COVID news 6/3/22

Hi all,

As summer approaches, many people will be traveling.  Please visit this post on What You Need to Know About International Travel where I discuss what to bring with you on an international trip and how to get a COVID test before you return to the United States. 

BA.2.12.1 is now dominant throughout most of the United States.  Some think that the BA.2 curve for cases may have peaked and may be starting to come down. But, at least in our area, wastewater levels of virus are still increasing, so I don’t think that we have hit the peak with this wave quite yet.

BA.4/BA.5 is just starting to trickle into Europe and the United States.  BA.5 arrived earlier to Portugal than other European countries and it now has outcompeted BA.2 there.  BA.4/5 has the most immune escape of any of the subvariants and there is a notable drop in neutralization titers against BA.4 and BA.5 viruses in boosted individuals and individuals with prior BA.1 breakthrough infections.   Now would be a good time to get a booster if appropriate. German scientists are predicting that Germany will have a BA.4/5 wave in July.  I expect that the United States may have a BA.4/5 wave in the late summer.

A new study showed that pulse oximeter measurements can be falsely high in patients of color (Asian, Black and Hispanic) which can mask hypoxemia. Because of this, some patients of color may have not gotten treatments such as oxygen and this may have worsened outcomes.  It is important to be aware of this.

Paxlovid was originally tested in patients with the Delta variant, decreasing severe disease in high risk patients by 89%.  A new real-world study from Israel during the Omicron wave shows that Paxlovid protects people over age 65 against hospitalization and death with Omicron infections too. During the Omicron wave, Paxlovid was associated with a 67% reduction in hospitalizations and an 81% reduction in Covid-19 mortality in patients 65 years and older.  With this new information, Paxlovid use will be even more important since we now know that more older Americans died of Omicron (BA.1) than did of the Delta variant. 

Evusheld, a monoclonal antibody cocktail of 2 mAbs, has been found in a real-world study at the Veterans Administration hospitals to protect immunosuppressed vets against Omicron which is great news.  Evusheld given prophylactically to this predominantly vaccinated (73%) high risk group was associated with lower rates of SARS-CoV-2 Omicron infections, hospitalizations, and all-cause mortality.

Finally, there is a fascinating article on how different areas of the brain relevant to the fight-or-flight response can cause massive changes in white blood cell distribution and function throughout the body in response to acute stress in mice.  Motor circuits in the brain regulate neutrophils, and parts of the hypothalamus related to fear regulate monocytes and lymphocytes in the body.

Have a good weekend,

Ruth Ann Crystal MD
Twitter: https://twitter.com/CatchTheBaby

COVID NEWS:

World

      United States

U.S. Cases:

Has the BA.2 wave peaked? Many cases are not reported. See what the wastewater shows below.

BA.2.12.1 dominates most of the U.S.

Community Transmission in California (data from CDC): https://abc7news.com/feature/coronavirus-cases-covid-19-map-bay-area-covid/9891245/

Wastewater in Santa Clara County:

It looks like virus levels are still going up and in Palo Alto they may surpass the original Omicron wave.

5/30/22 San Francisco is in a “big-time surge”.

At UCSF:

Asymptomatic positive rate at UCSF is 5.7% (down from 7.0%)

International Air Travel Summary:

*** Please read What You Need to Know About International Travel where I discuss what to bring with you on an international trip and how to get a COVID test before you return to the United States. 

6/3/22 Reuters: Omicron sub-variant BA.5 fuels Portugal's COVID-19 surge https://buff.ly/3Mgw8ug

• Portugal that now has the world's second-highest infection rate despite more than 90% of Portugal's population is fully vaccinated.

• The Omicron sub-variant BA.5 represented nearly 90% of new COVID-19 infections in Portugal.

6/3/22 Point of Care Reference tools for Physicians and HCP from the CDC and the IDSA (Infectious Diseases Society of America)

• COVID-19 OUTPATIENT TREATMENT GUIDELINES ROADMAP https://buff.ly/3Q26fS0

6/2/22 SF Chronicle: Alameda County to reinstate indoor mask mandate starting Friday amid rising COVID cases and hospitalizations https://buff.ly/3mgNoF7

6/2/22 AP: Congress Gridlock could delay COVID funds until Fall — or longer https://buff.ly/38WLZko

• President Joe Biden’s appeal for funds for vaccines, testing and treatments has hit opposition from Republicans, who’ve fused the fight with the precarious politics of immigration. 

• Congress is in recess, and the next steps are uncertain, despite admonitions from White House COVID-19 coordinator Dr. Ashish Jha of damaging consequences from “every day we wait.”

