COVID news & more 12/9/23
The JN.1 COVID variant, a descendant of the very mutated Pirola BA.2.86, is taking off around the world. A mutation made JN.1 able to evade our antibodies better. Daniele Focosi tweeted wastewater charts from around Europe and Australia showing that JN.1 is causing SARS-CoV-2 wastewater levels to skyrocket. Wastewater levels of SARS-CoV-2 in Austria are the highest that they have ever been during the entire pandemic. JN.1 is quickly becoming globally dominant.
Here in the United States, JN.1 is taking off exponentially in the Northeast and Midwest. Using current wastewater levels, JP Weiland predicted that in the Midwest, East Coast, and Mountain states, 1 in every 27 people is currently infected with COVID, which is very high. In the South and the West Coast of the United States, about 1 in every 59 people is currently infected with COVID. This will increase as JN.1 rapidly spreads.
As CDC Director Dr. Mandy Cohen said in her recent video message, it is not too late to be vaccinated against the three circulating respiratory viruses (COVID, Flu, RSV). Dr. Cohen also urged people to take additional measures now like avoiding sick people, washing hands, improving ventilation, and wearing a mask. Only 16% of adults have gotten the updated COVID XBB.1.5 vaccine in the United States. The updated vaccine protects against all of the latest COVID variants including the exponentially growing JN.1. With Christmas two weeks away, there is still time to get the vaccine and have enough time to make neutralizing antibodies. Flu shots and COVID vaccines can be scheduled via vaccines.gov.
Here in the U.S., COVID hospitalizations and Emergency Departments visits are increasing as the HV.1 wavelet is being pushed out by the formidable JN.1. The CDC update from yesterday stated that “the increase of this variant does not alter CDC’s COVID-19 recommendations, meaning that COVID vaccines, tests, and treatments continue to work well against the JN.1 variant.
Nationally wastewater levels show High COVID, High RSV, Low Influenza A and Influenza B, High Norovirus (stomach flu). Locally, Redwood City (Silicon Valley Clean Water) wastewater shows High COVID, High RSV, Low Influenza A, High Norovirus (stomach flu). If someone thinks that they had “food poisoning”, be careful and make sure to wash your hands often as it may actually be the very contagious Norovirus stomach flu. RSV levels are still high, but they appear to have just peaked and are starting to decrease.
Acute COVID infections
Regarding Rapid Antigen Testing for COVID, a new study finds that swabbing both the throat and nose increases the sensitivity of rapid antigen COVID testing for both healthcare worker-sampling and self-sampling. Researchers compared four methods of monitoring COVID and Influenza A virus activity in schools. Air sampling was found to be equivalent to PCR testing, cause-specific absenteeism reporting and school-based rapid antigen tests. The air sampling method tested cartridges left passively in the school cafeterias. The authors also noted that SARS-CoV-2 detection was more stable (endemic pattern) and Influenza A was more epidemic in November and December.
A new study in the International Journal of Infectious Diseases shows that babies exposed in utero to maternal SARS-CoV-2 infection had an increased risk of neurodevelopmental delay. At 12 months of age, 20% of COVID-exposed children, as compared to 5.9% of controls, were diagnosed with neurodevelopmental delay (risk ratio 3.44). Fine motor and personal-social skills were the most affected. On ultrasound after birth, 10% of COVID exposed infants had an abnormal result which was mostly mild ventriculomegaly. Of note, all mothers studied were unvaccinated and had COVID infections between April 2020 to July 2021.
A study looking at T cells after COVID mRNA vaccination shows that vaccination after COVID infection leads to substantial expansion and diversification of CD8+ T cells. The same was not observed before vaccination. Vaccination gave a true boost to immunity.
A study in Nature Immunology shows that the use of N1-methylpseudouridine into mRNA vaccines caused +1 ribosomal frameshifting with off-target cellular immune responses. Although not linked to any adverse outcomes, mistranslation of mRNA-based SARS-CoV-2 vaccines in humans causing off-target immune effects should be avoided with future mRNA-based vaccines.
A type of white blood cell called monocytes are reprogrammed from innate immune functions to a pro-clotting signature by SARS-CoV-2 infection. 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. Monocytes are also implicated in vagus nerve inflammation associated with SARS-CoV-2 infection.
