COVID wastewater levels have peaked and appear to be going down in most states, but wastewater virus levels are still at very high or high levels in most states. There are about 716,000 to 1,000,000 new COVID cases daily in America now and about 1 in every 40 to 47 people is currently infected. Mike Hoerger predicts a “lull” in cases in early November.
KP.3.1.1 remains the most common variant and was 52.7% of cases as of 9/14/24. The updated COVID vaccines match this variant well.
Variants
XEC is a recombinant variant of KS.1.1 and KP.3.3 that is being watched closely. There has been a lot of discussion about XEC on Twitter as it has shown a significant growth advantage, outpacing KP.3.1.1 in some countries, yet XEC has very similar spike protein mutations to KP.3.1.1 which has puzzled scientists. Ryan Hisner may have found why XEC has a growth advantage- it could be due to a mutation in the Nucleocapsid (N) protein.
Dr. Vipin Vashishtha also wrote an interesting tweet thread last week on COVID, the Gut-Lung Axis, immunity and the intestinal microbiome, and on probiotics for Long COVID.
A new poll posted by the CDC shows that 95% of people said that they would take more precautions if they knew virus levels in wastewater were high. Of those people, 76% would wash their hands more, 61% would avoid large gatherings, 59% would avoid people at high risk of COVID infection, 57% would tell their family or friends about high levels in wastewater, 52% would get vaccinated, 51% said they would wear a mask in indoor spaces.
Pediatrics
Chronic stress or adversity during development can result in accelerated brain maturation. Accelerated brain aging, seen as thinning of the cerebral cortex on MRI, is associated with an increased risk for the development of neuropsychiatric and behavioral disorders. Teenage girls were found to have the equivalent of 4.2 years in brain aging acceleration while teen boys had about 1.4 years of increased brain aging during pandemic lock downs. However, correlation is not causation and more studies are needed to see if this was due to lockdowns or to something else. It will also be important to study if teens’ brains recover later.
Clean Air in BC Schools put out a free, printable “zine” on how to keep air clean in schools. The pocket guide discusses ventilation, air filtration, measuring CO2 levels and wearing face masks.
Antiviral medications
The SELECT trial studied semaglutide 2.4 mg in people with cardiovascular disease and obesity but no diabetes. It found that those who took semaglutide had lower rates of all-cause death, cardiovascular (CV) death, and non-CV death compared to those who took a placebo. The reduction in non-CV deaths was mainly due to fewer deaths from infections, including COVID-19. Overall, the study suggests semaglutide reduces mortality risk in patients with obesity and cardiovascular disease, especially during the COVID-19 pandemic.
Hyundai Bioscience is partnering with the University of California San Diego (UCSD) to conduct a trial evaluating Xafty, a niclosamide-based oral antiviral, to treat Long COVID. Previous clinical trials have shown Xafty is safe and it improves acute COVID symptoms, especially in high-risk groups. Xafty was also found to have neuroprotective effects in preclinical animal studies on Parkinson’s disease. Led by Dr. Ajay Bharti, the new clinical trial will explore how Xafty may address Long COVID symptoms through virus suppression, inflammation reduction, and neuroprotection.
Because viral persistence may be a cause of Long COVID, scientists are studying the use of antiviral medications to treat or prevent Long COVID. A new report from Victoria Harris and colleagues from the PANORAMIC trial showed that people who took molnupiravir during acute COVID infection had better outcomes at 3 months and 6 months. However, Molnupiravir is not an ideal treatment because it is mutagenic. It is important to find new antiviral medications that work against SARS-CoV-2 with less secondary effects. "The key for successful treatment trials will probably hinge (among other things) on targeting the disease early; whether earlier initiation of antiviral therapy, longer duration of treatment, or a combination of different antivirals (with different mechanisms of action) yields better effectiveness," wrote Dr. Ziyad Al-Aly.
