COVID news and more 3/31/23
XBB.1.5 is at about 88% of cases now. There are a few new subvariants (XBB.1.16, XBB.1.9.1) which are descendants of XBB.1.5 that are being watched around the world. In India, XBB.1.16 is dominant and it is starting to be seen in Europe and North America. XBB.1.16 may have a growth advantage over XBB.1.5. It is unknown if these new variants will cause a new wave of infection or if our collective immunity wall will continue to protect us against them.
Here in the US, XBB.1.9.1 has been slowly rising by about 1% per week. Previously, the SARS-CoV-2 virus evolved with mutations in the spike protein, but now it appears that the virus is making mutations in the non-spike regions like the N protein and ORF proteins. According to Dr. Vipin Vashishtha, these types of new mutations may make it more difficult for our T cells to detect and target infected cells. We will have to wait to see if our immunity wall can continue to stop new subvariants and for now, cases and hospitalizations are much lower than before.
The New York Times is no longer reporting daily COVID cases and hospitalizations because the CDC is now only reporting weekly. Cases and hospitalizations do appear in the high range in parts of Montana, Arizona, Nebraska, Oklahoma and Wisconsin. But, wastewater virus levels appear lower in most places in the US now per the CDC map which is reassuring.
Vaccines
A new study shows that in people younger than age 30, mRNA vaccination is not associated with increased mortality, but that some young women had a slightly increased risk of death after AstraZeneca vaccination. In general, COVID infections were found to be more dangerous for young people compared to risk from vaccines. The NEJM reports no increase in stroke, heart attack or pulmonary embolism after the mRNA bivalent booster. Regarding people with B cell blood cancers like leukemia and lymphoma, a new study shows that vaccination can be helpful to boost T cell immunity against COVID.
Pregnancy
A large retrospective cohort study shows that mRNA COVID vaccination was associated with a lower rate of several adverse pregnancy outcomes including perinatal death, preterm delivery, neonates with very low birth weight, and NICU admission. A different study in JAMA shows that boys exposed to SARS-CoV-2 infection in utero may be at increased risk for neurodevelopmental disorders, but the same was not found in girls. Baby boys born to mothers with COVID infection in pregnancy had a significant increase of neurodevelopmental diagnoses at 12 months, even when controlling for preterm delivery. It is not known if this could lead to an increased risk of autism or schizophrenia in boys born to mothers who had COVID infection in pregnancy. There is a known difference in placental immune responses to a COVID infection seen in placentas from boys versus placentas from girls which may be playing a role.
Antiviral medications
Scientists have seen a few SARS-CoV-2 variants that are naturally resistant to Paxlovid and Ensitrelvir, but this was expected to happen at some point. We will need to continue to monitor variants and to develop new protease inhibitors and other antiviral drugs. In the future, papain-like protease (PLpro) inhibitor drugs may be used to fight SARS-CoV-2.
Dexamethasone has been shown to help treat severe acute COVID infections and now we know how. A new study shows that dexamethasone affects ion channel-mediated immune cell function, including cytokine production, to decrease risk of cytokine storm and death. In a different study, Palmitoylethanolamide (PEA) supplementation was found to reduce sP-selectin, IL-2, IL-1β levels in acute COVID infections. P-selectin is a key thrombo-inflammatory marker which is stored in platelets and endothelial cells that has been linked to COVID-19 complications.
Long COVID
A survey of people in the UK who have Long COVID, show that two-thirds of them experienced unfair treatment at work including bullying and disciplinary action. Fourteen percent lost their jobs because of Long COVID. Ironically, half of the respondents had contracted their COVID infection at work as they were front line workers.
We do not yet know what will be sequelae from SARS-CoV-2 eighteen years from now, but a new small study on 14 healthcare workers in China who got SARS-1 in 2003 shows that they still have abnormal metabolism of amino acids and lipids, B cell activation and reduced function of some T cells. They also noted an increase in fatigue, osteoporosis and necrosis of the femoral head.
Non-COVID news
Narcan nasal spray will be available over-the-counter soon to help treat opioid overdoses. A point-of-care PCR test from Visby Medical was approved by the FDA to detect gonorrhea, chlamydia and trichomonas in under 30 minutes using self-collected swabs.
ProPublica did an exposé on how Cigna insurance instantly rejects medical claims without even opening patient files, thus saving the company millions of dollars while costing patients more. Other insurance companies are thought to be doing the same.
