COVID news & more, 11/3/24

Wastewater levels of COVID are LOW as of October 29, 2024 per the CDC’s website, but WastewaterSCAN reports MEDIUM levels as of November 2nd, across the west, midwest and northeast. According to WastewaterSCAN, the highest levels of SARS-2 in wastewater is in Lewiston, ME at 2703 PMMoV, followed by Snohomish, WA at 1285 PMMoV and Dover, NH at 825 PMMoV. Most places in the Bay Area are low, although Santa Cruz county had a peak a few days ago.

According to JP Weiland, this week or next week should be the nadir of COVID infections and he expects the winter wave to start off slowly and then accelerate starting in mid-to-late November and into the winter holidays. Emergency room visits for COVID have been decreasing, but are starting to plateau. Currently, per JP Weiland there are about 220,000 new COVID infections per day in the United States and 1 in every 151 people is currently infected in America. Michael Hoerger’s numbers are a bit higher and he predicts that about 1 in every 123 people is actively infectious now. 

Variants 

XEC has become dominant in many places around the world and it is increasing in the United States. Last week, XEC represented 17% of American COVID cases, but KP.3.1.1 was still the most common variant here at 57%. US variant proportion data is only being reported every 2 weeks now. In places where XEC is most prevalent, its growth appears to have slowed to about 20% per week according to JP Weiland and Mike Honey. So, it may not cause as large a wave as some other variants have in the past. The latest COVID vaccines protect against XEC and against KP.3.1.1, so now would be a great time to be vaccinated in order to have good protection over Thanksgiving, Christmas and New Years holidays.

SARS-CoV-2 and the Brain 

A new study in mice shows that SARS-CoV-2 infects neurons in the ventral tegmental area (VTA) of the brain which affects its ability to make the neurotransmitter serotonin, an important regulator of mood and behavior. SARS-CoV-2 also caused neuronal damage via the buildup of the tau protein which became excessively phosphorylated by an enzyme called GSK3β. Normally, tau stabilizes microtubules in neuron cells, but if it becomes phosphorylated, it can form “tau tangles” which are seen in neurologic diseases such as Alzheimer’s disease. The loss of serotonin-producing neurons in the VTA by SARS-CoV-2 may partially explain long term neuropsychiatric effects in people who have had a COVID infection. 

The brain-vascular-immune interface plays a significant role in brain function and neurological diseases. When blood vessels do not function correctly, they can allow toxic proteins from the blood to leak into the brain via disruptions in the blood-brain barrier (BBB). For example, fibrin is a protein that is normally found in the blood. If fibrin leaks into the brain, it can activate immune responses and promote neuroinflammation and neurodegeneration in the brain. Genetic and pharmacological studies have shown that targeting fibrin can protect against neuroinflammation and neurodegeneration in animal models of multiple sclerosis, Alzheimer's disease, and COVID-19. The brain-vascular-immune interface, together with genetic susceptibility, affect neuroinflammation in Long COVID and in neurodegenerative diseases.

Figure 1: Integration of vascular risk factors with genetic susceptibility in neurological diseases

From: https://www.cell.com/cell/fulltext/S0092-8674(24)01037-7

Immunity to COVID 

A new preprint from Harvard shows that by December 2023, 99.4% of  Americans had been infected at least once by COVID and 99.9% of people had been exposed to the SARS-CoV-2 virus through infection or vaccination. Despite the high level of cumulative exposure to SARS-CoV-2, only 53.6% of the population was protected from infection and 82.6% were protected from severe disease when the JN.1 variant arrived in the winter of 2023. As the SARS-CoV-2 virus evolves and immunity from vaccination and infection wanes, effective protection against COVID-19 decreases over time with ongoing risks for reinfection, hospitalizations, and Long COVID.  

COVID Tests

Rapid antigen COVID tests require people to swab their nose for a sample. Charlie McCone wrote a Twitter post about studies showing that a rapid antigen COVID test may give a false positive if one uses a throat swab instead of, or in addition to, the nasal swab. This is due to a difference in acid levels in the throat versus the nose. 

