COVID news & more, 2/18/24

JN.1 represents more than 96% of COVID cases now. Emergency department visits and hospitalizations for COVID continue to decrease again this week. Emergency department visits for COVID are highest for babies under age 1 and for people 65 and older at this time. Flu is having a small resurgence due to Influenza B, especially in children. 

Although wastewater SARS-CoV-2 virus levels are still in the “HIGH” level for the U.S, they are going down. We are at 740,000 new COVID infections daily in the US, which translates to every 1 in 45 Americans is currently infected. SARS-CoV-2 virus levels are highest in South Dakota, Virginia and Georgia. 

From JP Weiland

The CDC is following a new variant called BA.2.87.1 that has been seen in 3 provinces in South Africa. Some people are worried that BA.2.87 could have the potential to cause a new COVID wave if it picks up more mutations. JP Weiland feels that BA.2.87 will most likely not be a problem because it has not had exponential growth like BA.2.86 did. For now, COVID cases are expected to continue to decrease over the next months.

An article in the Washington Post this week stated that the CDC was planning on dropping isolation recommendations for COVID infections, similar to new recommendations in California and Oregon. Epidemiologists and public health scientists immediately responded on Twitter that if the Centers for Disease Control & Prevention drops isolation for COVID positive individuals, this would not be in line with controlling or preventing disease.

From: https://twitter.com/luckytran/status/1758232701633487294

Like California, the CDC is expected to allow COVID positive people to return to work if they have no fever and their symptoms are improving like what is done with colds and flu. But, COVID is not a cold and it is not the flu. We know from that the SARS-CoV-2 virus can be readily spread even when infected people have no symptoms at all. COVID has long term consequences that colds and the flu do not have. Cognitive slowing and exhaustion from Long COVID is affecting many people around the world. Several large studies show that there is an increase in chronic diseases like heart disease (heart attacks, arrhythmias), stroke and diabetes in the year after a COVID infection. According to a video from Bernie Sanders this week, Long COVID is now the third most common neurological disorder in the U.S. That is huge. 

From: https://twitter.com/BernieSanders/status/1757857725050941688

The complement pathway is part of our immune system that reacts to the presence of viruses and bacteria by telling our bodies to destroy the invaders. If the complement system remains activated in a microbe-fighting state, it can start to injure healthy cells leading to tissue damage, microclots in the blood, and may actually lead to Long COVID symptoms.

A new study in Cell magazine shows that Complement dysregulation is a hallmark of Long COVID and that checking a combination of four complement biomarkers ( iC3b, TCC, Ba, and C5a) had a 79% predictive power for Long COVID. The authors also postulated that Complement Inhibitor drugs such as pegcetacoplan (targeting C3), iptacopan (targeting FB), and vemircopan (targeting FD) could potentially be used to treat Long COVID. 

These findings are consistent with another recent multicenter, prospective study from January 2024 that showed that Long COVID is accompanied by increased complement activation and thromboinflammation, activated platelets and platelet-monocyte aggregates, red blood cell lysis and reactivation of dormant viruses like CMV and EBV. The pieces of the Long COVID puzzle are starting to come together.

A study in Mitochondrion magazine shows that “mitochondrial dysfunction in Peripheral Blood Mononuclear Cells (PBMCs) may be contributing to the etiology of PASC.” (PASC is the acronym for post-acute sequelae of SARS-CoV-2 infection, which is also known as Long COVID.) The authors found altered mitochondrial function, increased ATP-linked respiration and increased oxygen consumption in Peripheral Blood Mononuclear Cells (PBMC) in people with Long COVID. “Every unit increase in non-mitochondrial respiration, ATP-linked respiration, basal respiration, spare respiration capacity, and maximal respiration increased the predicted odds of PASC between 1 % and 6 %.” 

HSC Viral Reservoir Theory

Hematopoietic stem cells (HSC) are found in the bone marrow and can differentiate into many different kinds of blood cells including PBMCs. PBMCs themselves do not have the correct receptors on them to become infected with SARS-CoV-2 easily. But, HSCs do have the receptors (ACE2 and TMPRSS) and they are easily infected by the virus. The authors postulate that there is a viral reservoir of SARS-CoV-2 virus that hangs out in the HSC bone marrow cells. The infected stem cells can then differentiate into infected PBMCs which contain SARS-CoV-2 viral RNA and proteins that could be causing altered mitochondrial function and immune activation in Long COVID. 

