IBD refers to the chronic inflammation of all or some regions of the digestive tract that periodically flairs up. In general, patients with IBD are at an increased risk of infection, especially when receiving steroid or immunosuppressant treatment. The type of immunosuppresive drug and the patient's sex and age affect the nature and magnitude of this risk.  Some COVID-19 symptoms mirror IBD manifestations, so it is currently recommended that medical practitioners test known IBD patients for a SARS-CoV-2 infection before assuming that their symptoms are the result of their autoimmune disorder.  

- IBD in COVID-19 Patients by Geographic Location 
- A guide to minimizing spread of infectious diseases for IBD patients during the COVID-19 pandemic 

Inflammatory Bowel Disease (IBD) in COVID-19 

Because as many as 10% of COVID-19 patients have the symptom of diarrhea, it is hypothesized that SARS-CoV-2 can infect gastrointestinal cells.  Symptoms such as loss of appetite and nausea have been commonly found with patients as well. It is known that the GI tract overall has a high expression level of ACE 2, with the duodenum and small intestine having an especially high level of expression. Viral RNA has been found in both the sputum and feces of COVID-19 patients.  

Michigan State University

University of Michigan - Ann Arbor

Current studies show that many organs that are heavily affected by COVID-19 have a high expression level of ACE2.

- Cardiovascular system
- Central nervous system (CNS)
- Gastrointestinal tract (GI)
- Kidney
- Liver 
- Lungs (Respiratory System)
- Peripheral nervous system (PNS)
- Testis

Organs and Organ Systems Affected by COVID-19

The inflammatory mediators associated with the cytokine storm in COVID-19 leads the increased permeability of the lungs.  This allows for SARS-CoV-2 and the inflammatory mediators to enter the bloodstream and migrate from the lungs to the intestine.  SARS-CoV-2 can decrease ACE2 expression and alter the gut microbiota which can alter normal immune responses.  Additionally, the inflammatory mediators can weaken the integrity of the gut, allowing for microbes and their metabolites to leak out.  This can cause microbial dysbriosis which may contribute to why diarrhea is a common symptom of COVID-19.  

Gut-Lung Axis of COVID-19

Tan, H. W., Xu, Y. M., & Lau, A. T. Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection. Reviews in Medical Virology, e2122. https://onlinelibrary.wiley.com/doi/full/10.1002/rmv.2122

Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection

Cholankeril, G., Podboy, A., Aivaliotis, V. I., Tarlow, B., Pham, E., Spencer, 
     S., Kim, D., Hsing, A., & Ahmed, A. (2020). High prevalence of concurrent 
     gastrointestinal manifestations in patients with severe acute respiratory 
     syndrome coronavirus 2: Early experience from California. 
     Gastroenterology. https://doi.org/10.1053/j.gastro.2020.04.008 
https://www.gastrojournal.org/article/S0016-5085(20)30471-6/fulltext

High Prevalence of Concurrent Gastrointestinal Manifestations in Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Early Experience From California

It has been observed that many COVID-19 patients develop renal conditions, including acute kidney injury.  Older patients or those who have kidney conditions are more likely to die from COVID-19 while hospitalized.  Kidneys are known to have a greater level of ACE 2 expression than the lungs.  Kidney disease caused by COVID-19 is directly related to ACE2 expression: a study confirmed by electron microscopy that viral particles have been found in the glomerulus of COVID-19 patients. 

Effects of COVID-19 on the Kidney

Liver injury has been observed in a percentage of COVID-19 patients.  Cholangiocytes, the epithelial lining cells of the bile ducts of the liver, are known to have a high level of ACE 2 expression.  Overall, the liver has a greater expression level of ACE 2 than the lungs.  However, no studies have shown that SARS-CoV-2 can infect hepatic cells.  

Effects of COVID-19 on the Liver

Effects of COVID-19 on the Gastrointestinal (GI) Tract

A main feature of symptomatic COVID-19 disease is respiratory infection. Severe damage to the lungs during respiratory distress may cause pulmonary fibrosis, necessitating lung transplants. Lasting damages to the lungs may occur even in recovering patients with mild infections. SARS-CoV-2 targets the following cell types:

- Type I pneumocytes (AT1) 
- Type II pneumocytes (AT2) 
- alveolar macrophages

ACE2 expression is primarily seen in AT2 cells which have been shown to be involved in the reproduction and transmission of the virus.  Viral targeting of alveolar macrophages is evidenced by N antigen expression.

Effects of COVID-19 on the Lungs

Patients with COVID-19 are likely to experience symptoms that can be attributed to  the virus affecting the cardiovascular system. Common complications to the system include arrhythmia, cardiac injury, fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation. Severe cases of COVID-19 may lead to lasting cardiac damage and those with pre-existing cardiac issues are likely to have worse prognoses. 

Effects of COVID-19 on the Cardiovascular System 

Impaired male fertility is a known symptom of COVID-19.  It is thought that the testes' high expression level of ACE2 and immunoactivity could contribute to this manifestation of the disease.  

Effects of COVID-19 on the Testis   

COVID-19 patients have shown symptoms of direct and indirect neurological effects, from changes in taste and smell, to immunologic factors in cerebral spinal fluid (CSF).  It is unknown whether these phenomena are the result of neurological damage, of SARS-CoV-2 infection, and/or of indirect effects of the immune response. Furthermore, studies in mice have shown that neurons are susceptible to infection, suggesting that cells of the CNS may contribute to the deteriorating breathing and respiratory function of COVID-19 patients. The image below is an early hypothesized mechanism of viral entry through nasal and oral mucosa cells, though there is not yet any evidence to support this hypothesis.

Effects of COVID-19 on the Central Nervous System

Some COVID-19 patients have presented with peripheral neurological symptoms. Although it is not a common complication of COVID-19, it is worth investigating all possible causes of the neurological symptoms that arise.

Effects of COVID-19 on the Peripheral Nervous System

- SARS-CoV-2 can be blocked by physical barriers in the placenta, such as densely branched microvilli and cytoskeletal network
- placenta can attack the virus with the following 3 molecular pathways: type III IFN signaling, secreted miRNAs triggering autophagy, and NF-κB pathway
- immunomodulation can be employed after viral infection to alleviate cytokin storm

Effects of COVID-19 on the Placenta

- There have been two reports of COVID-19 positive patients with conjunctivitis or conjunctival congestion
- Ocular secretions were seen in those with the SARS-CoV-2 positive serology
- This presents the possibility that the SARS-CoV-2 virus can cause conjunctivitis
- However, this relationship is not very clear at this point due to a lack of studies comparing the two
- It has also been suggested that the ocular system is a potential route of transmission of the virus

Effects of COVID-19 on the Ocular System

A study of eight patients found that the lung microbial composition of COVID-19 patients is primarily made up of bacteria typically found in the oral and upper respiratory tract.  It is thought that the gut microbiota plays an important role in buttressing antiviral immunity and has been shown to reduce viral-related enteritis, severe pneumonia cases that require ventilator assistance, and can prevent the spread of influenza in lung epithelia cells.  No clinical data suggest that modulating the gut microbiota is an effective treatment for COVID-19, but it may be a relevant therapeutic target.  

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