COVID news and more 8/12/23

The EG.5 variant is on the rise in the United States, Ireland, France, the UK, Japan and China and represents 35% of variants worldwide. The WHO upgraded EG.5’s status from a variant under monitoring to a variant of interest this week. COVID cases, hospitalizations (up 12.5%), and emergency department visits are increasing, but are increasing more gingerly than in previous surges because of our collective immunity wall (from vaccinations and prior COVID infections). Wastewater virus levels are increasing again across the United States, but are starting from a much lower level than in previous waves.

The US variant tracker was last updated about a week ago on 8/5/23 showing that EG.5 was 17.3% of cases, XBB.1.16 was 15.6% and a few other XBB descendants were thrown in the mix. EG.5 is a descendent of XBB.1.9.2 with an additional mutation at 465 that makes it less susceptible to our body’s neutralizing antibodies. Dr. Eric Topol wrote an excellent article on new subvariants EG.5 and the FLip mutation which both have a growth advantage over regular XBB because of new mutations that make them less likely to be neutralized by our antibodies. He discusses how we need the fall XBB.1.5 boosters as soon as possible since this booster should protect us against EG.5. Reports say that the fall booster will not be available until October, or perhaps late September though.

COVID infection is associated with an increased risk of getting Type 2 Diabetes. A new study of 15 million people from the UK shows that COVID vaccination markedly reduced the incidence of Type 2 Diabetes after COVID infection. This is yet another reason to be vaccinated. Intravenous Remdesivir given to immunocompromised people who were hospitalized for COVID infections was found to reduce mortality for all variant waves. Petter Brodin reviewed children’s immune responses to SARS-CoV-2 infection and vaccination. 

Long COVID:

The CDC reported this week that in adults with prior COVID infection, 11% report having Long COVID, down from 18.9% reported earlier in the pandemic. For the general U.S. adult population overall (people who have and have not had COVID infections), Long COVID incidence declined from 7.5% down to 6% where it has remained the same since January 2023. Vaccinations can reduce Long COVID risk some and the initial numbers may reflect higher risk before vaccinations were available. Unfortunately, more than one quarter of adults (26.4%) with Long COVID report significant activity limitations and may not be able to work.

In a highly vaccinated population who had received at least 3 doses of COVID vaccines in Australia, 18.2% developed Long COVID during the Omicron wave. Female sex, being 50-69 years of age, pre-existing health issues, residing in a rural or remote area, and receiving fewer vaccine doses were significant independent predictors of Long COVID. About 1 in 5 (18%) of people who developed Long COVID in this study were no longer able to do their work or study. Long COVID is disabling people around the world. Measures that reduce COVID infections (vaccinations, masking, better indoor air quality) will also reduce Long COVID. 

The first major survey of doctors with Long Covid in Britain shows the debilitating impact of Long COVID on their health, life and working ability. More than half (54%) of UK doctors got a COVID infection during the first wave in 2020 when few had access to protective equipment (PPE). Seventy-seven percent (77%) of doctors with Long COVID say that they got COVID on the job while taking care of patients. Most (60%) of doctors with Long COVID can no longer perform their day-to-day activities. This will have long term impacts on the doctors’ lives, but also the healthcare system.

In the U.S., many people with Long COVID are unable to get disability payments and are struggling to make ends meet. Some are going to court because of the system. According to Social Security disability attorney Kevin LaPorte, the Social Security Administration denies two-thirds of initial disability applications. People who then appeal will get denied 90% of the time. After that, the disabled person can go to court to appeal the decision before a judge. Jumping through all of these hoops can be extremely hard for very sick people with Long COVID.

I highly recommend novelist Madeline Miller’s piece in the Washington Post entitled “Long COVID has derailed my life. Make no mistake: It could yours, too.” The New York Times bestselling author of The Song of Achilles and Circe, writes about her experiences with Long COVID. She concludes the very well written essay: “Because the truth is that however immortal we feel, we are all just one infection away from a new life.”