PBMCs become monocytes that circulate in the blood for one day looking for a place in the body to land to become macrophages that stay in tissues. Infected macrophages (made from infected monocytes which came from infected PBMCs which came from infected HSCs) can stay within tissues for several months. The location of where the SARS-CoV-2 infected macrophages take up residence could help explain the wide variety of symptoms in Long COVID.

Diagram adapted from Molecular mechanisms of HIV-1 persistence in the monocyte-macrophage lineage https://buff.ly/42GBmtl

A group from Sweden followed autoantibody levels in healthcare workers and in severe COVID patients for 16 months. They found that autoantibodies after COVID infection are common and lasted at least 12 months in 60% of people. They discovered 3 new-onset autoantibodies- anti-CALU, MYO16, and SNURF IgG in people with neurologic symptoms of Long COVID (neuro-PASC).

A group from the Karolinska Institute studied 121 people with disabling Long COVID who initially had mild to moderate acute COVID infections and compared them to controls who had similar initial mild to moderate COVID infections, but no Long COVID. The individuals with severe Long COVID had elevated plasma antibodies to SARS-CoV-2 which suggested chronic antigen stimulation from a viral reservoir of SARS-CoV-2 in the body. The higher the SARS-CoV-2 antibodies, the lower the CD8+ memory T cells found (inverse relationship), suggesting that low T cells to SARS-CoV-2 allow the virus to persist in tissues which then triggers elevated IgG antibody levels, even if SARS-CoV-2 antigen is not found in the blood.

An abstract from the Society of Maternal-Fetal Medicine meeting last week shows that about 1 in 10 pregnant individuals with a COVID infection during pregnancy will develop Long COVID. The most common defining symptoms among individuals with PASC were post-exertional malaise (82%), fatigue (75%) and dizziness (62%). The trimester of COVID infection was not related to the development of Long COVID.

In 2022, the percentage of U.S. adults who reported ever experiencing Long COVID was 6.9% for all US adults and ranged from 2% in the U.S. Virgin Islands to 11% in West Virginia. In seven states the prevalence of Long COVID exceeded 8.8%.

In non-COVID news, there was an excellent review on how large language model artificial intelligence (AI) is changing neuroscience. Authors discussed how "Neuroscientists today are literally 'drowning in information but starving for knowledge’'.

There was also a top-notch review of the effects of dietary fiber on metabolic health and obesity. The authors discuss that “obesity is a complex chronic progressive disease characterized by excess body weight and dysregulation in enteroendocrine and neurohormonal signaling pathways favoring increased appetite and energy storage.” The safety concerns of obesity medications were reviewed in the International Journal of Obesity. Adverse events associated with treatment with liraglutide, semaglutide, tirzepatide, orlistat, naltrexone-bupropion, or phentermine-topiramate were discussed. 

Have a good rest of your holiday weekend,

Ruth Ann Crystal MD

COVID news notes:

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

JN.1 is more than 96% of cases

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

Hospitalizations and ER visits over the entire pandemic:

Hospitalizations and ER visits over the last year:

Weekly ED visits for respiratory illnesses, by age and disease: https://www.cdc.gov/ncird/surveillance/respiratory-illnesses/index.html

All 3 viruses, all ages in the ED:

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

Biobot: https://biobot.io/data/

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

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

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

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

Santa Clara County wastewater: https://covid19.sccgov.org/dashboard-wastewater

CDC Respiratory vaccination trends: https://www.cdc.gov/respiratory-viruses/data-research/dashboard/vaccination-trends-adults.html

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

https://twitter.com/JPWeiland/status/1758272144063021183

https://twitter.com/JPWeiland/status/1756098652735418579

NWSS wastewater data helping confirm my suspicion that Biobot had a bad reading this week.  NWSS numbers pointing down hard, in agreement with other metrics.

