COVID, H5N1 news & more 11/9/24

The CDC reports that wastewater levels of COVID are still LOW as of one week ago on 11/2/24 and that the Midwest region is starting to show a slight uptick. Per JP Weiland, there are presently about 217,000 new COVID infections per day in the United States and 1 in every 153 people is currently infected in America. Mike Hoerger’s numbers are a bit higher and he predicts that about 1 in every 115 people is actively infectious now. 

The highest wastewater SARS-CoV-2 levels according to WastewaterSCAN now are Bangor, ME at 1271 PMMoV; S. Parker, CO at 1186 PMMoV; Ottumwa, IA at 1134; and Lewiston, ME at 1123 PMMoV. WastewaterSCAN does not have information on New Mexico and several other states though. Here in the Bay Area, wastewater levels of SARS-CoV-2 are LOW. 

From: CDC NWSS: https://www.cdc.gov/nwss/rv/COVID19-nationaltrend.html 

According to composite wastewater data from Sara Anne Willette using information from the CDC’s NWSS site and the WastewaterSCAN site on 11/6/24, we are seeing hot spots in Luna county, New Mexico; Mono county, California; Pike county, KY; and Lincoln county, ME. 

From: https://iowacovid19tracker.org/

Variants 

The KP.3.1.1 variant decreased from 57% of COVID cases two weeks ago to 52% this week. XEC now represents 28% of cases, up from 17% two weeks ago. XEC is increasing, but it is not doubling like other variants have in the past and is not expected to cause a large COVID wave. The updated vaccines work against both of these variants. Scientists are starting to see new variant MV.1 in a few places in the US, but it has not made much of an impact. 

Acute COVID infections, General COVID info

Autoantibodies to interferon-α (IFN-α) in the blood are associated with severe acute COVID infection. However, using a technique called FlowBEAT, researchers from Emory found that transient IgA1 autoantibodies to interferon-α (IFN-α) in the nose were helpful to tamp down immune response to COVID infection and were associated with milder cases of COVID.

Looking at almost 7 million people in South Korea from 2020 to 2022, researchers found significantly increased risks of autoimmune and autoinflammatory connective tissue disorders following COVID infection, especially in people with severe COVID-19 infection, those infected with the Delta variant, and in unvaccinated individuals. 

From: https://jamanetwork.com/journals/jamadermatology/article-abstract/2825849

Seniors and Immunocompromised people

A new randomized trial shows that for immunocompromised individuals and seniors aged 65+, easy access to home testing, telemedicine, and quick Paxlovid delivery lessened COVID infection severity, reduced ICU admissions and lowered healthcare costs.

Vaccines

A new study from Regeneron shows that giving Regeneron monoclonal antibodies (mAbs) casirivimab plus imdevimab at the same time as vaccination caused the immune system to make less neutralizing antibodies in humans, nonhuman primates and in mice. Booster vaccinations were able to increase neutralizing antibodies to normal levels, however.

Antiviral treatments

Ibuzatrelvir is a new antiviral drug from Pfizer that works against the Mpro of SARS-CoV-2. A new Phase 2b, double-blind, randomized clinical trial of 240 US adults showed that Ibuzatrelvir reduced viral load after 5 days at different doses of the medication. Ibuzatrelvir does not have the same drug-drug interactions as Paxlovid. A Phase 3 study would need to be completed before Ibuzatrelvir could go on the market. 

On 11/1/24, the EPA made recommendations for improvement of ventilation in indoor spaces like schools and offices to prevent the spread of respiratory viruses. 

Long COVID

A study from the University of Washington found that individuals with Long COVID experienced significant cognitive decline and reduced quality of life two years after infection. People who believed that they had recovered from Long COVID showed improvement of most symptoms, but they still had higher levels of fatigue, pain, and cognitive issues compared to people without Long COVID. These findings raise concerns about the long-term impact on individuals' ability to sustain participation in work, education, and social activities if they have or have had Long COVID.

Figure 2

From: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10158-w

A study from the Mayo Clinic compared 247 people with Long COVID to 40 controls. Long COVID patients frequently reported pain, neurological problems, sleep disturbances, skin conditions, and genitourinary issues. In addition, 58% of Long COVID patients screened positive for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), 27% for generalized joint hypermobility (GJH), and many had orthostatic intolerance. The authors discuss research and clinical findings to better help understand Long COVID and the commonly overlapping illnesses that are associated with Long COVID.

