NEWS ABOUT INFECTIOUS DISEASES ABOUND
Doesn’t it seem like infectious diseases are everywhere. There is clearly an impression that there are more viral diseases out there infecting increasing numbers of humans, whether here in the U.S. where we have rediscovered that Measles can be a serious disease in children, or in Africa, where new outbreaks of different viruses appear to happen basically every week. Is this impression correct? We don’t know and have not seen in the medical literature anything to support such a suspicion (but we continue looking). Assuming our impression does get confirmed, does that mean that infectious agents are getting more aggressive or – what appears more likely – are our immune systems weakening and, if so, why? So, here is some of the recent news!
The SARS-CoV-2 virus is still around and changing
LONG COVID – In a recent paper in JAMA Network Open involving 12,276 participants, females were demonstrated to have a significantly higher risk of long COVID in comparison to males, even though males had more severe disease and demonstrated a higher mortality. Overall, female sex was associated with a 1.31-times higher risk of long COVID in a full model with matching on demographic and enrollment factors, social determinants of health, and hospitalization and vaccination status during first infection. In a reduced model including only age, race, and ethnicity, female sex showed an even higher risk ratio for long COVID (1.44). Though this difference was small, it nevertheless suggests that factors downstream of an individual’s sex attenuate the estimated risk ratio of long COVID.
This difference was apparent at all ages, except between 18 and 39 years, and if the analysis in females was restricted to only non-pregnant women, applied to women of all ages. The association of long COVID risk, thus, was associated with female sex, which in turn was also associated with age, pregnancy, and was menopausal status dependent, with no elevated risk observed in women between ages 40 and 55 years. Trying to explain this finding, the authors concluded after a review of the literature and in consideration of their data that differences in hormonal levels may partially explain the higher prevalence of long COVID in females younger than 55 years.
The authors also conclude that the sex-specific predilection of women to long COVID may have similar causes as other post viral sequelae, such as Epstein-Barr, Lyme disease, and others. But there, of course, is also similarity with autoimmune conditions which are known to be much more frequent in women than men, though – like here with COVID – men have more severe disease. Moreover, autoimmune diseases also tend to flare with termination of fetal-placental tolerance peripartum and, often, during months postpartum.
This so-called prospective NIH RECOVER Adult cohort study, thus, pointed out that females infected by the SARS-CoV-2 virus demonstrate the same predilection toward long COVID as females demonstrate to other post-viral and especially autoimmune conditions. As the authors noted, these findings further highlight the need to identify biological mechanisms contributing to sex specificity.
THIS WINTER’S DOMINANT VIRAL STRAIN – In a Medical News article, the JAMA noted that the so-called XEC is this winter’s likely dominant SARS-
CoV-2 variant. It apparently arose from the recombination of two other variants, both descendants of the original Omicron virus, and closely related to variants targeted by this year’s COVID-19 vaccines (called JN.1 and KP.2).
This is likely the reason why COVID in this year’s “flu season” apparently is playing only a second or even third fiddle, with other flu and flu-like viruses dominating the scene. Indeed, flu viruses which during the COVID pandemic had almost completely disappeared, this year have been making a quite remarkable comeback, probably enhanced by the population's hesitance about getting flu shots.
It needs to be restated here, despite the controversy surrounding vaccinations since the pitiful performance of FDA and CDC during the COVID pandemic, that the CHR still strongly recommends that women trying to conceive or already pregnant receive anti-COVID as well as anti-flu vaccinations. As we have repeatedly noted in these pages, there are two major reasons for this recommendation: (i) Both infections – if caught while pregnant – are usually clinically more severe than in the non-pregnancy state; and,(ii) if the mother is vaccinated, she passes her immunity to her offspring which, therefore, also has passive immunity for at least three months post-birth.