An article came out this week in The Sick Times discussing how people with severe Long COVID cannot access health care because they are too sick to leave their beds. There needs to be a better system for evaluating and treating people with severe Long COVID and it is important to include them in clinical trials and studies as well.
Dr. Claire Taylor tweeted this week about a new study presented at the European Respiratory Society (ERS) 2024 International Congress in Vienna showing that some people with Long COVID symptoms of breathlessness and fatigue can have normal CT pulmonary angiogram scans, but have abnormal VQ scans showing abnormal lung blood supply. Researchers at Imperial College London studied 41 people who had mild COVID infections, but continued to experience symptoms like breathlessness and fatigue, even though their CT scans were normal. The study found these patients had abnormal lung perfusion and reduced gas diffusion capacity. Dr. Laura Price, a respiratory physician at Royal Brompton Hospital, said that this appears to be due to pulmonary microangiopathy affecting small blood vessels in the lungs that leads to shortness of breath. We know from other studies that SARS-CoV-2 can damage endothelial cells that line blood vessels. Dr. Taylor stresses the importance of using VQ scans to see perfusion issues.
A new paper looks at the complex mechanisms including microvascular alterations and immunometabolic interactions behind post-exertional malaise (PEM), a symptom common in both Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Physical exercise in people with Long COVID and/or ME/CFS can cause reduced oxygen extraction, mitochondrial dysfunction, and immune system activation, which can lead to fatigue, pain, and worsened post-exertional malaise symptoms. The review discusses how these conditions may share a common pathology and the challenges in finding effective treatments for PEM.
Last week, the CDC disclosed that a household contact of the person hospitalized in Missouri with H5N1 bird flu and a health care worker who took care of that individual when they were hospitalized both had been ill. The first health care worker tested negative for influenza. Now, a second health care worker who took care of that person also reported a mild respiratory infection that had resolved. Antibody testing for H5N1 is pending for the second healthcare worker. Per the CDC, “the risk to the public remains low”, but the case is being followed closely to make sure that there was no human-to-human transmission of H5N1.
Other news:
Eric Topol tweeted about two new studies on plastic pollution and human health:
A rare disagreement between NWSS, ED data, and WWScan. ED&WWScan agree, and NWSS is the outlier. I'm going to split the difference for these estimates:
“New poll finds half of Americans believe they'll never get COVID again. The data shows that COVID surges at high levels throughout the year.
Denial is one hell of a drug.”
9/17/24 Ipsos: Half of Americans never think they'll get COVID again https://buff.ly/3zndVuN
9/19/24 CDC MMWR: Support for Wastewater Monitoring and Influence on Protective Behavioral Intentions Among Adults — United States, July 2024 https://buff.ly/4gq1C1D
Recombinant variant XEC (a recombinant of KS.1.1 and KP.3.3) looks a likely next challenger against the dominant DeFLuQE variants.
Here are the leading countries reporting XEC.
Strong growth has been reported from Denmark during August, reaching 18%.
France and Spain have reached 11%.
For Denmark, XEC is showing a strong growth advantage of 9.5% per day (67% per week) over JN.1.* + DeFLuQE variants. That predicts an imminent crossover.
For France, XEC is showing a strong growth advantage of 11.2% per day (78% per week) over JN.1.* + DeFLuQE variants. That predicts a recent crossover.
For Spain, XEC is showing a growth advantage of 6.1% per day (43% per week) over JN.1.* + DeFLuQE variants. That predicts an imminent crossover.
Acute COVID infections, General COVID info
We cannot have long lasting or herd immunity to SARS-CoV-2 because the virus continues to evolve and change.
Immunity against SARS-CoV-2 - wanes/declines/disappears with time (months). This applies to immunity from natural infection and vaccine-derived immunity.
