COVID news 12/23/22
Hi all,
As the arctic blast covers most of the country this weekend, a new unwanted guest has also arrived- the new variant XBB.1.5. XBB.1.5 is outpacing other variants quickly in the Northeastern U.S. A steep rise of hospitalizations in New York coincides with the arrival and growth of XBB.1.5. The bivalent booster should protect people against the new XBB.1.5 variant, but unfortunately only 14% of those eligible in the United States have gotten the updated bivalent booster so far.
This week, the CDC wastewater map shows high SARS-CoV-2 virus levels in wastewater across the United States. In the Bay Area, the level of SARS-CoV-2 is high but has decreased slightly since last week. Influenza A levels are also high in the Bay Area, although they may be peaking. It would be a good time to wear a mask and to stay home if you feel sick.
In Asia, there is a new wave of COVID cases in Hong Kong, South Korea and Japan. China has done a flip-flop from their zero-Covid policy and Covid infections are spreading across the country. China is reporting no new deaths from Covid, but the hearses lined up in front of busy crematoriums tell a very different story. It is expected that 800 million people in China, or about 10% of the planet's population, may become infected over the course of the next 90 days. This may have serious repercussions for the entire world. When so many people are infected at once, new mutations may arise. Having a significant portion of China sick at the same time could also affect the global economy and may increase the global spread of Covid as well.
New studies are giving us a glimpse into SARS-CoV-2 virus's effect on the human immune system. A new article shows that repeat exposures to the virus from infection or vaccination increase IgG antibodies made from B cells, but T cell levels plateau after three exposures. This supports a New England Journal article from last week that said that measuring levels of neutralizing antibodies should be used as correlates of protection (COPs) to predict clinical outcomes.
Another study this week looked at nasal biopsies from people with PASC-related loss of smell (hyposmia) which showed that T cell–mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue. Patients who lost their sense of smell were found to have 75% fewer sensory neurons in their nasal epithelium because of T cell mediated inflammation. Interestingly, an article from last March showed that the SARS-CoV-2 virus can reprogram macrophages to increase inflammation and can cause them to attack cells in the body. This type of macrophage proinflammatory reprogramming may be key to how microglia in the brain cause neuroinflammation in some long Covid patients.
A new article this week shows that children who have had Covid, can have persistent SARS-CoV-2 viral RNA in their tonsils and adenoids, which is associated with prolonged immune activation and clonal expansion of antigen specific B and T cells. A previous article from Brazil also noted residual virus in children’s tonsils and adenoids. These two articles bring up many questions. If children have persistent virus in their pharyngeal lymphoid tissues, could they still be infectious? If so, children could act as vectors and spread SARS-CoV-2 to others. It also brings some questions about how a reservoir of a virus might affect a child’s immune system over the long term.
Also regarding Covid infection in children, a new study shows that pediatric croup due to Omicron infection is much more severe than non-Covid croup. Children who had croup due to Omicron were much more likely to have stridor and hypoxia, and were more likely to need to be admitted to the hospital and to the ICU.
This week, someone asked me if I thought that their five-year-old child should get the new bivalent booster. I immediately said yes. Not only does the updated bivalent booster broaden immunity and help protect against the new variants like BQ 1.1 and XBB, giving a child a booster may help protect others as well. An article by Katelyn Jetelina regarding the bivalent boosters for kids under age 5 also brings up that getting the bivalent booster helps protect children against getting a co-infection of SARS-CoV-2 and other respiratory illnesses like the flu at the same time. Of note, only kids under five who received the initial Moderna series are eligible to receive the bivalent booster at this time.
A study this week showed that nasal IgA antibodies wane 9 months after Covid hospitalization and are not induced by subsequent vaccination. Nasal vaccines will be a next important step in protecting people from Covid as the subsequent nasal IgA antibodies produced can block viral transmission and prevent breakthrough infections.