The amount of time that kids spend online may alter their developing brains, increasing their risk for mood disorders. In fact, 9 and 10 year old children who spent more time on smartphones, tablets, video games and television had structural brain changes and a small but significant increase in anxiety and depression two years later. Last year’s severe hepatitis outbreak in children that caused 7% to need liver transplants appears to have been caused by Adeno-Associated Virus 2 (AAV2).
Lactation cookies might taste good, but they did not increase milk production in humans in a randomized control trial. A new study looks at the link between obesity and inflammation and its effect on autoimmunity with chronic stimulation of innate and adaptive immune cells. Mitochondrial antioxidant and dietary supplement MitoQ reversed organ damage from HIV infection and antiretroviral therapy in humanized mice studied at UCLA.
Have a good weekend,
Ruth Ann Crystal MD
Twitter: https://twitter.com/CatchTheBaby
Other news:
3/14/23 FDA Clears Single-Use PCR Test That Rapidly Detects STIs in Women https://buff.ly/3lNcZJl
30 minute point-of-care PCR test for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in women. From Visby Medical.
3/22/23 Science: Deadly parasite threatens California sea otters https://buff.ly/42MeI24
New strain of Toxoplasma kills the marine mammals quickly and may pose a seafood hazard for humans.
3/26/23 The Guardian: NHS staff shortages in England could exceed 570,000 by 2036, leaked document warns https://buff.ly/42HwT9l
The NHS is already operating with 154,000 fewer full-time staff than it needs, and that number could balloon to 571,000 staff by 2036 on current trends.
3/25/23 ProPublica: How Cigna Saves Millions by Having Its Doctors Reject Claims Without Reading Them https://buff.ly/3LRPQQK
“Van Terheyden was right to be suspicious. His claim was just one of roughly 60,000 that Dr. Dopke denied in a single month last year, according to internal Cigna records.”
The Cigna review system allows its physicians to instantly reject claims without opening patient files.
3/23/23 NPR: 80-hour weeks and roaches in the call room? More medical residents unionize https://buff.ly/3TLlkKc
3/13/23 Effectiveness of Lactation Cookies on Human Milk Production Rates: A Randomized Controlled Trial https://buff.ly/3ZifEs9
(n=176) were randomly assigned to eat daily Lactation Cookies with “galactagogues” (oatmeal, brewer’s yeast, flax seeds, and fenugreek), or conventional cookies.
Lactation cookies do not increase milk production.
3/29/23 NPR: The FDA has approved the overdose-reversing drug Narcan for over-the-counter sales https://buff.ly/3ZnzTol
2/24/23 JAMA: Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes https://buff.ly/3Za4Xsu
https://jamanetwork.com/journals/jama/fullarticle/2801974
C-peptide levels is a measure of pancreatic beta cell function.
Verapamil partially preserved C-peptide secretion at 1 year and was well tolerated in children and adolescents with newly diagnosed type 1 diabetes.
3/24/23 Science Daily (UCLA): Dietary supplement MitoQ, a mitochondrial antioxidant, may reverse organ damage caused by HIV and antiretroviral therapy as seen in study in humanized mice https://buff.ly/3M1UZWl
MitoQ may be a treatment for mitochondrial dysfunction in HIV in humans.
3/29/23 HealthDay: Too Much Time Online Might Raise Kids' Odds for Mental Health Woes: Study https://buff.ly/3M8MgSe
Children’s screen use may alter developing brains, increase their risk for mood disorders.
3/30/23 Nature: Severe Hepatitis outbreak in children linked to AAV2 virus https://buff.ly/42RE5Qi
More than 1000 children with severe hepatitis in Spring 2022.
7.3% required liver transplant.
Adeno-associated virus 2 found in the children's blood and liver.
3/30/23 Science: The link between Obesity and Autoimmunity https://buff.ly/3zlVrr6
Metabolic overload from obesity can affect immunometabolism, which can alter susceptibility to autoimmune diseases.
Undernutrition impairs immunity, causing inefficient responses to infections and vaccinations.
Overnutrition favors chronic activation of both innate and adaptive immune cells, with subsequent (low-grade) systemic inflammation.
h/t Eric Topol
COVID news:
World reported cases https://medriva.com/charts/world-monitor.php
These numbers do not make sense.
