First, I’d like to share some exciting non-Covid news. A study of a heart rate monitor called the WHOOP in pregnant people demonstrated that there is an inversion of maternal heart rate variability seven weeks prior to delivery for both premature and full-term pregnancies. So, a non-invasive heart rate monitor could potentially predict when a person will have their baby. The FDA cleared a new rapid-acting magnet therapy for treatment-resistant depression, called SAINT which is being licensed by Magnus Medical from Stanford University. And finally, the FDA granted breakthrough device designation for the OverC Multi-Cancer Detection Blood Test (MCDBT) for the early detection of cancers including esophageal, liver, lung, ovarian, and pancreatic cancer in adults aged 50 to 75 years with average risk. This could be a game changer.
XBB.1.5 is the latest Omicron variant that originated in New York and now is spreading in the northeastern United States. Last week, the CDC had reported that XBB.1.5 represented 40% of cases, but today they corrected that stating that XBB.1.5 is actually 28% of cases nationally. In areas in which XBB.1.5 represents 75% or more of cases, there has been an increase in hospitalizations especially for people age 70 and over. Hospitalizations are rising in New York State, Connecticut, New Jersey and Massachusetts. J. Weiland predicts that XBB.1.5 infections will start to spike in the southern states January 14th and that the entire United States will have more than 75% XBB.1.5 by January 28th.
XBB.1.5 is highly transmissible and is very immune evasive. This week, Yunlong Cao’s lab showed that the XBB.1.5 variant is more infectious because it binds more strongly to the ACE2 receptors on human cells better than previous variants. The ACE2 receptor is the cellular doorway that allows a COVID infection into our bodies.
Dr. Akiko Iwasaki of Yale tweeted her concerns about Dr. Cao’s findings on XBB.1.5’s higher binding affinity for human ACE2 receptors because this would mean that XBB.1.5 could infect human cells with lower levels of ACE2 receptors. Infection of long lived human cells that have lower levels of ACE2 receptors could lead to viral persistence in the body and could possibly increase the risk of Long COVID per Dr. Iwasaki.
XBB.1.5 is very immune evasive and is resistant to all monoclonal antibodies with the exception of an experimental antibody called SA55. However, Paxlovid pills work against all Covid variants and are effective in preventing hospitalizations and death from COVID. Unfortunately, Paxlovid is not being used as much as it should because of fears of viral rebound. Even if viral rebound happens after taking Paxlovid, symptoms tend to be mild. Without Paxlovid, some people may be at increased risk for severe disease and even death.
The bivalent booster shot has been shown to help protect against severe disease and death in XBB infections, but unfortunately only about 37% of people age 65 in the U.S. have gotten a bivalent booster and only 15% of all people eligible have received a bivalent booster.
China is now in a humanitarian crisis because of rampant COVID. Official reports do not reflect hospitalizations and deaths from COVID in China. On Dec 26th, 52% of passengers arriving on a flight from China to Italy tested positive for COVID. Even before China stopped their Zero-COVD policy, wastewater samples taken at international entry points from different countries to Malaysia from June through December 2022 already showed that 96% of flights had at least someone positive for COVID. The BBC reports that some young people in China are actively trying to expose themselves to the virus in order to get an infection. Their logic is that they will be able to get over their COVID infection and be feeling good again before going on the Chinese New Year holiday which happens at the end of January.
A large study of more than 130,000 electronic health records from the Veteran’s Administration showed that a third dose of the Moderna vaccine was significantly more effective against symptomatic infection and hospitalizations than a third dose of the Pfizer vaccine during Delta and Omicron variant waves. The Moderna vaccine contains 100 µg of mRNA per dose, in contrast to the Pfizer vaccine which has 30 µg of mRNA per dose. Using three times the amount of mRNA in a dose of vaccine could stimulate the immune system to make higher levels of antibodies.
This week, Dr. Wes Ely tweeted about a new study in Nature showing that the SARS-CoV-2 virus can actually reprogram monocytes, a type of white blood cells, causing them to become prothrombotic. Monocytes that increase blood clotting may explain, at least in part, some of the clotting abnormalities seen in COVID infections including abnormal blood clots like pulmonary emboli during acute COVID infections, microclots in capillaries which can affect oxygen transport to tissues even after a COVID infection, and could even explain the increases in cardiovascular diseases like stroke and heart attacks in the year(s) after a COVID infection. COVID may start with a respiratory infection in the lungs, but COVID can also be a hematologic disease causing blood clots throughout the body.
Take precautions such as getting the bivalent booster, masking indoors with a KN95/N95 and/or testing all participants before an event, taking Paxlovid if you get a COVID infection, staying home if you feel sick can help to protect against XBB.1.5.