A new article in Cell magazine looked at the Receptor for Advanced Glycation Endproducts (RAGE) pathway in monocytes. The SARS-CoV-2 virus can attach to the RAGE (receptor) which allows it to enter and infect the monocyte. Activation of the RAGE pathway in monocytes is associated with more severe COVID infection. Deactivation of the RAGE pathway in monocytes is associated with patient healing.
Long COVID
A new study shows that people with Long COVID have pronounced cognitive slowing that is 3 standard deviations slower than age-matched controls who recovered from COVID without Long COVID (no PCC). This was seen in Long COVID patients in both the UK and Germany.
A randomized, placebo-controlled trial in Hong Kong of a synbiotic (prebiotics + probiotics) called SIM01 modulated the gut microbiome and helped to reduce fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and general malaise symptoms in people with Long COVID. Three beneficial bacteria were included- Bifidobacterium adolescentis helped fatigue, gastrointestinal upset, and memory loss. Bifidobacterium bifidum helped alleviate fatigue and general unwellness symptoms and Bifidobacterium longum correlated with an improvement in mental concentration.
SIM01 is not available in the United States, but there are other prebiotics available. A study earlier this year showed that gut microbiome changes may be a signature for ME/CFS. Low amounts of butyrate-producing bacteria such as F. Prausnitzii (F. Prau) in the gut are associated with increased fatigue severity in ME/CFS, suggesting a possible link between gut bacteria and ME/CFS symptoms. All ME/CFS participants in this study had lower F. Prau in their gut, but they also were found to have lower bacteria associated with tryptophan metabolism. Of note, tryptophan is used to make serotonin. A paper in Cell magazine in October from the M. Levy's lab showed that SARS-CoV-2 viral fragments and viral RNA from a reservoir possibly in the gut can lead to abnormally low peripheral serotonin which triggers cognitive impairment in Long COVID from reduced vagus nerve signaling to the hippocampus in the brain.
For people with Long COVID, it can be very difficult to find clinicians who understand Long COVID. Colorado is looking to expand Long COVID care beyond specialty clinics with a new program called Project ECHO. Project ECHO will offer primary care providers seven free online courses to learn the basics of Long COVID care. In addition, the program will connect the primary care providers with Long COVID specialists for support and to discuss complex patients.
In non-COVID news, the FDA approved two new gene therapies to treat sickle cell disease. Although low dose naltrexone (6 mg) was found not to reduce fibromyalgia pain, it did improve memory problems associated with fibromyalgia. Bodybuilding protein supplements can affect male fertility because they can contain high levels of estrogen.
The US government plans to use their “march-in rights” to lower some medication prices. If research for the drug discovery was paid for with government funding, the government could seize the patents and grant additional licenses to third parties to make the drugs less expensively.
Stanford University is offering free online courses including Computer Science 101, Machine Learning Specialization, Advanced Cybersecurity, Intro to the Internet of Things, Game Theory, and others. Physicians and health care providers who need to fulfill the new DEA requirement on opioids can take this online class for free through NEJM.
Using a gas powered leaf blower for 1 hour emits as much pollution as driving a Toyota Camry from Los Angeles to Denver. Many cities are banning them for this reason and asking people to replace them with rechargeable ones instead. Fifty-two sea turtles with “cold stun” in New England were flown to warmer Florida for rehabilitation.
Have a good rest of your weekend,
Ruth Ann Crystal MD
COVID data:
US Variant tracker: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
JN.1 is taking over.
U.S. Region 2 (Northeast) JN.1’s rise:
12/8/23 Eric Topol
Variants in locations around the globe:
https://outbreak.info/
CDC COVID data tracker: https://covid.cdc.gov/covid-data-tracker/index.html#datatracker-home
CDC COVID Hospitalizations (blue) and Emergency Room (orange) visits tracker: https://covid.cdc.gov/covid-data-tracker/index.html#trends_weeklyhospitaladmissions_7dayeddiagnosed_00
Weekly ED visits for respiratory illnesses, by age and disease: https://www.cdc.gov/ncird/surveillance/respiratory-illnesses/index.html
US Wastewater Monitoring:
CDC Wastewater Monitor https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
NEW CDC wastewater reporting: https://www.cdc.gov/nwss/rv/COVID19-nationaltrend.html
and
CDC wastewater map: https://www.cdc.gov/nwss/rv/COVID19-currentlevels.html
(last updated 11/25/23)
Biobot: https://biobot.io/data/
Wastewater SCAN dashboard: https://data.wastewaterscan.org/
National wastewater levels show High COVID, High RSV, Low Influenza A and Influenza B, High Norovirus (stomach flu)
Redwood City (Silicon Valley Clean Water) wastewater shows High COVID, High RSV, Low Influenza A, High Norovirus (stomach flu)
California statewide view https://buff.ly/3YObiul
Sewer Coronavirus Alert Network (SCAN) project by Stanford University:
CDC Respiratory vaccination trends: https://www.cdc.gov/respiratory-viruses/data-research/dashboard/vaccination-trends-adults.html
12/6/23 CDC Director Dr. Cohen’s video message
https://twitter.com/CDCDirector/status/1732547659292967203
CDC Director Mandy Cohen, MD, MPH, said it's not too late to be vaccinated against the three respiratory viruses for those who haven't already, and she urged people to take additional measures like avoiding sick people, washing hands, improving ventilation, and wearing a mask.
