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Effect of SARS-CoV-2 infection upon male gonadal function: A single centerbased study
Ling Ma, Wen Xie, Danyang Li, Lei Shi, Yanhong Mao, Yao Xiong, Yuanzhen Zhang, Ming Zhang
.
1 Reproductive Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan
430071, Hubei Province, P. R. China.
2 Department of Laboratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan
430071, Hubei Province, P. R. China.
3 Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan
430071, Hubei Province, P. R. China.
4 Department of Obstetrics & Gynecology, Zhongnan Hospital, Wuhan University,
Wuhan 430071, Hubei Province, P. R. China.
5 Department of Laboratory Medicine, Wuhan Leishenshan Hospital, Wuhan 430071,
Hubei Province, P. R. China.
Contributions:
Yuanzhen Zhang and Ming Zhang contributed substantially to the study design, and
Ming Zhang also participated in manuscript draft and revision. Ling Ma was in charge
of manuscript draft. Wen Xie took responsibility for samples processing and laboratory
tests. Danyang Li helped in hormones detection. Lei Shi, Yao Xiong and Yanhong Mao
were in charge of data collection and analysis.
Funding Information:
Health Commission of Hubei Province scientific research project (No. WJ2019Q048
to M.Z.)
Conflict of interest:
We declare no conflict of interest.
Abstract: Since SARS-CoV-2 infection was first identified in December 2019, it
spread rapidly and a global pandemic of COVID-19 has occurred. ACE2, the receptor
for entry into the target cells by SARS-CoV-2, was found to abundantly express in testes,
including spermatogonia, Leydig and Sertoli cells. However, there is no clinical
evidence about whether SARS-CoV-2 infection can affect male gonadal function so far.
In this study, we compared the sex-related hormones between 81 reproductive-aged
men with SARS-CoV-2 infection and 100 age-matched healthy men, and found that
serum luteinizing hormone (LH) was significantly increased, but the ratio of
testosterone (T) to LH and the ratio of follicle stimulating hormone (FSH) to LH were
dramatically decreased in males with COVID-19. Besides, multivariable regression
analysis indicated that c-reactive protein (CRP) level was significantly associated with
serum T:LH ratio in COVID-19 patients. This study provides the first direct evidence
about the influence of medical condition of COVID-19 on male sex hormones, alerting
more attention to gonadal function evaluation among patients recovered from SARSCoV-2 infection, especially the reproductive-aged men.
Key words: SARS-CoV-2, COVID-19, male gonadal function, sex-related hormones,
reproductive system
Introduction
Since the first report in Wuhan in December 2019, a novel coronavirus-induced
pneumonia (called COVID-19 by WHO) spread rapidly and triggered a global
pandemic outbreak [1]
. COVID-19 is caused by a previously unknown beta-coronavirus
which is now named SARS-CoV-2 due to its high sequence similarity (~80%) with
SARS-CoV[2]
. Except for the respiratory symptoms such as cough, fever and even acute
respiratory failure, evidences of SARS-CoV-2 attack to multiple organs such as
digestive, cardiovascular, urinary systems have been reported [3-5]
. Angiotensinconverting enzyme 2 (ACE2) is considered as the receptor for binding and entry into
host cells by SARS-CoV-2
[6-7]
. Theoretically, any cells expressing ACE2 may be susceptible to SARS-CoV-2 infection. According to the online database The Human Protein Atlas portal, testes shows the highest expression level of ACE2 protein and mRNA in the body [8]
. Based on scRNA-seq profiling of human testes, Wang ZP et al. also reported that ACE2 is predominantly enriched in spermatogonia, Leydig and Sertoli cells[9]
. All the findings suggest the potential risk of male gonad to be vulnerable to SARS-CoV-2 attack.
In the condition of viremia, virus may seed into the male reproductive track because the blood-testes barrier is not perfect enough to completely isolate virus[10]. A wide breath of viruses, such as Zika, Ebola, Marburg viruses, etc. have been found in male testes and semen [11]
. Virus-induced testes damage can impair gonadal hormone secretion and spermatogenesis, as seen in HIV or mumps-induced orchitis [12]
. Previous study on SARS suggested the SARS-CoV can cause orchitis [13]
. However, there is no clinical information about whether SARS-CoV-2 infection can affect male gonadal function so far. In this study, we compared the sex-related hormones between reproductive-aged men with SARS-CoV-2 infection and age-matched healthy men, and found serum luteinizing hormone (LH) was significantly increased, but the ratio of
testosterone (T) to LH and the ratio of follicle stimulating hormone (FSH) to LH were dramatically decreased in male with COVID-19. This study provides the first direct evidence about the influence of medical condition of COVID-19 on male sex hormones,
alerting more attention to gonadal function evaluation among patients recovered from
SARS-CoV-2 infection, especially the reproductive-aged men.