COVID Testing With Cough Audio Analysis

Using a multilayer deep learning artificial intelligence model, the Cough2COVID-19 framework is able to analyze cough sounds to diagnose a COVID infection. The AI-driven approach has high accuracy, with 98% specificity, 97% sensitivity and an AUC of 0.981. The Cough2COVID-19 framework incorporates the “CoughFeatureRanker” algorithm to identify key features in audio to best detect COVID.

Pediatrics

A cohort study published in JAMA looked at 172,136 children and young adults and found that elevated BMI significantly increased the risk of post-acute sequelae of SARS-CoV-2 (PASC, or Long COVID) in a dose-dependent manner. Children and teens with obesity had a 25.4% increased risk of Long COVID, while those with severe obesity had a 42.1% increased risk compared to peers at a healthy weight. “In this cohort study, elevated BMI was associated with a significantly increased PASC risk in a dose-dependent manner, highlighting the need for targeted care to prevent chronic conditions in at-risk children and young adults.” 

Vaccines

Southwest District Health is a regional health department serving people in six counties in Idaho. Marking a first in the nation, the health department’s board decided to ban Southwest District Health from giving COVID vaccines despite expert testimony on the vaccine's necessity. The decision sparked concern about its impact on vulnerable populations including the homeless and the uninsured. Although policymakers in Texas prohibited health departments from promoting COVID vaccines and Florida’s surgeon general opposed medical consensus by advising against them, government bodies nationwide have not taken steps to completely block vaccine access until now.

Antiviral treatments

Shionogi announced this week that their Phase 3 trial, called SCORPIO-PEP, showed that their oral drug Ensitrelvir prevented symptomatic COVID infection in people exposed to infected family members. The study involved about 2,400 participants and found that Ensitrelvir was safe and effective, making it a potential new option for preventing COVID-19 after exposure. Ensitrelvir is available in Japan and in Singapore.

A retrospective cohort study of 7,290 high risk adult patients from Dubai during the Omicron wave shows that nirmatrelvir plus ritonavir (Paxlovid) given during acute COVID infection significantly reduced hospitalization rates by 61% and Long COVID symptoms by 58% in adult outpatients as compared to untreated patients. High risk individuals included people age ≥ 65 years, those with obesity (≥ 25 kg/m2), diabetes, cardiovascular disease or hypertension, chronic lung disease, immunocompromising conditions, chronic kidney disease, pregnant individuals, those with sickle cell anemia, neurodevelopmental disorders, and individuals dependent on medical-related technology such as tracheostomy. Early Paxlovid antiviral treatment was effective to mitigate severe COVID disease and prolonged Long COVID symptoms with the Omicron variant in high risk adults.

Fig. 1: COVID related hospitalizations by day 28

From: https://www.nature.com/articles/s41598-024-76472-0/figures/1

Long COVID

A new article looks at three systematic reviews which show that exercise therapy for Long COVID patients experiencing post-exertional malaise (PEM) is not safe. Even exercise programs that involve gradually increasing activity levels can be harmful for these patients and causing them long term damage. 

Graphic designer Jane Vangool made these great Long COVID graphics that can be downloaded here.

H5N1

H5N1 has been detected in pigs on a backyard farm in Oregon for the first time. This is dangerous because pigs are susceptible to both human influenza viruses and the H5N1 bird flu virus, meaning that the viruses could “mix” genetically to form a type of flu virus that could infect humans more readily. 

Other news

Tauopathies are neurodegenerative diseases characterized by the buildup of tau protein in conditions like Pick’s disease and Alzheimer’s disease. In a study using a transgenic zebrafish model, researchers screened over 1,400 drugs and found that carbonic anhydrase (CA) inhibitors reduced tau toxicity. CRISPR experiments confirming similar effects. Glaucoma drug and CA inhibitor methazolamide improved outcomes in mouse models, suggesting that CA inhibitors could be promising treatments for tauopathies like Alzheimer’s in the future.

