COVID news 6/10/22

Hi all,

BA.4 and BA.5, or BA.4/5 for short, now make up about 13% of the COVID infections in the United States.  BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, they contain different mutations in the receptor binding domain. BA.4/5 have very strong immune escape which is related to their L452R and F486V mutations and therefore will outcompete BA.2 and BA.2.12.1 in the next few weeks in the United States. Most likely, we will see a BA.4/5 (or just a BA.5) wave peak in about 4 to 5 weeks.

We don't know how big our BA.4/5 wave will be. Portugal has a big BA.5 wave now and England's BA.4/5 wave is just starting. South Africa had a much smaller BA.4/5 wave than its first Omicron wave, but Portugal's BA.5 wave is at least as large as its first Omicron wave.

BA.4/5 is very immune evasive and shows reduced neutralization in triple (3 doses of Pfizer) vaccinated people and also in vaccinated people who got BA.1 breakthrough infection, thus raising the possibility of repeat Omicron infections. In addition, BA.4/5 is 20x more resistant to Evusheld (the monoclonal antibody cocktail given to immunocompromised people for pre-exposure prophylaxis) than BA.2. The good news is that the monoclonal antibody Bebtelovimab works against BA.4/5 and Sotrovimab, which was 20x less effective against BA.2, works better against BA.4/5.

So what can you do? Masking indoors, better ventilation indoors will help. Moderna just announced by press release that their bivalent booster vaccine shows a superior response against Omicron variants. This bivalent vaccine contains both mRNA for the original virus and mRNA for Omicron BA.1. This combination showed an 8-fold increase in neutralizing antibodies and those with prior infection had an even stronger response. The bivalent booster shot was found to be safe and showed increased protection against all variants compared to the original virus. Hopefully, this bivalent Moderna vaccine will be evaluated for EUA soon. Pfizer is also working on a bivalent vaccine that includes mRNA for the original SARS-CoV-2 virus and mRNA specific to the Omicron variant.

This week, I am including several articles on Long COVID and also a really helpful Twitter thread from Prof. Trisha Greenhalgh of Oxford University where she shares Long COVID resources for patients and online e-modules for doctors on Long COVID. In addition, Yale announced that they are recruiting patients for their Long COVID study and Dr Akiko Iwasaki will be one of the primary investigators.

A new study shows that babies born to mothers who got a COVID infection in pregnancy showed more than double the amount of developmental delay at 1 year of age than controls. Third trimester infections caused the most neurodevelopmental delay in offspring. Therefore, it is very important for people of childbearing age to get vaccinated against COVID especially if they are going to try to become pregnant.

Finally, if you are traveling internationally this summer, you will no longer need a negative COVID test to return to the United States as of this Sunday. This is good for the airlines who are happy now that mask restrictions and COVID tests requirements are lifted, but I have concerns about people inadvertently spreading variants from around the world as many countries are trying to go back to "business as usual".

Have a good weekend,

Ruth Ann Crystal MD

Twitter: https://twitter.com/catchthebaby

World

United States

US Hospitalization hot spots:

Test positivity for the US is 13% per NYTimes. This is still mostly BA.2.12.1.

US Reported Cases via the NY Times, but most cases are not reported since testing is done at home.

CDC: US COVID sub variant proportions https://buff.ly/3zMdWE5

• BA.4/ BA.5 make up about 13% of cases now.  They will probably become dominant in 4 to 5 weeks.

Wastewater virus levels now in the Silicon Valley:

6/10/22 CNBC:  U.S. drops Covid testing requirement for international travelers https://buff.ly/3zv8cAB

• The Biden administration will drop the Covid-19 testing requirement for inbound air travelers from abroad on Sunday.

6/10/22 Thread by Prof Chris Pagel on the new BA.5/4 wave in England

6/10/22 Press Release: Moderna Announces Omicron-Containing Bivalent Booster Candidate mRNA-1273.214 Demonstrates Superior Antibody Response Against Omicron https://buff.ly/3O4rcdg

• Bivalent vaccine contains mRNA for the original virus and mRNA for Omicron.

• Dosage is 50 mcg and has similar side effects to the original booster.

• 8x increase in neutralizing antibodies noted at 1 month after booster and those with prior infection had a stronger response.

• Bivalent booster showed increased protection against all VOCs compared to the original virus studies.

• Durability is unknown. The efficacy of a different bivalent vaccine for the Beta variant lasted for more than 6 months giving us a hint to the durability of this new bivalent vaccine.

6/7/22 @RajlabN’s tweet thread with data on why he thinks BA.5 will outcompete BA.4 and the other sub variants. BA.5 has shown a relative growth advantage over both BA.2.12.1 in the US and over BA.4 in other countries.

6/9/22 Cell: Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum https://buff.ly/399917D

• BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike.

• BA.4/5 immune escape is strongly related to the L452R and F486V mutations.

