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Case Report
Elevated prostate-specific antigen (PSA) levels from acute
COVID-19 infection confounding cancer disease
surveillance
Y.-J. Tan
1,
�and Y. Tan
2
1
Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore
2
Family Medicine, Private Practice, Singapore, Singapore
�Address correspondence to Dr Y.-J. Tan, Department of Neurology, National Neuroscience Institute, Singapore General Hospital Campus, Outram Road, 169608
Singapore, Singapore. email: whyjae@gmail.com,tan.you.jiang@singhealth.com.sg
Learning points for clinicians
Severe acute respiratory syndrome coronavirus 2 can in-
crease prostate-specific antigen (PSA) levels, even amongst
post-prostatectomy patients, confounding disease surveil-
lance. Therefore, PSA measurements during active corona-
virus disease 2019 (COVID-19) infections should be avoided.
If PSA elevations coincided with active COVID-19 infections,
repeating PSA measurements 2 weeks later appears reason-
able to prevent unnecessary worry and unneeded altera-
tions to existing treatment plans.
Case description
A 69-year-old male was found to have elevated prostate-specific
antigen (PSA) levels on a routine visit to his family physician. He
previously underwent a radical prostatectomy more than a year
ago for his prostatic acinar adenocarcinoma (Gleason 9; pT2).
Pathohistological assessments showed apical margin involvement,
for which he underwent multiple volumetric modulated arc ther-
apy (VMAT) cycles and received three-monthly leuprorelin acetate
injections, resulting in persistently undetectable total PSA levels
(<0.01 lg/l). Four days before the consultation, he developed mild
respiratory symptoms and a severe acute respiratory syndrome co-
ronavirus 2 (SARS-CoV-2) antigen rapid test (ART) of his nasal
swab returned positive. He then visited his family physician on the
fourth day of coronavirus disease 2019 (COVID-19) for a routine
check of PSA level, which showed a remarkable increase to 0.046
lg/l from <0.01 lg/l measured 3 months ago. His nasal swab ART
performed on the day of consultation remained positive.
Importantly, he was compliant to his leuprorelin injections, and
other plausible causes of raised PSA levels such as recent digital
rectal examinations or ejaculations were absent.
Understandably worried, he visited his urologist 5 days later
(Day 9 of COVID-19; negative nasal swab ART), who considered the
possibility of treatment failure and disease recurrence. PSA meas-
urements were then repeated, which decreased significantly
to 0.014 lg/l (Figure 1). Noteworthily, his serum testosterone levels
continued to be suppressed (0.37 nmol/l; normal: 8.4–28.7 nmol/l).
In view of the rapid and remarkable improvement of his PSA lev-
els, and the temporal proximity to SARS-CoV-2 infection, this tran-
sient increase in PSA was thus attributed to COVID-19. He was
thereafter maintained on his current treatment of three-monthly
leuprorelin injections.
Discussion
Although elevations in PSA levels due to COVID-19 infections have
been previously described, these were mainly observed in unse-
lected patient groups and those with benign prostatic hyperplasia,
rendering our case amongst the first reports of falsely-elevated
PSA levels due to an active COVID-19 infection, confounding the
surveillance of prostatic carcinoma recurrence.
1,2
SARS-CoV-2
increases PSA levels via various pathogenic processes. Priming of
the viral S-glycoprotein by the transmembrane serine protease 2
(TMPRSS2) facilitates its binding to angiotensin-converting enzyme
2 (ACE2), facilitating SARS-CoV-2’s entry into the host cells.
3
This
down-regulates ACE2’s modulatory effects on angiotensin II,
resulting in the activation of pro-inflammatory processes within
susceptible organs.
1
The prostatic columnar epithelium, which
produces PSA and expresses both ACE2 and TMPRSS, therefore
provides a reasonable and unifying basis explaining the pathome-
chanisms linking SARS-CoV-2 infections and elevated PSA levels.
1,2
However, this also poses the unsettling possibility that remnants
of prostatic tissue or adenocarcinoma might persist despite the
patient’s earlier radical prostatectomy and VMAT.
Alternatively, PSA elevations can occur when SARS-CoV-2 infect
non-prostatic PSA-producing tissues that also express ACE2 and
TMPRSS2. While PSA is mainly produced by the prostate, low con-
centrations of PSA may also be found in non-prostatic tissues such
as the salivary and urethral glands.
4
Remarkably, ACE2 and
TMPRSS2 have been demonstrated in human saliva and were
thought to be secreted by the acinar cells, facilitating SARS-CoV-2’s
Received: 26 December 2023. Revised (in revised form): 1 January 2024.
# The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved.
For permissions, please email: journals.permissions@oup.com
QJM: An International Journal of Medicine, 2024, 00(0), 1–2
https://doi.org/10.1093/qjmed/hcae008
Advance Access Publication Date: 16 January 2024
Case Report
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entry into the salivary glands, rendering them potential sources of
PSA during COVID-19 infections.
5,6
Comparatively, the expression
of ACE2 and TMPRSS2 by, or infection of, SARS-CoV-2 of the ure-
thral glands remains scientifically unproven.
The nature of this report renders it difficult to pinpoint the tis-
sue which, induced by COVID-19, caused an increase in PSA lev-
els. Regardless, it serves to build awareness amongst clinicians of
how COVID-19 infections can elevate PSA levels even amongst
post-prostatectomy patients, and that PSA measurements should
be avoided whilst the infection is active. In scenarios similar
to our patient’s, in whom elevated PSA levels coincided
with active COVID-19 infections, it appears reasonable to
repeat these measurements two weeks later to avoid causing un-
necessary worry and unneeded alterations to existing treat-
ment plans.
Author contributions
You-Jiang Tan (Conceptualization [lead], Supervision [equal],
Writing—original draft [lead], Writing—review & editing [equal])
and Youhong Tan (Writing—original draft [supporting],
Writing—review & editing [equal])
Ethics approval: not needed for case reports.
Conflict of interest
None declared.
References
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Figure 1. Schematic timeline of the significant events relative to his first day of COVID-19 infection, including the measurements of prostate-specific
antigen (PSA) levels.
2 | Y.-J. Tan and Y. Tan
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