US reported cases https://medriva.com/charts/usa-monitor.php
https://www.nytimes.com/interactive/2021/us/covid-cases.html
US cases
NY Times new tracking from weekly CDC reports https://www.nytimes.com/interactive/2023/us/covid-cases.html
Variant tracker in US: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
XBB.1.5 is at 87.9%
XBB.1.9.1: went from 1% to 2.4% to 3.3% to 4.6% over 4 weeks. It is slowly rising.
3/31/23 Thread from vaccine expert Vipin M. Vashishtha:
After successfully employing ‘convergent evolution’ at the Spike protein, the SARS-CoV-2 virus has now adopted a new strategy: to evade T cells immunity by inducing more mutations in the non-spike regions like in the N protein & ORF proteins.
These changes are manifested in new emerging sub-lineages like XBB.1.16, XBB.1.9.1, CH.1.1.12 & other offsprings of XBB.1.5. XBB.1.16 & these newer sublineages are more efficiently blocking the communication between virus-infected cells and T cells….Hence, making it difficult for T cells to detect and target infected cells, thus allowing the virus to replicate, spread unhindered and persist longer in the body.
Wastewater Monitoring:
CDC Wastewater Monitor https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
Sewer Coronavirus Alert Network (SCAN) project by Stanford University:
3/29/23 Science: Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors https://buff.ly/42WOmuD
A natural Mpro variation ∆P168 confers resistance to nirmatrelvir (Paxlovid) and ensitrelvir (Xocova).
We need to monitor for resistant SARS-CoV-2 variants and to develop new protease inhibitors and other antiviral drugs.
3/29/23 NEJM: No Increase In Stroke, Myocardial Infarction, and Pulmonary Embolism after Bivalent Booster https://buff.ly/3Ztv3Wy
3/28/23 JAMA: Risk of Adverse Surgical Outcomes Among Patients With Recent COVID-19 Infection https://buff.ly/3M5xDiL
29,093 patients (mean age, 66.1 years; 90.0% men; 67.5% White patients) underwent surgery at VA hospitals.
Recent COVID-19 infection was not associated with risk of adverse postoperative outcomes, regardless of timing within the previous 60 days.
3/28/23 Eurekalert (Australia): COVID vaccine induces robust T cell responses in blood cancer patients https://buff.ly/3GsBoLB
https://www.eurekalert.org/news-releases/984301
Even if people have a blood cancer affecting their B cells, mRNA vaccination can boost their T cell immunity.
Cell Reports pre-print: Robust SARS-CoV-2 T cell responses with common TCRαβ motifs towards COVID-19 vaccines in hematological malignancy patients impacting B cell immunity https://buff.ly/42R3hX8
3/28/23 Nature: Potent and selective covalent inhibition of the papain-like protease (PLpro) from SARS-CoV-2 https://buff.ly/3JYoR3d
Opportunity for further development of covalent PLpro inhibitors.
3/24/23 Frontiers in Immunology: Immune and ionic mechanisms mediating the effect of Dexamethasone in severe COVID-19 https://buff.ly/3zDzhRj
Dexamethasone affects ion channel-mediated immune cell function, including cytokine production, to decrease risk of cytokine storm and death in severe COVID infections.
Dexamethasone treatment in severe COVID-19 inhibited pro-inflammatory and immune exhaustion pathways, circulating cytotoxic and Th1 cells, interferon (IFN) signaling, genes involved in cytokine storm, and Ca2+ signaling.
Dexamethasone attenuates inflammatory cytokine release via Kv1.3 suppression.
3/23/23 JAMA: Neurodevelopment of Offspring of Mothers With SARS-CoV-2 Infection During Pregnancy https://buff.ly/3lSNXbQ
In 18,355 babies born during the COVID-19 pandemic, there was a statistically significant increase of neurodevelopmental diagnoses in boys but not girls at 1 year of age, even when controlling for preterm delivery.
Male offspring risk (adjusted OR, 1.94) but not female offspring (adjusted OR, 0.89) have increased neurodevelopmental diagnoses at 12 months of age.
While it is not clear that these changes will lead to autism, intellectual disability or schizophrenia, other research has shown that maternal infection during pregnancy can be associated with increased risk for these diseases.
This difference may be related to placental immune response: Prior studies have shown that SARS-CoV-2 infections in pregnancy show an upregulation of types 1, 2 and 3 interferon signaling in male placentas and downregulation in female placentas.
3/2023 Green Journal OB GYN: Pregnancy Outcomes in Patients After Completion of the mRNA Coronavirus Disease 2019 (COVID-19) Vaccination Series Compared With Unvaccinated Patients https://buff.ly/3zj4zfR
2,069 in the vaccination group and 13,796 in the control group in 2021.