Nature magazine had a special collection of 12 papers this week on the Human Tumor Atlas Network (HTAN) that analyzed hundreds of thousands of human and animal cells. They made detailed 3D maps and cell atlases that reveal how cancer develops and evolves, offering insights into early diagnosis and treatment strategies. These studies, including the use of CRISPR and molecular clocks, showed that cancer can arise from a mix of cell types, challenging the belief that it starts from a single cell. Understanding the diverse cell interactions within tumors could lead to more effective treatments and preventive measures.

Dr. Eric Topol tweeted this week about "An unanticipated discovery: the brain suppresses the immune response by producing autoimmune "guardian peptides" that block neuroinflammation, which may be especially important in neurodegenerative diseases." Delivering guardian peptides in extracellular vesicles can stop neuroinflammation and may lead to antigen-specific therapy against brain inflammation in the future. 

In addition to weight loss, treatment for diabetes, and the reduction of cardiovascular disease, GLP-1 drug semaglutide has been found to have yet another medical benefit- helping with osteoarthritis of the knees. Semaglutide (Ozempic) causes people to lose weight which helps relieve knee pain by putting less pressure on the joints, but it turns out that Semaglutide also has anti-inflammatory properties which also helps arthritic knee pain.

Credit: Dr. P. Marazzi/Science Photo Library

Please remember to vote by this Tuesday.

Have a great rest of your weekend,

Ruth Ann Crystal MD

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COVID news notes:

US Variant tracker: https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Will update next week.

10/26/24 https://x.com/Mike_Honey_/status/1850359288382075135

Variants around the world: https://outbreak.info/

World wastewater maps (reflects COVID cases): https://www.arcgis.com/apps/dashboards/c778145ea5bb4daeb58d31afee389082

CDC COVID data tracker: https://covid.cdc.gov/covid-data-tracker/index.html#datatracker-home

COVID Emergency Dept visits: https://covid.cdc.gov/covid-data-tracker/#ed-visits_all_ages_combined

CDC Respiratory viruses (COVID, Flu, RSV) Hospitalizations (for those states reporting): https://www.cdc.gov/resp-net/dashboard/index.html

Walgreens positivity rate: https://www.walgreens.com/businesssolutions/covid-19-index.jsp

US Wastewater Monitoring:

CDC wastewater reporting: https://www.cdc.gov/nwss/rv/COVID19-nationaltrend.html

CDC wastewater through 10/26/24

CDC wastewater map: https://www.cdc.gov/nwss/rv/COVID19-currentlevels.html

Through 10/26/24

National SARS-CoV-2 data from Sara Anne Willette: https://iowacovid19tracker.org/

Composite NWSS and WastewaterSCAN through 10/29/24 

Composite data of Wastewater SARS-CoV-2 as of 10/29/24

Wastewater SCAN: https://data.wastewaterscan.org/

As of 11/2/24:

Lewiston, ME is highest at 2703 PMMoV

Snohomish, WA                 1285 PMMoV

Dover, NH                            825 PMMoV

California statewide view https://buff.ly/3YObiul

Sewer Coronavirus Alert Network (SCAN) project by Stanford University: 

Santa Clara County wastewater: https://publichealth.santaclaracounty.gov/health-information/health-data/disease-data/covid-19/covid-19-wastewater

Marin county: https://coronavirus.marinhhs.org/surveillance

COVID deaths per week: https://covid.cdc.gov/covid-data-tracker/#trends_weeklydeaths_weeklypctdeaths_00

JP Weiland: https://twitter.com/JPWeiland

https://x.com/JPWeiland/status/1852480585685500083

November 1st update: 

This week or next will be the min until 2025. 

Expect the winter wave to start off slow and accelerate mid-late Nov into the holidays. Estimates: 

• 220,000 new infections/day 

• 1 in every 151 people currently infected 

• Numbers are 62% below 12-month average

JP Weiland’s Winter Outlook:

I have not changed my winter outlook so far from mid September.  Yes, we are slightly below the predicted minimum, but I think the rough trajectories and timing still stand.

Michael Hoerger modeling:  http://pmc19.com/data/, https://x.com/michael_hoerger/status/1850974559752671457

PMC COVID-19 Forecasting Model, Oct 28, 2024 

Comparable transmission to last week, as is the norm when bottoming out on a "lull." 

