First of all, I would like to congratulate Dr. Carolyn Bertozzi, Stanford professor and two time StartX founder, for winning the Nobel Prize in chemistry with Barry Sharpless and Morten Meldal. Amazing work!
In COVID news, BA.5 continues to cause a wave of cases and hospitalizations in Western Europe (Austria, Germany, France, Italy) although some of the Omicron subvariants are starting to add to new COVID cases as well. According to Dr. Ashish Jha, the White House Coronavirus Response Coordinator, "We are seeing this increase in Europe, and Europe tends to precede us by about four to six weeks... And so it stands to reason that as we get into November, December, maybe January, we are going to see an increase in infections across much of the country." So how can we stop or slow down this next wave?
Many of the new variants are descendants of BA.5 or BA.2 and therefore, the new bivalent booster shots that contain mRNA for BA.4/5 could make a huge difference in boosting people's immunity against the new variants. But, unfortunately, only about 4 to 5% of people who qualify for the bivalent booster have gotten them. Because Congress did not approve funding, the federal government no longer has enough money for a proper media campaign to let people know why these new bivalent boosters are so important. People are tired of the pandemic. People are tired of wearing masks and of avoiding large groups indoors. But, people also simply do not know that they qualify for the new bivalent boosters. As of this week, every vaccinated person age 5 and older can and should get the new bivalent booster. We could really use solid public health messaging right about now.
As mentioned above, the CDC approved bivalent boosters for children this week making every vaccinated person age 5 and older eligible for the booster. This booster is different from past boosters. The addition of BA.4/5 mRNA makes it better to help us fight the new variants that scientists predict are coming. A press release from Pfizer-BioNTech shows that after only 7 days, people who received the bivalent boosters already had a substantial increase in the Omicron BA.4/BA.5 neutralizing antibody levels. Vaccines and boosters have been shown to decrease severe Covid infections, hospitalizations and death from Covid and they can also decrease the risk of getting Long COVID. We are so fortunate to have these available.
New subvariants BQ.1.1 (a BA.5 descendant) and XBB (BA.2 descendant) are the most likely to cause the next wave of Covid infections. We are seeing increases in BQ.1.1 in Europe (France, Belgium, UK) and in the U.S. in New York and Maryland. Singapore and Bangladesh have XBB waves now. In many countries, several subvariants of Omicron are co-circulating now.
BQ.1.1 is more than doubling every week (1.0% to 2.4% to 5.7%).
BQ.1 is not quite doubling every week (1.1% to 1.8% to 3.3% and now to 5.7%).
BA.4.6 went up ½ percent per week but now is stagnant.
BF.7 is going up 1% per week approximately.
XBB is not in the U.S. at this point.
Because of the weather, people are spending more time indoors. Respiratory infections like Influenza are also increasing as they do seasonally, but things can be more manageable this year if people get bivalent boosters and flu shots, if they use Paxlovid if appropriate and if we use masks indoors when there is a surge of infections in our community. When children get bivalent COVID boosters, grandparents can be more protected from COVID as well. Rapid antigen tests still work for all of the subvariants, so using these tests before indoor gatherings is another layer of protection. It is especially important to test with rapid antigen tests (RATs) before events as a new JAMA study of more than 63,000 people shows that for symptomatic people with Omicron infections, 80% are still positive for contagious virus on day 5 and 35% are still positive on RAT on day 10. Among persons asymptomatic at testing, 49% remained positive on RAT on day 5, and 19% were still positive on day 10. We do have a lot more tools in our arsenal this year to help to protect ourselves against COVID, but we need to use them.
This week, the Florida Surgeon General Dr. Ladapo put out a "mRNA vaccine guidance" recommending that men age 18 to 39 not get mRNA vaccines. This was quickly condemned by medical and public health leaders including federal officials who called Florida’s recommendation “flawed and a far cry from the science.” The editor of Science magazine, Holden Thorp, put out an op-ed examining the responsibility of academia and the scientific community to stop misinformation being spread by a faculty member.
Finally, a new article discussed in cardiologist Dr. Alice's excellent Twitter thread on Long COVID shows that certain vascular transformation blood biomarkers are significantly elevated in Long COVID as compared to controls, and that angiogenesis markers (ANG-1/P-SEL) provided 96% classification accuracy for Long COVID. The authors concluded that these vascular transformation blood biomarkers hold potential for diagnostics, and drugs that modulate angiogenesis may have therapeutic benefit for treating Long COVID.
10/13/22 NPR: What the White House sees coming for COVID this winter https://buff.ly/3Cw59rN
"We are seeing this increase in Europe, and Europe tends to precede us by about four to six weeks," Jha told NPR. "And so it stands to reason that as we get into November, December, maybe January, we are going to see an increase in infections across much of the country."