Methods
Study design and patients
We performed a retrospective study involving 81 male patients with COVID-19 as the study group, who were hospitalized in Wuhan Leishenshan Hospital from Mar 5 to Mar 18, 2020. All cases were laboratory-confirmed as SARS-CoV-2 positive using quantitative RTPCR (qRT-PCR) on nasal and pharyngeal swab specimens. The diagnosis of COVID-19 and the severity was determined according to the New Coronavirus Pneumonia Prevention and Control Program (7th edition) published by the National Health Commission of China. Briefly, the mild type was defined as “having malaise only without positive chest radiologic findings”; the common type was defined as “having common respiratory infection symptoms such as fever, cough and positive chest radiologic changes”; the severe type was determined if any of the following conditions existed, including dyspnea (respiratory rate ≥ 30 per minute), low finger oxygen saturation (≤93% at rest), low PaO2/FiO2 (≤ 300mmHg) or rapid progress of chest radiological abnormality (>50% within 24-48 hours); and the very severe type was determined if respiratory failure (mechanical ventilation needed), shock or multiple organ dysfunctions was complicated.
All patients aged from 20~54 years (with a median of 38 yrs). After finishing laboratory tests required for the routine medical purposes, the residual serum samples were collected for male hormone profiles detection. The control group came from the population who previously received reproductive function evaluation and were classified as having normal fertility. 100 age-matched healthy men were randomly selected and the data of their sex-related hormones were collected.
This study was reviewed and approved by the Medical Ethical Committee of Zhongnan Hospital of Wuhan University (approval number 2020033). The residual serum samples used in this study were usually discarded as a medical waste otherwise.
And we didn’t directly contact with the patients and exert no burden or harm on them.
Therefore, written informed consent was waived.
Ling Ma, Wen Xie, Danyang Li, Lei Shi, Yanhong Mao, Yao Xiong, Yuanzhen Zhang, Ming Zhang
.
1 Reproductive Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan
430071, Hubei Province, P. R. China.
2 Department of Laboratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan
430071, Hubei Province, P. R. China.
3 Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan
430071, Hubei Province, P. R. China.
4 Department of Obstetrics & Gynecology, Zhongnan Hospital, Wuhan University,
Wuhan 430071, Hubei Province, P. R. China.
5 Department of Laboratory Medicine, Wuhan Leishenshan Hospital, Wuhan 430071,
Hubei Province, P. R. China.
Contributions:
Yuanzhen Zhang and Ming Zhang contributed substantially to the study design, and
Ming Zhang also participated in manuscript draft and revision. Ling Ma was in charge
of manuscript draft. Wen Xie took responsibility for samples processing and laboratory
tests. Danyang Li helped in hormones detection. Lei Shi, Yao Xiong and Yanhong Mao
were in charge of data collection and analysis.
Funding Information:
Health Commission of Hubei Province scientific research project (No. WJ2019Q048
to M.Z.)
Conflict of interest:
We declare no conflict of interest.
Abstract: Since SARS-CoV-2 infection was first identified in December 2019, it
spread rapidly and a global pandemic of COVID-19 has occurred. ACE2, the receptor
for entry into the target cells by SARS-CoV-2, was found to abundantly express in testes,
including spermatogonia, Leydig and Sertoli cells. However, there is no clinical
evidence about whether SARS-CoV-2 infection can affect male gonadal function so far.
In this study, we compared the sex-related hormones between 81 reproductive-aged
men with SARS-CoV-2 infection and 100 age-matched healthy men, and found that
serum luteinizing hormone (LH) was significantly increased, but the ratio of
testosterone (T) to LH and the ratio of follicle stimulating hormone (FSH) to LH were
dramatically decreased in males with COVID-19. Besides, multivariable regression
analysis indicated that c-reactive protein (CRP) level was significantly associated with
serum T:LH ratio in COVID-19 patients. This study provides the first direct evidence
about the influence of medical condition of COVID-19 on male sex hormones, alerting
more attention to gonadal function evaluation among patients recovered from SARSCoV-2 infection, especially the reproductive-aged men.
