COVID news and more 4/15/23
XBB1.16 levels are now doubling each week and it is just starting to put pressure on XBB.1.5. However, XBB.1.16 is not expected to make a big wave of infection here in the United States. Wastewater testing shows us that virus levels are fairly low overall in the U.S. now. Since case numbers are not being accurately reported now, wastewater is the most reliable way to tell what is going on.
In some good news, the White House is launching a $5 billion program called “Project Next Gen” to expedite the development of vaccines and therapies for SARS-CoV-2. The project will have three goals: making long-lasting monoclonal antibodies, nasal vaccines for mucosal immunity and pan-coronavirus vaccines that can work against multiple SARS-CoV-2 variants and even different types of coronaviruses. This week, two different labs reported monoclonal antibodies that can neutralize the latest variants. The Ho lab from Columbia University reported that human monoclonal antibodies called 12–16 and 12–19 can neutralize all SARS-CoV-2 variants including BQ.1.1 and XBB.1.5. Weill Cornell Medicine reported that an antibody called S7-28–1157 found from the blood of someone who had a prior COVID infection was highly effective at neutralizing all of the original variants and also seven Omicron subvariants. Neither of these monoclonal antibodies are available commercially yet.
The SARS-CoV-2 virus, and especially Omicron variants, can suppress MHC-I expression in human cells which allows the virus to evade CD8 T cells. Per Dr. Iwasaki, this would not lead to a generalized immunodeficiency, but reflects a specific survival mechanism for SARS-CoV-2. Because the virus can evade immunity from our T cells, infected cells may survive better which could lead to viral reservoirs of SARS-CoV-2 in the human body. Antiviral or monoclonal antibody therapy may be needed to rid the body of these viral reservoirs in human tissues.
Regarding T cells, this week, a group reported that an in silico, AI-designed T cell vaccine appeared to work well in hamsters. The vaccine used 17 epitopes from viral proteins to alert T cells to the virus. Clinical studies have not yet been done.
Therapies
The Infectious Disease Society of America has new guidelines regarding convalescent plasma saying that it should not be used for immunocompetent or immunocompromised people who are hospitalized with COVID-19 infections. Fortunately, a study from the Sato lab last week showed that the XBB variants appear to be at least somewhat susceptible to the monoclonal antibody Sotrovimab.
Long Covid
An interesting new study from Italy found that in post COVID-19 (Long COVID) patients who suffered from cognitive issues, parts of their brain did not have normal blood flow. The group used an Arterial Spin Labeling (ASL) brain MRI protocol to measure cerebral blood flow. Cerebral hypoperfusion (low blood flow in the brain) in the long Covid group predominantly affected the frontal cortex, and the parietal and temporal cortex, especially in the right hemisphere. The figure included below shows that there is a lot less blood flow in the brains of people with Long COVID and cognitive symptoms like brain fog.
A study from Brazil from January 2023 looking at doctors and nurses who had prior mild Covid infections, unexpectedly, one and four people were found to have cognitive deficits in visuoconstruction skills. Normally seen in 5 to 8% of people in the general population, the visuoconstruction defects were found in 25% of the people who had previously had mild COVID infections. For the study, people were asked to copy a complex drawing, and those who produced abnormal drawings showed an increased volume of white matter on brain MRI thought to be due to brain inflammation. PET scans showed decreased glucose uptake in certain areas of the brain which could be related to brain metabolism. In the patients who could not draw the figure correctly, inflammatory markers were also found to be elevated in their blood.
AHRQ is seeking applications fromLong COVID clinics that wish to implement a new model of care. Eric Topol tweeted about a patient who saw multiple physicians and neurologists over a six month period and was given the diagnosis of long Covid. However, her relative entered her symptoms into the ChatGPT AI program, and it found the true diagnosis- an autoimmune disease related to a CASPR antibody. COVID infections can increase the risk of autoimmune diseases and It can be important to test for some of these esoteric autoimmune antibodies in some patients with long Covid. A review article this week in Nature Rheumatology discussed the increased risk of different autoimmune diseases after COVID infections which can include new onset rheumatoid arthritis, lupus, inflammatory bowel disease, vasculitis and Type I diabetes.
