COVID is the gift that keeps on giving
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By SÃO PAULO RESEARCH FOUNDATION
A study by the University of São Paulo reveals that COVID-19 can persist in sperm for over three months, potentially reducing semen quality. This research highlights the virus’s significant impact on male fertility and suggests new immune functions for sperm, including pathogen defense.
Researchers from the University of São Paulo
have discovered that the COVID-19 virus can linger in the sperm of
infected individuals for up to 110 days post-infection, impacting semen
quality. This finding underscores the virus’s ability to infiltrate and damage
the male reproductive system, suggesting a quarantine period for those planning
to conceive post-recovery.
Persistence of COVID-19 in Reproductive Systems
Scientists have shown for the first time that SARS-CoV-2, the virus that causes COVID-19, can remain in the sperm of patients for up to 90 days after hospital discharge and up to 110 days after the initial infection, reducing semen quality.
The study, by
researchers at the University of São Paulo (USP) in Brazil, is reported in an
article published in the journal Andrology. The
authors suggest that people who plan to have children should observe a period
of “quarantine” after recovering from COVID-19.
More than four years after the start of the pandemic, we know SARS-CoV-2 is able to invade and destroy several types of human cells and tissue, including the reproductive system, where the testicles serve as a “gateway.”
Although scientists have noted that the virus is more
aggressive than other viruses toward the male genital tract, and autopsies have
found it in testicles, it has rarely been detected in semen by polymerase chain
reaction (PCR) analysis, which focuses on viral DNA.
Study Methodology and Initial Findings
To fill this knowledge gap, the study used
real-time PCR and transmission electronic microscopy (TEM) to detect
viral RNA in semen and spermatozoa donated by men who were
convalescing from COVID-19.
The semen samples were taken from 13 patients aged between 21 and 50 who had had mild, moderate, and severe COVID-19 and had been admitted to Hospital das Clínicas (HC), the hospital complex run by the university’s medical school (FM-USP).
The analysis was conducted up to 90 days
after discharge and 110 days after diagnosis. Although the PCR test results
were negative for SARS-CoV-2 in semen in all cases, the virus was detected in
sperm from eight of 11 moderate to severe COVID-19 patients (72.7%) within 90
days of discharge, which does not mean it was not present for longer, according
to the authors.
Detailed Observations on Sperm Impairment
SARS-CoV-2 was also detected in one of the
mild COVID-19 patients. In sum, the virus was detected in sperm from nine of
the 13 patients (69.2%). Two others had ultrastructural gamete impairment
similar to that seen in patients with a COVID-19 diagnosis. The authors
therefore concluded that 11 of the patients had the virus in their sperm.
“Moreover, we found that the sperm produced
‘extracellular traps’ based on nuclear DNA. In other words, genetic material in
the nucleus decondensed, the sperms’ cell membranes ruptured, and the DNA was
expelled into the extracellular medium, forming networks similar to those
described previously in the systemic inflammatory response to SARS-CoV-2,” said
Jorge Hallak, a professor at FM-USP and corresponding author of the article.
The networks in question are neutrophil
extracellular traps (NETs). Neutrophils, a type of white blood cell, form the
first line of the immune system, immobilizing and killing pathogenic bacteria,
fungi, and viruses. When hyperactive, however, NETs can harm tissue elsewhere
in the organism.
TEM analysis showed that the sperm produced
extracellular traps based on nuclear DNA to neutralize the pathogen,
“sacrificing themselves” to contain the pathogen in a mechanism known as a
suicidal ETosis-like response (ETosis meaning death via extracellular traps).
Implications for Reproductive Medicine
“The finding that spermatozoa are part of the
innate immune system and help defend the organism against attack by pathogens
is unique in the literature and makes the study very important. It can be
considered a scientific paradigm shift,” Hallak said.
Until now, he added, sperm were known to have
four functions: binding the genetic contents of male gametes to female gametes,
fertilizing female gametes, promoting embryo development until the twelfth week
of pregnancy, and co-determining the development of certain chronic diseases in
adulthood, such as infertility, hypogonadism, diabetes, hypertension, some
types of cancer, and cardiovascular disorders, among others.
The discovery described in the study adds a
novel function to their role in reproduction. “The possible implications of our
findings for the use of sperm in assisted reproduction should be urgently
considered by physicians and regulators, especially with regard to the
technique used by Brazilian laboratories that perform gamete micromanipulation
in more than 90% of cases of conjugal infertility, which involves the injection
of a single spermatozoon into the egg and is known as intracytoplasmic sperm
injection, or ICSI,” Hallak said.
Hallak advocates postponement of natural
conception and particularly of assisted reproduction for at least six months
after infection by SARS-CoV-2, even if mild COVID-19 ensues.
Ongoing Research and Additional Discoveries
Hallak was one of the first members of the
scientific and medical communities to suggest more caution in reproduction protocols during
the pandemic. He has studied the impact of COVID-19 on reproductive and sexual
health since 2020, when he volunteered on the front line as an emergency room
physician at HC-FM-USP.
His research group, which includes colleagues
in FM-USP’s Department of Pathology, has already made important discoveries in
the field, such as the higher risk of severe COVID-19 infection and death from
the disease for men simply because of their sex, possibly because of the
abundance of ACE2 receptors and TMPRSS2 in testes, whereas ovaries have only
ACE2 receptors. The virus uses ACE2 to invade cells; TMPRSS2 is a protein that
enables the virus to bind to ACE2 on the cell surface.
In a study conducted
with members of HC-FM-USP’s Clinical Urology Division, the group found that
health workers experienced a sharp drop in libido and sexual satisfaction, as
well as increased consumption of pornography and more frequent masturbation,
due to the pandemic.
Further Studies on Long-term Effects
The group also discovered that
the testes are potential targets for infection by the virus, which causes
subclinical epididymitis (inflammation of the epididymis, a narrow tube
attached to each testicle that stores, matures, and transports sperm cells),
and showed for the first time the severity of the testicular lesions associated
with COVID-19.
Reference: “Transmission electron microscopy
reveals the presence of SARS-CoV-2 in human spermatozoa associated with an
ETosis-like response” by Jorge Hallak, Elia G. Caldini, Thiago A. Teixeira,
Maria Cassia Mendes Correa, Amaro N. Duarte-Neto, Fabiola Zambrano, Anja
Taubert, Carlos Hermosilla, Joël R. Drevet, Marisa Dolhnikoff, Raul Sanchez and
Paulo H. N. Saldiva, 12 March 2024, Andrology.
DOI: 10.1111/andr.13612
The group of physicians and scientists at
HC-FM-USP, led by Professor Carlos Carvalho, is currently investigating the
lagging effects of infection by SARS-CoV-2 in more than 700 patients originally
assessed for a Thematic Project funded by FAPESP.