STAT news reported that the RECOVER Long Covid trial from the NIH is unfortunately moving at a “glacial pace “. Enrollment for the studies has been very slow and so we will not have data probably until later in 2023. However, there is a new exciting discovery from Yale regarding treating brain fog and cognitive symptoms in people with Long COVID. Twelve patients with brain fog from long Covid were put on a combination of Guanfacine and NAC. Four of the 12 patients dropped out of the study, but of the remaining eight patients who completed the study, all eight had resolution of their long Covid brain fog. In fact, one of the patients needed to stop the Guanfacine for a short period because of hypotension and her brain fog returned. When she restarted the Guanfacine, her brain fog went away again. Now, this is a very small study and it needs to be repeated with a larger placebo matched study. But, it does give us hope that larger studies may show that Guanfacine and NAC used together could treat brain fog in people with long Covid.
Have a great holiday week.
Take care,
Ruth Ann Crystal MD
P.S. Make sure to check out the articles on how the shingles can increase your risk for stroke because of prothrombotic plasma exosomes and how future medicines that target BRD8 may be a promising treatment for glioblastoma brain tumors.
Comedy Wildlife Photography Awards winning images https://buff.ly/3HOdQlz
Jennifer Hadley
Jagdeep Rajput
12/21/22 Nature: Twitter changed science — what happens now it’s in turmoil? https://buff.ly/3WasGqW
Twitter had a major role in science communication. For many scientists, Twitter was an essential tool for collaboration and discovery — a source of real-time conversations around research papers, conference talks and wider topics in academia.
Musk fired many people who work on content moderation and Twitter will no longer stop misinformation about COVID-19 on the site.
Hate speech and abuse is rising on the site as well and people are trying other social media sites like Mastodon and Post.
12/21/22 Nature: BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network https://buff.ly/3Gc1L8F
Glioblastoma is the most common and deadly adult brain malignancy.
Bromodomain-containing protein 8 (BRD8) blocks the binding of protective p53 to chromatin.
Targeting BRD8 may be a promising therapeutic strategy for patients with TP53WT Glioblastoma.
f) BRD8 drives the EP400 complex as a barrier to restrain p53 targets by sequestering H2AZ and enforcing a compact chromatin state through its bromodomain (BD). High-level expression of BRD8 and H2AZ promotes cellular proliferation, whereas low expression triggers growth arrest. in TP53WT GBM cells. Highlighted within the tumor mass are proliferating Glioblastoma (GBM) cells.
12/20/22 The Conversation: Chickenpox and shingles virus lying dormant in your neurons can reactivate and increase your risk of stroke – new research identified a potential culprit https://buff.ly/3vc0ubf
Reactivation of the chicken pox and shingles virus VZV (Varicella Zoster Virus) causes the formation of exosomes containing high levels of clotting and inflammatory proteins in the blood of shingles patients.
Shingles patients have 9x the level of clotting proteins than healthy controls and the clotting protein exosomes were found to be elevated 3 months after the original shingles rash.
This may be a potential way that shingles can cause an increased risk of stroke during and soon after infection.
Original article:
10/6/22 J of Infectious Disease: Zoster-Associated Prothrombotic Plasma Exosomes and Increased Stroke Risk https://buff.ly/3WjlR6y
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COVID news:
https://medriva.com/charts/world-monitor.php
World
https://www.nytimes.com/interactive/2021/us/covid-cases.html
US cases
US hospitalizations- Seniors rates of hospitalizations are high
https://ourworldindata.org/coronavirus
Variant tracker in US: https://covid.cdc.gov/covid-data-tracker/#variant-proportions
Wow, XBB is now dominant in the Northeast:
Rapid growth of XBB.1.5
Wastewater Monitoring:
CDC Wastewater Monitor https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
Yikes again
Biobot: https://biobot.io/data/
Sewer Coronavirus Alert Network (SCAN) project by Stanford University:
Palo Alto Influenza A in the wastewater:
12/23/22 A new variant alert (XBB.1.5) by Eric Topol MD https://buff.ly/3YQbQ2f
In New York State, XBB evolved further to XBB.1.5, with 3 new mutations. A steep rise of hospitalizations in New York coincides with the arrival and growth of XBB.1.5.
XBB.1.5 has the most growth advantage as compared to BA.5 of any of the new variants.
XBB has already become dominant in the northeast.
12/22/22 STAT news: After nine months, an update on NIH’s long Covid research https://buff.ly/3FSOXTr
The NIH’s $1 billion long Covid research project is moving "at a glacial pace."
