COVID news 3/18/23
XBB.1.5 is still hovering at 90% of cases and so far there are no new variants on the horizon. Cases are decreasing, there are fewer hospitalizations for COVID and the CDC US wastewater virus map is looking better overall. J. Weiland predicts that hospitalizations will continue to decrease next month especially as the weather here warms up and people can go outside more. In England, I have seen one report by Chris Pagel that hospitalizations for COVID are still rising however.
Wednesday March 15th was the first International Long COVID Awareness Day. Dr. David Putrino of Mount Sinai posted a message of hope on Twitter mentioning different people who are working to understand causes and possible treatments for Long COVID. A Nature correspondence from the UK reviewed the importance of patient and public involvement in epidemiological studies of long COVID. They briefly discussed the development of the Symptom Burden Questionnaire for Long COVID (SBQ-LC) which was developed with patient partners and has been licensed more than 90 times across 50 countries since. US Senators Markey, Kaine, Duckworth marked International Long COVID Awareness Day by reintroducing a bill to help millions of Americans living with Long COVID.
A new study from the Cleveland Clinic shows that in Long COVID patients with chronic headache, there is an “immunometabolic rewiring” with an initial phase of hyperinflammation that triggers the chronic Long COVID headaches, followed by immuno-metabolic reprogramming related to proinflammatory M1 macrophages and nitric oxide production. Dysregulated neurotransmitter metabolism (serotonin, dopamine, glutamate, and GABA) was also noted to affect these chronic headaches.
Charlie McCone, a Long COVID patient activist, tweeted about his serious difficulties getting disability payments for his long COVID because of an extraordinary amount of roadblocks in the Social Security Disability system. In an interview, he also said “We can’t move past COVID until we have treatments for Long COVID.”
A study of children aged 2 and 6 in Sweden shows that CD4+ T cells made by the body after a cold from the OC43 coronavirus can protect young children from SARS-CoV-2 infection. This protection decreased with increased age however. The Pfizer bivalent booster has now been approved by the FDA for children aged 6 months to four years.
Vaccines
A new study shows that it is very important to get several good nights of sleep after COVID vaccination. Sleeping less than 6 hours per night in the days around COVID vaccination led to lower antibody levels, especially in men. A study in the Lancet shows that giving the second Pfizer mRNA vaccine dose in the same arm as the first dose resulted in more neutralizing antibodies and higher levels of spike-specific CD8 T-cells. This may be related to boosting of the same lymph nodes that drain the area from the first vaccination.
The UK and Canada have announced that they will be giving spring COVID booster vaccinations to high risk people. But in the US, the FDA and CDC have not yet said anything about spring boosters. In fact, the US CDC may only recommend yearly boosters for COVID to be given at the same time as flu vaccines. But, COVID is not a seasonal virus like the flu and we have seen large waves in the summer as well as the winter. Drs Eric Topol and Bob Wachter discussed when to get a booster and Dr. Topol recommended that immunocompromised people consider getting another bivalent booster now since it has been more than 6 months since the last booster and we know that immunity wanes. In addition, Evusheld monoclonal antibodies no longer work against the newer variants leaving the immunocompromised less protected.
Although the US FDA and CDC have not given advice on another booster yet, they did send “a scathing 4-page letter to Florida's Surgeon General” warning him that Ladapo's latest VAERS analysis was "incorrect, misleading and could be harmful to the American public."
In non-COVID news, Weight Watchers will work with a telemedicine company to bring the new anti-obesity medication Ozempic to dieters, a stinky giant seaweed blob is heading towards Florida beaches and Novo Nordisk and Sanofi have joined Eli Lilly saying that they will reduce insulin prices significantly before they are fined next year by Medicaid. A study of a closed-loop (artificial pancreas) system using a continuous glucose monitor in combination with an insulin pump in 2 to 5 year old kids with Type I diabetes showed that those using the closed-loop system had 3 hours more per day spent in the target glucose range and that the benefits of the closed-loop system were seen on the first day of use.
Early Onset Colorectal Cancer (EO-CRC), defined as colorectal cancer diagnosed in people younger than age 50, is increasing globally and anticipated to become the leading cause of cancer death in individuals aged 20 to 49 in the US by 2030. The 2 to 4% yearly rise in many countries of EO-CRC since the 1990s is thought to be related to the increase in sugar, processed foods and red meat in the Western diet along with a sedentary lifestyle that all increase the risk of metabolic syndrome. Another study shows that children of women who took a common anti-nausea drug in pregnancy, Bendectin containing dicyclomine, in the 1960s and 1970s may have three times the risk of colon cancer.
