COVID news and more 8/19/23
We are presently in a COVID surge. SARS-CoV-2 levels are increasing in wastewater across the United States and COVID hospitalizations have increased by 60% over 4 weeks, though hospitalizations are very low compared to the three last summers. The present wavelet is being caused by subvariants EG.5, FL151, and XBB1.16.6. It has been a while since people have had their last vaccination or COVID infection, so waning immunity is playing a role in this surge as well. JP Weiland calculated that there are now more than 600,000 new cases of COVID each day in the United States which correlates to a high level of community spread.
In addition to the increase in COVID hospitalizations, Emergency Department visits for COVID infections have increased as well, especially for babies 0 to 1 year of age. Young children are often less protected because most have not been vaccinated against COVID.
A new report from the CDC shows that bivalent (original + BA.5) vaccination of children ages six months to five years offered very high protection against severe COVID illness. Vaccines were 80% effective in protecting kids under age five from emergency department or urgent care visits. The bivalent vaccine was more protective than the original monovalent vaccine in the children studied. Many countries have not offered vaccination to young children, but the data shows that vaccinating this age group affords them high protection against moderate to severe disease.
Regarding the wave that we are in now, the Fall 2023 updated XBB.1.5 booster vaccine should protect well against the EG.5 and FL.1.5.1 variants that are circulating now. In a press release, Moderna showed that their updated Fall 2023 XBB.1.5 vaccine significantly boosted neutralizing antibodies against both EG.5 and FL.1.5.1 variants. The updated XBB 1.5 boosters are expected to be available sometime in mid to late September. Because the COVID public health emergency officially ended in May 2023, vaccines now need to go through a full Product Licensing Application (PLA) instead of an Emergency Use Authorization (EUA) from the FDA and this takes more time to complete.
BA.2.86
In the last 3 days, variant hunters on Twitter have noted a new variant found on three continents. There have only been six cases noted so far, but BA.2.86 has been found in Israel, Denmark, Michigan (United States), and in the UK. Having the variant show up in different places around the world at the same time shows that it could be a fit lineage. The WHO has added BA.2.86 to its variant monitoring list.
BA.2.86 has certain mutations that theoretically may allow it to bypass our immunity defenses. But, it’s too early to say what will happen. The world has complex immunity walls built with our antibodies and T cells from prior vaccinations and COVID infections at this point in the pandemic. Subvariants BA.5, BQ, BA.2, XBB.1.16, and EG.5 each had a few new mutations in the SARS-CoV-2 spike protein that gave them a competitive advantage by making them less likely to be neutralized by our antibodies, or by allowing them to attach more strongly to human ACE2 receptors. Unlike those other variants with a few mutations, BA.2.86 has 35 new mutations in its spike protein. BA.2.86 is more like Omicron in that respect. Omicron had 32 new spike mutations compared to Delta which gave it a large growth advantage and caused a large wave.
Will the Fall 2023 XBB.1.5 booster protect us against BA.2.86? We don’t know yet. If you look at these great charts from Raj Rajnarayanan, you can see that BA.2.86 has many more mutations than XBB.1.5 or BA.2. These mutations may make BA.2.86 resistant to our neutralizing antibodies from prior COVID infections and vaccinations. We will have to wait to get more information.
Vaccines
Katelyn Jetelina wrote a great article yesterday summarizing upcoming Fall vaccine options against Influenza, COVID and RSV. She reviews who can get each of the vaccines and when a person should get them. A new study found that a second BA.5 bivalent booster vaccine was not sufficient to produce a broad antibody response to newer variants and that the updated XBB.1.5 booster would be necessary for neutralization. As mentioned above, the updated XBB.1.5 booster is expected to be available mid-September in the U.S.
Giving boosters COVID shots in the same arm as the first dose was given, elicits higher levels of neutralizing antibodies and spike-specific CD8 T cells. This is thought to be due to stimulation of the same lymph nodes that were used for priming (the initial vaccination). Yale reported on a new type of vaccine delivery system using polymer nanoparticles that when given to mice via the nose, the nanoparticles carried the mRNA into the lungs and caused a robust immune response that protected the mice against SARS-CoV-2 challenge.
COVID infections have been shown to increase the risk of autoimmune diseases in several studies. A new study of 4 million people shows that COVID vaccination can reduce the risk of getting a new autoimmune disease after a COVID infection.
A study in JAMA this week showed the 52 physicians in the U.S. who propagated most of the misinformation on COVID-19 on social media. Misinformation categories included vaccines, medications, masks, and other (ie, conspiracy theories). Sadly, such misinformation may have led to over 300,000 COVID-19–related deaths that were considered preventable if public health recommendations had been followed.
