Investigating the mode of transmission of COVID-19 through genital secretions, semen, the birth canal, and lactation: A systematic review

Abstract

In a global pandemic, the coronavirus has brought new challenges to reproductive and sexual health. This systematic review has been conducted with the aim of investigating a) the transmission of coronavirus disease 2019 (COVID-19) through female-to-male sexual secretions and vice versa, b) vertical transmission to the fetus, c) transmission to the newborn through the birth canal, and d) transmission through breast milk. In this review study, to find related articles, databases were searched using English and Persian keywords from the beginning of 2019 to the end of 2023. Based on the entry and exit criteria and the qualitative evaluation of the studies based on the STROBE criterion, the final studies were summarized. According to the initial search, 5970 articles were reviewed. After removing duplicate articles and the inappropriateness of the title, the abstract of the article was not related to the objectives of the project, there was no relevant study, and retrospective studies were excluded. Finally, 120 articles were selected as final articles. The general results show that transmission of the virus through the vagina to the blood of the fetus causing septicemia, vertical transmission from the mother to the fetus, transmission through the water bag, genital secretions, and ejaculate fluid are considered rare and ruled out. Transmission through rectal secretions during anal or oral sex requires more extensive studies. It is not possible to transmit the virus through breast milk. The long-term reproductive impact of COVID-19 on the reproductive systems of women and men is unclear.

Introduction

The spread of the coronavirus disease 2019 (COVID-19) and deaths in more than 160 countries caused the declaration of an epidemic around the world.[1,2,3,4,5] Restrictions on access to family planning services, reduction in sexual relationships in the form of group sex relationships, reduction in sexual relationships among transsexuals, and the educational and communication gap between healthcare services and mother and child were the most important concerns during the COVID-19 era.[6] In different methods of sexual intercourse, having anal, oral, or combined sexual intercourse can cause the transmission of the virus during marital intercourse.[7,8,9] Rubin ES et al. 2020 shows that COVID-19 can be detected in the vulva;[10] however, it confirms the evidence of vaginal transmission of the virus and the role of the sexual route in the transmission of the disease.[11] The transmission of the virus in saliva and the rectum through oral and anal sex has also been reported during sexual intercourse.[12] In connection with the transmission of the virus from mother to baby, Ashraf et al.[13] (2020) raised the possibility of vertical transmission from mother to baby. Schwartz et al.[14] (2020) confirmed the presence of the coronavirus in vaginal secretions. Then, contradictory studies were reported about transmission from vaginal secretions.[15,16,17] Currently, the status of transmission of this virus through the reproductive system is still controversy regarding perinatal outcomes in infants, but vertical transmission of COVID-19 during vaginal delivery has been confirmed. Therefore, the possibility of contamination of the nasopharynx of the baby, possible infection of the baby, an increase in the rate of cesarean section, a lowering of the decision threshold for cesarean section,[18,19] an increase in the maternal and fetal outcomes of cesarean section, prematurity of the baby, and the need for neonate intensive care (NICU) admission and significant radiographic signs of the baby’s lungs can be expected.[20] Increasing the financial burden of treatment, increasing the duration of hospitalization,[3,19] and increasing perinatal complications (such as preeclampsia) are among the long-term consequences of COVID-19 transmission during pregnancy and childbirth.[19] The increase in the number of screening requests for sexually transmitted diseases and the increase in the number of questions about sexual transmission related to COVID-19 are among the most important issues related to the presence of the virus in vaginal fluid.[20,21,22,23] Considering the possibility of the spread of new strains of the virus in the future, the unpredictable pathogenic behavior of the virus, the performance of the health system in dealing with COVID-19, and the sixth position among the 15 determined and leveled ranks,[24] the researchers decided to consider a complete compilation of reliable information in this field in the continuation of the systematic review process.