• BA.4/5 shows reduced neutralization by serum from:

  • Triple vaccinated individuals (AstraZeneca or Pfizer) compared to BA.1 and BA.2.

  • Vaccinated people who got BA.1 breakthrough infection, raising the possibility of repeat Omicron infections.

  • Therapeutic monoclonal antibodies.

6/9/22 JAMA: Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy https://buff.ly/3xyoXcR

• 222 offspring of mothers infected with SARS-CoV-2, compared with the offspring of 7550 mothers in the control group (not infected) delivered during the same period.

• Babies exposed to SARS-CoV-2 in utero have more than 2x the risk of neurodevelopmental disorders at 1 year of age, even when correcting for preterm delivery. (6.3% vs 3.0%)

• Greatest effect seen with infection in the 3rd trimester. 

6/9/22 Nature: Clinical outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in southern California https://buff.ly/3NCIqPa

• Omicron variant infections were associated with substantially reduced risk of progression to severe clinical outcomes compared to Delta variant infections within Kaiser Permanente, a large, integrated healthcare system in southern California. 

• Omicron compared to Delta variant infection:

  • 41% less hospital admission, 

  • 50% less intensive care unit admission, 

  • 64% less mechanical ventilation

  • 79% fewer deaths

6/8/22 Eric Topol MD: Omicron Subvariants Mutation Map

6/6/22 THREAD on LONG COVID information for non-specialists (GPs, patients) by Trisha Greenhalgh (Oxford)

• Mechanisms include chronic inflammation, thrombosis (‘micro clots’) and endothelial damage. This impacts various organs—e.g. autonomic nervous system. Autoimmunity.

• What GPs (general practitioners) can do:

• Tests for 

  • fatigue, 

  • Autonomic dysfunction (rapid rise in pulse rate on standing) may indicate POTS (postural orthostatic tachycardia syndrome), 

  • brain fog, 

  • allergy type symptoms, 

  • sleep disturbances, 

• P.T. for breathing pattern disorders https://www.physiotherapyforbpd.org.uk/

• Post-COVID-19 Tachycardia Syndrome (POTS): A Distinct Phenotype of Post-Acute COVID-19 Syndrome https://buff.ly/3Qcoi8l

  • Symptoms of autonomic dysfunction (rapid rise in pulse rate on standing) may indicate POTS (postural orthostatic tachycardia syndrome). Often misdiagnosed as anxiety, sadly.

• Long COVID resources for Patients (UK):

  • NHS Long COVID Rehab booklet (downloadable) https://buff.ly/3xDiYnl

  • WHO: Support for rehabilitation: self-management after COVID-19-related illness https://buff.ly/3xzZSya

  • The Long COVID Self-Help Guide by Specialists from the Post COVID Clinic at Oxford: 

    • Buy now from Amazon in the UK: The Long Covid Self-Help Guide: Practical Ways to Manage Symptoms: https://buff.ly/z2wrNW

    • Will be available on Amazon’s U.S. website in Sept 2022

  • NHS: Your COVID Recovery https://buff.ly/3iJtGi8

• Vaccination may help with some Long COVID symptoms

  • 5/18/22 BMJ: Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study https://buff.ly/39FZk04

  • The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days.

• Support Groups for Long COVID:

  • Long Covid SOS https://longcovidsos.org

  • Long Covid Support https://longcovid.org

  • Long Covid Kids https://longcovidkids.org

• For healthcare providers: 

  • COVID-19 rapid guideline: managing the long term effects of COVID-19 https://buff.ly/3aKg4nM

  • RCGP Course: Long term effects of COVID-19 and Post-COVID-19 syndrome https://buff.ly/3xDNzkk

  • Long COVID - elearning for healthcare https://buff.ly/2Wp2UFC

  • The COVID-19 Yorkshire Rehabilitation Scale (C19-YRS): Application and psychometric analysis in a post COVID-19 syndrome cohort https://buff.ly/3NGHPMz

  • The C19-YRS is a validated patient-reported outcome measure for use in clinic and research. 

6/9/22 Research Square: Persistence of residual SARS-CoV-2 viral antigen and RNA in tissues of patients with long COVID-19 (LC) https://buff.ly/3NQKbs0

• Residual virus was found in the appendix and breast tissue of 2 patients who exhibited Long COVID symptoms, 175 to 462 days upon positive diagnosis.  

• Viral nucleocapsid protein (NP) was found in the appendix, and tumor-adjacent tissue of the breast, but not within the breast tumor itself.

• Negative-sense viral RNA found suggests ongoing viral replication.

• Positive finding in the breast tissue also corroborated with recent reports that immunocompromised patients had also experienced LC symptoms and persistent viral replication. 

• Overall, our findings, along with emerging LC studies, raises the possibility of the gastrointestinal tract functioning as a reservoir.

6/9/22 JAMA: Concordance of SARS-CoV-2 RNA in Aerosols From a Nurses Station and in Nurses and Patients During a Hospital Ward Outbreak https://buff.ly/3mAXeSu

• Nosocomial infection may result from aerosol-borne SARS-CoV-2 introduced by employees and patients into common hospital areas like breakrooms and the nurses station.

