This week, I wanted to highlight some interesting non-COVID news. There are 2 new weight loss drugs, semaglutide (Wegovy) and tirzepatide (Mounjaro), that can safely lead to more than a 20% body weight loss. This week, the Thaiss lab reported that there are specific bacteria in the gut microbiome that motivate mice to exercise. Wow! Consumer Reports tested popular dark chocolates, including some from Hershey’s and Trader Joes, and found high levels of heavy metals lead and cadmium. It looks like Ghirardelli may be a better way to go. Finally, a study shows that the time that breast milk is expressed can affect a baby’s sleep due to cortisol and melatonin level variability in the milk.
COVID:
The CDC SARS-CoV-2 wastewater map this week shows that there are very high levels of virus (red) in the wastewater of many states right now. Official tests show a positivity rate of 12%. Here in Santa Clara county, we have a high level of virus in our wastewater and are considered a hot spot in the state. As Bob Wachter reminds us, it would be a good time to wear a high quality mask indoors. I would add that it is also important to get your bivalent booster if you have not yet gotten it (only 12% of qualified people over age 5 have) and your flu shot. The government is now offering 4 more free home COVID tests per household at COVIDTests.gov and it may be a good idea to have everyone test before enjoying holiday get-togethers.
Older Americans are being hospitalized at a higher rate and 90% of COVID deaths now are in people age 65 and over. The bivalent booster offers excellent protection against both hospitalization and death, but unfortunately only 34% of seniors over age 65 have been boosted. In addition, doctors have been hesitant to prescribe Paxlovid despite its impressive effectiveness at preventing hospitalizations and deaths. Better communication is needed even for doctors which is why five medical societies put out information on “Vax & Pax: How to Keep Your Patients Safe This Winter” to remind healthcare providers to use both.
In some parts of Asia including Hong Kong, South Korea and Japan, SARS-CoV-2 cases are spiking again. Here in the U.S., BQ.1.(1) now represents 69% of known cases and XBB has arrived and represents 16% of cases in the northeast. The White House presented their Winter Preparedness Plan yesterday with recommendations for increased testing, masking, vaccinations and boosters and using Paxlovid liberally. A review in the NEJM says that neutralizing antibody levels (nAbs) should be used as a “correlate of protection”, but they did not report what level of nAbs are needed to be well protected. People may get breakthrough COVID infections, but vaccines and boosters ensure that most people will not be hospitalized.
Long COVID:
This week, Web MD reviewed how the spike protein from residual SARS-CoV-2 virus in the body may trigger microclots in capillary vessels in Long COVID patients. Wes Ely MD reviewed in a Twitter thread how Long COVID affects the brain and how SARS-CoV-2 may cause our brains to age prematurely. He notes that “we are all at risk of losing brain power from Long COVID.” Katelyn Jetelina talked about how to gauge your risk of Long COVID and Dr. Svetlana Blitshteyn of the Dysautonomia Clinic cautioned that when medical professionals tell patients that their Long COVID is due to a “Functional Neurologic Disorder” (FND) which translates to being a psychosomatic disorder, they are gaslighting most patients.
In more positive Long COVID news, a 6 week pacing protocol was shown to reduce post-exertional symptom exacerbation (PESE) episodes from 3.4 times per week down to 1.1 episodes per week in a small study. Finally, Dr. Monica Verduzco-Gutierrez, a PMR doctor who has experienced Long COVID herself, discussed that there is an AAPM&R Collaborative of 41 Long COVID clinics which has made PASC (Long COVID) Consensus Guidelines for evaluation and treatment of different Long COVID symptoms and presentations.
Have a good weekend,
Ruth Ann Crystal MD
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We've never had medications that can safely achieve ≥20% body weight loss. With over 1 billion people with obesity and >40% of American adults, the implications (both good and bad) are profound.
New anti-obesity drugs—semaglutide (Wegovy) and tirzepatide (Mounjaro)—that represent one of the most important breakthroughs in medicine.
12/13/22 The bright side of the Covid pandemic: mRNA vaccines by Eric Topol MD https://buff.ly/3Hzq41d
mRNA vaccine platform is successfully used to make a universal flu vaccine effective in multiple experimental models and a mRNA cancer vaccine that reduces melanoma recurrence by 44%.
Fascinating!