This will depend on vaccinations, boosters with the bivalent vaccine and precautions that people take (masks, indoor gatherings, etc), pandemic fatigue.
Dr. Jha thinks that most people will need a once yearly Covid shot like the Flu shot except for high-risk people (elderly, immunocompromised) who may need more than one shot per year.
10/13/22 U.S. extends public health emergency for COVID-19
Vascular transformation blood biomarkers- especially ANG-1/P-SEL.
10/12/22 Molecular Medicine (Canada): Elevated vascular transformation blood biomarkers in Long-COVID indicate angiogenesis as a key pathophysiological mechanism https://buff.ly/3EG9FXr
16 blood biomarkers of vascular transformation, including ANG-1, P-SEL, MMP-1, VE-Cad, Syn-1, Endoglin, PECAM-1, VEGF-A, ICAM-1, VLA-4, E-SEL, thrombomodulin, VEGF-R2, VEGF-R3, VCAM-1 and VEGF-D.
14 were elevated in Long Covid.
Vascular transformation blood biomarkers were significantly elevated in Long-COVID, with angiogenesis markers (ANG-1/P-SEL) providing classification accuracy of 96%.
Vascular transformation blood biomarkers hold potential for diagnostics, and modulators of angiogenesis may have therapeutic efficacy.
BA.2.75.2 and BA.4.6 both show complete escape from cilgavimab and a combination of cilgavimab and tixagevimab (Evusheld).
In Swedish blood donors, neutralization of BA.2.75.2 by serum antibodies was significantly lower than all other variants tested.
Bebtelovimab still potently neutralizes BA.2.75.2 and BA.4.6.
10/13/22 MedRxiV: Post-acute symptoms four months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study https://buff.ly/3erq1bV
44,000 Danish people filled in a questionnaire 4 months after Omicron infection.
Giving a booster shot (3 doses vs 2) reduced the risk of PASC/ Long Covid during the Omicron wave in Denmark.
10/13/22 Press Release: Pfizer and BioNTech Announce Positive Early Data From Clinical Trial of Omicron BA.4/BA.5-Adapted Bivalent Booster in Individuals 18+ Years https://buff.ly/3rYdcIY
7 days after bivalent booster, people already had a substantial increase in the Omicron BA.4/BA.5 neutralizing antibody levels.
10/12/22 CDC Expands Updated Bivalent (WT + BA.5) COVID-19 Vaccines to Include Children Ages 5 Through 11 https://buff.ly/3Mts4su
Bivalent Pfizer booster for children ages 5 through 11 years.
Bivalent Moderna booster for children and adolescents ages 6 through 17 years.
10/12/22
10/11/22 Politico: Biden administration scrambling to get more people boosted before winter https://buff.ly/3CmNx1q
Only 5% of the eligible population has gotten the new bivalent booster.
“The CDC has a manufacturing capacity for [vaccine] recommendations, but it has no marketing capacity. They underestimate how much work it takes to get the word out.” Schaffner said.
Little funding for marketing, pandemic fatigue are affecting the roll out.
“It is obviously harder to run a [media] campaign when Congress decides not to fund it,” White House Covid-19 Response Coordinator Dr. Ashish Jha said.
10/13/22 Latest variants
10/12/22
BQ.1.1 rising in France, UK, Belgium, and in the US in New York and Maryland
10/11/22 JAMA: COVID-19 Symptoms and Rapid Antigen Test Positivity at a Community Testing Site https://buff.ly/3VgMMzE
n = 63,277
During the Omicron BA.1 period, 5 days after symptom onset, 80% of participants remained positive via a rapid antigen test.
People should wait until they have a negative rapid antigen COVID test before returning to work or school. Five days of isolation is not enough. If someone is positive on a rapid antigen test, they can transmit the virus to others.
Among symptomatic persons, 80% remained positive via RAT on day 5, and 35% remained positive on day 10, regardless of vaccine status.
Among persons asymptomatic at testing, 49% remained positive on day 5, and 19% remained positive on day 10.
10/11/22 Nature: COVID vaccines and children: they’re safe and they work — so why is uptake so patchy? https://buff.ly/3MqPkqQ
10/10/22 Nature: A comprehensive SARS-CoV-2–human protein–protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets https://buff.ly/3VfJkFF
Comprehensive SARS-CoV-2–human protein–protein interactome network consisting of 739 high-confidence binary and co-complex interactions, validating 218 known SARS-CoV-2 host factors and revealing 361 novel ones.
The researchers identified 23 drug candidates.
Carvedilol, shows clinical benefits in COVID-19 patients and antiviral properties in a human lung cell line infected with SARS-CoV-2.
Carvedilol is a beta blocker, also known as Coreg, that can treat high blood pressure and heart failure.