In a new article, a team from Australia summarized mechanisms that may be causing post-acute sequelae of coronavirus disease 2019 (PASC or Long COVID) including immune dysregulation with exhausted T cells and autoimmunity, gut dysbiosis, and immunothrombosis.

Box 1. Proposed mechanisms for post-acute sequelae of coronavirus disease 2019 (PASC) pathogenesis

From: https://onlinelibrary.wiley.com/doi/full/10.5694/mja2.52456

Yesterday 11/8/24, PolyBio had their Fall 2024 symposium on Long COVID research. The Patient-Led Research Collaboration tweeted the talks in this mega thread. There were many great talks including research on lymph node germinal centers having a lower number of B cells in people with Long COVID (from Dr. Michela Locci, University of Pennsylvania), on the salivary proteome in Long COVID (Dr. Marcelo Freire, UCSD), and on potential SARS-CoV-2 persistence and T cell activity in the female reproductive tract (Dr. Nadia Roan, UCSF as part of the UCSF LIINC study of the Female Reproductive Tract). 

A new small study from Hungary of 32 post-COVID-19 (PC) patients compared to 31 healthy volunteers shows a link between mitochondrial dysfunction and persistent symptoms in Long COVID patients. In Long COVID, researchers found structural abnormalities in the mitochondria and elevated markers of oxidative stress and disrupted mitophagy. Importantly, they found that lower levels of circulating cell-free mitochondrial DNA (ccf-mtDNA) were associated with increased symptom severity in Long COVID suggesting that ccf-mtDNA levels could be used as a novel biomarker for diagnosing and monitoring Long COVID. 

Figure 3:

From: https://link.springer.com/article/10.1007/s11357-024-01398-4/figures/3

There appears to be similarities between amyloid microclots in Long COVID patients and those found in ischemic stroke patients. Drs Pretorius and Kell have previously found fibrinaloid microclots in Long COVID that contain amyloid proteins and are very resistant to breakdown by fibrinolysis. In a new study, they show that in eight stroke patients were also found to have fibrinaloid clots in larger blood vessels that stain strongly for amyloid and were difficult to break down. "These findings represent a previously unreported characteristic of stroke clots, highlighting the potential for amyloid-targeted therapies to overcome their fibrinolytic resistance."

Figure 3: The fluorescent green dye shows amyloid in the clots from 2 stroke patients.

From: https://www.medrxiv.org/content/10.1101/2024.11.01.24316555v1

The Bateman Horne Center put out a new Caregiver Resource Guide for people taking care of people with severe ME/CFS. Recommendations can also be useful for people without a caregiver.

The Hypothalamic-Pituitary-Adrenal (HPA) axis is important in the body’s response to stress. In Long COVID, some studies show that morning cortisol levels are low, while other reports have shown high morning cortisol in some people with Long COVID. A new article shows that the gut microbiota regulate the circadian stress response of the HPA-axis in mice and that hyperactivation of the HPA-axis from microbial depletion in the gut can affect the way the body can respond to stress throughout the day including morning cortisol levels. 

From: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(24)00399-1

H5N1

As of 11/6/24, Turlock, California which is known for dairy farming has an astronomical level of Influenza A in their wastewater. Turlock is at 2618 PMMoV of Flu A; Ottumwa, Iowa is at 368 PMMoV; and Los Angeles county doubled in the last few days to 155 PMMoV of Influenza A (probable H5N1) in wastewater. As more virus is circulating, there are more chances for humans and other animals to become infected. If the virus mutates to make it better able to spread from human-to-human, this could lead to another pandemic. We need to keep a close eye on H5N1. 

From: https://data.wastewaterscan.org/

A CDC study shows that 7% of dairy workers in Michigan and Colorado tested June through August 2024 had antibodies showing recent H5N1 bird flu infection. Without testing animals and people who work with them, H5N1 bird flu infections are going undetected. The results of the recent study prompted the CDC to expand testing, enhance PPE guidance, and recommend preventive Tamiflu for exposed, asymptomatic workers. 

A new preprint study from Cambodia shows that after almost a decade without human H5N1 bird flu infections, Cambodia had 16 cases of humans with bird flu between February 2023 and August 2024. Fourteen of the human cases involved a novel reassortant H5N1 virus that combined gene segments from both clade 2.3.2.1c which is endemic to Southeast Asia and clade 2.3.4.4b which has been seen globally. The new reassortant virus has new mutations including PB2 E627K which is linked to transmission between species and airborne transmission. In addition, in Figure 1b, it appears that 7 of the 16 humans died from the H5N1 bird flu infection as seen by the highlighted cross symbol. 