Pediatrics
Young infants less than six months of age are unable to get vaccinated against SARS-CoV-2. A new study in Pediatrics shows that infants born to pregnant people with a COVID infection had five times the risk of getting an Omicron infection than during previous COVID waves. Omicron has an increased transmissibility for infants and therefore it is very important to vaccinate people who are pregnant or who are postpartum so as to protect the baby. Last week, an article showed that boys had a higher risk of neurodevelopmental issues at one year of age after a maternal COVID infection. This week, an article in JAMA showed that babies whose mothers had mild or asymptomatic COVID infection at any time during their pregnancy were found to be developmentally similar to those whose mothers never had Covid. The infants were tested for cognition, language, and motor development at ages 5 to 11 months. There was a case report this week of two infants with brain injury after maternal COVID infection. However, those children were born early in the pandemic before COVID vaccines were available.
Vaccines
There were two important studies on the bivalent booster vaccine this week. The bivalent booster has mRNA to both the original SARS-CoV-2 virus and to Omicron BA 4/5. Real world data from Israel shows that the bivalent booster decreased hospitalizations by 72% and deaths by 68% in people over age 65. Another study in the New England Journal of Medicine showed that the bivalent boosters also work well against newer Omicron subvariants BQ.1(1) and XBB subvariants.
Other news
In non-Covid news this week, experts in the United Kingdom are worried that parking lots could collapse under the weight of heavy electric vehicles. Electric vehicles are roughly 33% heavier than their gasoline counterparts. For instance, a Ford F-150 pickup electric pick up is 2000 to 3000 pounds heavier than the F-150 gasoline version. The heavy weight of electric vehicles could also do more damage to smaller and lighter non-electric cars in an accident.
A new study in Cell magazine showed that bacteria called lactobacillus reuteri make a tryptophan metabolite which helps immune checkpoint inhibitor treatment in mice with melanoma. It is interesting to see that the microbiome can affect cancer treatments. There was also a comprehensive review in Cell magazine about advances in cancer immunotherapy.
68 years ago, Dr. Jonas Salk’s polio vaccine was declared safe and successful which led to the elimination of polio here. We have come a long way with new vaccine technology since that time. The FDA has put out a warning that some Halyard masks and respirators do not work.
The White House also warned that some illegal fentanyl tablets are being laced with a horse tranquilizer called Xylazine (aka tranq). Because Xylazine is a tranquilizer sedative, and not an opioid, naloxone cannot reverse this drug.
One of the most exciting scientific news from this week is that a new biomarker called α-synuclein can tell if someone has Parkinson’s disease. Alpha-synuclein can pick up if a person has very early disease and it may be a target for therapy for Parkinson’s disease in the future.
And finally, psychologists have discovered the best dance moves to attract the opposite sex. It turns out that heterosexual men and women have distinct preferences in the type of dancing they find attractive including “a bizarre preference for men who used faster bending and twisting movements of their right knee.”
Have a good weekend,
Ruth Ann Crystal MD
Twitter: https://twitter.com/CatchTheBaby
Other news:
1/11/23 AP: US official warns at NTSB of risks posed by heavy electric vehicles https://buff.ly/3QwYOTH
In a crash, a heavy electric car can do more damage to a lighter gasoline car.
Ford’s F-150 Lightning EV pickup is 2,000 to 3,000 pounds heavier than the same model’s combustion version. The Mustang Mach E electric SUV and the Volvo XC40 EV, she said, are roughly 33% heavier than their gasoline counterparts.
“These bigger, heavier batteries are going to cause more damage,” he said. “It’s a simple matter of mass and speed.”
4/9/23 Business Insider: Experts fear deteriorating parking lots could collapse under the weight of heavy electric vehicles, says report https://buff.ly/41eGUsZ
Electric vehicles are significantly heavier than gasoline-powered cars, given the weight of the batteries necessary to power them.
4/12/23 FDA: Protection Failure with Certain O&M Halyard Respirators and Masks https://buff.ly/3ohWQwx
Halyard Surgical N95 Respirators, Surgical Masks, and Pediatric Face Masks recall
3/31/23 Business Insider: A library went viral for having baby cribs attached to its desks. The single mom behind it says she wanted the library to serve entire families. https://buff.ly/40VBEuH
Cancer treatment and the microbiome
4/6/23 Cell: Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment https://buff.ly/401xOie
Probiotic Lactobacillus reuteri (Lr) translocates to, colonizes, and persists within melanoma, where via its released dietary tryptophan catabolite I3A, it locally promotes interferon-γ-producing CD8 T cells, thereby bolstering immune checkpoint inhibitor (ICI) treatment.