LONG COVID - A recent paper in JAMA Network Open involving 12,276 participants, females were demonstrated to have a significantly higher risk of long COVID in comparison to males, even though males had more severe disease and demonstrated a higher mortality (1). Overall, the female sex was associated with a 1.31-times higher risk of long COVID in a full model with matching on demographic and enrollment factors, social determinants of health, and hospitalization and vaccination status during first infection. In a reduced model including only age, race, and ethnicity, the female sex showed an even higher risk ratio for long COVID (1.44). Though this difference was small, it, nevertheless suggests that factors downstream of an individual’s sex attenuate the estimated risk ratio of long COVID.
This difference was apparent at all ages, except between 18 and 39 years and – since the analysis in females was restricted to only non-pregnant women – applied to women of all ages. The association of long COVID risk, thus, was more associated with the female sex, which in turn was also associated with age, pregnancy, and was menopausal status dependent, with no elevated risk observed in women between ages 40 and 55 years. Trying to explain these findings, the authors concluded after a review of the literature and in consideration of their data that differences in hormonal levels may partially explain the higher prevalence of long COVID in females younger than 55 years.
The authors then also conclude that the sex-specific predilection of women to long COVID may have similar causes as other post viral sequalae, such as Epstein-Barr, Lyme disease, and others. But there, of course, is also similarity with autoimmune conditions which are known to be much more frequent in women than men, though – like here with COVID – men have more severe disease. Moreover, autoimmune diseases also tend to flare with termination of fetal-placental tolerance peripartum, and often during several months postpartum.
This so-called prospective NIH RECOVER Adult cohort study, pointed out that females infected by the SARS-CoV-2 virus demonstrate the same predilection toward long COVID as females demonstrate to other post-viral and especially autoimmune conditions. As the authors noted, these findings further highlight the need to identify biological mechanisms contributing to sex specificity.
THIS WINTER’S DOMINANT VIRAL STRAIN – In a Medical News article, the JAMA noted that the so-called XEC was this winter’s likely dominant SARS-CoV-2 variant (2). It apparently arose from the recombination of two other variants, both descendants of the original Omicron virus, and closely related to variants targeted by this year’s COVID-19 vaccines (called JN.1 and KP.2).
This is likely the reason why COVID in this year’s “flu season” apparently played only a second or even third fiddle, with other flu and flu-like viruses really dominating the scene. Indeed, flu viruses which during the COVID pandemic had almost completely disappeared, this year have been making a quite remarkable comeback, probably enhanced by the population’s hesitance to get flu shots.
It needs to be restated here, despite the controversy surrounding vaccinations since the pitiful performance of FDA and CDC during the COVID pandemic, the Center for Human Reproduction (CHR) still strongly recommends that women trying to conceive or already pregnant receive anti-COVID as well as anti-flu vaccinations. As we have repeatedly noted in these pages, there are two major reasons for this recommendation: (i) Both infections – if caught while pregnant – are usually clinically more severe than in the non-pregnancy state; and (ii) if the mother is vaccinated, she passes her immunity to her offspring which, therefore, also has passive immunity for at least three months post-birth.
References
1. Shah et al., JAMA Network Open 2025; 8(1):e245
2. Rubin R. JAMA 2024332(23)”1961-1962
Immunization practices at the center of discussion
GENERAL COMMENTS - Since we are already talking about immunizations, a few minutes on immunizations in general appear timely. As noted above, vaccinations have become very controversial after the federal government sent during the COVID pandemic so many misdirections out into the ether of public opinion. The nomination of Robert F. Kennedy, Jr. as Secretary of Health and Human Services (HHS) – neither a physician nor a trained scientist and well known as an anti-vaxxer – also did not help much in instilling new trust into federal health care agencies.
MORE AND BIGGER MEASLES OUTBREAKS ALMOST ALL OVER THE U.S. - And finally, after for years having eradicated Measles from the country, the Centers for Disease Control (CDC) is almost daily reporting more outbreaks and rising tallies of measles since the beginning of 2025. According to the CDC, as of early May, over 1000 cases have been reported - likely only a fraction of really occurring cases.