Figure 1b shows the high mortality rate in people for the reassortant H5N1 bird flu virus.

From: https://www.medrxiv.org/content/10.1101/2024.11.04.24313747v1.full.pdf

Other news:

In the last few days, doctors and nurses from Twitter have been leaving in droves to join BlueSky at https://bsky.app/. If you join, look for the Medsky feed and the Medsky Starter Packs to find friends. My Bluesky handle is @drruth.bsky.social. 

An article in Science magazine discussed the election and possible changes to policy and funding for the NIH and other governmental agencies with the new administration. Some scientists on Twitter recommend downloading available data from government websites as access may change. 

The FDA plans to discontinue the popular decongestant phenylephrine present in cold medicines because it doesn't work. 

A new blood panel called N3-MASH (CXCL10, CK-18, body mass index) is able to discriminate metabolic dysfunction-associated steatotic liver disease (MASLD) from healthy controls and can measure improvement without need for liver biopsy. 

A study shows that supplementing with indole lactate (ILA) in animal models of Multiple Sclerosis reduces brain inflammation and helps with remyelination of nerves.

In a worlds' first, a group from Japan reports that 2 years after transplant of corneal epithelial cell sheets derived from human induced pluripotent stem cells (iPSCs), vision was improved in the 4 patients studied. 

Vancouver dad Douglas Lenhart won the Taylor Swift ‘Concert of a Lifetime’ grand prize with VIP box seats for 14 people to Swift's opening concert and $25,000. He is taking family and friends and also donated 4 of the seats to the Make-A-Wish-Foundation to grant the wishes of some critically ill children.

Have a great rest of your weekend,

Ruth Ann Crystal MD

---

COVID news notes

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

 Through 11/4/24 

US Wastewater Monitoring:

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

Through 11/2/24

We are just starting to see an increase in wastewater SARS-CoV-2 levels in the Midwest.

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

Through 11/2/24

CDC wastewater SARS-2 level through 11/2/24

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

Combination of data from CDC NWSS and WastewaterSCAN as of Nov 6, 2024

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

The highest wastewater SARS-CoV-2 levels according to WastewaterSCAN now are Bangor, ME at 1271 PMMoV; S. Parker, CO at 1186 PMMoV; Ottumwa, IA at 1134; and Lewiston, ME at 1123 PMMoV. WastewaterSCAN does not have information on New Mexico. 

 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

As of 10/31/24 

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

https://x.com/JPWeiland/status/1855045793356398782

November 8th update:

Lowest overall October numbers since 2020 by a large margin, but expect numbers to increase as weather cools off.

Estimates:

• 217,000 new infections/day

• 1 in every 153 people currently infected

• Crossed 3.00 infections per capita on this calibration

Michael Hoerger modeling:  http://pmc19.com/data/, https://twitter.com/michael_hoerger

Canada wastewater https://health-infobase.canada.ca/wastewater/

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

 @nichtGenes61287

11/7/24 https://x.com/nichtGenes61287/status/1854555175815422186/photo/1

Variants 

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

• KP.3.1.1 is down to 52% from 57% two weeks ago.

• XEC is 28% up from 17% two weeks ago. It is increasing but not doubling like other variants have.

11/5/24 Marc Johnson on MV.1 https://x.com/SolidEvidence/status/1853834486225727541

In the samples uploaded in the last 2 weeks alone I saw MV.1* in KS, MI, MA, FL, PA, DE, and NY. 

In fact, in samples from Muskegon county, MI and Miami, FL, MV.1* was the dominant lineage.

I'm not saying that MV.1* is going to have a JN.1 level sweep, but I do think we'll be seeing more of it.

