A systematic literature review of 24 studies aimed to determine the potential effects of COVID-19 on male fertility, specifically in terms of male reproductive hormones, seminal parameters, and pregnancy outcomes.  Six studies included in the review assessed semen samples from COVID-19 male patients, but only one of these studies detected viral mRNA in the semen.  One of the aforementioned studies examined seminal parameters and detected changes in these parameters, such as a decrease in sperm concentration.  There were contradictory findings pertaining to how COVID-19 infection affects testosterone levels, but it was generally noted that testosterone levels were decreased among male patients with COVID-19.  Lastly, preliminary studies determined that the chance of preterm delivery is higher among pregnant women who are infected with COVID-19.

Effects of COVID-19 on Male Fertility 

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.  

Michigan State University

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

Abassi, Z. A., Skorecki, K., Heyman, S. N., Kinaneh, S., & Armaly, Z. (2020). Covid-19 infection and mortality: a physiologist’s perspective enlightening clinical features and plausible interventional strategies. American Journal of Physiology-Lung Cellular and Molecular Physiology, 318(5), L1020-L1022.

https://journals.physiology.org/doi/full/10.1152/ajplung.00097.2020

https://doi.org/10.1152/ajplung.00097.2020

Covid-19 infection and mortality: a physiologist’s perspective enlightening clinical features and plausible interventional strategies

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

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.  

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 

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

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