740k infections/day from NWSS,  Biobot's a full third higher at 1M/day

1 in 45 Americans currently infected

Michael Hoerger modeling:  http://pmc19.com/data/

Variants 

Variant hunters on Twitter are watching BA.2.87.1 which has many new mutations. Like BA.2.86 (Pirola), it may lead to a new COVID wave if it gets a few more mutations to make it harder to neutralize.

JP Weiland responded https://twitter.com/JPWeiland/status/1758931085830803634

2/16/24 BioRxiV: Robust Neutralization of SARS-CoV-2 Variants Including JN.1 and BA.2.87.1 by Trivalent XBB Vaccine-Induced Antibodies https://buff.ly/3I47Dkl

• Neutralizing antibodies from XBB infection vs Trivalent XBB vaccine WSK-V102C from China showed that the vaccine neutralized JN.1 and BA.2.87.1 better.

• BA.2.87.1 is a variant under monitoring (VUM). “While it originates from the ancestral BA.2 lineage, BA.2.87.1 is genetically distinct from the currently circulating Omicron lineages (Fig. 1b). It exhibits over 100 mutations, with more than 30 in the spike protein.

• The WestVac BioPharma’s Coviccine® Trivalent XBB Vaccine (WSK-V102C) is approved in China and “incorporates the RBDs of the XBB.1.5, BA.5, and Delta variants, fused with the spike protein's heptad repeat (HR) domain and self-assembling into stable trimeric protein particles. The vaccine is further enhanced with a squalene-based oil-in-water emulsion adjuvant, added post-purification and mixing for increased efficacy.”

2/12/24 CIDRAP: CDC tracking BA.2.87.1 SARS-CoV-2 variant https://buff.ly/3wlJh31

• The CDC is following a new variant called BA.2.87.1 that has been seen in 3 provinces in South Africa. Fortunately, BA.2.87 is not spreading rapidly. 

Acute COVID infections, General COVID info

2/13/24 Washington Post: CDC plans to drop five-day covid isolation guidelines https://buff.ly/48hXKue

Twisted logic

2/15/24 TIME: How Long Should You Isolate With COVID-19? https://buff.ly/3I3Dv90

2/8/24 TIME: Why Do I Keep Getting COVID-19 But Those Around Me Don’t? https://buff.ly/3P0MMmb

• Genetics account for 70% of a person's likelihood of getting a COVID infection.

Long COVID

2/15/24 CDC: Long COVID Prevalence Among Adults — United States, 2022 https://buff.ly/498XQFH

• The percentage of U.S. adults in 2022 who reported ever experiencing Long COVID was 6.9% for all US adults and ranged from 2% in the U.S. Virgin Islands to 11% in West Virginia.

• Prevalence of Long COVID exceeded 8.8% in seven states. 

https://twitter.com/vipintukur/status/1758180571048738828

2/14/24 Cell: Complement dysregulation is a prevalent and therapeutically amenable feature of long COVID https://buff.ly/3uIM7yv

• Complement dysregulation is a hallmark of long COVID.

• Complement biomarkers associate with the diagnosis of long COVID.

• Complement inhibition is a potential therapy for long COVID. 

• “There are now several complement inhibitors in clinical use that could be repurposed to treat long COVID. Our findings suggest that the preferred target is the alternative pathway, which can be suppressed by drugs such as pegcetacoplan (targeting C3), iptacopan (targeting FB), and vemircopan (targeting FD).42” 

These findings of complement activation in LC are similar to what was found in this article from a few weeks ago:

1/19/24 Science: Persistent complement dysregulation with signs of thromboinflammation in active Long Covid https://buff.ly/494OM4p

COMPLEMENT ACTIVATION IN LONG COVID:

1/19/24 Science (Cervia-Hasler et al, U Zurich): Persistent complement dysregulation with signs of thromboinflammation in active Long Covid https://buff.ly/494OM4p

• "patients experiencing Long COVID exhibited changes to blood serum proteins indicating activation of the immune system’s complement cascade, altered coagulation, and tissue injury (see the Perspective by Ruf below). 