Acute COVID infections, General COVID info

11/6/24 Eurekalert: Nasal swab tests predict COVID-19 disease severity, Emory study finds https://buff.ly/3Chtbum

“While autoantibodies in the blood were linked to bad prognosis, producing them only in the nose soon after infection is linked to efficient recovery.” Ghosn

11/6/24 Science: Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19 https://buff.ly/3YY2lAo

11/6/24 JAMA Dermatology: Long-Term Risk of Autoimmune and Autoinflammatory Disorders After COVID-19 https://buff.ly/3CgX8L0

https://jamanetwork.com/journals/jamadermatology/article-abstract/2825849

Looking at almost 7 million people in South Korea from 2020 to 2022

Seniors and Immunocompromised people

10/28/24 NPJ preprint: A randomized trial of at-home COVID-19 tests, telemedicine, and rapid prescription delivery for immunocompromised individuals https://buff.ly/3AzfeYg

https://www.researchsquare.com/article/rs-5314583/v1

Vaccines

11/6/24 Science: Monoclonal antibodies against the spike protein alter the endogenous humoral response to SARS-CoV-2 vaccination and infection https://buff.ly/3YTUCTR

Antiviral treatments

11/2/24 Clinical Infectious Diseases (Pfizer study): Virologic Response and Safety of Ibuzatrelvir, a Novel SARS-CoV-2 Antiviral, in Adults With COVID-19 https://buff.ly/40A8GTO

Recommendations from the EPA on ventilation in schools and in offices. https://buff.ly/3O0Y6O7

Long COVID

11/5/24 BMC Infectious Diseases: Long COVID and recovery from Long COVID: quality of life impairments and subjective cognitive decline at a median of 2 years after initial infection https://buff.ly/48NwmpJ

A study from the University of Washington found that individuals with Long COVID experienced significant cognitive decline and reduced quality of life two years after infection. 

Figure 2

From: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10158-w

10/24/24 Frontiers of Neurology: Overlapping conditions in Long COVID at a multisite academic center https://buff.ly/3YUgazC

A study from the Mayo Clinic compared 247 people with Long COVID to 40 controls.

58% of Long COVID patients screened positive for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), 27% for generalized joint hypermobility (GJH), and many had orthostatic intolerance.

11/3/24 Medical Journal of Australia: Beyond acute infection: mechanisms underlying post‐acute sequelae of COVID‐19 (PASC) https://buff.ly/3Ayjmrm

Summary:

• Immune dysregulation is a key aspect of post-acute sequelae of coronavirus disease 2019 (PASC), also known as long COVID, with sustained activation of immune cells, T cell exhaustion, skewed B cell profiles, and disrupted immune communication thereby resulting in autoimmune-related complications.

• The gut is emerging as a critical link between microbiota, metabolism and overall dysfunction, potentially sharing similarities with other chronic fatigue conditions and PASC.

• Immunothrombosis and neurological signalling dysfunction emphasise the complex interplay between the immune system, blood clotting, and the central nervous system in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

• Clear research gaps in the design of PASC studies, especially in the context of longitudinal research, stand out as significant areas of concern. 

Box 1. Proposed mechanisms for post-acute sequelae of coronavirus disease 2019 (PASC) pathogenesis

From: https://onlinelibrary.wiley.com/doi/full/10.5694/mja2.52456

On Friday 11/8/24, PolyBio had their Fall 2024 symposium on Long COVID research. The Patient-Led Research Collaboration tweeted the talks in this mega thread. 

https://x.com/patientled/status/1854968526240727152

Dr. Marcelo Freire from UCSD talking about Mucosal-System molecular signatures in Long COVID.

https://x.com/patientled/status/1854998739817316857

"Potential SARS-CoV-2 persistence & T cell activity in the female reproductive tract" —— Nadia Roan, PhD from UCSF, LIINC study of the Female Reproductive Tract 

11/4/24 GeroScience (Hungary): Novel biomarkers of mitochondrial dysfunction in Long COVID patients https://buff.ly/4fczDkZ

lower levels of circulating cell-free mitochondrial DNA (ccf-mtDNA) were associated with increased symptom severity in Long COVID suggesting that ccf-mtDNA levels could be used as a novel biomarker for diagnosing and monitoring Long COVID. 

Figure 3:

From: https://link.springer.com/article/10.1007/s11357-024-01398-4/figures/3

11/4/24 MedRxiV (Pretorius, Kell): The clots removed from ischaemic stroke patients by mechanical thrombectomy are amyloid in nature https://buff.ly/4egFhkH

https://www.medrxiv.org/content/10.1101/2024.11.01.24316555v1

Figure 3: The fluorescent green dye shows amyloid in the clots from 2 stroke patients.

From: https://www.medrxiv.org/content/10.1101/2024.11.01.24316555v1

Caregiving Webinar from Bateman Horne Center: https://bit.ly/3Yvek6W https://x.com/BatemanHorne/status/1853921518012813599

The Hypothalamic-Pituitary-Adrenal (HPA) axis is important in the body’s response to stress. In Long COVID, some studies show that morning cortisol levels are low, while other reports have shown high morning cortisol in some people with Long COVID. This new article shows that the gut microbiota regulate the circadian stress response of the HPA-axis in mice and that hyperactivation of the HPA-axis from microbial depletion in the gut can affect the way the body can respond to stress throughout the day. 

