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Most of the COVID-19 news these days is positive: new infections in the U.S. and countries, like Israel, have been declining rapidly and, with its deaths from the disease. At the same time, the news in big parts of the world, especially Europe and Brazil, is not that favorable. Especially as many countries in Europe are yet again, in almost complete lockdown. Like so many other issues regarding the SARS-CoV-2 virus, why different regions in the world behave so differently is not clear. An anonymous recent editorial in Nature strongly pointed out the substantial uncertainties still surrounding COVID-19, including the statistical models that scientists develop and base predictions on (Nature. 2021;589:492).
One aspect, however, appears convincing: how quickly and by how much a population gets vaccinated against the virus appears to affect infection and death rates. In other words, available vaccines are highly effective, best demonstrated by the country of Israel. This little country is such a good example not only because she vaccinated the population in the most efficient ways; but also, because before vaccines became available, the country had one of the worst infection rates in the world, mostly driven by the British B.1.1.7 virus variant, reported to be more infectious and, clinically more virulent than the earlier D614 and D614G strains, prevalent in initial COVID-19 times.
What the Israeli experience, therefore, suggests is that the vaccines currently available are still highly effective against the B.1.1.7 strain and, hopefully, also against all the other new strains that have raised their ugly heads in South Africa, Brazil, the U.K. and, now also in the U.S., including New York City. What published data, indeed, also have hinted at is, that anti-SARS-CoV-2 vaccines may even be effective in preventing disease in already infected individuals during initial stages of infection. Especially, considering that so many people infected by the virus are experiencing long-term sequalae often for months after being virus-free (“long-haulers;” apparently 50-80% of COVID patients still have symptoms after 3 months, according to Anthony Komaroff, MD in the Harvard Health Letter), vaccinations in many of these patients instantly stop their symptoms (Pam Belluck in The New York Times, March 18, 2021, and Brenda Goodman, Medscape, March 17, 2021). An excellent review of the post-acute COVID-19 syndrome (“long haulers”) was recently published.
For the first time, studies on pregnant and lactating women are being published and formal studies on vaccinations are underway. As CHR has been recommending for some time in preceding issues of The VOICE, increasing consensus now favors vaccination of women trying to conceive, women who already are pregnant and women who are breastfeeding.
A just published study by Spanish investigators researched the oocytes of two women, by PCR diagnoses as infected by the SARS-CoV-2 virus on day of egg collection and found no evidence of viral contamination. This is a very reassuring finding; but since this study investigated only two women with mild disease, a final verdict on whether eggs can be infected by the virus awaits additional information.
In an interesting study from Iran, published in the journal Reproduction, the investigators looked at the immune environment in seminal plasma of COVID-19 patients and controls and found significant differences: ACE2 enzymatic activity, markers of inflammation and SOD activity, with the former two being higher and SOD being lower. These abnormalities persisted for some time and were statistically associated with poorer semen parameters. These authors, therefore, confirm earlier reports addressed in this newsletter, suggesting that the virus can invade and can cause damage to the male reproductive tract. In an appropriate recommendation, the authors suggest careful investigation of semen parameters post-COVID-19 infections in males.
Polycystic ovary syndrome (PCOS) is considered the most frequent cause of female infertility. Now British investigators have presented evidence for significantly increased risk over controls to acquire COVID-19 infections for women with PCOS. Considering that many PCOS patients have evidence of immune system hyperactivity, this association may not come as a surprise. CHR, however, recommends caution in interpreting this data because of potentially biased patient selection in the study: The investigators relied on coded PCOS diagnoses but PCOS is a basket of different phenotypes with different etiologies and, as CHR investigators intensively studied and reported, with varying ontogeny. Coded PCOS diagnoses tend to favor the classical phenotype (phenotype A) and to disfavor the lean phenotype (phenotype D) since women with D phenotype are not as easily discernable as A phenotypes. Consequently, it appears quite likely that in this study reported risks apply only (or mostly) to phenotype A PCOS patients. CHR, nevertheless, considers this study as further evidence that infertile women in treatment should be vaccinated as soon as possible.
The same group of investigators in a separate study recently reported that administration of the oral diabetes medication, metformin, a medication also frequently prescribed to PCOS patients, not to be associated with increased COVID risk.
Three recent articles, one in a medical journal and two in the lay press, deserve some attention: In an article in STAT on March 25, 2021, Eve C. Feinberg, MD, an associate professor at Feinberg School of Medicine of Northwestern University in Chicago, IL, and a rising star in the ASRM hierarchy, took on in her article the “fake news” that in recent months has been all over the Internet, claiming that COVID-19 vaccinations caused infertility. A main argument of anti-vaccination proponents has been that the vaccine (which is supposed to elicit an immune response) contains a protein called syncytin-1 which is vital for the placenta. Consequently, antibodies the vaccine would induce against this protein would also act against the early placenta of a fetus.
