Table 1.
Characteristics of included studies.
| First author [reference number] | Accessed Date | Site | Age, median (min-max), years | Stage/Severity of disease | Number of included patients (n) | Number of samples tested (n) | Tissue assayed | Study design | Main conclusion | Limitations | Mean days until semen/testicular samples collection (min-max) | Sample SARS-CoV-2 positive (n, %) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Li D (3) | May, 2020 | Shangqiu, China | NP | 38 | Semen | Cohort study | SARS-CoV-2 can be present in the semen of patients with COVID-19. | Small sample size and the short subsequent follow-up. Lack of specific methods for the study of semen. | NP | 6 (15.8) | ||
| Recovered | 23 | 2.5 (2-3) | 2 (8.69) | |||||||||
| Acute | 15 | 7.3 (2-13) | 4 (26.67) | |||||||||
| Paoli D (13) | April, 2020 | Rome, Italy | 31 | Mild | 1 | 1 | Semen | Case report | Semen sample search for SARS-CoV-2 RNA was negative. | It cannot be ruled out whether the virus can be detected in a more severe disease case. No semen parameters measured. | 8 | 0 |
| Kayaaslan B (14) | August, 2020 | Ankara, Turkey | 33.5 (18-54) | Acute | 16 | Semen | cross-sectional study | SARS-CoV-2 was not detected in semen and sexual transmission via semen does not have an important role in the person-to-person transmission of SARS-CoV-2. |
First, the study was conducted in a relatively limited number of patients and mild to moderate cases. Second, the semen parameters of the patients were not obtained. | 1 (0-4) | 0 | |
| Mild | 11 | 1 (0-7) | ||||||||||
| Moderate | 5 | 1 (0-7) | ||||||||||
| Holtmann N (15) | May, 2020 | Dusseldorf, Germany | Recovered | 18 | Semen | Pilot cohort study | SARS-CoV-2 RNA could not be detected in semen of recovered and acute COVID-19–positive men. A mild COVID-19 infection is not likely to affect testis and epididymis function, whereas semen parameters did seem impaired after a moderate infection. | The sample size was relatively small, and there were only 2 patients with COVID-19 active infection; no sperm analysis was obtained from the individuals examined before the pandemic outbreak. | 32.7 [8–54]b | 0 | ||
| 42.7 ± 10.4a | Mild | 14 | 34.9 ± 11.7a | |||||||||
| 40.8 ± 8.7a | Moderate | 4 | 25.5 ± 8.3a | |||||||||
| Song C (16) | April, 2020 | Wuhan, China | 13 | cross-sectional study | 2019-nCov is absent from the semen and testes in men infected by COVID-19 at both acute and recovery phases. Thus, it is highly unlikely that the 2019-nCov can be sexually transmitted by men. | Small sample size and single sampling | 30 (14-42) | 0 | ||||
| 33 (22-38) | Recovered | 12 | Semen | 29.8 (14-42) | ||||||||
| 67 | Deceased | 1 | Testis | 41 | ||||||||
| Pan F (17) | April, 2020 | Wuhan, China | 37 (18–57) | Recovered | 34 | 34 | Semen | Cross-sectional study | SARS-CoV-2 virus was not detected in the semen of recovered patients 1 month after diagnosis. The long-term effect of SARS-CoV-2 on male reproductive function is not clear. | Identification of SARS-CoV-2 on qRT-PCR of single ejaculated semen samples. Semen quality was not assessed. | 31 [29–36]b | 0 |
| Ma L (18) | June, 2020 | Wuhan, China | 31 (25-46) | Recovered | 12 | Semen | Cross-sectional, pilot study |
SARS-CoV-2 was undetectable in semen. | All the semen samples came from non-severe patients and most of them were in the recovery stage. The sample size is limited. |
78.5 (56-109) | 0 | |
| mild | 1 | |||||||||||
| moderate | 11 | |||||||||||
| Temiz MZ (19) | October, 2020 | Istanbul, Turkey | 37.2 (20-60) | Acute | 20 | 20c | Semen | A cross-sectional, pilot study |
COVID-19 has no specific deteriorative effect on male reproductive health at a short-time period. | The study has limited sample size, short follow-up time and lack of testicular histological examination. | 9.5 (2-10) | 0 |