6/2/22 Research Square: Oral Nirmatrelvir (Paxlovid) and Severe Covid-19 Outcomes During the Omicron Surge in Israel https://buff.ly/3NjB2Z4

• Paxlovid decreased severe disease by 89% with the Delta variant.

• During the Omicron wave, Paxlovid was associated with a 67% reduction in Covid-19 hospitalizations and an 81% reduction in Covid-19 mortality in patients 65 years and above. 

• However, no significant benefit in avoidance of severe Covid-19 outcomes was shown in younger adults.

6/2/22 Nature: Targeted isolation of diverse human protective broadly neutralizing antibodies (bnAb) against SARS-like viruses  https://buff.ly/3xncZ61

• bnAbs may be used for next-generation antibody prophylactic and therapeutic applications and provide a molecular basis for effective vaccines.

6/1/22 ABC7 News: UCSF Study shows people are recovering from COVID in a week but testing positive on antigen test for over 10 days with Omicron https://buff.ly/3GVXWmU

• If you test positive on an antigen test, you are still infectious and should isolate even if you no longer have symptoms.

• 80% of symptomatic people at day five were still positive. A third of symptomatic people were still positive at 10 days.

6/1/22 NY Times: During the Omicron Wave, Death Rates Soared for Older People https://buff.ly/3N7gZNg

• Almost as many Americans 65 and older died in four months of the Omicron surge as did in six months of the Delta wave.

• Immunity wanes and boosters are needed to fight Omicron.

6/2/22 YaleNews: COVID vaccines do not impact fertility or pregnancy outcomes, study shows https://buff.ly/3xcgdc5

• “The findings provide further evidence that existing mRNA vaccines are safe for pregnant women and those planning to become pregnant,” said Prof. Akiko Iwasaki. 

• Unvaccinated pregnant women are at increased risk for severe consequences of COVID-19 infections, including hospitalization and intensive care stays than unvaccinated pregnant women, and face increased risk of delivering a preterm or stillborn infant.

6/1/22 JAMA: Association of COVID-19 Vaccination During Pregnancy With Incidence of SARS-CoV-2 Infection in Infants https://buff.ly/3m956KL

• Decreased risk of COVID-19 for months in babies born to women vaccinated during pregnancy.

6/1/22 AJOG: Gestational diabetes mellitus and COVID-19: results from the CRONOS study https://buff.ly/3MdVHMt

• Gestational diabetes mellitus, combined with periconceptional overweight/obesity BMI >25, is independently associated with severe maternal course of COVID-19, especially when the mothers require insulin and COVID-19.

5/31/22 JAMA: Racial and Ethnic Discrepancy in Pulse Oximetry and Delayed Identification of Treatment Eligibility Among Patients With COVID-19  https://buff.ly/3ad1tRe

• Pulse oximeter vs. ABG. 

• Pulse oximeter measurement discrepancies among patients of color (Asian, Black and Hispanic) tied to delayed COVID-19 care and possibly may worsen outcomes.

(photo: Grace Cary/Getty Images)

6/2/22 Vidal.fr: Le COVID long, dernierné des syndromes postinfectieux https://buff.ly/3mbavkM

Summary of the Nature review article on Post Acute Infection Syndromes (PAIS) including Long COVID written in French.

Original article: 

5/19/22 Nature (A. Iwasaki’s lab): Unexplained Post-Acute Infection Syndromes (PAIS) https://buff.ly/38zncTh

Excellent review article summarizes what is known about unexplained PAISs, including ME/CFS, provides context for post-acute sequelae of SARS-CoV-2 infection (PASC), a.k.a. Long COVID, and delineate the need for basic biomedical research into the underlying mechanisms.

5/31/22 Nature: Genetic determinants of mannose-binding lectin (MBL) activity predispose to thromboembolic complications in critical COVID-19 https://buff.ly/3NKsXMx

• A recent study demonstrated that the complement recognition protein mannose-binding lectin (MBL) can bind to glycosylated SARS-CoV-2 spike protein.

• MBL2 haplotypes determine risk for thrombotic complications in critically ill COVID-19 patients. 

  • Genetically determined MBL activity confers risk for pulmonary embolism in a U-shaped manner, where haplotypes associated with intermediate MBL activity are protective.

Great news:

5/30/22 MedRxiV: Evusheld (Tixagevimab/Cilgavimab) for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data https://buff.ly/3N2Xd5w

• Using national real-world data from predominantly vaccinated (73%), immunocompromised Veterans, administration of tixagevimab/cilgavimab (Evusheld) was associated with lower rates of SARS-CoV-2 infection, hospitalization, and all-cause mortality during the Omicron surge.

5/30/22 MedRxiV: Protection against Omicron conferred by mRNA primary vaccine series, boosters, and prior infection https://buff.ly/3LRQbiE

• California prison during Omicron wave

• 24,000 Omicron cases and 270,000 controls

• A third mRNA dose provided significant, additional protection over two doses against Omicron infection, including among individuals with prior infection. 