10/10/22 JAMA: Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters After COVID-19 (Long COVID, PASC) https://buff.ly/3T7pg73
Modeling study on Long Covid/PASC based on pooling 54 studies and 2 medical record databases with data for 1.2 million individuals from 22 countries.
6.2% Long Covid at 3 months after symptomatic SARS-CoV-2 infection
6.2% (3.7% + 3.2% + 2.2%)
3.7% respiratory problems,
3.2% persistent fatigue with bodily pain or mood swings
2.2% cognitive problems
The Long COVID symptom clusters 3 months after symptomatic SARS-CoV-2 infection were more common in women:
10.6% in women aged 20 years or older
5.4% in men aged 20 years or older.
2.8% in both sexes younger than 20 years of age.
Long Covid duration:
15% (1 in 6) of those with Long Covid have symptoms for at least a year.
Common duration is 4 months if not hospitalized with initial infection and 9 months if hospitalized.
10/9/22 MedRxiV: Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the NIH RECOVER Program https://buff.ly/3efMokz
Large study (n= 200,000) COVID-19 infection between August 2021 and January 2022.
Vaccination was associated with a 34% to 38% reduced risk of Long COVID after a breakthrough infection.
10/9/22 Eric Topol MD: The marked contrast in pandemic outcomes between Japan and the United States https://buff.ly/3Eui93U
Japan has a higher density of people living near each other and has a much older population than the US. But the Japanese use masks and the 3 Cs and they are better vaccinated and boosted.
Boosters:
95% of Japanese compared with 40.8% of Americans have had a booster shot.
Only 42% of those 65+ in the US have gotten 2 boosters.
Boosters save lives for all ages 18+ and especially for older adults.
Antiviral:
In the US, Paxlovid is given to less than 25% of the eligible (age 50+), and less people age 80+ are getting Paxlovid than those age 45.
Poster from Japan:
10/8/22 Nature: Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial https://buff.ly/3SPEayx
Bivalent booster vaccines can induce potent, durable and broad antibody responses against multiple variants, providing a new tool in response to emerging variants.
seasonality (being indoors, return to school and office)
immune waning (~9-10 months since the first Omicron wave infected half of UK pop & since anyone under 75 had a booster)
new variants
At present, BQ.1, BA.2.75.2 and BF.7 are the most concerning variants in terms of both growth and neutralization data in the UK.
10/8/22 Science: Severe COVID-19 induces autoantibodies against Angiotensin II (AngII) that correlate with blood pressure dysregulation and disease severity https://buff.ly/3MgxerL
Angiotensin-converting enzyme 2 (ACE2), is the main entry receptor of SARS-CoV-2.
A significant proportion of hospitalized patients with COVID-19 developed autoantibodies against AngII, whose presence correlates with lower blood oxygenation, blood pressure dysregulation, and overall higher disease severity.
There may be some epitope mimicry between AngII and SARS-CoV-2 Spike/RBD.
Florida Surgeon General Dr. Ladapo’s Vaccine Guidance scandal:
Holden Thorp's editorial on the anti-vaccine disinformation spread by the Florida Surgeon General who is also faculty at the University of Florida.
What is the responsibility of academia to shut down misinformation from within? The scientific community needs to respond to medical disinformation.
10/11/22 Washington Post: Experts slam Florida surgeon general’s warning on coronavirus vaccines https://buff.ly/3Vn8KB6
Ladapo’s recommendation — extrapolated from a short state analysis that has not been peer-reviewed, carries no authors and warns that its findings are “preliminary” and “should be interpreted with caution” — was swiftly condemned by medical and public health leaders, who said the Florida surgeon general’s announcement was politics masquerading as science and could lead Americans to forgo life saving interventions.
“I’m hesitant to even call it a paper; it isn’t published anywhere. The idea that [the analysis] … is being used to change policy — it does not have the scientific chops to do that.” Dr. Bob Wachter
Federal officials called Florida’s recommendation “flawed and a far cry from the science.”
10/8/22 Kristen Panthagani, MD, PhD: A critical review of Florida’s new vaccine analysis https://buff.ly/3RO49Fc
The Florida State Surgeon General issued new guidance around the COVID vaccines based on an analysis they performed saying results show “an increased risk of cardiac-related death among men 18-39” for the mRNA vaccines, and recommend this group not receive these vaccines.
“Study” flaws: Given the arbitrary selection of cardiac outcomes, the lack of validation, the small sample size, and the failure to control for COVID infection as a confounding variable, overall these results are largely unreliable, and personally I would not base any decisions on them.
Furthermore, while we can’t say for sure, this whole analysis smells of p-hacking, which occurs when people slice and dice the data a whole bunch of ways until they find a result they like.