Long COVID
Last week, a study showed that SARS-CoV-2 can disrupt mitochondria in our cells which may be a root cause for Long COVID in some people. Even after the virus was cleared, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired because key mitochondrial genes were down-regulated after the infection. Eric Topol reviewed how the virus could hijack our mitochondria leading to reduced energy production for human cells.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS or ME) is a debilitating disease that causes extreme exhaustion, muscle weakness, cognitive problems and sleep disturbances. Because there were no biomarkers found to measure in ME, the medical community wrongly assumed that it was a psychological disorder for years. People with Long COVID often get POTS (postural orthostatic tachycardia syndrome) and many become very sick with ME/CFS. A new study shows that people with ME/CFS have a high level of a protein called WASF3 in their muscles which disrupts the ability of mitochondria to produce energy in cells. This may be the cause for exercise intolerance in people with ME/CFS and treatments that target the WASF3 protein may help to treat ME/CFS and Long COVID.
In non-COVID news, Stanford engineering students had fun making a motorized couch to get around campus. More than 43,000 patients treated at Santa Clara Valley Healthcare may qualify for billing refunds. Three new articles in Nature magazine show that platelet factors including Platelet Factor 4 (PF4) can reduce inflammation and improve cognition in aging brains. Young mice and humans have higher levels of PF4 in their blood than older ones. Giving older mice the blood a fraction of blood plasma from young mice containing platelets improved their cognitive function.
Scientists were able to implant a genetically modified pig’s kidney into a man who was brain dead and it worked well for over a month. This may lead to animal-human transplants in the future which could give hope to thousands of people on waiting lists for organ donations.
GPT Artificial Intelligence (A.I.) detectors mistakenly flagged documents written by non-native English speakers 61% of the time. This obviously needs to be fixed before university professors can use A.I. detectors to see if a student wrote a paper themselves.
A.I. is starting to be used more in healthcare. Amazon Web Services launched HealthScribe that listens to physician-patient conversations and creates text-based summaries or notes. Nabla reviewed which companies offer AI medical scribes and Abridge announced that they are EPIC EMR’s first “Pal” meaning that their generative A.I. will be integrated into EPIC at some medical centers.
Have a good rest of your weekend,
Ruth Ann Crystal MD
COVID news:
WHO Weekly Epidemiological Updates: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
Walgreens positivity rate: https://www.walgreens.com/businesssolutions/covid-19-index.jsp
US Variant tracker: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
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
8/15/23 CBS: COVID hospitalizations accelerate for fourth straight week https://buff.ly/448UrmV
Southeastern states seeing highest hospitalizations.
Emergency room visits for people 75+ and children ages 0 to 11 years old are highest.
Babies age 0 to 1 year have the highest rates of emergency room visits for COVID.
In some states — like the region spanning Arkansas, Louisiana, New Mexico, Oklahoma and Texas — the share of COVID-19 ER visits involving children ages 0 to 11 have already far surpassed older adults.
Weekly ED visits for respiratory illnesses, by age and disease: https://www.cdc.gov/ncird/surveillance/respiratory-illnesses/index.html
COVID is causing the increase in ED visits
Babies age 0 to 1 year have the highest ED visits
US Wastewater Monitoring:
CDC Wastewater Monitor https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
Seeing more orange and red
Biobot: https://biobot.io/data/
Sewer Coronavirus Alert Network (SCAN) project by Stanford University:
Wastewater Austria (from Wolfgang Hagen): https://abwassermonitoring.at/dashboard/
JPWeiland Update 8/17/23 https://twitter.com/JPWeiland/status/1692307567123546355
August 17th update (Biobot): US community spread is back up to "high" with an estimated 610,000 daily new infections.
Similar levels in all 4 US regions.
610,000 new infections/day
1 in every 550 new people were infected today
1 in every 55 people currently infected
“This rise is still due to EG.5.1, FL.5.1, and XBB.1.16.6 along with some immune waning.
It is not due to the new, heavily mutated variant BA.2.86.
There was the US' first sequence reported today (Michigan).
We are watching this one (BA.2.86) *very* closely.”
“The BA.2.86 variant that has very high "potential" could land anywhere in the bubble on this chart (note: not a probability map). First 4 sequences in a few short days on 3 contents is not a great sign. I'm still hoping it's just a "scariant"”
From Raj Rajnarayanan: Comparing BA.2.86 to XBB.1.5 and to BA.2.