6/9/22 Lancet: Neutralization sensitivity of SARS-CoV-2 Omicron subvariants to therapeutic monoclonal antibodies https://buff.ly/3QcsrsV

Omicron subvariants have more immune escape to monoclonal antibodies:

• Evusheld (cilgavimab and tixagevimab):

  • The L452R/Q substitution rendered approximately 2–5-x resistance.

  • BA.2.12.1 is 4x more resistant to Evusheld.

  • BA.4/5 is 20x more resistant to Evusheld than BA.2.

• Bebtelovimab works against all Omicron subvariants..

• Sotrovimab was 20x less effective against BA.2 but, 

  • Omicron subvariants with the L452R substitution, BA.2.11 and BA.4/5, are more sensitive to sotrovimab than BA.2.

6/8/22 JAMA: Reducing SARS-CoV-2 in Shared Indoor Air https://buff.ly/3xwgVkS

• Improving air quality has the potential to reduce not only infections with SARS-CoV-2 but also infections with other respiratory viruses and bacteria, reactive airway disease (eg, asthma) triggered by antigens, pulmonary and cardiovascular injury from inhalation of harmful respiratory particulates (eg, wildfires, smog), and toxicity from inhalation of volatile organic compounds. 

• A once-in-decades opportunity now exists to make sustained improvements to public and private indoor air quality, reduce COVID-19 risk, and improve school, workplace, and consumer health and safety.

6/8/22 CDC MMWR: Ventilation Improvement Strategies Among K–12 Public Schools, February 14–March 27, 2022 https://buff.ly/3H7lFR1

• Ventilation is a key strategy recommended to reduce COVID-19 spread in school settings.

6/8/22 Science: SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations (myeloid and T cell activation, proinflammatory cytokine production, and an interferon response) post recovery https://buff.ly/3xkxpLq

• Post-acute sequelae of COVID-19 (PASC) or long COVID

• Compared to Influenza A, SARS-CoV-2 caused more permanent injury to the lung and kidney and uniquely impacted the olfactory bulb (OB) and epithelium (OE) in hamsters.

• In both hamsters and humans, there was myeloid and T cell activation, proinflammatory cytokine production, and an interferon response noted a month post viral clearance despite a lack of detectable infectious virus.

• These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.

6/6/22 Yale: Study Empowers Long COVID Patients as They Struggle to Find Relief https://buff.ly/3aK4AAC

6/6/22 KQED: If You Get COVID, Should You Try to Get Paxlovid? Here's How https://buff.ly/3NSx4Gp

Everything you need to know about Paxlovid:

• how to get it in the Bay Area

• who qualifies for Paxlovid

  • High risk includes people with obesity, depression, diabetes, cancer, etc.

• what "Paxlovid rebound" is

• where to find a Paxlovid prescription near you with or without insurance.

Biden-Harris Administration Requires Insurance Companies and Group Health Plans to Cover the Cost of At-Home COVID-19 Tests, Increasing Access to Free Tests https://buff.ly/3qdvHZZ

6/6/22 PCDE: Risk of incident diabetes post-COVID-19: A systematic review and meta-analysis https://buff.ly/3H6U4Q9

• Pooled analysis of 4 large retrospective studies. 

• 59 % higher risk of developing incident diabetes in post-acute COVID-19 phase versus healthy controls.

• Screening for diabetes is essential during post-acute COVID-19 phase regardless of the disease severity or history of steroid use.

• Given the high risk of DM even in the pediatric population, we emphasize on vaccinating all persons irrespective of age.

6/6/22 Science: Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes https://buff.ly/3GVBSZp

• Omicron BA.1 breakthrough infection in Pfizer BNT162b2-vaccinated individuals resulted in strong neutralizing activity against Omicron BA.1, BA.2 and previous SARS-CoV-2 VOCs, but not against the Omicron sublineages BA.4 and BA.5.

from the NY Times: US Coronavirus Latest Case Count https://buff.ly/3H3bYmM

6/6/22 Science: The circadian immune system https://buff.ly/3mn1XqY

• When it comes to vaccination, new research suggests it's better to be vaccinated in the morning than in the afternoon or evening. It's all part of the body's complex circadian immune system

6/6/22 NBC: The U.S. has discarded over 82 million Covid vaccine doses, led by CVS and Walmart https://buff.ly/3ml2wSg

• Vaccine providers say declining demand, large minimum orders and multidose vials make it hard to avoid waste while still offering shots to anyone who wants them.

6/6/22 Rolling Stone: Ron DeSantis Bullied the Special Olympics Into Dropping Its Vaccine Requirement https://buff.ly/3GXTrs4

• DeSantis threatened to levy an eight-figure fine ($27.5 million) against the Special Olympics if it didn’t drop its Covid-19 vaccine requirement for its games in Orlando this weekend.