JP Weiland: https://twitter.com/JPWeiland
“As of December 4th: As predicted, a huge jump in numbers this week. 40% increase over last week. Pirola is increasing a lot.
850,000 new infections/day
1 in every 390 new people were infected today
1 in every 39 people currently infected
There is a big differential between regions at the moment. Looking at biobot and other metrics:
Midwest, East coast, and Mountain states: 1 in every 27 are currently infected. Very high.
South and West Coast States: about 1 in 59.”
No changes to JP Weiland’s forecast:
12/9/23
Variants
12/5/23 Eric Topol: From a Detour to Global Dominance, The rise of the JN.1 variant https://buff.ly/3Rg1DJu
Globally, Pirola descendent JN.1 is causing large increases in cases as seen by skyrocketing virus levels in wastewater. https://twitter.com/dfocosi/status/1732802560178766186
D. Focosi showed charts showing that SARS-CoV-2 wastewater levels are skyrocketing in Austria and The Netherlands, Germany, Denmark, Sweden, Switzerland and France, Australia.
Austria:
U.S.
Acute COVID infection
11/8/23 Cell: RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity https://buff.ly/3NdQHuF
Receptor for Advanced Glycation Endproducts (RAGE) pathway in monocytes
RAGE activation in monocytes strongly correlates with COVID-19 severity at admission
Patients’ healing is associated with deactivation of the RAGE pathway
RAGE and the S1-RBD of SARS-CoV-2 interact directly in silico and in vitro
RAGE is involved in monocyte permissiveness to SARS-CoV-2 entry
4/6/2022 Nature: FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation https://buff.ly/37rMOAw
Testing
12/6/23 JAMA: COVID-19 Rapid Antigen Tests With Self- vs Health Care Worker–Collected Specimens https://buff.ly/3Rx6pnn
Including both throat swab and nasal swab increases the sensitivity of rapid antigen COVID testing for both healthcare worker-sampling and self-sampling.
Pediatrics
12/5/23 International Journal of Infectious Diseases: Developmental impairment in children exposed during pregnancy to maternal SARS-COV2: A Brazilian cohort study. https://buff.ly/46PYA0j
All mothers studied were unvaccinated, April 2020 to July 2021.
Babies exposed in utero to maternal SARS-CoV-2 infection had increased risk of neurodevelopmental delay.
At 12 months of age, 20% of COVID-exposed children and 5.9% of controls were diagnosed with neurodevelopmental delay (risk ratio, 3.44).
Fine motor and personal-social were the subdomains most impaired.
10% of exposed infants had an abnormal result on head ultrasound, mainly mild ventriculomegaly which is a swelling in the brain caused by cerebrospinal fluid buildup.
12/5/23 JAMA: Four Methods for Monitoring SARS-CoV-2 and Influenza A Virus Activity in Schools https://buff.ly/46UlKmd
Four methods of monitoring COVID and Influenza A virus activity in schools were found to be equivalent- air sampling, PCR testing, cause-specific absenteeism reporting and school-based rapid antigen tests. The air sampling method tested cartridges left in the school cafeterias. The found that SARS-CoV-2 detection was more stable (endemic) and Influenza A was more epidemic in November and December.
Vaccines
12/6/23 Nature Immunology: Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8+ T cells in persons with previous COVID-19 https://buff.ly/3ReWrWa
Vaccination after COVID infection leads to substantial expansion and diversification of CD8+ T cells, not observed before vaccination.
12/6/23 Nature: N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting https://buff.ly/3T9LIPH
The use of N1-methylpseudouridine into mRNA vaccines causes +1 ribosomal frameshifting with off-target cellular immune responses.