• Vaccination should remain a priority--even in settings with high levels of transmission and prior infection.

Fascinating:

5/30/22 Nature: Brain motor and fear circuits regulate leukocytes during acute stress  https://buff.ly/3PRwFpt

• Distinct brain regions relevant to fear and the fight or flight response cause massive changes in leukocyte distribution and function throughout the body during acute stress in mice. 

  • Acute stress causes brain motor circuits to induce rapid neutrophil mobilization from the bone marrow to peripheral tissues via skeletal muscle-derived neutrophil-attracting chemokines. 

  • The paraventricular hypothalamus sends Corticotropin Releasing Hormone (CRH) neuron-mediated leukocyte shifts to protect against autoimmunity, but impair immunity to SARS-CoV-2 and influenza infection.  

    • This controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow through direct, cell-intrinsic glucocorticoid signaling via the adrenal gland.

5/30/22 Association between Self-reported Masking Behavior and SARS-CoV-2 Infection Wanes from Pre-Delta to Omicron-Predominant Periods - North Carolina COVID-19 Community Research Partnership https://buff.ly/3LXTFA4

• Odds of infection for those who did not always compared to those who always wore a mask was 66% higher pre-Delta, 53% higher during Delta, declining to 16% higher during Omicron"

• Omicron's hyper-transmissibility necessitates better masks like KN95 or N95.

5/28/22 Trevor Bedford’s twitter thread on BA.4/5 will probably outcompete BA.2.12.1

• In the US, we see that BA.2.12.1 currently has a logistic growth rate of 0.05 per day, while BA.4 and BA.5 have logistic growth rates of 0.09 and 0.14 per day.

• This suggests BA.4 and BA.5 are fitter than BA.2.12.1 as one might expect given the additional spike F486V mutation and others.

• In other countries, we see growing epidemics of BA.2.12.1, BA.4 and BA.5, particularly in Portugal where BA.5 got an early start and is beginning to push cases past BA.2 levels.

• There is a notable drop in neutralization titers against BA.4 and BA.5 viruses in boosted individuals and individuals with BA.1 breakthrough infections. https://buff.ly/3lOQwrM

• Thus, we expect at least some portion of the BA.4 / BA.5 epidemics to be driven by increased vaccine breakthrough and increased reinfection relative to current BA.2 circulation.

Here's a reminder of the different variants:

SUMMARY OF OMICRON SUBVARIANTS (from last week):

BA.1 = The Original Omicron (November 2021 to February 2022)

BA.2

• More symptoms than BA.1

• Prior BA.1 infection does not protect against BA.2

• Antiviral pills (Paxlovid and Molnupiravir) work against BA.2. 

BA.2.12.1

• L452Q mutation in spike

• BA.2.12.1 is now dominant in the U.S.

• Monoclonal antibody that works against BA.2.12.1:  Bebtelovimab

• Like BA.4/5, BA.2.12.1 replicates more in lung cells than BA.2.

BA.4/5 

• L452R mutation in spike

• More immune evasion than BA.2.12.1 so may outcompete.

• Prior BA.1 or BA.2 infection in unvaccinated does not protect against BA.4/5.

• Triple vaccinees (3 doses) of AstraZeneca or Pfizer have less neutralization of BA.4/5  than BA.1 and BA.2.

• Serum from vaccinated people who had breakthrough infections (BTI) with BA.1 has significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

• More pathogenic than BA.2 in hamster model

• Like BA.2.12.1, BA.4/5 replicates more in lung cells than BA.2.

• Antigenically distinct to BA.1.

• Monoclonal antibody that works against BA.4/5:  Bebtelovimab

___________

5/28/22 Bloomberg: A Heart-Failure Drug Tames Palpitations in Long COVID Patients (PASC) https://buff.ly/3avbPfB

• 11% of coronavirus patients report palpitations or an increased heart rate.

• Suggestive of postural orthostatic tachycardia syndrome, or POTS.

• POTS is more prevalent among women of childbearing age; often coincides with lightheadedness, brain fog, and gastric upset; and can eventually lead to chronic fatigue.

• Corlanor, which goes by the generic name ivabradine, along with specific exercises, to hundreds of patients with POTS, including many so-called Covid long-haulers. 

• “Within a month or two, patients will come back to me and say, ‘I feel better, my heart rate is now much lower,’ and then I start titrating them off the drug,” she says.

Travel: Insurance Providers for Overseas Coverage https://buff.ly/3a4R0aL

In What You Need to Know About International Travel, I discuss what to bring with you on an international trip and how to get a COVID test before you return to the United States.