Feinberg, however, correctly points out in her article (which we recommend reading for further detail) that vaccines do not contain syncitin-1 and, therefore, do not damage the placenta of early pregnancy, causing infertility. She further reemphasizes what CHR has pointed out now for several month: the risk-benefit assessment in weighing vaccination or not is clearly in favor of vaccination because COVID-19 in pregnancy is a significantly more severe disease than in the non-pregnant state.
Adjoas Smalls-Mantey, MD, DPhil, in ABC News reported that the new Johnson&Johnson vaccine, which in contrast to the earlier Pfizer and Moderna vaccines, is not based on RNA technology and, instead, uses another virus to deliver genetic information to the immune system, can also be safely administered to pregnant women. The reason is that the vaccine does not contain live virus. The Johnson&Johnson vaccine also has the additional advantage of requiring only one vaccination!
Finally, Gray et al, investigators from Harvard University in Boston, MA, in an article still at pre-proof stages in the American Journal of Obstetrics and Gynecology pregnant and lactating women after vaccination in pregnancy produced similar levels of antibody responses as non-pregnant women. Those antibody levels, in addition, were higher than those of women who developed COVID-19 while pregnant. Finally, in women who underwent vaccinations in pregnancy, the investigators also demonstrated antibodies in cord blood of newborns and in breastmilk, suggesting passive transfer of immunity from mother to fetus.
The politicization of the COVID-19 pandemic, unfortunately, continues, with political left and right seeing everything regarding the pandemic differently. Demonstrating this dangerous development for all of medicine, are two articles that appeared within 48 hours in the two leading newspapers of right and left: On March 25, 2021 Marty Makary, MD, MPH, a professor at the Bloomberg School of Public Health and Cary School of Business of John Hopkins University in Baltimore, ME, penned an article, “Herd immunity is near, despite Fauci’s denial,” in the conservative Wall Street Journal. Two days later, on March 27, 2021, a group of writers, mostly former federal health care bureaucrats, pined in the progressive New York Times under the heading, “Herd immunity won’t save us”
The issue here is not the disagreement in opinions between so-called experts because we welcome disagreements between scientists and consider those supportive of scientific progress. The problem is that interpretation of scientific data by “experts,” increasingly follows political ideology rather than objective analysis of scientifically obtained data. We have made this point before during the pandemic but had hoped that with a change in administration things would be getting better. It now increasingly becomes apparent that these expectations are not being met; indeed, the politicization of medicine appears to be getting worse.
Steve Cuozzo, not only the New York Post’s food critic who also often writes about real estate, this time penned an interesting opinion piece on March 20, 2021, where he addressed the observation, to our best knowledge never addressed in print, that among all five New York City boroughs, Manhattan has by far the lowest COCID-19 rates. He also points out that common wisdom among public health officials routinely associates population density with infection risk; yet Manhattan, with all its skyscrapers, has by far the highest living density among all of New York’s boroughs. (71,000 residents/square mile vs. 36,000 in Brooklyn, the 2nd-densest borough). Manhattan’s infection rate is around 2% while all other boroughs are around 4%. And the same difference also exists in mortality rates.
Manhattan, of course, as Cuozzo also notes, has more and larger restaurants than other boroughs, which the state (erroneously) for the longest time considered a major source of infection during the pandemic. He correctly points out that trying to find explanations for why Manhattan has been doing so much better during the pandemic than the other boroughs, while standard criteria held sacrosanct by most public health officials, would have suggested exactly the opposite, might lead to smarter city and state policies. We fully agree!
COVID-19 has not been all-bad. The CDC now confirmed that, as we predicted in these pages before, this year’s fall and winter flu season was unusually mild. The same had also happened in the Southern hemisphere that precedes us by six months. Our prediction, therefore, was not too difficult to make.
Public health officials, of course, attribute this to the COVID-19 mitigation measures which, at the same time, also protect from influenza infections. Though that is, indeed, an explanation, we are not certain it is the only one, because “slow” flu seasons do occur intermittently. The last one for our hemisphere was in 2011-2012. Because of fear of an infectious double whammy, with COVID-19 and the flu, a record number of people got immunized against the flu this year and that, of course, may also have contributed.
Usually, flu seasons reach into March and April; but the 2019/2020 season, the one preceding the COVID-19 pandemic, ended already weeks earlier than usual, suggesting that changes in flu prevalence in the U.S. started already in the year before the COVID-19 pandemic. Since between 20,000 and 50,000 people die every year in the U.S. from the flu, and this year there were almost no fatalities, this is for a change good news, whatever the underlying reasons may be!
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.
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