Materials and Methods

The aim of this study was to investigate a) the transmission of COVID-19 through female-to-male sexual secretions and vice versa, b) vertical transmission to the fetus, c) transmission to the newborn through the birth canal, and d) transmission through breast milk. This article was put on the agenda as a review and in a systematic way. A systematic search of previous research in a purposeful and focused manner on a specific topic that is mentioned above is performed. In this regard, the combination and evaluation of research are performed using specific and predetermined criteria, which ultimately lead to the presentation of results. The method of searching in this study is performed using keywords related to the subject in several specific and valid databases. In such studies, quality filters are also applied in the selection of previous research studies. Also, sampling strategies, type of the study, study period, and their limitations are examined. The statistical population of this study includes published scientific articles that refer to the issue of transmission of COVID-19 through female-to-male sexual secretions and vice versa, vertical transmission to the fetus, transmission to the newborn through the birth canal, and transmission through breast milk. Protocol: This review study was conducted after approval by the research council and obtaining the ethical code approved by Islamic Azad University (ir.iau.ps.rec. 1400.199). This study was completed based on the protocols registered on the PROSPERO website with the code 251736, according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) format, and using the The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Search strategy: In this study, the following databases were used to find related studies in line with the goals of the project: Cochrane, IranMedx, Scientific Information Database (SID), PubMed, Google Scholar, Scopus, ScienceDirect, UpToDate, and Web of Science. Studies were reviewed from the beginning of the coronavirus epidemic 2019 until 2023 and based on the inclusion and exclusion criteria. The English keywords included sexual transmission, sexual, oral sex, rectal sex, Sexual Behavior, Sexual Partners, hetrosexual, Sexual Abstinence, Sexual Health, Sexual Maturation, Vagina, Vaginal Smears, Vaginal Discharge Vaginal, normal vaginal delivary, covid-19, corona virus, sars-covid-2, cesarean section, infant, baby, fetus, newborns, placenta, fetomaternal, transmition, breastfeeding, neonate intensive care (NICU), which were investigated by combining AND and OR. Selection of studies: The selection of studies was put on the agenda based on inclusion and exclusion criteria and relevance. The studies in Persian and English and the format of a full article were finally reviewed. Also, the list of sources used in all published articles in this field was checked. Study selection criteria are as follows: 1. studies that are in English and Farsi and have a full article format; 2. studies that have been conducted on sexual contact (heterosexual, oral sex, and rectal sex) transmission through semen and vaginal secretions; 3. studies that mention transmission through oral and anal sex; and 4. articles in the form of case reports and original research studies that have been refereed. Study exclusion criteria are as follows: 1. studies that do not get the corresponding points according to the checklists related to the meta-analysis of descriptive studies; 2. studies that are related to the infection of people with multiple partners; 3. texts presented in the form of letters to the head secretary, short articles, and articles presented in congresses and conferences. Excavating Information: According to the initial search, 5970 articles were reviewed, and after removing duplicate articles, 1018 articles were reviewed. Among them, 603 articles were removed due to the inappropriateness of the title. Then, 415 articles were analyzed. Twenty articles were excluded because the abstract of the article was not related to the objectives of the project, and 275 articles were excluded because they were not relevant. Finally, 120 articles were selected as final articles and entered the quality review stage [Figure A]. Checking the quality of studies: The information about the articles was prepared based on the checklist form and extracted and entered into Excel. To prevent bias, all the steps of extracting and checking the sources were performed by two authors independently of each other, and if the sources were rejected, the relevant reason was mentioned. In case of disagreement between two researchers, the review of the article was performed by a third person. In all stages of searching and using references, ethical principles were observed. Then, to obtain the data from the articles, data extraction worksheets were designed and adjusted in the form of eight indicators, and based on coding, each of the worksheets was completed by the researchers. The investigated indicators in each paper were article title, first author, type of the study, investigated variable, year of publication, demographic information related to each title, quality of the study, and final conclusion of the study. The quality of the studies was evaluated according to the checklist of descriptive studies in STROBE epidemiology. The revised checklist consists of 11 items, and a maximum of one point is assigned for each methodological element. The total quality score is finally 22. Scores of 16–22 are high quality, 15–8 are average quality, and less than 8 means low quality studies.[25] In this research, studies that had poor quality were deleted. After reviewing and comparing the worksheets specific to each of the extracted articles, the obtained data were compiled and the final description and analysis were performed based on the objectives of the project.

Figure A.

Study algorithm

Result

The following practical findings were presented in a classified manner with separate thematic axes. The aim of this study was to investigate a) the transmission of COVID-19 through female-to-male sexual secretions and vice versa, b) vertical transmission to the fetus, c) transmission to the newborn through the birth canal, and d) transmission through breast milk.