The RECOVER initiative’s two adult cohorts have hit 50% of their enrollment targets for patients with acute Covid infections, and 80% for post-acute infections, after nearly two years of working to sign people up.
The agency expects to start clinical trials for treatments in the first six months of 2023 in five key symptom areas:
immune dysregulation,
cognitive dysfunction,
autonomic dysfunction,
sleep disorders, and
fatigue and difficulty exercising.
The trials are expected to test drugs, biologics, devices, and behavioral treatments.
12/22/22 Pediatric Emergency Care: Pediatric Croup Due to Omicron Infection Is (Much) More Severe Than Non-COVID Croup https://buff.ly/3PKxsJt
n = 88 in the Omicron croup cohort and 411 in the classic croup cohort.
Omicron croup patients were more likely to have:
stridor at rest (Odds ratio [OR], 1.82)
hypoxia (OR 7.22)
repeat dosing of inhaled epinephrine in the ED more often (OR, 3.51)
require respiratory support (OR, 10.18)
Higher hospital admission rates (OR, 7.26)
ICU care more frequently (OR, 4.07).
Pediatric patients with Omicron croup develop more severe disease than do children with classic croup. They are more likely to require additional emergency department treatments and hospital admission than patients with croup before the COVID pandemic.
12/13/22 Yale: Potential New Treatment for “Brain Fog” in Long COVID Patients https://buff.ly/3Ym4vqV
Guanfacine has been used for ADHD, Traumatic Brain Injury (TBI), PTSD, prefrontal cortex disorders for years.
NAC is an antioxidant used for TBI.
The combination of extended release Guanfacine (1 to 2 mg) and N-acetylcysteine (NAC) 600mg relieved Long COVID Brain Fog in 8 out of 10 patients in this small trial:
2023 Neuroimmunology Reports: Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19” https://buff.ly/3I1V1eO
Combined treatment with the α2A-adrenoceptor agonist, guanfacine, and the anti-oxidant, N-acetylcysteine (NAC) reduced the cognitive deficits (“brain fog”) associated with long-COVID19 in eight out of twelve patients.
Two patients stopped treatment due to hypotension and/or dizziness, common side effects of guanfacine, and two patients were lost to follow-up.
The remaining eight patients reported improved working memory, concentration and executive function, including the resumption of normal workloads.
One patient temporarily stopped guanfacine due to a hypotensive episode and reported a return of cognitive deficits that abated with resumed guanfacine treatment.
Although placebo-controlled trials will be needed to demonstrate efficacy, the established safety of guanfacine and NAC suggests they may be immediately useful in treating the cognitive deficits of long-COVID19.
12/21/22 Clin Infectious Disease: The epidemiology of Long COVID in US adults https://buff.ly/3hL4tbM
"An estimated 7.3% of all respondents reported long COVID, corresponding to approximately 18,828,696 adults.
One-quarter of respondents with long COVID reported their day-to-day activities were impacted ‘a lot’ and 28.9% had SARS-CoV-2 infection >12 months ago."
The prevalence of long COVID was higher among respondents who were female, had comorbidities or were not (versus were) boosted or not vaccinated.
12/21/22 Open Forum Infectious Disease: Persistent symptoms and sequelae after SARS-CoV-2 infection not requiring hospitalization: Results from Testing Denmark, a Danish cross-sectional survey https://buff.ly/3PMkXwM
At 12+ weeks after Covid infection, non-hospitalized SARS-CoV-2 PCR-positive individuals had significantly reduced physical and mental health, and one in four reported persistence of at least one long-COVID symptom.
Long COVID, PASC
12/21/22 NEJM : Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster https://buff.ly/3G9DPCW
“Persons who received the BA.5-containing bivalent booster had better neutralizing activity against all omicron subvariants (especially against BA.2.75.2, BQ.1.1, and XBB) than those who received either one or two monovalent boosters.”
12/21/22 WSJ: Mystery of Smell Loss After Covid-19 Might Be Solved https://buff.ly/3FQes7C
People with long-term loss of smell after COVID infection had an average of 75% fewer olfactory sensory neurons than people who did not have COVID.
Inflammation causes a reduction of sensory neurons in the nasal epithelium.