• 1 in 123 actively infectious 

• Higher transmission than during 42% of the pandemic 

• Nearly 3 million weekly infections 

Every indication is that the 10th wave is on the way. I expect to see levels qualitatively higher next week. If lucky, that could be another 1-2 weeks off. However, based on the WastewaterSCAN and Walgreens data, I doubt we're so lucky.

His prediction: http://pmc19.com/data/

Puerto Rico COVID-19 dashboard: https://covid-19-puerto-rico.org/2024-06-29/index.html

Tara Moriarty Canadian COVID data: https://x.com/MoriartyLab

UK

UKHSA Dashboard: https://ukhsa-dashboard.data.gov.uk/

UK COVID PCR Test Positivity Map: https://jamestindall.info/skeuomorphology/ladb_covid/index.html

10/28/24 Emmanuel: https://x.com/ejustin46/status/1850806636895436803

“FOUR PATTERNS of COVID-19 WAVES from April to October 2024, in Wastewater Data

He highly recommends data from  @nichtGenes61287.

Data through 11/2/24

Austria, Slovenia, France, USA, Sweden, Switzerland, Italy, Holland, New Zealand, Finland, Germany, Canada

11/2/24 https://x.com/nichtGenes61287/status/1852742742155141512/photo/1

Variants 

11/2/24 https://x.com/JPWeiland/status/1852796080917709189

JP Weiland: Update on XEC:

In the countries where it's most prevalent and we have decent sequencing, XEC* growth appears to have slowed to a crawl. ~+20%/wk.

If you recall, I've been doubtful of this lineage since August.  

Data from @Mike_Honey_ PowerBI:

Acute COVID

COVID and the Brain

10/30/24 PLOS ONE (Japan): SARS-CoV-2 propagation to the TPH2-positive neurons in the ventral tegmental area induces cell death via GSK3β-dependent accumulation of phosphorylated tau https://buff.ly/4hvDr1Y

10/17/24 https://x.com/brownecfm/status/1846976831154700472

From the text: 'COVID-19 can accelerate progression of dementia and induce BBB disruption and inflammatory blood clots causally linked with neuroinflammation and neuronal loss'. BBB - Blood Brain Barrier. Neurological sequelae of C-19 will be a huge challenge in the future.

@EricTopol

The brain-vascular-immune interface, a basis of neuroinflammation in #LongCovid and neurodegenerative conditions, an insightful open-access @CellCellPress perspective by @AkassoglouLab and colleagues https://cell.com/cell/fulltext/S0092-8674(24)01037-7…

10/23/24 MedRxiV (Harvard): National- and state-level SARS-CoV-2 immunity trends from January 2020 to December 2023: a mathematical modeling analysis https://buff.ly/48t4nLN

https://www.medrxiv.org/content/10.1101/2024.10.22.24315935v1

By December 2023, 99.4% of  Americans had been infected at least once by COVID and 99.9% of people had been exposed to the SARS-CoV-2 virus through infection or vaccination. Despite the high level of cumulative exposure to SARS-CoV-2, only about 53.6% of the population was protected from infection and 82.6% were protected from severe disease when the JN.1 variant arrived in the winter of 2023. 

Rapid Antigen Tests

10/26/24 https://x.com/loscharlos/status/1850344509399498959

Including throat swabs on COVID rapid antigen test (RAT) instead of just a nasal swab like test directions say can cause a false positive test because of pH per Charlie McCone.

COVID Testing With Cough Audio Analysis

10/24/24 Nature: Cough2COVID-19 detection using an enhanced multi layer ensemble deep learning framework and "CoughFeatureRanker" https://buff.ly/3UuEWUt

Figure 1

From: https://www.nature.com/articles/s41598-024-76639-9/figures/1

Pediatrics

10/28/24 JAMA: BMI and Postacute Sequelae of SARS-CoV-2 in Children and Young Adults https://buff.ly/3NIgqLL

“In this cohort study, elevated BMI was associated with a significantly increased PASC risk in a dose-dependent manner, highlighting the need for targeted care to prevent chronic conditions in at-risk children and young adults.” 