Key words: SARS-CoV-2, COVID-19, male gonadal function, sex-related hormones,
reproductive system
Introduction
Since the first report in Wuhan in December 2019, a novel coronavirus-induced
pneumonia (called COVID-19 by WHO) spread rapidly and triggered a global
pandemic outbreak [1]
. COVID-19 is caused by a previously unknown beta-coronavirus
which is now named SARS-CoV-2 due to its high sequence similarity (~80%) with
SARS-CoV[2]
. Except for the respiratory symptoms such as cough, fever and even acute
respiratory failure, evidences of SARS-CoV-2 attack to multiple organs such as
digestive, cardiovascular, urinary systems have been reported [3-5]
. Angiotensinconverting enzyme 2 (ACE2) is considered as the receptor for binding and entry into
host cells by SARS-CoV-2
[6-7]
. Theoretically, any cells expressing ACE2 may be susceptible to SARS-CoV-2 infection. According to the online database The Human Protein Atlas portal, testes shows the highest expression level of ACE2 protein and mRNA in the body [8]
. Based on scRNA-seq profiling of human testes, Wang ZP et al. also reported that ACE2 is predominantly enriched in spermatogonia, Leydig and Sertoli cells[9]
. All the findings suggest the potential risk of male gonad to be vulnerable to SARS-CoV-2 attack.
In the condition of viremia, virus may seed into the male reproductive track because the blood-testes barrier is not perfect enough to completely isolate virus[10]. A wide breath of viruses, such as Zika, Ebola, Marburg viruses, etc. have been found in male testes and semen [11]
. Virus-induced testes damage can impair gonadal hormone secretion and spermatogenesis, as seen in HIV or mumps-induced orchitis [12]
. Previous study on SARS suggested the SARS-CoV can cause orchitis [13]
. However, there is no clinical information about whether SARS-CoV-2 infection can affect male gonadal function so far. In this study, we compared the sex-related hormones between reproductive-aged men with SARS-CoV-2 infection and age-matched healthy men, and found serum luteinizing hormone (LH) was significantly increased, but the ratio of
testosterone (T) to LH and the ratio of follicle stimulating hormone (FSH) to LH were dramatically decreased in male with COVID-19. This study provides the first direct evidence about the influence of medical condition of COVID-19 on male sex hormones,
alerting more attention to gonadal function evaluation among patients recovered from
SARS-CoV-2 infection, especially the reproductive-aged men.
Methods
Study design and patients
We performed a retrospective study involving 81 male patients with COVID-19 as the study group, who were hospitalized in Wuhan Leishenshan Hospital from Mar 5 to Mar 18, 2020. All cases were laboratory-confirmed as SARS-CoV-2 positive using quantitative RTPCR (qRT-PCR) on nasal and pharyngeal swab specimens. The diagnosis of COVID-19 and the severity was determined according to the New Coronavirus Pneumonia Prevention and Control Program (7th edition) published by the National Health Commission of China. Briefly, the mild type was defined as “having malaise only without positive chest radiologic findings”; the common type was defined as “having common respiratory infection symptoms such as fever, cough and positive chest radiologic changes”; the severe type was determined if any of the following conditions existed, including dyspnea (respiratory rate ≥ 30 per minute), low finger oxygen saturation (≤93% at rest), low PaO2/FiO2 (≤ 300mmHg) or rapid progress of chest radiological abnormality (>50% within 24-48 hours); and the very severe type was determined if respiratory failure (mechanical ventilation needed), shock or multiple organ dysfunctions was complicated.
All patients aged from 20~54 years (with a median of 38 yrs). After finishing laboratory tests required for the routine medical purposes, the residual serum samples were collected for male hormone profiles detection. The control group came from the population who previously received reproductive function evaluation and were classified as having normal fertility. 100 age-matched healthy men were randomly selected and the data of their sex-related hormones were collected.
This study was reviewed and approved by the Medical Ethical Committee of Zhongnan Hospital of Wuhan University (approval number 2020033). The residual serum samples used in this study were usually discarded as a medical waste otherwise.
And we didn’t directly contact with the patients and exert no burden or harm on them.
Therefore, written informed consent was waived.