| Rawlings SA (20) | July, 2020 | California, USA | 38 (28-45) | Acute | 6 | 6 | Semen | Case series | SARS-CoV-2 was not present in semen. | The sample size was small, and the semen parameters of the patients were not analyzed. | 12 (6-17) | 0 |
| Pavone C (21) | August, 2020 | Palermo, Italy | 41.1 (31-60) | 9 | Semen | Sampling study | Sexual transmission of SARS-CoV-2 by men recovering from mild symptoms of COVID-19 is highly unlikely. | Severe acute COVID-19 cases were not included in the selection criteria of this study | 42.2 (7-88) | 0 | ||
| Acute | 2 | 10 (7-13) | ||||||||||
| Recovered | 7 | 51.4 (34-88) | ||||||||||
| Ning J (22) | April, 2020 | Wuhan, China | 35 (23-46) | 17 | Semen | Cross-sectional, pilot study |
SARS-CoV-2 was not present in semen. | The sample size was small and the retrospective method was used, and the observation and follow-up time of COVID-19 patients was relatively short. | 27 (12-64) | 0 | ||
| 38 (23-46) | Acute | 9 | 30 (14-64) | |||||||||
| 30 (28-45) | Recovered | 8 | 18.5 (12-36) | |||||||||
| Guo L (23) | June, 2020 | Jinan, China | 41 (20-62) | 23 | Semen | cross-sectional study | There was no SARS-CoV-2 RNA detected in semen samples, which indicates the unlikely possibility of sexual transmission through semen at about 1 month after first detection. | The sample size was small, no critical cases and no testicular biopsy. The semen parameters of the patients were not analyzed to show the abnormality of semen quality and quantity. | 32 (27.5-33) | 0 | ||
| Acute | 12 | 31 (26-34) | ||||||||||
| Recovered | 11 | 31 (26-34) | ||||||||||
| Li H (24) | October, 2020 | Wuhan, China | 46.7 (27-83) | 29 | The male reproductive system could be vulnerable in COVID-19, characterized by spermatogenic dysfunction, a significant decrease in sperm count, and immune reactions in testis and epididymis. | The sample size of this study was small, and these COVID-19 patients could not be evaluated prospectively. | ||||||
| 40.8 (27-53) | Recovered | 23 | Semen | cross-sectional study | 25.8 (4-42) | 0 | ||||||
| 69.3 (51-83) | Deceased | 6 | Testis | Case control | NP | 6 | ||||||
| Özveri H (25) | July, 2020 | Istanbul, Turkey | 49 | Acute | 1 | Case report | COVID-19 patients may show isolated genital symptoms such as testicular/spermatic cord pain and discomfort without other systemic symptoms. | Specific data for testicular biopsies and semen samples were not provided. | 2 | 0 | ||
| 1 | Testis/Spermatic cord | 0 | ||||||||||
| 1 | Semen | 0 | ||||||||||
| Barton LM (26) | April, 2020 | Oklahoma, USA | 59.5 (77-42) | Deceased | 2 | 2 | Testis | Case series | One case showed testicular atrophy and the other showed normal testis. | Small sample size and semen samples were not provided. | 1 | NP |
| Gagliardi L (27) | May, 2020 | Pisa, Italy | 14 | Acute | 1 | 1 | Testis | Case report | In COVID-19 children could have testicular involvement, characterized by orchiepididymitis. | Specific data for testicular biopsies and semen samples were not provided. | 1 | NP |
| Bridwell RE (28) | August, 2020 | Texas, USA | 37 | Acute | 1 | 1 | Testis | Case report | Reproductive system complications (orchitis) may be one of the characteristics of SARS-CoV-2 infection. | Specific data for testicular biopsies and semen samples were not provided. | 15 | NP |
| Marca AL (29) | July, 2020 | Modena, Italy | 43 | Acute | 1 | 1 | Testis/Scrotum | Case report | SARS-CoV-2 infection can cause epididymitis and may have short- and long-term effects on male reproductive system. | The testes were only macroscopically examined and specific data for semen sample was not provided. |
1 | NP |
| Duarte-Neto AN (30) | May, 2020 | S~ao Paulo, Brazil | 69(mean) | Deceased | 2 | 2 | Testis | Case series | COVID-19 is a systemic disease that can affect the reproductive system, characterized by orchitis. | Detailed pathological results of testicular biopsy were not provided. | 5 | NP |