12/21/22 Science: Persistent post–COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium https://buff.ly/3v7N14k
Nasal biopsies from people with PASC (Long COVID) related smell loss (hyposmia) showedT cell–mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post–COVID-19 smell loss.
Ongoing inflammatory signaling was accompanied by a reduction in the number of olfactory sensory neurons relative to olfactory epithelial sustentacular cells.
The authors referenced this interesting article:
3/15/222 Mucosal Immunity: Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages https://buff.ly/3YBfPzP
Analysis of macrophages from patients with mild COVID-19 has shown that acute SARS-CoV-2 infection drives a proinflammatory reprogramming that is thought to induce long-term alterations in the function of other immune cells.
SARS-CoV-2 infection leaves a pro-inflammatory imprint in the monocyte/ macrophage compartment that drives aberrant macrophage effector functions and eicosanoid metabolism, resulting in long-term immune aberrations in patients recovering from mild COVID-19.
12/18/22 NPR: COVID spreading faster than ever in China. 800 million could be infected this winter https://buff.ly/3hxOEFh
"about 10% of the planet's population may become infected over the course of the next 90 days."
Most people are vaccinated with Sinovac or Sinopharm, but only 50% of older people in China have had a third dose booster.
12/21/22 Reuters: Hearses queue at Beijing crematorium, even as China reports no new COVID deaths https://buff.ly/3BR2xW5
Experts say China could face more than a million COVID deaths next year.
Those at highest risk are often not vaccinated, plus Chinese vaccines do not work as well against Omicron.
12/21/22 Cell: Impact of SARS-CoV-2 exposure history on the T cell and IgG response https://buff.ly/3BWdpBX
Repeated SARS-CoV-2 Spike exposures from COVID virus exposures or vaccination increase IgG antibody responses from B cells, but they do not affect spike-specific T cells in the circulation.
The proportion of T-cells reaches a plateau after three exposures.
Hybrid immunity induces more polyfunctional Spike CD4 T cells than vaccination only.
12/21/22 Science: Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children (MIS-C) https://buff.ly/3GbrL3V
Autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C.
12/21/22 Lancet: SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalization with COVID-19 and is not induced by subsequent vaccination https://buff.ly/3hMjv10
These findings may explain the lack of long-lasting nasal defense against reinfection and the limited effects of vaccination on transmission.
Nasal vaccines are needed to block infection with mucosal IgA.
12/20/22 Katelyn Jetelina: Boosters for kids under 5: A quick update https://buff.ly/3PNlONH
All children who received Moderna are eligible.
Kids who had 3 Pfizer shots are not eligible.
So far, vaccine uptake is only 8.4% for this age group.
It's a good idea for young kids to get the bivalent booster to broaden their immunity against the new Omicron variants and to protect against getting a co-infection with the flu or other respiratory infection.
12/19/22 Nature Immunology: Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children https://buff.ly/3VdgKTU
Children who have had COVID have persistent viral RNA in their tonsils and adenoids associated with prolonged immune activation and clonal expansion of antigen-specific B and T cells.
In four post-COV donors, their nasopharyngeal swab PCR had been positive over 100 d before surgery, including one 303 d before surgery.
Viral RNA copies significantly correlated with the percentages of S1+RBD+ B cells among GC B cells in post-COV tonsils (Fig. 8b).
12/19/22 Nature Nanotechnology: The potential impact of nanomedicine on COVID-19-induced thrombosis https://buff.ly/3PEiW5L
12/13/22 Nature: Dr. Fauci responds to Musk’s Twitter attack and rates world’s COVID response https://buff.ly/3VUZnIY
Re: Musk's attack on Twitter:
"I don’t pay attention to that, Max, and I don’t feel I need to respond. I don’t tweet. I don’t have a Twitter account. A lot of that stuff is just a cesspool of misinformation, and I don’t waste a minute worrying about it." -Dr. Fauci
Fauci quote on mental health's toll from the pandemic:
Per Dr. Claire Taylor, impact of COVID reinfections on different body systems taken from this article: 11/10/22 Nature Medicine: Acute and post acute sequelae associated with SARS-CoV-2 reinfection https://buff.ly/3hyZp9R