A Stanford group announced that a GMR biosensor assay can quickly check a patient’s genes at the point-of-care to see if they have a certain combination of COMT gene SNPs which make them able to use hypnosis for postoperative pain. A woman was cured of HIV using an umbilical cord blood transplant from a baby who is homozygous CCR5 Δ32. One-percent of the Northern Europeans are homozygous for this mutation which protects them from an HIV infection.
In the lab, mouse and human motor neuron cells were treated with a designer DNA drug that may be able to delay paralysis in Amyotrophic Lateral Sclerosis (AML) patients in the future. And finally, in a Nature article titled “The Mice with Two Dads” researchers were able to make eggs from the cells of male mice that could be fertilized and resulted in seemingly healthy, fertile babies. This proof of concept study is interesting, but the technique “is a long way from being used in humans.”
Have a good weekend,
Ruth Ann Crystal MD
Other news:
3/13/23 WSJ: WeightWatchers Moves Into the Ozempic Market With Telehealth Deal https://buff.ly/3TaIl99
WW is buying Sequence, which offers telehealth visits with doctors.
3/14/23 NY Times: A Giant Blob of Seaweed is Heading to Florida https://buff.ly/3mUjA53
The mass, known as the great Atlantic Sargassum belt, is drifting toward the Gulf of Mexico. Scientists say seaweed is likely to come ashore by summer to create a rotting, stinking, scourge.
3/15/23 Novo Nordisk Follows Eli Lilly’s Lead, Lowering Insulin Prices up to 75% - MedCity News https://buff.ly/3mXOY2i
Novo Nordisk semaglutide franchise for diabetes and weight loss is growing.
3/17/23 Reuters: Sanofi to cut US price of its most-prescribed insulin by 78% next year https://buff.ly/40hsAiO
The price decrease “will allow Sanofi, Novo and Lilly, which combined control about 90% of the U.S. insulin market, to avoid paying substantial rebates to the U.S. government Medicaid program in 2024.”
3/16/23 NEJM: Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes https://buff.ly/3ZSRV2N
Children who were at least 2 years of age but younger than 6 years of age who had Type 1 diabetes.
Those on the closed-loop system had 3 hours more per day spent in the target range of 70 to 180 mg/dL.
“The benefits of the closed-loop system were evident within the first day of use and were maintained consistently throughout the trial.
3/20/23 Green Journal Ob Gyn: Perinatal Outcomes After Bariatric Surgery Compared With a Matched Control Group https://buff.ly/407Bboj
Pregnancy after bariatric surgery is associated with:
decreased risk of preeclampsia, gestational diabetes or impaired fasting glucose, and LGA neonates;
increased risk of SGA neonates.
3/9/23 Nature: The mice with two dads: scientists create eggs from male cells https://buff.ly/3LfgthV
Researchers have made eggs from the cells of male mice — and showed that, once fertilized and implanted into female mice, the eggs can develop into seemingly healthy, fertile offspring.
“There are big differences between a mouse and the human,” Hayashi said.
3/16/23 Science: A common cancer at an uncommon age https://buff.ly/3JmPrmk
Early-onset colorectal cancer (EOCRC), also called young-onset colorectal cancer, is defined as colorectal cancer diagnosed in individuals aged less than 50 years.
EOCRC is increasing globally and anticipated to become the leading cause of cancer death in individuals aged 20 to 49 in the US by 2030.
Since the 1990s, the age-adjusted incidence of EOCRC has risen at an alarming rate of 2 to 4% per year in many countries, with even sharper increases in individuals younger than 30 years.
3/15/23 HealthDay: Drug Used in Pregnancies in 1960s, '70s May Be Tied to Colon Cancers Today https://buff.ly/3FnSLfO
The children of women who took a common anti-nausea drug in pregnancy, Bendectin (containing dicyclomine), in the 1960s and 1970s may have 3x higher risk of colon cancer.
3/14/23 Sci Direct (Stanford): New test quickly identifies patients whose postoperative pain can be effectively treated by hypnosis https://buff.ly/42jTjNu
Hypnotizability is a stable cognitive trait with a genetic basis.
It includes four specific single-nucleotide polymorphisms (SNPs), or genetic variations, found in the catechol-o-methyltransferase (COMT) gene for an enzyme in the brain that is responsible for dopamine metabolism in the prefrontal cortex.
The investigators developed a SNP genotyping assay on a giant magnetoresistive (GMR) biosensor array to detect the optimal combination of the COMT SNPs in patient DNA samples.
GMR biosensor arrays are reliable, cheaper, sensitive, and can be easily deployed in point-of-care settings using saliva or blood samples.