• “At the cellular level, Long Covid was linked to aggregates comprising monocytes and platelets. These findings provide a resource of potential biomarkers for diagnosis and may inform directions for treatments." —Sarah H. Ross 

“CONCLUSION

• Our data suggest that active Long Covid is accompanied by a blood protein signature marked by increased complement activation and thromboinflammation, including activated platelets and markers of red blood cell lysis. 

• Tissue injury may also be complement-mediated and, in turn, activate the complement system. (vicious cycle)

• Moreover, complement activation may be driven by antigen–antibody complexes, involving autoantibodies and antibodies against herpesviruses, as well as cross-talk with a dysregulated coagulation system. 

• In addition to offering a basis for new diagnostic solutions, our work provides support for clinical research on complement modulators for patients suffering from Long Covid.”

If the complement system remains activated in a microbe-fighting state, it can start damaging healthy cells leading to tissue damage and microclots in the blood, which may lead to Long COVID symptoms. Understanding the abnormal continued activation of the complement pathway could help scientists confirm Long COVID diagnosis and develop effective treatments. Larger trials are needed.

1/18/24 Science (W. Ruf): Immune damage in Long Covid https://buff.ly/4292hxv

• Links between the complement and coagulation systems could lead to Long Covid therapies.

• “Cervia-Hasler et al. undertook a proteomic screen measuring serum levels of 6596 human proteins. 

• Prospective study of 40 Long Covid patients, 73 recovered patients, and 39 healthy controls. 

• Most serum biomarkers that were elevated in patients with Long Covid at 6 months overlapped with those elevated in severe acute COVID-19.”

• Localized activation of the innate immune defense complement system as a likely culprit that induces thromboinflammation and prevents the restoration of fitness after acute COVID-19.

1/23/24 Smithsonian: Scientists Find Indicators in Blood Linked to Long Covid, Hinting at Future Treatments https://buff.ly/496BXpU

• "Patients with long Covid showed increased activation of the complement system, which targets pathogens and damaged cells. When it’s too active, this system can also damage healthy cells, writes Stat News’ Elizabeth Cooney. This heightened activity appeared when the long Covid patients were first infected, as well as during a follow-up after six months.

• Other recent research, which has yet to be peer reviewed, also found a link between the complement system and long Covid, according to MIT Technology Review’s Cassandra Willyard.

• In the new study, patients with long Covid had lower levels of a protein that helps prevent blood clots and higher levels of proteins tied to clot formation, writes Nature News."

1/18/24 STAT News: Could long Covid’s signs of immune dysregulation in the blood lead to a diagnostic test? https://buff.ly/42rPRRL

• "Scientists at the University of Zurich discovered high levels of proteins involved in the complement system — an important part of the immune system bridging innate and adaptive responses — that were disrupted in people with long Covid symptoms, but not in those who got better after the initial Covid-19 infection or in those who had recovered from long Covid symptoms after six months. The team also found damaged red blood cells and platelets as well as signs of harm to the endothelial cells that line blood vessels.

• These biomarkers appeared after the researchers performed high-throughput analyses of more than 6,500 proteins found in the blood serum of 113 people infected with Covid, including 40 people who developed long Covid, and controls who were not infected."

10/28/23 MedRxiV (Cardiff, UK): Complement dysregulation is a predictive and therapeutically amenable feature of Long COVID https://buff.ly/47cvSHG

• Four blood complement markers, namely the activation fragments iC3b, TCC, Ba, and C5a, had a predictive power for Long COVID of 0.785. 

2/14/24 FT: Scientists grapple with long Covid puzzle as millions fall sick https://buff.ly/48nahMV

• Vaccination reduces both the incidence and severity of Long COVID.

• WHO states that 6% of people will get Long COVID

• Persistent virus in the body leads to persistent stimulation of the immune system.

• LC may also be an autoimmune disease that could improve with IVIG.

• Ziyad Al-Aly and others have found that COVID infections can lead to increased risk of chronic disease such as heart disease (heart attack), stroke and diabetes.

2/15/24 MedRxiV: Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19 https://buff.ly/49zSlzG

• They followed autoantibody levels in healthcare workers and in severe COVID patients for 16 months.

• Autoantibodies after COVID infection are common and last at least 12 months in 60% of people.

