Learning Point for Clinicians: SARS-CoV-2 and Its Impact on PSA Levels in Post-Prostatectomy Patients

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The COVID-19 pandemic has brought about various challenges and complications in healthcare, some of which continue to be unveiled as we gather more data and experience in managing this novel virus. Among the emerging concerns is the impact of SARS-CoV-2, the virus responsible for COVID-19, on prostate-specific antigen (PSA) levels, particularly in post-prostatectomy patients. This case report sheds light on a 69-year-old male who experienced a significant rise in his PSA levels during an active COVID-19 infection, highlighting the need for clinicians to exercise caution when interpreting PSA measurements in such scenarios.

Case Description

The patient in question had previously undergone a radical prostatectomy more than a year ago for prostatic acinar adenocarcinoma (Gleason 9; pT2), with subsequent treatments including multiple Volumetric Modulated Arc Therapy (VMAT) cycles and three-monthly leuprorelin acetate injections. These treatments had successfully maintained his total PSA levels at undetectable levels (<0.01ug/L) for several months.

However, four days before his routine visit to his family physician, the patient developed mild respiratory symptoms and tested positive for SARS-CoV-2 through an Antigen Rapid Test (ART) of his nasal swab. During this visit, his PSA level, which had been consistently low, showed a remarkable increase to 0.046ug/L from <0.01ug/L measured three months ago. Importantly, other factors that could potentially elevate PSA levels, such as recent digital rectal examinations or ejaculations, were ruled out.

Concerned about this sudden PSA elevation, the patient visited his urologist five days later (day 9 of COVID-19; with a negative nasal swab ART). At this point, his PSA measurements were repeated, and they had significantly decreased to 0.014ug/L. Notably, his serum testosterone levels remained suppressed (0.37nmol/L; normal: 8.4- 28.7nmol/L). Given the rapid improvement in PSA levels and the temporal proximity to his SARS-CoV-2 infection, the transient increase in PSA was attributed to the active COVID-19 infection. Consequently, the patient continued his regular treatment with three-monthly leuprorelin injections.


Deep Dive into the Connection Between Epithelium, SARS-CoV-2, and Elevated PSA Levels

The statement you provided touches on a complex interplay between prostate physiology, viral infection, and clinical testing, and understanding it truly requires us to delve deeper into several key components:

The Epithelium in Question:

  • This refers to a specific layer of cells within the prostate gland, known as the prostatic acinar epithelium. These cells have two crucial functions relevant to our discussion:
    • PSA Production: They are the primary source of prostate-specific antigen (PSA), a protein measured in blood tests for prostate cancer detection.
    • Expression of ACE2 and TMPRSS2: They express high levels of two proteins critical for SARS-CoV-2 infection:
      • Angiotensin-converting enzyme 2 (ACE2) acts as the main entry point for the virus into human cells.
      • Transmembrane protease, serine 2 (TMPRSS2) facilitates the virus’s internalization and spread within cells.

SARS-CoV-2 Infection and its Potential Impact on PSA Levels:

  • The presence of both ACE2 and TMPRSS2 on prostatic acinar cells makes them susceptible to SARS-CoV-2 infection.
  • Several possible mechanisms could then lead to elevated PSA levels:
    • Direct Viral Damage: Infection might directly damage the acinar cells, disrupting their normal function and causing increased PSA release.
    • Inflammatory Response: The body’s immune response to the virus could trigger inflammation in the prostate, affecting PSA production and secretion.
    • Altered Androgen Signaling: SARS-CoV-2 might interfere with hormone signaling pathways governing PSA production, leading to a temporary rise in levels.

Plausible Explanation for the Connection:

  • The presence of ACE2 and TMPRSS2 on prostatic acinar cells creates a direct vulnerability to SARS-CoV-2 infection, increasing the likelihood of the virus impacting these cells compared to other tissues.
  • This potential infection or the related inflammatory response could then influence PSA production and release, leading to observed elevations in blood levels following COVID-19 diagnosis.

Discussion

This case raises intriguing questions about the relationship between SARS-CoV-2 and PSA levels, particularly in post-prostatectomy patients. While elevations in PSA levels due to COVID-19 infections have been previously reported, these were primarily observed in unselected patient groups and those with benign prostatic hyperplasia (BPH), making this case one of the first to document falsely-elevated PSA levels in the context of an active COVID-19 infection, thereby complicating the surveillance of prostatic carcinoma recurrence.

The underlying mechanism linking SARS-CoV-2 and PSA levels may involve the virus’s interaction with ACE2 and TMPRSS2 proteins. The viral S-glycoprotein is primed by TMPRSS2, allowing its entry into host cells via ACE2 receptors. This process leads to the down-regulation of ACE2’s modulatory effects on angiotensin II and the activation of pro-inflammatory processes within susceptible organs, including the prostate’s columnar epithelium. This epithelium is responsible for PSA production and expresses both ACE2 and TMPRSS2, providing a plausible explanation for the connection between SARS-CoV-2 infections and elevated PSA levels.

However, another possibility is that SARS-CoV-2 may infect non-prostatic tissues that also produce small amounts of PSA, such as the salivary and urethral glands. ACE2 and TMPRSS2 have been identified in human saliva, suggesting that SARS-CoV-2 may enter the salivary glands, potentially leading to an increase in PSA levels during COVID-19 infections. The involvement of urethral glands, on the other hand, remains scientifically unproven.

While this case does not definitively identify the specific tissue responsible for the PSA elevation, it serves as a crucial reminder for clinicians that COVID-19 infections can lead to PSA level fluctuations even in post-prostatectomy patients. To avoid unnecessary alarm and treatment modifications, it is advisable to refrain from conducting PSA measurements during active COVID-19 infections. Instead, in cases where elevated PSA coincides with an active COVID-19 infection, clinicians should consider repeating the measurements two weeks later for a more accurate assessment of the patient’s prostate health.

Conclusion

The case of a post-prostatectomy patient experiencing a transient PSA elevation during an active COVID-19 infection underscores the need for clinicians to exercise caution when interpreting PSA levels in such scenarios. This phenomenon sheds light on the complex relationship between SARS-CoV-2 and PSA production, emphasizing the importance of timing and clinical context in PSA measurement interpretation. As the medical community continues to navigate the challenges posed by COVID-19, this case provides a valuable learning point for clinicians in the surveillance and management of prostate cancer in the era of the pandemic.


reference link : https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcae008/7560599

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