11/5/24 Cell Metabolism: Gut microbiota regulates stress responsivity via the circadian system https://buff.ly/48FSrqo

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(24)00399-1

• Gut microbiota regulates diurnal rhythms of corticosterone

• Microbial depletion leads to disruption in rhythmicity of stress pathways in the brain

• Microbial depletion results in time-of-day-specific impairments in stress responsivity

• Diurnal oscillations of gut microbes modulate corticosterone release

Here, we uncover the gut microbiota as a regulator of HPA-axis rhythmicity. 

Microbiota transplantation confirmed that diurnal oscillations of gut microbes underlie altered glucocorticoid secretion and that L. reuteri is a candidate strain for such effects.

H5N1

Santa Clara County Influenza

Turlock is at 2618 PMMoV of Flu A

Ottumwa, IA is at 368 PMMoV

Los Angeles county doubled in the last few days and is at 155 PMMoV of Influenza A in the wastewater. 

11/7/24 CDC MMWR: Serologic Evidence of Recent Infection with Highly Pathogenic Avian Influenza A(H5) Virus Among Dairy Workers — Michigan and Colorado, June–August 2024 https://buff.ly/4hFshYM

A new CDC study shows that 7% of dairy workers in Michigan and Colorado tested last summer had antibodies showing recent H5N1 bird flu infection. 115 farm workers in Colorado and Michigan were included in the study, of which 8 were positive for H5 bird flu antibodies.

11/7/24 https://x.com/JPWeiland/status/1854670283312882151

11/4/24 Michael Mina https://x.com/michaelmina_lab/status/1853708102584983979

11/6/24 Scientists track emergence of novel H5N1 flu reassortant in Cambodia https://buff.ly/3CkhIKq

"After almost a decade with no human H5N1 cases, Cambodia experienced a startling rise in infections, with 16 cases reported from February 2023 to August 2024."

Sara Anne Willette H5N1 Bird Flu Data:

US Human H5N1 Influenza A cases: https://public.tableau.com/app/profile/sara.anne.willette/viz/USInfluenzaMaps/InfluenzaAH5ReportedCaseData

Animal H5 data are here: https://public.tableau.com/app/profile/sara.anne.willette/viz/USHPAIData/HPAIviaUSDA

H5 Influenza A California:

https://data.wastewaterscan.org/

Avian Flu H5N1 Influenza A https://www.cdc.gov/nwss/wastewater-surveillance/Flu-A-data.html

https://bnonews.com/index.php/human-cases-of-h5n1-bird-flu/

Human H5N1 count: https://www.cdc.gov/bird-flu/situation-summary/index.html

https://x.com/HmpxvT/status/1855286728640385512

Other news:

BlueSky is taking off with a mass exodus of #MedTwitter going to the app. 

U.S. FDA proposes ending use of popular decongestant phenylephrine present in cold medicines because it doesn't work https://buff.ly/40YuTv5

11/6/24 Science: Trump won. Is NIH in for a major shake-up? https://buff.ly/3YM6ZAe

11/4/24 Cell Metabolism: A blood-based biomarker panel for non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) https://buff.ly/3AriqoI

11/1/24 JCI - Accumulation of Epstein-Barr virus–induced cross-reactive immune responses is associated with multiple sclerosis https://buff.ly/4fzjlCx

https://www.jci.org/articles/view/184481#F1

10/28/24 BioRxiV (Johns Hopkins): Restoring the Multiple Sclerosis Associated Imbalance of Gut Indole Metabolites Promotes Remyelination and Suppresses Neuroinflammation https://buff.ly/3NQ8xE4

“ILA as a new potential anti-inflammatory remyelinating agent and provide novel insights into the role of gut dysbiosis-related metabolic alterations in MS progression.”

11/7/24 Lancet (Japan): Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan https://buff.ly/4fhik2f

Vancouver dad Douglas Lenhart won the Taylor Swift ‘Concert of a Lifetime’ grand prize with VIP box seats for 14 people to Swift's opening concert and $25,000. He is taking family and friends and also donated 4 of the seats to the Make-A-Wish-Foundation. https://buff.ly/3ChQlkm