In a recent interview, Fauci puts the C19 herd immunity fantasy to bed once and for all. No such thing can ever be achieved, due to lack of immune response durability
9/12/24 Journal of Virology: SARS-CoV-2 infection perturbs the gastrointestinal tract and induces modest microbial translocation across the intestinal barrier https://buff.ly/4d3hlAO
A new article shows that COVID infection can cause leaky gut which allows bacteria to go from the lumen of the gut, across the leaky colonocytes, and into the bloodstream. They found a "significant increase in plasma soluble CD14 (sCD14) that may be induced by LPS [from the translocated bacteria]... sCD14 significantly positively correlated with zonulin, an indicator of gut barrier integrity, and IL-6. These results demonstrate that GI perturbations such as microbial translocation can occur in even mild SARS-CoV-2 infections and may contribute to the COVID-19 inflammatory state."
9/9/24 PNAS: COVID-19 lockdown effects on adolescent brain structure suggest accelerated maturation that is more pronounced in females than in males https://buff.ly/4cY28km
Teenage girls were found to have the equivalent of 4.2 years in brain aging acceleration while teen boys had about 1.4 years of increased brain aging during pandemic lock downs.
“The new study mostly just shows that there may be some changes to the brains of teen girls in Washington State that happened sometime during the years of 2020-2022 which are unexpected. What caused these changes is impossible to pin down using this study design.”
Antiviral treatments
9/17/24 Press Release: Breakthrough in Long COVID: An investigator-initiated trial (IIT) with Hyundai Bioscience's Xafty by UCSD https://buff.ly/4d8osb6
Hyundai Bioscience is partnering with the University of California San Diego (UCSD) to conduct a trial evaluating Xafty, a niclosamide-based oral antiviral, to treat Long COVID.
8/30/24 J of American College of Cardiologists: The Effect of Semaglutide on Mortality and COVID-19–Related Deaths: An Analysis From the SELECT Trial https://buff.ly/47bGMia
The SELECT trial studied semaglutide 2.4 mg in people with cardiovascular disease and obesity but no diabetes.
Semaglutide did not reduce incident COVID-19; however, among participants who developed COVID-19, fewer participants treated with semaglutide had COVID-19–related serious adverse events (232 vs 277; P = 0.04) or died of COVID-19 (43 vs 65; HR: 0.66; 95% CI: 0.44-0.96). High rates of infectious deaths occurred during the COVID-19 pandemic, with less infectious death in the semaglutide arm, and resulted in fewer participants in the placebo group being at risk for CV death.
9/9/24 Lance ID (Z. Al-Aly): SARS-CoV-2 antivirals and post-COVID-19 conditionhttps://buff.ly/3Xs5F4L
It is important to find new antiviral medications that work against SARS-CoV-2 with less secondary effects. Since viral persistence may be a cause of Long COVID, antivirals may work to treat or prevent Long COVID. "The key for successful treatment trials will probably hinge (among other things) on targeting the disease early; whether earlier initiation of antiviral therapy, longer duration of treatment, or a combination of different antivirals (with different mechanisms of action) yields better effectiveness."
Long COVID
9/17/24 The Sick Times: For people with severe Long COVID, medical care is out of reachhttps://buff.ly/3TyoVMA
9/16/24 The Sick Times: Introducing Long COVID Essentials, a new resource series https://buff.ly/4ealHaD
9/17/24 Diabetes Care; Prevalent Metformin Use in Adults With Diabetes and the Incidence of Long COVID: An EHR-Based Cohort Study From the RECOVER Program https://buff.ly/3Tzeuse
A retrospective cohort analysis
The results suggest that metformin could lead to better outcomes for people with type 2 diabetes who contract COVID-19.
9/12/24 Long-COVID Patients Show Abnormal Lung Perfusion Despite Normal CTs https://buff.ly/4derVVp
European Respiratory Society (ERS) 2024 International Congress in Vienna.
Researchers at Imperial College London recruited 41 patients who experienced persistent post-COVID-19 infection symptoms, such as breathlessness and fatigue, but normal CT scans after a mild COVID-19 infection that did not require hospitalization.