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Other interesting medical news:
11/16/22 Fitness and Health Tracker WHOOP Identifies a Novel Pregnancy Digital Biomarker to Screen for Premature Birth https://buff.ly/3EJekaH
In singleton pregnancies, maternal heart rate variability (HRV) trends invert seven weeks prior to delivery. The timing of that inversion is consistent relative to the eventual delivery date for both premature and full-term pregnancies.
The study: 1/5/22 MedRxiV: Wearable-Derived Maternal Heart Rate Variability As A Novel Digital Biomarker of Preterm Birth https://buff.ly/3VRJemA
12/22/22 Nice: FDA Clears New, Rapid-Acting Magnet Therapy for Treatment-Resistant Depressionhttps://buff.ly/3Im6Yw1
In October 2021, researchers from the Stanford University School of Medicine published a study demonstrating the effectiveness of a new, rapid-acting magnet therapy on patients with treatment-resistant depression called SAINT, or Stanford accelerated intelligent neuromodulation therapy.
This past September, the FDA cleared the new therapy for marketing, paving the way for SAINT to be used in clinics and hospitals across the country.
“It works well, it works quickly and it’s noninvasive,” Dr. Nolan Williams.
FDA clearance was granted to a California company called Magnus Medical that will commercialize the protocol.
1/4/23 OncLive: FDA Grants Breakthrough Device Designation to OverC Multi-Cancer Detection Blood Testhttps://buff.ly/3jZMWgD
Early detection of cancers including esophageal, liver, lung, ovarian, and pancreatic cancer in adults aged to 50 to 75 years with average risk.
RSV and Flu have peaked and cases are high but are decreasing.
1/6/23 NEJM: IL-1RA Antibodies in Myocarditis after SARS-CoV-2 Vaccination https://buff.ly/3C0w3cw
Neutralizing antibodies against IL-1RA (interleukin-1 receptor antagonist) and a hyperphosphorylated IL-1RA isoform were observed in young male patients with biopsy-confirmed myocarditis after the receipt of SARS-CoV-2 mRNA vaccine.
1/4/22 AHA: Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditishttps://buff.ly/3X9lj3g
n = 16
Markedly elevated levels of full-length spike protein, unbound by antibodies, were detected in the plasma of individuals with post vaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired t test; P<0.0001).
No autoantibodies were noted.
1/4/22 Nature (VA Boston): Comparative effectiveness of third doses of mRNA-based (Moderna vs Pfizer) COVID-19 vaccines in US veterans https://buff.ly/3X8q9O0
Review of electronic health records of US veterans (n = 65,196 per group) who received a third dose of either BNT162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines during Delta and Omicron variant waves.
Compared to Pfizer vaccination x3, people who were vaccinated with Moderna vaccine x3 had significantly less symptomatic infections and hospitalizations.
The superior growth advantage of XBB.1.5 from Y.Cao’s data:
1) XBB.1.5 is equally immune evasive as XBB.1, but
2) XBB.1.5 has a much higher hACE2 binding affinity.
The fact that XBB.1.5 showed a much superior growth advantage than XBB.1 suggests that hACE2 binding affinity is important for SARS-CoV-2 spread.
BF.7 breakthrough infection (2 doses of Coronavac or mRNA vaccines (n = 9)) doesn't induce high neutralization against XBB.1 and XBB.1.5.
1/3/23 BioRxiV (Yunlong Cao): Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion https://buff.ly/3X3Evzh
Evusheld and Bebtelovimab could not neutralize XBB.1/XBB.1.5, while Sotrovimab remains its weak reactivity and notably, SA55 antibody is still highly effective.
XBB.1.5 is the new, highly transmissible variant spreading across the US
Concerns re:
Higher transmissibility
High immune evasion from our antibodies
Enhanced ability to infect different cells with lower levels of ACE2 could increase viral persistence and increase risk of and possibly severity of Long COVID as well per Dr. Iwasaki.
1/3/22 Nature: COVID drug Paxlovid was hailed as a game-changer. What happened? https://buff.ly/3vETxzL
Paxlovid reduces risks of severe COVID and death by 89%, but people worry about viral rebound and side effects like metallic taste.
Paxlovid is prescribed for only 0.5% in the UK and only 13% in the US.
Paxlovid works well against all variants to date including XBB.1.5.
Why is it underused?
Misinformation: People perceive COVID-19 as less risky than they did earlier in the pandemic.
Misconceptions: especially about rebound. Rebound can happen without taking Paxlovid as well. Rebound symptoms tend to be very mild, and are still far preferable to hospitalization or death.
In November, Japan authorized Ensitrelvir, a once-daily antiviral made by Shionogi.
12/26/22 Nature: Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19https://buff.ly/3GdvMUv
Transcriptionally, COVID-19 monocytes are characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation and clot formation.
