Reply to Author.

To the Editor

—We have read the letter by Srijit Das [1] which showed interest about our published article “SARS-CoV-2 Is Not Detectable in the Vaginal Fluid of Women with Severe COVID-19 Infection” [2]. We appreciate their close attention and comments. One of our main objectives of our article was to open discussion on this important subject.

Dr. Srijit Das reminded us that less expression of angiotensin-converting enzyme2 (ACE2) receptors might lead to the absence of SARS-CoV-2 in the vaginal fluid. Like SARS-CoV, SARS-CoV-2 also uses ACE2 as a cell receptor. The virus infects the target cell by binding to ACE2 through its surface spike protein, modulates the expression of ACE2, and causes severe injuries [3, 4]. On the basis of the literature, ACE2 is widely expressed in human tissues. The presence of ACE2 in uterus and vagina was confirmed after analyzing the data from the Human Protein Atlas and GeneCard [5]. Zheng et al. found deficient expression of ACE2 in the 6 week-gestation and 14 week-gestation, as assessed by combined single-cell transcriptome profiles from the early maternal–fetal interface [6]. According to this, it is thought that mother-to-fetus transmission of SARS-Cov-2 during the first trimester seemed unlikely. In summary, ACE2 provides viral entry into human cells. So far, no studies have confirmed the expression of ACE2 in the vagina of postmenopausal women. Even if it is confirmed, it only means that the vagina of the postmenopausal women is not the target organ of the virus and will not cause the corresponding pathological changes. But whether the negative detection of the virus in vaginal secretions can be explained by this remains to be verified. Interestingly, ACE2 is expressed in the cervix, endometrium, and ovary, so if these organs are exposed to the virus, the reproductive system may be affected to varying degrees in the long term, and the following research can focus on this effect.

Several researchers investigated the presence of SARS-Cov-2 in vaginal fluid. Fan et al. and Kteily K et al. tested the virus in the neonate nasopharyngeal swab samples, placenta, and vaginal/cervical fluid to find the possibility of vertically transmission. The same as our result, no virus was positive in the vaginal fluid of women [7, 8]. However, as pregnant women is also a special group, like our postmenopausal women, they can not represent reproductive women. Therefore, we need to test the vaginal secretions of nonpregnant and nonpostmenopausal women to further explore whether SARS-Cov-2 can be detected in the reproductive system. Because the COVID-19 is an epidemic disease, it is difficult to precisely seize the right time to detect the vaginal fluid of subjects. In following studies, if possible, virus in the reproductive system should be detected in the incubation period, and even in different periods of disease progression to show the more information of the relationship between SARS-Cov-2 and female reproductive system.