Discussion

Later studies related to the possibility of vertical transmission from mother to fetus were reported, some in favor and some in opposition. The COVID-19 pandemic has affected all aspects of reproductive and sexual health. The current review was conducted with a systematic review of 120 articles. Various studies related to the transmission of the virus through genital secretions concluded that droplets, contact, aerosol, and fecal–oral transmission are the main ways of transmitting the infection of COVID-19, and this initial finding was confirmed in all the primary articles.[135,136] In the future, due to the progress of the disease at a high speed and similar distribution in all parts of the world, the ability to detect COVID-19 in the lower genital tract of women will be noticed.[10,15,16,17,31,34,137] According to Tables 1 and 2 In this part, the researcher categorized and emphasized a the transmission of COVID-19 through female-to-male sexual secretions and vice versa. Other studies were designed in response to the transmission of COVID-19, among which the study of Rubin (2020) reported a pregnant woman infected with the virus who had vulvovaginal lesions and raised the possibility of transmission through these lesions.[10] In opposition to the above findings, other studies show that the SARS coronavirus 2 has been associated with oral and genital ulcers and describes a potential reactive dermatologic manifestation of COVID-19, but the transmission of the virus through an ulcer is not mentioned.[138,139] Later, sexual contact was proposed as a way to transmit Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and researchers sought to confirm or disconfirm the issue.[75] Kotlyar (2021) showed in their research that the rectal swap test is positive even after the nasopharynx is negative. This possibility has been raised in other studies as well.[140,141,142,143] In relation to the possibility of virus transmission through men’s semen, most of the studies showed the absence of virus transmission through ejaculate,[43,44,47,49,51,54] but Li (2020) showed in their study that there were positive results of SARS-CoV-2 in the semen of six patients (15.8%).[42] In this regard, Machado (2021) also found the virus in the semen of 6.66% of patients.[53] Some studies point to the short-term and long-term effects of COVID-19 on the male reproductive system, such as the effect of COVID-19 on the amount of male sex hormone secretions that were discussed in the study by Ling Ma et al. (2021).[46] Oligospermia, azoospermia, and sperm quality disorders have also been shown in Gacci et al. (2021).[52] Groner et al.[48] (2020) consider the effect of this virus on the reproductive system and reproductive health of men to be probable and suggest the need for more research. In favor of the result of this research, Nori and Salman (2023) reported that COVID-19 has a direct hematogenic spread to the testis and triggers the immunological response, which decreases sperm motility and counts[144] and changes the hormonal level, and the formation of antisperm antibodies is reported.[145,146] The other findings of this research are vaginal secretions that do not transmit the virus, but rectal secretions can be considered a route of transmission, which requires more extensive studies. Sexual contacts such as oral–anal contact play a role in the transmission of COVID-19. In favor of the above finding, even in Carosso A et al, (2020), the risk of virus transmission in feces during childbirth was mentioned.[68] Some of this result of the search is in favor and some is in opposition to each of the research aims. In this part, the researcher categorized and emphasized b) vertical transmission to the fetus. This research finding showed in Fornari’s[147] study (2020) that some children born to mothers infected with COVID-19 at the end of pregnancy and near the time of delivery tested positive for COVID-19, but there was no transmission. This issue has been confirmed in the studies of Yuan J et al. (2021) and Najafi, T. F et al. (2021).[148,149] Special attention is still being paid to the fact that women are not infected with COVID-19 at the time of trying to get pregnant and are not to be infected in the first trimester of pregnancy.[150] This is opposed to De Luca’s[151] (2023) study that mentions the possibility of transmission of COVID-19 via pregnancy. Although Goulioumis A et al.[152] (2022) have reported that the intrauterine infection remains controversial, anyway the expression of the ACE2 receptor on the placenta, the detection of IgM antibodies, and the COVID-19 genome in fetuses make the vertical transmission tenable. However, this article based on Hu X et al. (2020) showed in their findings that the vertical transmission of SARS-CoV-2 infection from mothers infected with COVID-19 in the last days of pregnancy is possible, but it is relatively low, and one baby of seven was infected (14.3%).[81] The findings of Sukhikh G et al.[95] (2021) showed that PCR and immunohistochemical analysis of placental tissue, umbilical cord blood, and child’s blood jointly showed vertical transmission of SARS-CoV-2 from mother to fetus. In connection with the possibility of vertical transmission of COVID-19, the review of 27 articles shows the absence of vertical transmission of this virus through the birth canal and amniotic sac from mother to fetus and newborn.[2,62,63,66,67,68,69,70,71,73,75,76,77,78,83,84,87,88,89,92,93,98,99,102,106,109] In favor of the above finding, Kim YK and Kim EH et al.[153] (2023) showed that vertical transmission in pregnancy (every trimester) is rare. This finding is consistent with that of Muhidin S et al.[154] (2020), who reported that although the rate of cesarean delivery, preterm delivery, simultaneous multi-organ involvement in the pregnant mother, and the chance of hospitalization in the intensive care unit increased, no vertical transmission from mother to baby was reported. However, in this research, Zamaniyan M et al.[114] (2023) showed that the high risk of maternal and neonatal outcomes of COVID-19 during pregnancy and the high probability of vertical transmission were seen. This report is consistent with the study by Melo GCd, and Araújo KCGMd[74] (2020) that showed that of 432 newborns born to mothers infected with COVID-19, 10 cases had positive results for primary SARS-CoV-2. Also, some reports indicated the vertical transmission of SARS-CoV-2 to newborns. The other studies, such as Alzamora MC et al. (2020), reported a severe case of COVID-19 that was delivered by cesarean section, the baby was immediately separated, and the baby’s PCR test was positive.[80] Some of this result in this search are in favor and some are in opposition to each of the research aims. In this part, the researcher had categorized and emphasized c) transmission to the newborn through the birth canal. Zimmermann P and Curtis N[79] (2020), by reviewing 11 articles and examining 333 babies, completely reject the possibility of virus transmission from vaginal secretions to the baby’s blood causing septicemia. In vaginal secretions, COVID-19 has rarely been seen. In the study by Wu et al.[17] in 2020, during further tests and investigations of mothers with COVID-19 and their babies, transmission to the baby through secretions of the birth canal was ruled out. In this regard, studies were conducted on the possible effect of elective cesarean delivery on reducing transmission through birth canal secretions and improving neonatal outcomes, but the elective cesarean section was not recommended in patients with COVID-19.[106] In the same way as this research finding, Yanting Wu et al.[155] (2020) suggested that vaginal delivery can be safe, and it does not seem that virus contamination happens through the vaginal secretion. Some of this result of the search is in favor and some is in opposition to each of the research aims. In this part, the researcher had categorized and emphasized d) transmission through breast milk.[81,147] Transmission through breast milk was investigated, and no transmission was seen. It seems that the nursing mother infected with COVID-19 infects the baby through her respiratory droplets, rather than the virus being transmitted through breast milk.[116,120,121,122,123,125,126,127,128] However, vaccination during the breastfeeding period cannot cause serious complications for the baby.[156,157] However, inter-departmental transfer of pregnant mothers or transferring them to other related departments for continuing care is associated with an increase in the possibility of contact between pregnant mothers, nursing mothers, and babies with the virus. Therefore, it is recommended to consider this issue in midwifery care.[154,158,159,160,161,162] The results of this study are in line with the results of Koç and Dilli[163] (2022) who highly advise breastfeeding while using proper infection control methods. The most important limitation of the plan was not having sufficient information or studies in the field of all aspects of the transmission of COVID-19 due to its emerging nature. Another limitation of this study was not mentioning the detailed research information in the selected articles. Cohort studies in this field did not exist at the beginning of the researchers’ work, and if they existed, they would have provided the possibility of more powerful arguments. The information obtained from the articles is generally retrospective in nature, and the researchers hope that this research will pave the way for future research in the field of emerging diseases.

