To the Editors:
Gagliardi et al1 have reported in the August issue a case report regarding a boy with orchi-epididymitis and concurrent SARS-CoV-2 infection, without any respiratory tract symptom, that was rapidly resolved with antibiotic treatment. The Authors underlined that the testis presents some conditions that might favor SARS-CoV-2 infection, such as the expression of ACE2, the putative SARS-CoV-2 receptor for virus docking to the host cell (not for entry). SARS-CoV-2 entry within the host cell needs the presence of ACE2 but also of the serine protease TMPRSS2.2 To this respect, while the testis has been shown to express the ACE2 protein3 the TMPRSS2 serine protease does not show a significant expression within the testis.4 In agreement with these findings, a recent study did not find any evidence of ACE2 and TMPRSS2 co-expression in high-fidelity RNA datasets.5 Thus, these data indicate that SARS-CoV-2 would not be able to enter within the testicular cells and in fact, different studies failed to show the presence of SARS-CoV-2 RNA in semen samples from acute infected nor recovered COVID-19 patients.4,5 The reported mild reduction of semen quality and testosterone secretion reported in few studies could be referred to pre-existing conditions, to the effects of acute inflammatory state or to the negative impact of drugs utilized to treat COVID-19. In agreement, it was not reported any evidence of the presence of SARS-CoV-2 in the testis of COVID-19 patients.6
The case report by Gagliardi et al claimed as the first described case of orchi-epididymitis with concurrent COVID-19 infection and suggesting that a testicular involvement could be expected in COVID-19 patients, in the way as it has been reported by the Authors is somehow misleading since it seems to associate COVID-19 to the orchi-epididymitis without any biologic data to prove their hypothesis and with different published studies showing that the testis does not express the whole molecular machinery allowing SARS-CoV-2 to enter the testicular cells. Although SARS-CoV-2 infection may present as asymptomatic or with mild up to severe symptoms, the patient described by the Authors with a putative COVID-19 orchitis did not show any respiratory tract symptom, and rapidly improved after broad-spectrum antibiotic therapy, thus suggesting a bacterial orchi-epididymitis rather than due to SARS-CoV-2.
On the other hand, if testis was a privileged organ for SARS-CoV-2 infection, cases of orchitis would have emerged since the start of COVID-19 pandemic last December 2019, with more than 19 million people infected as the date of August 7, 2020 (a number by defect),7 half of them being males.
Angelo Di Vincenzo, MD
Marco Rossato, MD, PhD
Clinica Medica 3, Department of Medicine – DIMED, University-Hospital of Padova, Padova, Italy
1. Gagliardi L, Bertacca C, Centenari C, et al. Orchiepididymitis in a boy with COVID-19. Pediatr Infect Dis J. 2020; 39:e200–e202
2. Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci USA. 2020; 117:11727–11734
3. Wang Y, Wang Y, Luo W, et al. A comprehensive investigation of the mRNA and protein level of ACE2, the putative receptor of SARS-CoV-2, in human tissues and blood cells. Int J Med Sci. 2020; 17:1522–1531
4. Pan F, Xiao X, Guo J, et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril. 2020; 113:1135–1139
5. Holtmann N, Edimiris P, Andree M, et al. Assessment of SARS-CoV-2 in human semen-a cohort study. Fertil Steril. 2020; 114:233–238
6. Yang M, Chen S, Huang B, et al. Pathological findings in the testes of COVID-19 patients: clinical implications. Eur Urol Focus. 2020; 6:1124–1129