• Molecular mimicry between places on the SARS-2 virus and human proteins.

• They found 3 new-onset autoantibodies associated with neurologic symptoms in Long COVID (neuro-PASC): anti-CALU, MYO16, and SNURF IgG. (Biomarker?)

  • CALU is a membrane-bound or secreted calcium-binding protein mainly expressed in

  • heart and skeletal muscle.

  • MYO16 is a cytoplasmic unconventional myosin with enhanced brain expression, and may be involved in the extension of neuronal membrane processes36.

  • SNURF is a small (71aa) nuclear protein of unknown function, primarily expressed in brain and muscle tissues and cardiomyocytes.

• Eric Topol: Self-directed (auto-) antibodies are common are Covid, persist to 12 months in 60% of people, correlate with neurologic symptoms, and reflect dysregulation of humoral immunity 

2/13/24 MedRxiV (Karolinska Inst): Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID. https://buff.ly/4bDgBTk

• 121 severe Long COVID patients who had mild to moderate acute COVID infections initially, in Sweden and Belgium, compared them to controls who had similar initial mild to moderate COVID infections, but no Long COVID.

• People with severe Long COVID had elevated plasma antibodies to SARS-CoV-2 which suggests a viral reservoir of SARS-CoV-2 in the body (chronic antigen stimulation).

• The higher the SARS-CoV-2 antibodies, the lower the CD8+ memory T cells (inverse relationship).

• This suggests that low T cells to SARS-CoV-2 allow the virus to persist in tissues which then triggers elevated IgG antibody levels, even if you cannot find SARS-CoV-2 antigen in the blood.

2 minute video on Long COVID, the 3rd leading neurologic disease in the US now.

https://twitter.com/BernieSanders/status/1757857725050941688

2/13/24 Society of Maternal-Fetal Medicine Abstract LB01: Development of post-acute sequelae of SARS-CoV-2 (PASC) after infection in pregnancy: NIH RECOVER-Pregnancy Cohort https://www.ajog.org/article/S0002-9378(23)02176-2/fulltext#%20

• 1,503 pregnant people with SARS-CoV-2 infection during pregnancy from December 2021 through August 2023 of which 51% were vaccinated.

• The prevalence of PASC at the first study visit 6 months or more after infection was 9.3%. The most common defining symptoms among individuals with PASC were post-exertional malaise (82%), fatigue (75%) and dizziness (62%).

• The trimester of COVID infection was not related to the development of Long COVID.

• Compared to non-pregnant adults in an NIH RECOVER cohort, the study suggested that the rate of Long Covid was lower in non-pregnant adults than in pregnant adults. 

• PASC prevalence after SARS-CoV-2 infection during pregnancy was lower than published NIH RECOVER-Adult cohort estimates of 23%.

In Long COVID, there was altered mitochondrial function, increased ATP-linked respiration and increased oxygen consumption in Peripheral blood mononuclear cells (PBMC).

“Mitochondrial dysfunction in PBMCs may be contributing to the etiology of PASC.” 

HSC viral reservoir theory

2/9/24 Mitochondrion: Altered mitochondrial respiration in peripheral blood mononuclear cells of post-acute sequelae of SARS-CoV-2 infection (Long COVID) https://buff.ly/3UCLXDw

• Biomarker?

• Peripheral blood mononuclear cells (PBMC) mitochondrial respiration was measured ex vivo from participants without a history of COVID (n = 19), with a history of COVID and full recovery (n = 20), and with PASC (n = 20).

• Mean mitochondrial basal respiration, ATP-linked respiration, maximal respiration, spare respiration capacity, ATP-linked respiration, and non-mitochondrial respiration were highest in COVID + PASC+ (p ≤ 0.04).

• Every unit increase in non-mitochondrial respiration, ATP-linked respiration, basal respiration, spare respiration capacity, and maximal respiration increased the predicted odds of PASC between 1 % and 6 %.

• Mitochondrial dysfunction in PBMCs may be contributing to the etiology of PASC.