8/17/23 CIDRAP: WHO adds BA.2.86 to SARS-CoV-2 variant monitoring list https://buff.ly/3qtb8Mh
BA.2.86 has been found in Israel and Denmark and now Michigan. It has many mutations so it is being watched.
8/18/23 JAMA: Will the Updated COVID Vaccines Protect Against the New EG.5 Variant? https://buff.ly/47Ayb8v
EG.5 has a moderate growth advantage and some antibody escape properties, but it is not clear if it is driving the new surge in COVID cases.
The fall updated XBB.1.5 booster vaccine should protect against EG.5.
8/18/23 CDC MMWR: Effectiveness of Monovalent and Bivalent mRNA Vaccines in Preventing COVID-19–Associated Emergency Department and Urgent Care Encounters Among Children Aged 6 Months–5 Years — VISION Network, United States, July 2022–June 2023 https://buff.ly/3DXFGJb
In children aged 6 months–5 years, vaccine effectiveness of bivalent dose was 80% compared to unvaccinated children.
Vaccines protect young kids.
Bivalent vaccine is more protective than monovalent.
8/17/23 Moderna Press Release: Moderna Clinical Trial Data Confirm Its Updated COVID-19 Vaccine Against XBB.1.5 Generates Robust Immune Response in Humans Against Widely Circulating Variants https://buff.ly/3DZuNGL
The updated Moderna XBB.1.5 COVID-19 vaccine for the fall 2023 vaccination season showed a significant boost in neutralizing antibodies against EG.5 and FL.1.5.1 variants.
8/17/23 Katelyn Jetelina: A guide to Fall vaccine (Influenza, COVID, RSV) options https://buff.ly/3KLBIXN
8/16/23 Science (Yale): Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination https://buff.ly/3KN34N7
Intranasal SARS-CoV-2 vaccine elicited robust immune responses that conferred protection against subsequent viral challenge in mice.
Nasal vaccine delivery system.
Another paper to show a link between COVID infection and autoimmune diseases.
8/16/23 Lancet: Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study https://buff.ly/3YMcwWT
1 million people with COVID and 3 million non-COVID individuals
COVID-19 is associated with an increased risk of developing various autoimmune diseases and the risk can be attenuated by COVID-19 vaccination.
8/15/23 PNAS: The COVID-19 baby bump in the United States https://buff.ly/45NEmVd
The COVID-19 recession resulted in an overall “baby bump” of births among US-born mothers, which marked the first reversal in declining fertility rates since the Great Recession.
8/15/23 JAMA: Communication of COVID-19 Misinformation on Social Media by Physicians in the US https://buff.ly/455a4Nw
The propagation of COVID-19 misinformation on vaccines, medication, masks, and other (ie, conspiracy theories) by 52 physicians in 28 different specialties across all the United States.
Approximately one-third of the more than 1.1 million confirmed COVID-19–related deaths as of January 18, 2023, were considered preventable if public health recommendations had been followed.
Other COVID newsletters:
Long COVID newsletter, a list of pertinent articles on Long COVID.
Dr. Wolfgang Hagen (Austria): allCoronavirusesarebastards.substack.com
8/14/23 BioRxiV: SARS-CoV-2 Neutralizing Antibodies Following a Second BA.5 Bivalent Booster https://buff.ly/45NEUdJ
A second dose of the BA.5 bivalent booster is not sufficient to broaden antibody responses and to overcome immunological imprinting.
An updated monovalent booster (XBB.1.5) is necessary for neutralization.
8/13/23 Eric Topol: Long Covid: Mitochondria, the Big Miss, and Hope https://buff.ly/3OVb80T
Mitochondrial dysfunction as a possible root cause of Long COVID by SARS-CoV-2 hijacking the human cells energy source to make more virus.
The Big Miss is the lack of research on possible treatments for Long COVID by the RECOVER trial in the US.
8/14/23 PNAS: WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) https://buff.ly/3sg3khl
Overexpression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3) can disrupt mitochondrial respiratory supercomplex formation and is associated with endoplasmic reticulum (ER) stress in human cells.
Skeletal muscle biopsy samples obtained from a cohort of patients with ME/CFS showed increased WASF3 protein levels and aberrant ER stress activation.
This may apply in Long COVID with ME/CFS.
8/14/23 Science: A protein (WASF3) that disrupts cells’ energy centers (mitochondria) may be a culprit in chronic fatigue syndrome https://buff.ly/3seKY0f
People with ME/CFS struggle with extreme exhaustion, cognitive problems (brain fog) and post-exertional malaise (thinking too much or doing too much or talking too much can cause a person to be bedridden and ill for days or weeks).