12/13/22 Nature: A microbiome-dependent gut–brain pathway regulates motivation for exercise in mice https://buff.ly/3FwxNul
Certain gut bacteria in the gastrointestinal microbiome make fatty acid amines (FAA) which stimulate TRPV1+ sensory nerves that signal the striatum part of the brain (by downregulating MAO) which causes a dopamine surge that motivates mice to exercise.
Using exercise experiments in germ-free mice, the researchers identified several bacterial species that can drive physical activity.
Summary of how the microbiome can cause motivate you to exercise (so far tested in mice):
12/15/22 New Scientist: Timing of expressing breast milk and a baby drinking it affects infant sleep due to melatonin and cortisol hormones https://buff.ly/3HDK2bt
Drinking “mistimed” expressed breast milk may affect a baby’s sleep.
12/15/22 Consumer Reports: Lead and Cadmium Could Be in Your Dark Chocolatehttps://buff.ly/3FvNKkx
Consumer Reports found dangerous heavy metals in chocolate from Hershey's, Theo, Trader Joe's and other popular brands. Here are the ones that had the most, and some that are safer.
Starting 12/15/22, households can request free COVID antigen tests from the government at COVIDTests.gov
12/15/22 USA Today: As COVID cases rise, White House announces more prevention efforts, including free tests https://buff.ly/3FtoKul
COVID-19 cases have climbed across 90% of the country in recent weeks.
Offering Americans four more free coronavirus tests per household.
Collaborating with communities to open pop-up or mobile vaccination sites.
Pre-positioning critical supplies like masks, gloves and gowns from the Strategic National Stockpile.
Providing more support to nursing homes and long-term care facilities.
Encouraging masking.
Although monoclonal antibodies are no longer effective, the government expects to have sufficient doses of the antiviral Paxlovid available at no cost for anyone who needs it.
12/15/22 J Medical Virology: Effect of using a structured pacing protocol on post‐exertional symptom exacerbation and health status in a longitudinal cohort with the post‐COVID‐19 syndrome https://buff.ly/3BHqAqf
31 people with PASC (Long COVID) completed the 6-week pacing protocol.
Fewer PESE episodes per week (3.4 to 1.1).
Statistically and clinically significant reduction in the average number of Post-exertional symptom exacerbation (PESE) episodes (from 3.4 episodes in Week 1 to 1.1 in Week 6), with an average decrease of 16% (p < 0.001) each week, and reduction across all three exertional triggers (physical, cognitive, and emotional).
Physical activity levels showed moderate improvements during the intervention period.
12/15/22 Patient Care: She Treats Long COVID and Got it Herself: Physiatrist Monica Verduzco-Gutierrez, MD, Advocates for Federal Research and Patient Support https://buff.ly/3UWs6M8
Long COVID symptoms discussed.
The RECOVER trial has started but will need funding.
Physicians will need to learn about things that they didn't learn in medical school like POTS (postural orthostatic tachycardia syndrome), autonomic dysfunction, post-exertional malaise and ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome).
AAPM&R Collaborative of 41 Long COVID clinics Consensus Guidelines for PASC or Long COVIDhttps://buff.ly/3BF8oxG
Discussion of the economic and personal burdens of Long COVID.
Long Covid is an incredibly debilitating disease and millions are suffering. We don’t know what the future will hold.
How to balance the risk of Long COVID on daily decisions using annual risk comparisons.
Annual risk comparisons:
Permanent impairment from driving is 1 in 700
Severe long Covid (unable to work) is 1 in 370
Needing reconstructive surgery after a dog bite: 1 in 400
Severely injured during a house fire: 1 in 20,000
12/14/22 Nature: SARS-CoV-2 infection and viral persistence in the human body and brain at autopsy https://buff.ly/3FPDKD9
In some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.
SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection.
Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case.
12/13/22 WebMD: Tiny, Menacing Microclots May Explain Long COVID’s Symptoms https://buff.ly/3PpFXJB
Since the beginning, COVID has been a clotting disease.
Now there is some evidence that SARS-CoV-2 spike protein from a viral reservoir in the body is triggering the body to make microclots in Long COVID.
Damage to blood vessel walls from inflammation also triggers clotting.
These microclots may block oxygenation in tiny capillary blood vessels.
Drs. Pretorius and Kell believe that the spike protein in the virus might be the trigger in people with long COVID.
A recent Harvard Medical School study detected the SARS-CoV-2 spike antigen in most long COVID patients up to 12 months after diagnosis, suggesting the presence of an active and persistent viral reservoir in the body after infection.