Vaccines

11/1/24 AP: An Idaho health department isn't allowed to give COVID-19 vaccines anymore. Experts say it's a first https://buff.ly/4fvnV4r

Southwest District Health 

Antiviral treatments

10/29/24 Nature: Nirmatrelvir plus ritonavir (Paxlovid) reduces COVID-19 hospitalization and prevents Long COVID in adult outpatients https://buff.ly/4foHmMo

https://www.nature.com/articles/s41598-024-76472-0

A retrospective cohort study of 7,290 high risk adult patients from Dubai during the Omicron wave shows that nirmatrelvir plus ritonavir (Paxlovid) given during acute COVID infection significantly reduced hospitalization rates by 61% and Long COVID symptoms by 58% in adult outpatients as compared to untreated patients. High risk individuals.

Fig. 1: COVID related hospitalizations by day 28

From: https://www.nature.com/articles/s41598-024-76472-0/figures/1

10/29/24 Press Release: Shionogi Announces Global Phase 3 Trial Demonstrates Post-Exposure Prophylactic Use of Ensitrelvir Prevents Symptomatic COVID-19 https://buff.ly/40nQeNR

Shionogi & Co., Ltd. announced that their Phase 3 trial, called SCORPIO-PEP

10/28/24 Shinogi Plans for Ensitrelvir https://www.shionogi.com/content/dam/shionogi/global/investors/ir-library/presentation/2024/%EF%BC%92q/E_FY2024_2Q_final.pdf

Long COVID

10/28/24 RISM: Using Exercise Therapy for Long COVID Without Screening for Post-Exertional Symptom Exacerbation Potentially Increases the Risks for Patients Who Suffer from it: A Reanalysis of Three Systematic Reviews https://buff.ly/4e6adE0

https://crimsonpublishers.com/rism/pdf/RISM.000748.pdf

Long COVID Graphics from Janine Vangool @uppercasemag

https://uppercasemag.notion.site/COVID-safety-measures-92e2bd05395b4b1297e21b105cdbdc98

H5N1

10/30/24 Reuters: US detects H5N1 bird flu in a pig on a backyard farm in Oregon for the first time https://buff.ly/3YNkwHN

https://x.com/NohaAboelataMD/status/1851826226631242161

Other news

https://x.com/Antonio_Caramia/status/1852440943808418180

10/31/24 Nature Chemical Biology: Carbonic anhydrase inhibition ameliorates tau toxicity via enhanced tau secretion https://buff.ly/4ed2Qef

Eric Topol: “The unexpected potential for a glaucoma drug to be used to help prevent #Alzheimers disease.”

10/30/24 Nature: Ultra-precise 3D maps of cancer cells unlock secrets of how tumours grow https://buff.ly/4f4W7E9

Special edition of Nature

In a tranche of 12 papers published in Nature journals on 30 October, researchers of the Human Tumor Atlas Network (HTAN) analysed hundreds of thousands of cells from human and animal tissues. Some of the studies describe 3D maps of the cells — known as cell atlases — in tumours, whereas others create ‘molecular clocks’ that trace the cellular changes that lead to cancer.

10/30/24 Nature: Endogenous self-peptides guard immune privilege of the central nervous system https://buff.ly/48vx4b2

https://www.nature.com/articles/s41586-024-08279-y

Eric Topol: "An unanticipated discovery: the brain suppresses the immune response by producing autoimmune "guardian peptides" that block neuroinflammation, which may be especially important in neurodegenerative diseases."

https://x.com/mitchkim_mw/status/1851663836581167420

“the brain  engages with the immune system through  “guardian” peptides to ensure immune tolerance” to self proteins.

The repertoire of “self” dramatically changed at the peak of neuroinflammation, namely an intriguing depletion of guardian peptides could be observed.

Foreseeing a therapeutic opportunity, the repletion of depleted guardian peptides by delivering them in extracellular vesicles successfully mitigated neuroinflammation, offering an attractive, antigen-specific therapy!!