While Alaska, California, Georgia, Kentucky, New Jersey, New Mexico, New York City, Rhode Island, and Texas are considered most affected, the disease is likely already in most of the states (1). At the time of this writing, it is unclear whether so-far two or three fatalities have occurred. As of March 6, 2025, at least two deaths have been definitely attributed to measles, one in an infant and the other one in an unvaccinated adult (2). There may also have been reported a second infant deaths, which we, however, were unable to confirm.
Measles was declared eliminated from the U.S. in the year 2000 and the reason was obviously a very satisfactory level of heard immunity in the population through the highly successful measles, mumps, rubella (MMR) vaccine.
The CHR tests immunity to all three of these viral diseases in all patients because all three conditions - if acquired in pregnancy - can have devastating consequences on mothers, pregnancies, and newborns. And we have been nothing but astonished about the increase in the number of patients we have been found in more recent months and years deficient in immunity to one or more of these three diseases. This is obviously a sign of declining heard immunity in the population.
When a patient is diagnosed as no longer immune for any of these three diseases, the CHR uniformly strongly recommends a refresher vaccination with the MMR vaccine. Since it is a live virus vaccine, such a re-vaccination is recommended at least one month before conception. If we don’t raise our vaccination rate for measles (by MMR), the disease will return to the U.S. and an endemic condition, causing several hundred unnecessary deaths every year.
With Kennedy as new boss at HHS, immunization has, of course, attracted considerable attention in the country, especially since his messages have not always been very clear. The Advisory Committee for Immunization Practices (ACIP) of the CDC is charged with overseeing the country’s vaccination practices (3). It holds three regularly scheduled meetings each year. It will be interesting to see what Kennedy has in preparation for the country. In the meantime, he has promised. – literally within months – to announce what really causes autism. With rapidly increasing numbers (if valid) really a major concern, this announcement could be viewed as a somewhat funny exaggeration, considering how much research has gone into autism with very meager results. But hopefully, he will surprise us; just don’t make it up Robert F. Kennedy!
References
1. CDC. Measles (Rubeola). Febrauary 28, 2025. https://www.cdc.gov/measles/data-research/index.html
2. The Washington Post, updated March 7, 2025. https://www.washingtonpost.com/health/2025/03/06/measles-death-outbreak-new-mexico/
3. Advisory Committee on Immunization Practices (ACIP) of the CDC; February 26-28, 2025. https://www.cdc.gov/acip/index.html
THE “FERRARI OF VIRUSES” IS SURGING – This was the headline of a recent News article in Science magazine, referring to an antibody-dodging norovirus variant that appears to be driving a major outbreak in the U.S. and elsewhere (1).
The association with the Ferrari name comes from the fact that the virus is “racing” through cruise ships, homes, and long-term care facilities in a “remarkable” winter surge affecting especially the Northern Hemisphere, with everybody ending up in the bathroom, some in hospitals, and a small number even ending up dead.
The virus usually causes explosive diarrhea and vomiting which, fortunately, only lasts
for ca. 24 hours. Affected individuals, however, remain infectious because they continue shedding the virus which can remain infectious on surfaces for weeks since it is resistant to many disinfectants. Moreover, there currently exists no vaccine against this virus.
It is believed to cause in the U.S. alone approximately 20 million cases of acute gastroenteritis a year, results in ca. 70,000 hospitalizations and kills approximately 800 people annually. The costs caused by the virus have been estimated to be approximately $10.6 billion (!) annually.
A recent paper in Science Translational Medicine now, however, offers some hope for an oral norovirus vaccine which in a 1b clinical trial was found to be safe and elicited mucosal immunity in older adults between 55 and 80 years (2)
References
1. Cohen j. Science 2025;387(6731)”235236
2. Flitter et al., Science Transl Med 2025; 17:788
AND THEN THERE IS, OF COURSE, BIRD FLU (H5N1)
Here is a short summary of the (as of March 7, 2025) most recent National Situation Summary from the CDC regarding Bird Flu, also called the H5N1 virus (1):
H5 bird flu is widespread in wild birds worldwide and is causing outbreaks in poultry and U.S. dairy cows with several recent human cases in U.S. dairy and poultry workers
While the current public health risk is low, CDC is watching the situation carefully and working with states to monitor people with animal exposures.