4/7/23 CNN: Maternity units are closing across America, forcing expectant mothers to hit the road https://buff.ly/3MArIlK
States with the highest loss of access to obstetrical care are Minnesota, Texas, Iowa, Kansas and Wisconsin.
Without physicians and nurses to work in these areas, the units must close.
4/11/23
4/12/23 NPR quits Twitter after being falsely labeled as 'state-affiliated media' https://buff.ly/3UKIgKd
4/12/23 Hill: White House says fentanyl laced with ‘tranq’ drug Xylazine is ’emerging threat’ https://buff.ly/43u1mbi
Xylazine, aka “tranq,” is a sedative and pain reliever for large animals. It is not an opioid so naloxone cannot reverse it.
4/3/23 Am J Nutrition: Dietary interventions for perinatal depression and anxiety: a systematic review and meta-analysis of randomized controlled trials https://buff.ly/40XCgzT
Polyunsaturated fatty acids (PUFAs) and elemental metals (iron, zinc, and magnesium) were not found to improve symptoms of perinatal depression.
Meta-analysis showed that Vitamin D 1800 to 3500 IU per day resulted in small to medium improvements in perinatal depression and randomized clinical trials should be done.
4/2023 Annals of Family Medicine: Community Support Persons (CSP) and Mitigating Obstetric Racism During Childbirth https://buff.ly/41q5PKh
“involving community support persons in the birthing experience can counter obstetric racism impacting the maternal health experience for Black mothers.” The “approach contributes to safer hospital environments and effectively addresses implicit bias.”
4/13/23 Study: More Opioid Use Disorder (OUD) Patients Stay in Treatment When Offered Buprenorphine via Telemedicine - MedCity News https://buff.ly/3zYQGUo
4/13/23 Cell: Advances in Cancer Immunotherapies https://buff.ly/43udh91
5/2023 Lancet Neurology: Assessment of heterogeneity among participants in the Parkinson's Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study https://buff.ly/3UwHkZL
α-synuclein seed amplification assays (SAAs) can differentiate people with Parkinson's disease from healthy controls. It detects very early prodromal Parkinson’s disease before diagnosis and could be a target for therapy.
Michael J. Fox Foundation: Breaking News: Parkinson's Disease Biomarker Found https://buff.ly/3zX7dsf
4/12/23 Good: Psychologists have discovered the specific dance moves that attract the opposite sex https://buff.ly/3UCcq1R
Two recent studies have shown that heterosexual men and women have distinct preferences in the type of dancing they find attractive.
COVID news:
World reported cases https://medriva.com/charts/world-monitor.php
US reported cases https://medriva.com/charts/usa-monitor.php
NY Times new tracking from weekly CDC reports https://www.nytimes.com/interactive/2023/us/covid-cases.html
CDC Community Transmission levels: https://covid.cdc.gov/covid-data-tracker/#county-view?list_select_state=all_states&list_select_county=all_counties&data-type=Risk
Walgreens positivity rate: https://www.walgreens.com/businesssolutions/covid-19-index.jsp
https://ourworldindata.org/coronavirus
Variant tracker in US: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
XBB.1.16 is almost doubling each week (2.1% to 3.9% to 7.2%)
Per Eric Topol, XBB.1.16 will become dominant but probably will not cause a significant wave like past variants, but we still should be cautious.
XBB.1.9.1 is gaining about 1% per week
Wastewater Monitoring:
CDC Wastewater Monitor https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
Biobot: https://biobot.io/data/
Sewer Coronavirus Alert Network (SCAN) project by Stanford University:
FYI for Long COVID clinics:
AHRQ link: https://grants.nih.gov/grants/guide/notice-files/NOT-HS-23-008.html
4/13/23 CBS video: Virus sniffing dogs latest weapon in battle against COVID https://buff.ly/3KCcoCz
These labradors can test 300 people for COVID in 30 minutes just by smelling their socks.
via Mary Pope Handy
4/13/23 Lancet (Israel): Effectiveness of a bivalent mRNA vaccine booster dose to prevent severe COVID-19 outcomes: a retrospective cohort study https://buff.ly/3KBbIxx
For people age 65+ who got the bivalent mRNA booster:
72% reduction in hospitalizations
68% reduction in death
4/12/23 NEJM: Durability of Bivalent Boosters against Omicron Subvariants https://buff.ly/41vYpoZ
Although the two bivalent mRNA vaccines were designed to target the BA.4/5 subvariants, they worked well against infection or severe infection with the BQ.1–BQ.1.1 and XBB–XBB.1.5 subvariants.