In a large retrospective cohort study, receipt of the primary mRNA COVID-19 vaccination series was associated with a lower rate of several adverse pregnancy outcomes, including perinatal death, preterm delivery, neonates with very low birth weight, and NICU admission.
3/17/23 Illinois' Bold Move: 60,000 HEPA Air Purifiers To Be Distributed In Schools To Battle Respiratory Viruses https://buff.ly/42NAqTv
3/26/23
2/27/23 eClinical Medicine: Multiomic characterisation of the long-term sequelae of SARS-1 survivors: a clinical observational study https://buff.ly/3zcaqnm
n = 14 health workers in China who got SARS in 2003.
18 years after SARS-1 infection
Persistent fatigue, osteoporosis and necrosis of the femoral head.
Plasma multiomics analysis indicated an abnormal metabolism of amino acids and lipids, promoted host defense immune responses to bacteria and external stimuli, B-cell activation, and enhanced cytotoxicity of CD8+ T cells but impaired antigen presentation capacity of CD4+ T cells.
Symptomatic Long COVID (LC) vs. Silent Long COVID
3/24/23 Medical Xpress: Researchers expand disease tracking in wastewater https://buff.ly/3JRp7ks
Researchers at Stanford University, in collaboration with Emory University and Verily Life Sciences, have collected fast and accurate readings of a whole suite of respiratory viruses in their local Santa Clara sewer system.
Wastewater is currently the only source for accurate information about COVID-19 rates in communities. PCR testing is no longer widely available, and most people swab themselves at home where their results never reach public health agencies.
Since the COVID pandemic, the researchers are tracking Influenza A and B, RSV, Parainfluenza and others in addition to SARS-CoV-2 levels in wastewater.
3/22/23 Lancet Microbe: Wastewater concentrations of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, rhinovirus, and seasonal coronavirus nucleic-acids during the COVID-19 pandemic: a surveillance study https://buff.ly/3JPYSLc
Wastewater measures virus levels for an entire community. Results can be available within 24 hours which can guide public health responses.
3/26/23 The Guardian: Two-thirds of UK workers with long Covid have faced unfair treatment, says report https://buff.ly/3zu0TIx
According to ONS data, 2 million people in the UK have Long COVID.
Adjustments that could help people with Long COVID include flexible working, disability leave and a phased return to the workplace.
Of 3000 people with Long COVID surveyed:
2/3 experienced unfair treatment (harassment, disbelieved about LC, or threatened with disciplinary action).
14% lost their job.
3/27/23 Trades Union Congress (TUC): Workers' experience of Long Covid https://buff.ly/42Hv9wO
14% had lost their job because of reasons connected to Long Covid.
66% said they had experienced one or more types of unfair treatment at work.
16% bullying and/or harassment at work
8% threatened with disciplinary action
23% said their employer has questioned whether they have Long Covid and/or their symptoms.
Half of respondents (49%) believe they contracted Covid-19 at work.
3/27/23 Nature: Risk of death following COVID-19 vaccination or positive SARS-CoV-2 test in young people in England https://buff.ly/3ndGAfh
No increase in death in young people (under age 30) after mRNA vaccination, but there was an increase in death in young women after a first dose of AstraZeneca vaccination.
COVID infections (i.e. positive SARS-CoV-2 test) however did increase cardiac and all-cause death in young people.
3/14/23 Salon: Struggling with long COVID? You may find yourself in "Return to Oz" https://buff.ly/40uA6aN
"Return to Oz" speaks to long COVID the way few films have since or even before the pandemic, its characters, fantastical though they may be, struggling with cognitive issues like memory and speech, wrestling with forgiving themselves and most of all, being believed.”
3/7/23 Have COVID? Request Paxlovid Even if You're 'Not High Risk.' Here's Why | KQED https://buff.ly/3KjZDOm
Online 2/2023. 10/2022 J Nutr: Palmitoylethanolamide (PEA) Reduces Proinflammatory Markers in Unvaccinated Adults Recently Diagnosed with COVID-19: A Randomized Controlled Trial https://buff.ly/42OwWA
n = 30 PEA; n = 30 controls
PEA supplementation caused reduced sP-selectin, IL-2, IL-1β levels.
P-selectin is a key thrombo-inflammatory marker, is stored in platelets and endothelial cells that has been linked to COVID-19 complications.