CDC is using its flu surveillance systems to monitor for H5 bird flu activity in people.
There is no known person-to-person spread at this time.
The current public health risk is low.
Total U.S. cases as of March 7, 2025: 70
Deaths: Only 1 case (but likely more, - our comment)
A recent paper in Nature magazine explored the molecular and ecological factors driving the sudden expansion in H5N1 host range and assessed the likelihood of different zoonotic pathways leading to an H5N1 pandemic (2). The virus has become capable of transmission from mammal to mammal in multiple species, including in European fur farms, South American marine mammals, and U.S dairy cattle. Fear is now spreading that humans may be next. It has become apparent that in dairy cattle, farmed mink, and South American marine mammals, mammal to mammal transitions has occurred in several combinations of mammals, raising the question of whether humans might be hit next (2).
The swine has historically been considered the optimal intermediary host to help avian influenza viruses to adapt to mammals before the jump to humans takes place. It now, however, appears that changes in the ecology of the H5N1 virus have opened new evolutionary pathways, with especially dairy cattle, farmed mink, and South American sea lions representing such new pathways. The concern about spread to humans has now been growing for some time. A recent News report in the BMJ made this clear after a second admission to a hospital with the diagnosis was reported in the U.S (3).
References
1. CDC. Avian influenza (Bird Flu), March 7, 2025; https://www.cdc.gov/bird-flu/situation-summary/index.html
2. Peacock et al., Nature 2025; 637:304-313
3. Taylor L. BMJ 2025; 388:r396
AND THEN THERE ARE NEW DISEASES
Yes, there has been an outbreak reported in the western part of the Democratic Republic of Congo (Africa) which the WHO initially described as having resulted in 53 deaths among 431 cases (12.5% mortality) and as of February 27, 2025, reported as 60 deaths in 1096 cases of this still unidentified disease (5.6% mortality) (1).
And then there is a new dermatophyte, Trichophyton mentagrophytes genotype VII (TMVVII), as the cause of a newly emerging sexually transmitted fungal infection reported in four patients by the CDC’s weekly MMWR In a Notes from the Field report (2).
We have on prior occasions in these pages raised the question of whether the number of unusual infectious events have been increasing and – if that was, indeed, the case – whether such an observation would indicate increased evolution of pathogens and/or a weakening of the human immune system?A recent Viewpoint article in JAMA was supportive of such concerns by noting that the U.S. healthcare system faces growing challenges from emerging and reemerging pathogens and calling for improved alert systems for emerging infectious diseases (3). We would have to agree!
References
1. Dyer O. BMJ 2025;388:r417
2. Zucker et al., MMWR 2024;73(43):985-987
3. Bhadella N. JAMA 2025;333(2):115- 116
AND THE EPSTEIN-BARR VIRUS (EBV) SEEMS ALWAYS TO HAVE A ROLE TO PLAY
That the EBV may also have a role to play in autoimmunity has been for some time suspected. Now several investigators published an excellent review article in Nature Reviews Rheumatology on the subject, which we strongly recommend to interested readers.
EBV has in the past been associated with several autoimmune diseases, including SLE, Sjögren’s syndrome, rheumatoid arthritis, and multiple sclerosis. The article especially concentrates on the potential mechanisms by which the EBV likely promotes autoimmunity, which includes EBV nuclear antigen1 – mediated molecular mimicry of human autoantigens; EBV-mediated B cell reprogramming, including EBV nuclear antigen2-mediated dysregulation of autoimmune susceptibility genes, etc. (1).
Reference
1. Robinson etS al., Nat rev Rheumatol 2024;20:729-740