The researchers identified a distinct phenotype of patients with persistent post-COVID-19 infection symptoms characterized by abnormal lung perfusion and reduced gas diffusion capacity, even when CT scans appear normal. Price explains that this pulmonary microangiopathy may explain the persistent symptoms.
Previous studies have suggested that COVID-19 causes endothelial dysfunction.
9/6/24 Infection: Towards an understanding of physical activity-induced post-exertional malaise (PEM): Insights into microvascular alterations and immunometabolic interactions in post-COVID condition (PCC or Long COVID) and myalgic encephalomyelitis/chronic fatigue syndrome ME/CFS) https://buff.ly/4d71T6q
Figure 1:
Potential drivers of PEM include microvascular alterations and mitochondriopathy that can functionally culminate in reduced systemic oxygen extraction and oxidative phosphorylation capacity upon physical activities (a–b).
Altered bioenergetics limit the patients’ ability to be physically active and induce the accumulation of lactate, reactive oxygen species and cations (c).
Overexertion could manifest as delayed symptom exacerbation and systemic fatigue through subsequent immune activation that might aggravate bioenergetic inflexibilities and modulate CNS functions (d).
Transcutaneous vagus nerve stimulation [tVNS] for Long COVID clinical trial
A new clinical trial with tVNS for #LongCOVID in New York City by the Icahn School of Medicine at Mount Sinai. The study aims to compare two sets of stimulus parameters. The 50 participants also need to fulfill the 2015 IOM criteria for #MECFS.https://clinicaltrials.gov/study/NCT06585254
“Another Friday surprise: A 2nd health worker who cared for a Missouri person who had #H5N1 #birdflu got ill after the fact. Missouri only learned of this illness after he/she recovered, so no diagnostic test. Will be asked to submit blood for testing.”
9/20/24 STAT News: Second health care worker tied to Missouri bird flu case had respiratory symptoms https://buff.ly/4edAdhC
"Last week it was disclosed that a household contact of the confirmed case and a health worker who had cared for the individual while he or she was in hospital had also been ill. That first health worker tested negative for influenza." Now, a second health care worker who took care of the person hospitalized with H5N1 Avian flu developed mild respiratory symptoms, but had not been tested for influenza. Per the CDC, “the risk to the public remains low.”
9/18/24 BMJ: Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis https://buff.ly/3zruSnS
Overall, eletriptan, rizatriptan, sumatriptan, and zolmitriptan had the best profiles and they were more efficacious than the recently marketed drugs lasmiditan, rimegepant, and ubrogepant.
Regarding the new metformin study - I think it relied on a review of patient charts and diagnosis codes of long covid. I’ll have to confirm that, but any study relying on clinical documentation of “long covid” will vastly underestimate the true prevalence. It’s hard to make that diagnosis as it is somewhat of a judgment call, and there are no consensus confirmatory tests like blood work ( although there are lots of suggestive tests). I like the studies that prospectively assess long covid symptom development via surveys, etc rather than mining icd 10 codes. What do you think? I trust the Covid-OUT ~40% RR reduction more, though I would have to review how they measured this, but it was prospective.
Wow. A lot of information there, thank you.
Some eye openers too. Like 50% of US think they will never get Covid again in their lifetimes 😬
Great presentation as usual thank you,
Regarding the new metformin study - I think it relied on a review of patient charts and diagnosis codes of long covid. I’ll have to confirm that, but any study relying on clinical documentation of “long covid” will vastly underestimate the true prevalence. It’s hard to make that diagnosis as it is somewhat of a judgment call, and there are no consensus confirmatory tests like blood work ( although there are lots of suggestive tests). I like the studies that prospectively assess long covid symptom development via surveys, etc rather than mining icd 10 codes. What do you think? I trust the Covid-OUT ~40% RR reduction more, though I would have to review how they measured this, but it was prospective.