Table 1.

Frequency distribution of articles according to the topic and objectives of the study

Row	Purpose	Abundance	Percentage
1	The relationship between the transmission of COVID-19 through vaginal secretions	23	19.16
2	Correlation between transmission of COVID-19 through ejaculate	19	15.83
3	The relationship between vertical transmission of COVID-19 around and around childbirth through the birth canal	57	47.5
4	Transmission of COVID-19 through genital secretions and umbilical cord blood	0	0/0
5	Transmission of COVID-19 through vaginal secretions to the baby’s blood	1	0.83
6	Transmission of COVID-19 through breast milk	20	16.66
7	Total	120 articles	100/0
Type of study
The reviewed articles have been published between 2019 and 2023
10 prospective studies	5 observational studies
7 retrospective studies	26 review studies
3 systematic review studies and meta-analysis	9 experimental studies
2 clinical trials	18 case report studies and 4 case series
2 case–control studies	12 cross-sectional studies
3 case reports and reviews	7 cohort studies
1 narrative review	15 systematic review studies
Quality of studies
11 studies had excellent quality	109 studies had average quality	Studies that had poor quality are deleted

Table 2.

Determining all of the types of transmission of COVID-19

Conclusion

The results of this systematic review study, which was conducted with the aim of investigating the mode of transmission of COVID-19 through sexual secretions and the birth canal, showed that COVID-19 is not transmitted through vaginal secretions or ejaculate, but rectal secretions can be considered a route of transmission, which requires more extensive studies. Oral–anal sexual relations have played a vague role in the transmission of COVID-19 and have been reported in the form of uncertainty. Reproductive outcomes, including male sex hormone secretion disorders, oligospermia and azoospermia, and sperm quality, have been mentioned in studies. However, the viral attack on women’s reproductive system and other direct and indirect effects on men’s reproductive system in the long term are unclear and require a more comprehensive investigation. It is not possible to transfer COVID-19 from vaginal secretions to the baby’s blood and cause septicemia, vertical transmission, transmission through the birth canal and water sac, and transmission through the flow of breast milk, but there is a need for a more comprehensive investigation regarding the risk of transmission through contaminated feces to the baby during the delivery process. The most important limitations of the study were not having enough information or studies on all aspects of the transmission of COVID-19, not mentioning detailed research information in the selected articles, and lack of cohort studies on the aspects investigated by the researchers. According to the results of the research, it is necessary to put all-round investigations in the field of possible ways of disease transmission and public education about definite ways of transmission on the agenda of healthcare workers.

Financial support and sponsorship

The research budget is provided from the income of Islamic Azad University—Maybod Branch.

Conflicts of interest

There are no conflicts of interest.