The study:
9/2/22 Clin Infectious Disease: Persistent Circulating SARS-CoV-2 Spike Is Associated With Post-Acute Coronavirus Disease 2019 Sequelae https://buff.ly/3KXK4u8
SARS-CoV-2 spike protein was found in PASC (Long COVID) patients' plasma up to 12 months after diagnosis.
The presence of circulating spike protein supports the hypothesis that a reservoir of active virus persists in the body.
12/13/22 Cell: Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants https://buff.ly/3BF65L4
BQ.1, BQ.1.1, XBB, and XBB.1 are the most resistant SARS-CoV-2 variants to date.
Serum neutralization was markedly reduced, including with the bivalent booster.
All clinical monoclonal antibodies were rendered inactive against these variants.
The ACE2 affinity of these variants were similar to their parental strains.
12/12/22 Nature CV Research: Apparent risks of postural orthostatic tachycardia syndrome (POTS) diagnoses after COVID-19 vaccination and SARS-Cov-2 Infection https://buff.ly/3VRihjZ
Low incidence of POTS after COVID-19 vaccination, particularly when compared to SARS-Cov-2 post-infection odds, which were five times higher.
12/12/22 Nature Editorial: The risks of POTS after COVID-19 vaccination and SARS-CoV-2 infection: it’s worth a shothttps://buff.ly/3HrRTst
12/11/22 AP: Hospitalizations signal rising COVID-19 risk for US seniorshttps://buff.ly/3uJKjSn
Seniors are not being protected. Many have not had bivalent boosters.
Only 23% of nursing home staff are up to date on COVID-19 vaccinations.
Vaccines and boosters prevent serious illness and hospitalization and death. Breakthrough infections can be expected, but masking and other mitigation measures can help protect against infections.
Messaging has been confusing.
Doctors are hesitant to prescribe the antiviral pill Paxlovid quickly in the elderly, which prompted five major medical societies to hold a web-based educational session for doctors,
“Vax & Pax: How to Keep Your Patients Safe This Winter.”
12/11/22 Immunity: Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodieshttps://buff.ly/3PoEIKB
Genomic variants in the immunoglobulin heavy chain (IGH) are part of the reason that there is a lot of variability in neutralizing antibodies after COVID.
The human immunoglobulin heavy chain (IGH) locus is exceptionally polymorphic, with high levels of allelic and structural variation. Thus, germline IGH genotypes are personal, which may influence responses to infection and vaccination.
Single polymorphisms in IGH genes can influence the function of SARS-CoV-2 neutralizing antibodies.
12/10/22 NEJM: A Covid-19 Milestone Attained — A Correlate of Protection for Vaccines https://buff.ly/3Br0Eiy
Reviewing trial data from multiple studies, neutralizing antibody levels should be the correlates of protection (CoPs) for COVID vaccines, i.e. a way to predict clinical outcomes and should be used for regulatory approvals.
Titer levels needed are not discussed.
12/9/22 NY Times: Opinion: Covid-19 Isn’t a Pandemic of the Unvaccinated Anymore https://buff.ly/3Faqx7h
Updated bivalent boosters reduce the risk of mortality from Covid in Americans over the age of 12 by more than 93% compared with the population of unvaccinated.
90% of Covid deaths in the US are now in people age 65+
For Americans age 65+, only 34% are bivalent boosted, compared with 69% initially vaccinated with the original monovalent vaccine.
Only 12.7% of Americans over the age of 5 have gotten the bivalent booster which protects better against Omicron and its descendant variants.
We need clearer communication — from public health officials to politicians and the media. Even with up-to-date vaccination and bivalent boosting, infection represents a considerable threat to older adults.
Physicians telling people with Long COVID that they have a “Functional Neurologic Disorder '' (FDN), meaning that their symptoms are psychosomatic, is gaslighting by the medical system.
Telling people with Long COVID to do CBT (cognitive behavioral therapy) will not cure their Long COVID.
12/9/22 Andrology: Evidence for residual SARS‐CoV‐2 in corpus cavernosum in penis of patients who recovered from COVID‐19 infection https://buff.ly/3Phjn5O
For patients 1 month post-COVID infection, the cause of erectile dysfunction could be the SARS-CoV-2 viral infection that is also affecting corpora cavernosa so it is important to wait more than a month to do surgery for erectile dysfunction.