3/16/23 Cell: HIV-1 remission and possible cure in a woman after haplo-cord blood transplant https://buff.ly/40ejvHH
First woman possibly cured of HIV by transplanting HIV-resistant stem cells (homozygous CCR5 Δ32) from umbilical cord blood.
About 10% of white Northern Europeans carry the Δ32 mutation in CCR5; however, only 1% are homozygous for the mutation.
CCR5Δ32/Δ32 haplo-cord blood transplant achieved remission and a possible HIV-1 cure for a person of diverse ancestry, living with HIV-1, who required a stem cell transplant for acute leukemia.
3/17/23 Science Daily: DNA treatment could delay ALS paralysis https://buff.ly/40gWELz
Loss of TDP-43 protein triggers loss of stathmin-2 which helps neurons regenerate.
In both mouse and human motor neuron studies, a DNA designer drug restored protein levels.
"Our findings lay the foundation for a clinical trial to delay paralysis in ALS by maintaining stathmin-2 protein levels in patients using our designer DNA drug," Cleveland said.
3/17/23 Science: Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies https://t.co/ek9IzimjAP
COVID news:
World reported cases https://medriva.com/charts/world-monitor.php
Obviously, Morocco number is an error.
US reported cases https://medriva.com/charts/usa-monitor.php
https://www.nytimes.com/interactive/2021/us/covid-cases.html
US cases
https://ourworldindata.org/coronavirus
Hospitalizations:
Variant tracker in US: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
XBB.1.5 remains at 90%.
Wastewater Monitoring:
CDC Wastewater Monitor https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
Sewer Coronavirus Alert Network (SCAN) project by Stanford University:
United States outlook per J Weiland
England
3/17/23 Nature: Patient and public involvement within epidemiological studies of long COVID in the UK https://buff.ly/3Z01vQh
Patient and public involvement (PPI) and patient advisory groups (PAGs) have given input for different Long COVID studies.
Symptom Burden Questionnaire for Long COVID (SBQ-LC) was made with patient involvement and has been licensed more than 90 times across 50 countries.
4/2022 BMJ: Development and validation of the symptom burden questionnaire for long covid (SBQ-LC): Rasch analysis - PubMed https://buff.ly/3TFqiZ3
Charlie McCone with #LongCOVID is trying to get Social Security disability, a thread
3/16/23
3/16/23 Lancet preprint: Persisting Olfactory Impairments in Recovered COVID-19 Patient: A Three-Year Follow-Up https://buff.ly/3ZVNN20
155 COVID-19 recovered patients and 170 healthy controls with a three-year follow-up.
95% of patients recovered their sense of smell by 3 years.
COVID increases long term cardiovascular risks
3/6/23 BioRxiV (Cleveland Clinic): Immunometabolic rewiring in long COVID patients with chronic headache https://buff.ly/3FruQfE
Prospective study. Longitudinal multi-omics analysis of blood leukocyte transcriptomics, plasma proteomics and metabolomics of long COVID patients with chronic headache.
Summary:
(i) Hyperinflammation was involved in triggering the onset of long COVID-headache
(ii) Sustained inflammation might contribute to the development of long-term post-COVID headache,
Despite viral clearance, long COVID patients continued to sustain low-grade inflammation, evidenced by persistent increases of inflammatory markers such as IL-6 and IFN-γ and chemokines such as CXCL10, CCL7 and CCL8 even up to more than 3 months post headache symptom onset.
(iii) immuno-metabolic reprogramming in long COVID-headache patients might drive the accumulation of arginine and lipid metabolites to fuel sustained inflammation via nitric oxide-based pro-inflammation.
Role of proinflammatory M1 macrophage-driven sustained inflammation in long COVID, likely contributing to chronic headache.
Apart from lipid metabolism, arginine metabolism also plays an indispensable role in macrophage polarization, in which pro-inflammatory M1 macrophages convert arginine to citrulline and nitric oxide (NO) through NO synthase (NOS).
(iv) Dysregulated neurotransmitter metabolism (serotonin, dopamine, glutamate, and GABA) might be the hallmark of long COVID chronic headache (Fig. 8).
CRP level did not predict long COVID headaches
Increased glucose metabolism prior to the onset of headache symptoms, may be the energy source to ignite hyper-inflammation.
Fig 8. Overview of immuno-metabolic rewiring in long COVID patients with chronic headache
3/14/23 PNAS (Sweden): Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age https://buff.ly/3yLlUOn
OC43 virus, one of the coronaviruses that cause common colds, boosts the immune response to COVID-19 in young children (age 2 and age 6) via memory CD4+ T cells.
