We would like to present a guest blog from Prof. Joris Vermeesch, Ph.D. This blog originally posted on the Noninvasive Prenatal Testing Online Resource Page on the 17th March summarizes our current understanding of any possible interference of SARS-CoV-2 infection on the outcomes of NIPT testing.
Currently I am sitting home. All meetings, be it local, national or international, have been canceled including the quarterly Belgian prenatal gathering. I should now be in Nimes, preparing for an international masters course. All due to the worldwide coronaviral pandemy, COVID-19. Wondering about the NIPTupdate, I cannot but wonder about the effect of coronavirus on NIPT. Could viruses either be interfering with the NIPT test results or could viruses be detected when performing NIPT?
Before addressing NIPT, one wonders the effect of COVID-19 on pregnancy? From the website of the Royal College of Obstetricians and Gynaecologists I learn that pregnant women do not appear to be more severely unwell if they develop coronavirus than the general population. As this is a new virus, how it may affect the pregnancy is not yet clear. It is expected the large majority of pregnant women will experience only mild or moderate cold/flu like symptoms. More severe symptoms such as pneumonia appear to be more common in older people, those with weakened immune systems or long-term conditions. There are no reported deaths of pregnant women from coronavirus at the moment. There is no evidence to suggest an increased risk of miscarriage. There is also no evidence that the virus can pass to the developing baby while you are pregnant. It is therefore considered unlikely that the virus will lead to fetal abnormalities.
Could viruses be detected when performing NIPT? One approach to perform NIPT is based on massive parallel shotgun sequencing (MPSS) of plasma DNA fragments. One study has shown viral specific reads in the MPSS NIPT data of pregnant women infected by human cytomegalovirus. HCMV maternal primary infection during pregnancy could lead to a congenital infection and could have severe clinical complications for the newborn. The overall prevalence of congenital HCMV infection has been estimated to be 0.7%. Hence, detecting CMV by NIPT would be welcomed. This proof-of-concept study needs validation. While this approach may allow for the detection of CMV, it is very unlikely COVID-19 could be detected. CMV is a β-herpesvirus, a family of DNA viruses and the integrates in monocytes of the women. Circulating free floating DNA exists out of 90% of white blood cell DNA. 2-8% of this fraction is derived from monocytes. Coronavirus is an RNA virus. RNA is not measured when performing NIPT. And even if one would, the RNA is encapsulated and would with standard methods not be extracted.
Could COVID-19 or other infections interfere with NIPT? At present, we do not have any evidence viral infections interfere with NIPT. However, this cannot be excluded. NIPT results can be jeopardized by the presence of large amounts of circulating DNA derived from other maternal cells. Interference with NIPT results has been reported in pregnant women having cancer during the pregnancy. The cancer derived DNA is measured together with the placental DNA and has been shown to cause false positive test results. Similarly, in women who underwent tissue transplants before pregnancy, inaccurate gender determination was a result of the presence of the transplant tissue. And it is well established that high body mass reduces the sensitivity of NIPT because the relative fraction of placental DNA in plasma is lower due to the increased presence of DNA from adipose tissue. Hence, it cannot be excluded that due to viral infection some tissues are affected, cells die and shed more DNA in the maternal blood stream. COVID-19 invades the lung cells which eventually die and will shed their DNA. The presence of more maternal DNA would lower the fetal fraction and, indirectly, reduce the sensitivity of NIPT. A low fetal fraction is a reason for a test failure. However, it will require epidemiological studies on COVID-19 or other viral infected pregnant women to identify a correlation between test accuracy or test failures. The data could already be out somewhere in large-volume testing laboratories…