From the discussion:

The cells in the bone marrow known as human hematopoietic stem/progenitor cells (HSC) highly express ACE2 and TMPRSS2, making them susceptible to SARS-CoV-2 during the initial infection… SARS-CoV-2 RNA has been detected in the bone marrow of post-mortem samples. (Jurek et al., 2022) PBMC lack ACE2 receptor expression and do not support productive SARS-CoV-2 infection but generate a monocyte-accentuated immune response upon stimulation with SARS-CoV-2, as stated above. (Kazmierski et al., 2022) Further, productive infection in the PBMC would be demonstrated by viral hijacking in favor of glycolysis, with a decrease in mitochondrial respiration as seen in patients with acute SARS-CoV-2 infection. (Gibellini et al., 2020, Zhang et al., 2021) 

Altered monocyte bioenergetics have been observed in patients with COVID-19 pneumonia with reduced basal and maximal respiration, spare respiratory capacity, and proton leak. The monocytes also secreted TNF and IFN-γ in vitro. (Gibellini et al., 2020) As such, these findings of altered mitochondrial function in PBMC support the residual reservoir and immune dysregulation theories of PASC pathogenesis and are further derived as follows.

In combination, these understandings lead to a probable second hypothesis from this work: 

that reservoirs of viral RNA and proteins in HSC, upon HSC differentiation, remain in PBMC and lead to altered PBMC mitochondrial function through immune activation, sustained inflammation, and the symptoms seen in PASC. Thus, the longevity of PASC would be relative to the extent of HSC viral infiltration and related to the risk factor of viremia levels. 

As such, this study presents a novel cellular mechanism under the currently hypothesized mechanisms of long COVID pathogenesis. The evidence for this HSC viral reservoir theory is compelling and further supported by the systemic and multi-organ symptom nature of PASC - all of which can be linked to the actions and interactions of PBMC-related activities. That is to say, monocytes circulate for approximately one day before becoming resident in tissues throughout the body as macrophages for several months. Therefore, the location of that residency would explain the vast array of symptoms seen in PASC. To elucidate and verify this theory, however, additional research is imperative.

Figure 4A: A representative trace of mitochondrial respiration and the differences between COVID + PASC+ (pink), COVID + No PASC (blue), and COVID- (black). 

The traces are obtained using an XFe96 analyzer and Mito Stress Test Kit that utilizes oligomycin (orange), FCCP (green), rotenone, and antimycin A (yellow) sequentially to calculate basal respiration, ATP-linked respiration, proton leak, maximal respiration, spare capacity, and non-mitochondrial oxygen consumption. 

National Library of Medicine (Stat Pearls): Biochemistry, Electron Transport Chain https://buff.ly/3SErYS6.

Electron Transport Chain in the inner membrane of mitochondria. Diagram by Emma Gregory.

The electron transport chain is a series of four protein complexes that lead to the creation of ATP in oxidative phosphorylation. It occurs in mitochondria in cellular respiration. Electrons come from breaking down organic molecules, and energy is released.

Aerobic cellular respiration is made up of three parts: glycolysis, the citric acid (Krebs) cycle, and oxidative phosphorylation. 

In glycolysis, glucose metabolizes into two molecules of pyruvate, with an output of ATP and nicotinamide adenine dinucleotide (NADH). Each pyruvate oxidizes into acetyl CoA and an additional molecule of NADH and carbon dioxide (CO2). 

The acetyl CoA is then used in the citric acid cycle, which is a chain of chemical reactions that produce CO2, NADH, flavin adenine dinucleotide (FADH2), and ATP. In the final step, the three NADH and one FADH2 amassed from the previous steps are used in oxidative phosphorylation, to make water and ATP.

Oxidative phosphorylation has two parts: the electron transport chain (ETC) and chemiosmosis. 

The ETC is a collection of proteins bound to the inner mitochondrial membrane and organic molecules, which electrons pass through in a series of redox reactions, and release energy. The energy released forms a proton gradient, which is used in chemiosmosis to make a large amount of ATP by the protein ATP-synthase.

From Peripheral blood mononuclear cells (PBMCs)

Peripheral blood mononuclear cells (PBMCs) have round nuclei and include: 

70-90% lymphocytes (T cells, B cells, and NK cells), 

10-20% monocytes, and 

1-2% dendritic cells

2/9/24 Science: Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults https://buff.ly/49EKlgG

• "Of 34 seronegative young adults inoculated, 18 developed sustained infections, which were accompanied by a systemic interferon-dominated inflammatory response preceding that in nasal lining fluid.