The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood.
Cross-reactive CD4+ T cells to COVID and the OC43 cold virus seen early in childhood decline with age.
3/14/23 Reuters: U.S. FDA expands authorization of Pfizer bivalent COVID-19 shots in kids ages 6 months to 4 years https://buff.ly/40f6tK5
The amended authorization is for children six months through four years of age who have completed their initial three-dose vaccination with Pfizer's original shot.
3/15/23 International Long COVID Awareness Day- Putrino Lab offers a message of hope
3/15/23 Senators Markey, Kaine, Duckworth Reintroduce Bill to Help Millions of Americans Living With Long COVID https://buff.ly/3JrHZ9B
3/14/23 Nature: Who’s the most infectious of all? The COVID super-superspreaders https://buff.ly/3Lu8Qo6
17 studies
Some people shed more virus particles than others do:
20% of people with COVID were 3x more infectious than an average person.
6% of people with COVID were 8x more infectious.
3/16/23 STATnews: FDA offers radio silence on question of spring Covid boosters, as other countries push ahead https://buff.ly/3YY0VlT
“People who are at high risk of developing severe illness if they contract Covid are being offered spring booster shots in Canada and the UK. Will the US follow suit? Not clear, but it's looking like probably not.”
3/12/23 SF Chronicle: Is it time for another COVID booster shot? Here's what officials are saying https://buff.ly/3ZIu59P
Many got the bivalent booster more than 6 months ago. So far, the CDC has not yet recommended another booster and may be moving towards a yearly vaccination like the flu.
But COVID is not the flu- it does not circulate only in the late fall and winter.
Last March, before the rollout of the bivalent boosters, the CDC recommended that those who were immunocompromised or over age 50 receive an updated shot four months after their previous dose.
Those who are immunocompromised or at high risk for disease — in a tough spot after the FDA last month pulled its authorization of Evusheld, a preventive monoclonal antibody treatment for COVID-19 — may consider getting a sixth shot now at their local pharmacy, said Dr. Eric Topol.
But that’s not an official recommendation, and doctors are taking a wait-and-see attitude.
The U.K. this past week announced a plan to offer vulnerable people an additional COVID booster shot this spring, targeting those 75 and older and residents of care homes, plus immunocompromised people aged 5 and over.
Charlie McCone discusses Long COVID on ABC 7 news
“We can’t move past COVID until we have treatments for Long COVID.”
3/13/23 Cell: A meta-analysis of the associations between insufficient sleep duration and antibody response to vaccination https://buff.ly/3mSfZnN
Sleeping less than 6 hours per night in the days around COVID vaccination led to lower antibody levels, especially in men.
Optimizing sleep duration around the time of vaccination may boost antibody response.
3/7/23 Lancet preprint: Differences in SARS-CoV-2 Specific Humoral and Cellular Immune Responses after Contralateral and Ipsilateral COVID-19 Vaccination https://buff.ly/3ZTATlq
Giving the second Pfizer mRNA vaccine dose in the same arm as the first dose, caused higher neutralizing antibody activity and higher levels of spike-specific CD8 T-cells.
This may be related to boosting the same lymph nodes that drain the area of vaccination.
3/13/23 MedPage Today: CDC, FDA Heads Fire Back at Ladapo Letter https://buff.ly/40q4enp
The heads of the FDA and CDC sent a scathing 4-page letter to Florida's Surgeon General warning him that Ladapo's latest VAERS analysis was "incorrect, misleading and could be harmful to the American public."
1/2022 Nature: COVID-19: Endemic doesn’t mean harmless https://buff.ly/3GTOHCK
“To an epidemiologist, an endemic infection is one in which overall rates are static — not rising, not falling.
"The same virus can cause endemic, epidemic or pandemic infections: it depends on the interplay of a population’s behavior, demographic structure, susceptibility and immunity, plus whether viral variants emerge."
Malaria, tuberculosis are endemic in some areas.
Malaria killed more than 600,000 people in 2020. Ten million fell ill with tuberculosis that same year and 1.5 million died.
3/16/23 TF1 info: Trois ans du confinement : le Covid long, "la bombe à retardement" de la pandémie https://buff.ly/3n4NraM
10 à 20% d'entre eux sont atteints de Covid long
"Autre difficulté dans le Covid long : la prise en charge, tant les symptômes et la durée varient.
"C'est un problème de santé publique", continue le spécialiste. "Des athlètes ne peuvent plus concourir dans leur discipline sportive, des adultes ne peuvent plus aller au travail, des enfants ne peuvent plus aller à l'école... Ces invalidités sont d'une grande gravité."