Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, many efforts have been made to understand how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads within the community. The respiratory route is considered predominant, transmission occurring through respiratory droplets and contact with contaminated surfaces.
The virus has also been observed to be present in blood, urine, feces, and tears, though not in semen. Vaginal secretions have not been consistently shown to be positive for the virus in most studies. The authors of a new study in the Journal of Clinical Medicine affirm that the presence of the virus in the vagina is rare, irrespective of pregnancy.
How was the study done?
In this study from Israel, both pregnant and non-pregnant women were tested for the virus by reverse transcriptase polymerase chain reaction (RT PCR). Of the 51 women in the study, less than a third were pregnant, and almost 90% were hospitalized when they first presented.
The non-pregnant group had a mean age of 50 vs. 30 years for the pregnant group, and the prevalence of chronic underlying disease was 51% vs. 19%, respectively. The former cohort also showed higher leukocyte counts and neutrophil counts. The latter group had a higher rate of hospitalization.
Of 16 patients who were infected during pregnancy, 13 delivered during the study period, just under half by Cesarean delivery. None of the babies were positive for the virus in the first 24 hours of life or required anything beyond routine care.
One woman, 60 years old, with multiple underlying diseases, tested positive for the virus twice in two separate samples of vaginal secretions. This woman had a history of hysterectomy and was on several medications, including immunosuppressive or immunomodulatory drugs, and biologics, along with thyroid hormone replacement and others.
Both positive vaginal samples were on the day of her admission but by different methods. The first sample was tested for the spike and ORF1b genes, while the repeat test was for the envelope (E) and N2 nucleocapsid genes.
Extremely low viral load in vaginal secretions
The cycle threshold (Ct) levels are negatively associated with the amount of messenger ribonucleic acid (mRNA) encoding the antigen of interest. The mRNA indicates the level of protein translation going on at the time.
Late detection of viral mRNA for the gene of interest indicates a higher number of cycles and a correspondingly lower viral load. In these samples, the Ct values ranged from approximately 35 to 42, indicating low levels of ongoing transcription.
The gene positivity in these samples was therefore very low, however, compared to the nasopharyngeal samples.
True evidence of vaginal SARS-CoV-2 colonization?
The presence of the virus in the female reproductive tract, including the uterus, may conceivably affect the endometrial cycle and the development of an embryo following conception.
One study first reported the detection of SARS-CoV-2 in the vaginal secretions of a pregnant woman with the infection. However, most studies so far have failed to detect the virus in vaginal secretions of infected women aged over 50 years, even though they had severe COVID-19; or in pregnant women with mild COVID-19.
Another study did detect the virus in the vaginal secretions of 2 of 35 women aged between 21 and 93 years.
Reasons for this low detection rate, ranging from 2% to approximately 6% in various reports, are only putative. For one, the low incidence of viremia (1% to 37%, depending on the study) may explain why the spread of the virus from the respiratory tract to other organs is slow and only occasional.
Secondly, it is possible that the viral mRNA detected in a few patients is due to either fecal contamination or infection spreading from the gut to the reproductive tract.
Perineal cleaning was carried out before vaginal sampling, reducing the chances of fecal contamination. Again, earlier studies indicate that the virus appears in the feces after the early phase of the infection. In contrast, in the current study, the vaginal secretion was positive soon after the patient was diagnosed with COVID-19. This patient also had a high viral load, as indicated by her positive nucleocapsid protein assay.
What are the implications?
The presence of the viral mRNA in the vaginal secretions of only one patient out of the 51 COVID-19-positive women is reassuring, especially as even the single positive test showed a viral load at the limit of detection for the assays used, and several-fold less than the nasopharyngeal swab taken at the same time.
The chances of a false positive result are also minimal since two different assays were used, testing different viral genes. None of the newborns were positive for viral RNA, ruling out vertical transmission.
The prospective nature of the study lends strength to its conclusions. Further research utilizing simultaneous sampling of blood, urine and feces could help establish a connection between viremia and the viral spread to other organs if present. Larger studies would be required to understand the risk factors for, and infectivity of, vaginal colonization with this virus.
Polypurine hairpins found to effectively halt SARS-CoV-2 replication