The vaccine effectiveness (VE) was higher against hospitalization and death than against infection and VE waned gradually from its peak over time.
VE for Moderna was higher than for Pfizer.
4/11/23 Frontiers Immunology: DNA immunization with in silico predicted T-cell epitopes protects against lethal SARS-CoV-2 infection in K18-hACE2 mice https://buff.ly/3KBpj7Y
The original COVID vaccines were targeted to B cells to make antibodies.
In silico (using computer modeling software) predicted MHC class I/II ligands were found to induce robust T-cell responses and protect against severe disease in K18-hACE2/BL6 mice susceptible to SARS-CoV-2 infection.
4/13/23 Medical Xpress: T-cell vaccine for COVID-19 may last longer than current vaccines https://buff.ly/3KAP4VV
"To our knowledge, this study is the first to show in vivo [in a living organism] protection against severe COVID-19 by an AI-designed T-cell vaccine," said Girish Kirimanjeswara, associate professor of veterinary and biomedical sciences, Penn State.
17 epitopes from SARS-CoV-2 proteins that are recognized by the immune system were used.
4/12/23 Nature Reviews Rheumatology: High risk of autoimmune diseases after COVID-19 https://buff.ly/3zXWCNK
SARS-CoV-2 infection is linked to a substantially increased risk of developing a diverse spectrum of new-onset autoimmune diseases including rheumatoid arthritis, lupus, inflammatory bowel disease, vasculitis and Type I diabetes.
4/12/23 IDSA COVID-19 Guideline, Part 1: Treatment and Management https://buff.ly/41picq4
4/10/23 Nature (Italy): Cerebral hypoperfusion in post-COVID-19 (Long COVID) cognitively impaired subjects revealed by arterial spin labeling MRI https://buff.ly/3KyB4Mi
n = 24 Long COVID patients with cognitive complaints
Arterial spin labeling (ASL) is a new brain MRI technique to measure cerebral blood flow (CBF).
There was significant hypoperfusion in a widespread cerebral network in the post-COVID-19 group, predominantly affecting the frontal cortex, as well as the parietal and temporal cortex, especially on the right.
Result of group analysis of MRI-ASL data. The group averaged cerebral blood flow (CBF) maps (ml/100 g/min) calculated for the post-COVID-19 group (left column) and healthy subjects (middle column). Right column depicts regions that show significant hypoperfusion in post-COVID-19 patients compared to healthy controls.
4/10/23 PNAS: Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants https://buff.ly/41nJH3h
SARS-CoV-2 virus encodes multiple viral factors that can modulate major histocompatibility complex class I (MHC-I) expression in the host cells.
SARS-CoV-2, and especially Omicron, suppress MHC-I which helps it to evade CD8 T cell recognition.
Omicron subvariants are even more capable than other VOCs in suppressing MHC I expression to evade CD8 T cell immunity.
Such a mechanism will not lead to generalized immunodeficiency but reflects a specific survival mechanism for SARS-CoV-2.
Immune evasion from CD8 T cells could allow infected cells to survive better in the host. The virus could establish a safe niche for prolonged replication. To eliminate such persistent reservoirs, we need to employ antivirals or antibody therapy.
4/10/23 Wash Post: White House launching $5 billion program to speed coronavirus vaccines https://buff.ly/3KsI1hN
“Project Next Gen” will partner with private sector companies to expedite development of vaccines and therapies like “Operation Warp Speed” did in 2020.
Three goals:
Monoclonal antibodies that are long-lasting
Nasal vaccines for mucosal immunity
Pan-coronavirus vaccines that work against many viruses and multiple variants
4/10/23 BioRxiV (Ho lab, Columbia U): Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking https://buff.ly/3MEAJdB
Two human monoclonal antibodies, called 12-16 and 12-19, neutralize all SARS-CoV-2 variants tested, including BQ.1.1 and XBB.1.5.
They also blocked infection in hamsters challenged with Omicron BA.1 intranasally.
4/10/23 PNAS: Airborne disease transmission during indoor gatherings over multiple time scales: Modeling framework and policy implications https://buff.ly/3Kx4wCv
Ventilation and break times are critical in preventing high viral load levels.
4/9/23
4/7/23 Pediatrics: SARS-CoV-2 During Omicron Variant Predominance Among Infants Born to People With SARS-CoV-2 https://buff.ly/3Uw5bJ6
Babies aged 0 to 6 months cannot receive the COVID vaccines.