| Achua JK (31) | November, 2020 | Florida, USA | 56 (20-87) | Deceased | 6 | 6 | Testis | Case control | The histological and ultrastructural features of the testes of one patient showed COVID-19 viral particles. | The sample size was small and it was unable to assess the long-term consequences of the SARS-CoV-2 virus on spermatogenesis. | 11 (2-36) | 1 (16.7) |
| Caner E (32) | October, 2020 | Istanbul, Turkey | 38 (18-75) | NP | 91 | 91 | Testis | Cross-sectional, pilot study |
Testicular pain was observed in COVID-19 patients, but no inflammatory markers related to predict of testicular pain or epididymal-orchitis were found. | Spermiogram and scrotal Doppler ultrasonographic evaluation could not be done for the patients. |
11.8 | NP |
| Chen L (33) | October, 2020 | Wuhan, China | 58.3 (43.0-73.0) | NP | 142 | 142 | Testis/Scrotum | Cross-sectional, pilot study |
SARS-CoV-2 infection might specifically affect the testis, epididymis, or both. | Detailed pathological results of testicular biopsy were not provided. | 15.4 (7-28) | NP |
| Ma X (34) | November, 2020 | Wuhan, China | 68.8 (51-83) | Deceased | 5 | 5 | Testis | Case control | SARS-CoV-2 could infect testicular cells through the spike glycoprotein binding mechanism. | The sample size was small, and the pre-death semen samples of the patients were not obtained. | 16.2 (5-29) | 2 (40) |
| Yang M (35) | May, 2020 | Wuhan, China | 65 | Acute | 12 | 12 | Testis | Cross-sectional study | Testes from COVID-19 patients exhibited significant seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation. Most of the testis (90%) had no evidence of SARS-CoV-2. | The sample size of this study was small, and the cases included were only in the acute stage of COVID-19. | 41 (23-75) | 1 (8.3) |
| Alkhatatbeh H (36) | July, 2020 | Zarqa, Jordan | 43 (1-78) | 253 | Testis | Descriptive study | This study did not identify any patients with COVID-19 with symptoms or signs of orchitis. | This study lacked testicular pathological examination and semen parameter analysis. | 15 (9-21) | NP | ||
| Asymptomatic | 53 | |||||||||||
| Mild | 152 | |||||||||||
| Severe | 48 | |||||||||||
| Ruan Y (37) | November, 2020 | Wuhan, China | 31 (21-49) | Recovered | 74 | 70d | Semen | Cohort study |
Direct urogenital involvement was not found in the recovered COVID-19 male patients. SARS-CoV-2 RNA was undetectable in the urogenital secretions, and semen quality declined slightly. | The sample size was small and the semen parameters were lacking before infection. | 80 (64-93) | 0 |
| Mild | 11 | 0/70d | ||||||||||
| Moderate | 31 | |||||||||||
| Severe | 32 | |||||||||||
| 61d | EPS | No SARS-CoV-2 was expressed in EPS of patients with COVID-19. | 0/61d | |||||||||
| Quan W (38) | March, 2020 | Wuhan, Xiangyang, and Shenzhen, China | NP | 23 | EPS | Descriptive study | No SARS-CoV-2 was expressed in EPS of patients with COVID-19. | First, EPS were tested only in mild and common patients, there were no samples of severe patients. Second, no semen samples were obtained. | NP | 0 | ||
| 60.3 ± 15.3 | Confirmed patients | 18 | ||||||||||
| 45.6 ± 14.7 | Suspected patients | 5 | ||||||||||
| Zhang S (39) | June, 2020 | Wuhan, China | 57.5 (29-76) | Acute | 10 | 10 | EPS | Cross-sectional study | Negativity of SARS-CoV-2 in EPS and possibly exclude the sexual transmission of COVID-19. | The sample size was small and there was no semen sample. | 16.4 (3-29) | 0 |
aReported as standard deviation. bReported as Interquartile range (IQR). c3 patients with negative pharyngeal swabs were considered to be diagnosed with COVID-19 in this study. dOnly 70 semen samples and 61 prostate samples were obtained from 74 patients. EPS, expressed prostatic secretion; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2; COVID-19, Coronavirus Disease 2019; NP, Not provided; qRT-PCR, quantitative real-time polymerase chain reaction.