A new study (above) showed high levels of WASF3 in the muscles of people with ME/CFS which disrupts the cells’ ability to generate energy.
High levels of WASF3 interfered with the assembly of mitochondrial proteins into molecular complexes that support normal energy production.
8/11/23 eBioMedicine: Differences in SARS-CoV-2 specific humoral and cellular immune responses after contralateral and ipsilateral COVID-19 vaccination https://buff.ly/3P1tQUw
Both ipsilateral and contralateral vaccination induce a strong immune response, but secondary boosting is more pronounced when choosing vaccine administration-routes that allows for drainage by the same lymph nodes used for priming.
Higher neutralizing antibody activity and higher levels of spike-specific CD8 T-cells.
8/12/23 Lancet: Venous insufficiency and acrocyanosis in long COVID: dysautonomia https://buff.ly/3OV2cIO
33 year old man with rapid purple discolouration of his legs on standing with decrease of tingling and return of normal color to legs when laying back down.
Other news:
Stanford engineering students built a motorized couch and it's a lot of fun https://buff.ly/3qurbt1
8/15/23 In Ecuador, emissions and hospitalizations fell 'in lockstep' with electric stove adoption https://buff.ly/44d9T1A
A new analysis of one of the world’s largest residential electrification programs suggests switching from gas to electric stoves can reduce climate emissions and hospitalization rates faster than previously thought if the power grid is green.
8/15/23 MedCity News: 43K Patients treated at Santa Clara Valley Healthcare in California Could Get Refunds, Bill Corrections As Part of Discounted Care Settlement https://buff.ly/3KNeYql
Eric Topol: An impressive trio of papers makes a strong case for platelet factor 4 (PF4) as the key to reducing inflammation and improving cognition in the aged brain model.
8/16/23 Nature: Platelet factors attenuate inflammation and rescue cognition in ageing - Nature https://buff.ly/3KG561K
Platelet-derived factors as potential therapeutic targets to abate inflammation and rescue cognition in old age.
Circulating levels of the platelet-derived chemokine platelet factor 4 (PF4) (also known as CXCL4) were elevated in blood plasma preparations of young mice and humans relative to older individuals.
8/16/23 Nature: Platelet-derived exerkine CXCL4/ platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice - Nature Communications https://buff.ly/3OCq1nr
8/16/23 Nature: Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice - Nature Aging https://buff.ly/3OH3LZp
In mice, peripheral administration of klotho, a longevity and cognition-enhancing protein, increased the levels of multiple platelet factors in plasma, including PF4.
PF4, but not klotho, crosses into the brain.
8/16/23 Pig kidney works in a donated body for over a month, a step toward animal-human transplants https://buff.ly/3soL2dC
A brain-dead man’s kidneys were replaced with a single kidney from a genetically modified pig.
8/17/23 How do prices of drugs for weight loss in the U.S. compare to peer nations’ prices? - Peterson-KFF Health System Tracker https://buff.ly/3qzlPNc
8/17/23 Nature Metabolism: Liraglutide (Victoza) restores impaired associative learning in individuals with obesity https://buff.ly/3OFC831
Adaptive learning is reduced when metabolic sensing is impaired in obesity, as indexed by reduced insulin sensitivity.
This RCT shows that one dose of anti-obesity GLP-1 drug Liraglutide restores associative learning (under dopaminergic midbrain control) in people with obesity.
8/13/23 Healio: Data show potential cardioprotective effects of birth control pills use https://buff.ly/3QP85ZD
8/10/23 JAHA: Associations of Oral Contraceptive Use With Cardiovascular Disease and All‐Cause Death: Evidence From the UK Biobank Cohort Study https://buff.ly/47zAecW
CNN: The FDA warns Do not use certain pregnancy, ovulation, UTI tests, made by Universal Meditech https://buff.ly/3E3iHMA
AI:
8/14/23 The Markup: AI Detection Tools Falsely Accuse International Students of Cheating https://buff.ly/3QBCc6w
7/14/23 Cell, Patterns: GPT detectors are biased against non-native English writers https://buff.ly/45yWIsV
Upcoming Stanford University lecture:
Unlocking Pandora's Box: Generative AI in Healthcare. https://buff.ly/45aqEvF
Sep 27, 2023 05:00 PM
8/16/23 Abridge Becomes Epic’s First Pal, Bringing Generative AI to More Providers and Patients https://buff.ly/44urt1f
https://www.abridge.com/
Thank you for all you do!