroenterology and Hepatology. 2020; in press.