Although not linked to adverse outcomes, mistranslation of mRNA-based SARS-CoV-2 vaccines in humans causing off-target immune effects should be avoided with future mRNA-based vaccines.
Long COVID
12/4/23 MedRxiV (Oxford and Germany): Long COVID is associated with severe cognitive slowing https://buff.ly/3T9MJat
Two online cognitive tests, Simple Reaction Time (SRT) and Number Vigilance Test (NVT), were given to 270 patients diagnosed with Long COVID (PCC) at two different clinics in UK and Germany were compared to two control groups: had COVID and recovered without Long COVID (No-PCC group) and uninfected individuals (No-COVID group).
People with Long COVID (PCC) had pronounced cognitive slowing that was 3 standard deviations slower than age-matched controls who recovered from COVID without Long COVID (no PCC). This was seen in Long COVID patients in both the UK and Germany.
Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in Long COVID (PCC) patients.
"These results robustly demonstrate pronounced cognitive slowing in people with PCC [Long COVID] which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest Long Covid."
Simple Reaction Time (SRT) Test:
Number Vigilance Test (NVT)
12/7/23 Lancet: A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial https://buff.ly/3Gwn4kC
A randomized, placebo-controlled trial of a synbiotic (prebiotic + probiotic) called SIM01 modulated the gut microbiome to successfully alleviate fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and general malaise in people with Long COVID.
2 sachets daily of either SIM01 (n=232) or placebo (n=231) were given to people with at least one Long COVID symptom for 6 months.
At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and general unwellness compared to the placebo group.
The synbiotic (prebiotic + probiotic) preparation (SIM01) is a micro-encapsulated lyophilised powder containing 20 billion colony-forming units of three bacterial strains, B adolescentis, Bifidobacterium bifidum, and Bifidobacterium longum with three prebiotic compounds including galacto-oligosaccharides, xylo-oligosaccharides, and resistant dextrin, which has been shown to promote the growth of these bacterial strains but also other probiotic strains.
Bifidobacterium adolescentis showed positive correlations with alleviation in fatigue, gastrointestinal upset, and memory loss.
Bifidobacterium bifidum increases correlated with alleviation in fatigue and general unwellness.
Bifidobacterium longum correlated with an alleviation in difficulty in concentration.
Long COVID symptom alleviation at 6 months
12/1/23 Denver Post: Colorado looks to expand Long COVID care beyond specialty clinics https://buff.ly/4a9Q3IH
Project ECHO offers primary care providers seven free online courses to learn the basics of long COVID care and connects them with specialists to learn how to manage certain conditions locally and to discuss complex patients.
AI:
11/29/23 Arxiv: Towards Accurate Differential Diagnosis with Large Language Models https://arxiv.org/abs/2312.00164
12/8/23 Geoffrey Hinton interview by Eric Topol:
Other news:
12/1/23 HealthDay: Most Men Taking Bodybuilding Protein Supplements Don't Know They Can Harm Fertility https://buff.ly/3Nei8Vp
"Male bodybuilders should take into consideration that protein supplements contain high levels of estrogen and might harm their fertility."
Free course for new DEA opioid requirement for doctors and APPs: NEJM Knowledge+ Free Pain Management and Opioids course https://buff.ly/46FJkDi
12/6/23 AP: 52 sea turtles experiencing 'cold stun' in New England flown to rehab in Florida https://buff.ly/41d28ZF
10/26/23 Fast Company: Why gas leaf blowers are being banned across the country https://buff.ly/468iIdT
Operating a gas-powered leaf blower for 1 hour emits as much smog-forming pollution as driving a Toyota Camry from L.A. to Denver.
12/5/23 Lancet: Naltrexone 6 mg once daily versus placebo in women with fibromyalgia: a randomised, double-blind, placebo-controlled trial https://buff.ly/3GAWk2o
Low dose of 6 mg of naltrexone did not reduce fibromyalgia pain, but it did improve memory problems associated with fibromyalgia.
12/8/23 AP: FDA approves 2 gene therapies for sickle cell. One is the first to use the editing tool CRISPR https://buff.ly/3TfUQlE
12/7/23 Reuters: US sets policy to seize patents of government-funded drugs if price deemed too high https://buff.ly/3t7TvTo
March-in rights: If research for the drug discovery was paid for with government funding, the government can grant additional licenses to third parties to make the drugs less expensively.
12/8/23 Santa Claus liked my post on BlueSky
Thank you so much.