• Modeling of the immune response identified CD8+ T cell and early mucosal IgA responses as strongly associated with viral control, suggesting that vaccines that optimally induce these responses may help reduce transmission." 

AI:

2/9/24 Neuron: Data science opportunities of large language models for neuroscience and biomedicine https://buff.ly/48cproa

• "Neuroscientists today are literally 'drowning in information but starving for knowledge’'’.

• “Large language models (LLMs) are a new asset class in the machine-learning landscape. Here we offer a primer on defining properties of these modeling techniques. We then reflect on new modes of investigation in which LLMs can be used to reframe classic neuroscience questions to deliver fresh answers. 

We reason that LLMs have the potential to 

• (1) enrich neuroscience datasets by adding valuable meta-information, such as advanced text sentiment, 

• (2) summarize vast information sources to overcome divides between siloed neuroscience communities, 

• (3) enable previously unthinkable fusion of disparate information sources relevant to the brain, 

• (4) help deconvolve which cognitive concepts most usefully grasp phenomena in the brain, and much more.”

• Eric Topol MD: A *brilliant* review for how large language model AI is changing that, as biology becomes an engineering discipline.

Other news:

2/15/24 JAMA: Prevalence of Immunosuppression Among US Adults https://buff.ly/42Fzscr

• 6.6% (7.9% of women and 5.2% of men) of Americans are immunosuppressed, up from about 2.7% in 2013.

2/14/24 NY Times Opinion | The Increase in Measles Cases Is Utterly Avoidable https://buff.ly/49kyd4P

• "Measles is airborne, wildly contagious and deadly. While the measles vaccine is greatly protective, losing herd immunity against the disease would result in many victims, and not just those who are willfully unvaccinated.

• A small percentage of fully vaccinated people will develop breakthrough measles infections if exposed to the disease. While their cases may be mild, they can transmit the disease to others. That’s how measles will spread to infants too young to be vaccinated, older people and the immunocompromised. (In the United States, babies get vaccinated against measles between 12 and 15 months of age.)”

2/9/24 International Journal of Obesity: What is the evidence regarding the safety of new obesity pharmacotherapies https://buff.ly/48cDxG0

Diagram summarizes all safety concerns for the different GLP-1 and other anti-obesity drugs.

Fig. 1: Adverse events associated with treatment with liraglutide, semaglutide, tirzepatide, orlistat, naltrexone-bupropion, or phentermine-topiramate, in people living with obesity.

L: liraglutide, S: semaglutide; T: tirzepatide; O: Orlistat; N-B: Naltrexone-Bupropion; P-T: Phentermine-Topiramate.  CI: contraindication

2/7/24 Nature Reviews Gastroenterology & Hepatology: Effects of dietary fiber on metabolic health and obesity https://buff.ly/3w149ML

Per Eric Topol, A new 5★ review on dietary fiber and the interaction with gut hormones, the gut microbiome, obesity, and metabolic health 

Key points

• Obesity is a complex chronic progressive disease characterized by excess body weight and dysregulation in enteroendocrine and neurohormonal signaling pathways favoring increased appetite and energy storage.

• Therapeutics based on the manipulation of enteroendocrine pathways in the gastrointestinal tract are the most efficacious for weight loss and improving metabolic function.

• Prospective and epidemiological studies have demonstrated associations between fiber consumption and metabolic health, highlighting the role of the gut microbiota in linking dietary intake of fiber with beneficial effects.

• Microbiota-derived metabolites, including short-chain fatty acids, indole derivatives and bile acids, have been implicated in the pathogenesis of obesity and metabolic dysregulation.

• Heterogeneity exists between fibers in terms of their chemical and physical structures, which determines the effects of fiber on the gastrointestinal tract, the gut microbiota and energy homeostasis.

• Increased consumption of dietary fiber has the potential to induce structural, physicochemical and gastrointestinal site-specific benefits that are relevant for the treatment of obesity and metabolic syndrome.