Infants were positive for COVID five times more during Omicron than during prior COVID waves.
Increased transmissibility of the Omicron variant to infants raises the importance of vaccinating people who are pregnant or postpartum so as to protect the baby.
4/7/23 Weill Cornell Medicine: Researchers Find an Antibody that Targets Omicron and Other SARS-CoV-2 Variants https://buff.ly/3GuCGFC
Antibodies were derived from patient blood samples. Antibody S728-1157 proved highly effective at neutralizing not only older variants but also seven subtypes of Omicron.
4/6/23 MedRxiV: Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir (Paxlovid) https://buff.ly/4057dB6
NMV-r treatment in non-hospitalized vaccinated patients with Covid-19 was associated with a reduction in the development of symptoms commonly observed with PASC and healthcare utilization.
4/6/23 iScience: SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients https://www.cell.com/iscience/fulltext/S2589-0042%2823%2900681-8#%20
In vitro exposure to SARS-CoV-2 activates the expression of the human endogenous retrovirus (HERV) HERV-W proinflammatory envelope protein (ENV) in peripheral blood mononuclear cells, in ACE2 receptor and infection-independent manner.
HERV-W ENV protein in serum and lymphocytes correlates with COVID-19 severity.
4/10/23 JAMA: Infant Neurodevelopment and Exposure to Maternal SARS-CoV-2 Infection During Pregnancy https://buff.ly/41s2EBE
n =407 babies born to mothers with mild or asymptomatic infection in pregnancy
No association was found between mild or asymptomatic maternal SARS-CoV-2 infection during pregnancy and infant cognition, language, or motor development at ages 5 to 11 months.
Babies whose mothers had mild or asymptomatic COVID-19 at any time during pregnancy were developing similarly to those whose mothers had never had COVID.
4/6/23 Pediatrics: Maternal SARS-CoV-2, Placental Changes and Brain Injury in 2 Neonates https://buff.ly/3nXgptU
Brain injury seen in 2 newborns whose mothers had COVID infections in pregnancy. The infants were born early in the pandemic, before Covid vaccines were available.
2 neonates born to SARS-CoV-2 positive mothers, who displayed early-onset (day 1) seizures, acquired microcephaly, and significant developmental delay over time.
In both infants, the neurologic findings at birth mimicked the presentation of hypoxic-ischemic encephalopathy of the newborn that progressed.
1/17/23 BrainFacts.org: The Risks of Even Mild COVID: 1 in 4 Showing Cognitive Deficits After Mild Case, Brazilian Study Finds https://buff.ly/4111o96
130 volunteers, mostly women, mean age of 38 years, four to six months post-infection with mild COVID-19 early in the pandemic. Most were physicians and nurses.
After mild COVID infection, 1 in 4 showed significant cognitive impairment in visuoconstruction skills — the visual ability to spatially reproduce designs or patterns — matching the increased levels of inflammation they were seeing on blood panels as well as in neuroimaging.
“Usually, you’d find like 5-8% of people in the general population in this age group that would show this kind of change. But 25% was too much. So, we investigated.”
Those who were drawing the bad copy showed increased volume of white matter on their brain MRIs, likely due to swelling from inflammation, while their PET images showed decreased brain glucose uptake, which researchers surmised was possibly due to cells being less active and thus consuming less glucose.
Marco Romano-Silva and colleagues reported people with mild COVID-19 who drew the impaired Rey-Osterrieth Complex Figure (ROCF) copies had markers of increased inflammation on blood panels.
1 in 4 people with mild COVID-19 struggled to draw the ROCF, indicating significant cognitive impairment in visuoconstruction skills.
8/24/22 Molecules: Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2 https://buff.ly/3Mx4TQb
When cell lysates transfected with S protein were incubated with nattokinase, the S protein was degraded in a dose- and time-dependent manner.
Immunofluorescence analysis showed that S protein on the cell surface was degraded when nattokinase was added to the culture medium.
Nattokinase exhibits potential for the inhibition of SARS-CoV-2 infection via S protein degradation.
FYI:
PolyBio Research Foundation https://buff.ly/4172uA9
18+ projects studying Long COVID
The LongCovid Research Consortium is a scientific collaboration to rapidly and comprehensively study LongCovid. The program includes scientists and clinicians from institutions including Harvard Medical School, Stanford University, the J. Craig Venter Institute, University of Pennsylvania, the Icahn School of Medicine at Mount Sinai and Yale University.