These results identify a potential mechanism by which monocyte dysfunction may contribute to COVID-19 pathology.
“White Cells (monocytes) switch gene expression from an established innate immune profile to a pro-clotting signature in COVID.
We’re immunocompromised.
These data explain how the COVID virus places our bodies at risk for macro (large) blood clots in acute disease(which we see often), brain disease due to microclotting, and possibly later cardiovascular disease.
Monocytes of COVID patients display abnormal markers of inflammation & clotting that drives us to immuno-thrombosis & vascular platelet + cell aggregates.
“Our innate immunity is being re-wired by COVID!”
1/2023 Psychiatry Research (Changsha, China): Two-year follow-up of brain structural changes in patients who recovered from COVID-19: A prospective study https://buff.ly/3IqKAle
Pre-Omicron (i.e. infections 2 years ago)
Half of the patients (n =8) had mild COVID, the other half had severe COVID (n = 8).
Gray Matter Volume (GMV) was assessed by voxel-based morphometry (VBM) using brain MRI.
The main findings of our two-year follow-up study:
(a) Insomnia gradually improved with longer follow-up;
(b) Clinical sequelae were mainly present in the nervous system and respiratory system, and headache, fatigue, dyspnea, and chest pain were the most common symptoms;
(c) GMV reduction in the cerebellum and vermis was persistent at 2 years, but the GMV of the left frontal and temporal lobes recovered by 2 years.
(d) decreased GMV was correlated with AIS score and inflammatory markers.
Fig. 3. Results of VBM analysis and post hoc ROI analysis between COVID-19one and HCs, COVID-19two and HCs, and COVID-19one and COVID-19two.
Official death tolls are impossibly low, and some worry new variants may escape detection.
The BA.5.2 and BF.7 Omicron subvariants, which are now causing most infections globally, are also dominant in China. BQ.1 and XBB, which have recently been spreading in Europe and North America, have turned up in limited numbers in several provinces.
1/6/23 BBC: China Covid: Young people self-infect as fears for elderly grow https://buff.ly/3WUuKng
Some young Chinese people are visiting infected friends to try to get a COVID infection now so that they are recovered by the upcoming Chinese New Year holiday.
1/5/23 Economist: "All around the world, Covid surveillance is faltering. That, rather than the surge of cases in China, is the main reason for worry." https://buff.ly/3jLYsw9
The number of virus sequences submitted to GISAID has dropped 90%.
GISAID is the world’s largest database of SARS-CoV-2 sequences.
1/4/23 Lancet preprint (Australia): Understanding SARS-CoV-2 Delta and Omicron Variant Transmission and Vaccine Impact in Schools and Child-Care Settings in Australiahttps://buff.ly/3IGWJTt
Vaccination reduced SARS-CoV-2 transmission rates in schools, although less so for omicron than delta variants.
Despite higher community-based transmission rates, in-school transmission remained low and stable with high attendance, suggesting that community restrictions, rather than school closures, best mitigated COVID-19 impacts.
1/4/23 Science: Vaccination with Span, an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in micehttps://buff.ly/3QecUck
“Our results highlight the importance and feasibility of a universal vaccine to fight against SARS-CoV-2 antigenic drift.”
1/3/23 WWJ News Radio: Coronavirus found in wastewater samples from 96% of flights https://t.co/lQZef2RQJf
Wastewater samples taken at international entry points to Malaysia from June through December 2022 showed that 96% of flights were positive for COVID.
12/28/22 BBC: China Covid: US considers restrictions on Chinese arrivals https://buff.ly/3WKL3Tw
On Dec 26th, 52% of passengers arriving on a flight from China to Italy tested positive for COVID on arrival.
"There are mounting concerns in the international community on the ongoing Covid-19 surges in China and the lack of transparent data, including viral genomic sequence data," US officials said in a statement quoted by news agencies.
11/1/22 Nature, Molecular Psychiatry: SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein https://buff.ly/3gZB24V
Microglial NLRP3 inflammasome activation is a major driver of neurodegeneration.
Using a model of human monocyte-derived microglia.
SARS-CoV-2 and spike protein-mediated microglial inflammasome activation was significantly enhanced in the presence of α-synuclein fibrils and was entirely ablated by NLRP3-inhibition.
SARS-CoV-2 infected hACE2 mice treated orally post-infection with the NLRP3 inhibitory drug MCC950, have significantly reduced microglial inflammasome activation, and increased survival in comparison with untreated SARS-CoV-2 infected mice.
Microglia are resident populations of macrophages in the CNS that respond to pathogen-associated molecular patterns (PAMPs) and host- or environment-derived danger-associated molecular patterns (DAMPs) to drive innate immune responses and inflammation within the brain.
Recent evidence has highlighted the role of intracellular protein complexes, known as the inflammasomes, in CNS innate immunity.