Long COVID causes:

Mitochondrial dysfunction appears to be at least one of the root causes of Long COVID as demonstrated in a new study. Researchers found that even after the SARS-CoV-2 virus was cleared by the body, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired in people with Long COVID. In order to produce more virus, SARS-CoV-2 hijacks human mitochondria, the energy powerhouse of cells, by inhibiting certain mitochondrial genes. Treatments to enhance mitochondrial function may reduce symptoms of both acute COVID infection and of Long COVID. An article in STAT news summarizes how the virus disrupts our mitochondria.

Peripheral blood mononuclear cells (PBMCs) are blood cells with a round nucleus and include immune cells such as lymphocytes, monocytes, natural killer cells or dendritic cells. A team in Amsterdam reports that the SARS-CoV-2 virus switches on an enzyme called IDO2 in human PBMCs and in the brain. This in turn activates the Kynurenine cycle, the breakdown products of which may cause COVID pathology and symptoms of Long COVID. IDO2 expression is driven by the aryl hydrocarbon receptor (AHR) and is associated with reduced mitochondrial functioning and autophagy. In vitro, the team found that SARS-CoV-2 virus increase of IDO2 expression could be stopped by an AHR antagonist. AHR antagonists potentially could be a pharmaceutical target to turn off the IDO2 enzyme and subsequently the Kynurenine pathway from spinning out of control in Long COVID. 

Other data and theories may support that the SARS-CoV-2 virus turns on the IDO2 enzyme. In 2019,  Alex Kashi, Ron Davis and Rob Phair hypothesized using mathematical modeling that an IDO Metabolic Trap may be a cause of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Many people with Long COVID have ME/CFS which is a disabling and complex illness that causes overwhelming exhaustion that is not improved by rest. The new data from Amsterdam showing that the SARS-CoV-2 virus activates IDO2 may support the IDO Metabolic Trap hypothesis as a cause for ME/CFS and for Long COVID with ME/CFS. In addition, a group in Australia published a paper in June 2023 showing that for up to 12 months after a SARS-CoV-2 infection, the Kynurenine pathway can be activated leading to cognitive impairment (brain fog) in Long COVID. IDO2 and the Kynurenine pathway will need to be studied further in people with Long COVID.

In April 2023, the Erturk lab published a paper showing that the SARS-CoV-2 spike protein can accumulate in the Skull-Meninges-Brain Axis and that this could have potential implications for long term neurological complications in Long COVID. The Erturk lab has made a new technique called DISCO-MS which uses robot-assisted spatial proteomics and AI analysis to make cell level imaging possible. The 3D videos of the spike protein in the skull’s bone marrow are incredible. This week, the Erturk lab published more about the unique functions of the skull’s bone marrow in brain health and in neurologic disorders. The article includes fascinating 3D videos of connections called SMCs that go from the skull to the meninges that surround the brain and can bring substances like cytokines to the brain while circumventing the usual blood-brain barrier. 

In non-COVID news, the FDA approved the first oral treatment specifically for postpartum depression. Scientists have made a vaccination against Epstein -Barr Virus (EBV) in mice and will work towards making such a vaccine for humans. EBV is implicated in mononucleosis, Multiple Sclerosis, Hodgkin lymphoma, Burkitt lymphoma and nasopharyngeal cancers.  

A bacteria called A. Baylyi has been engineered to detect colon cancer and this animated explainer video shows how. Daily sugar-sweetened drinks like soda or fruit drinks are linked to liver problems, including liver cancer, in older women. Novo Nordisk reported this week in a press release that their weight loss drug Wegovy (semaglutide) was also found to decrease an overweight person’s risk of stroke and heart attacks by 20%. This may help with insurance coverage of the medication.

The two roads into Western Maui are still closed after the catastrophic Lahaina fire, but that didn’t stop local Maui residents who packed up their boats with food, water, gas stoves, diapers and generators to bring to their Lahaina ohana (family).

Have a good rest of your weekend,

Ruth Ann Crystal MD

COVID news:

WHO Weekly Epidemiological Updates: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports

US Variant tracker: https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Last updated this 8/5/23

CDC COVID data tracker: https://covid.cdc.gov/covid-data-tracker/index.html#datatracker-home

CDC COVID Hospitalizations (blue) and Emergency Room (orange) visits tracker: https://covid.cdc.gov/covid-data-tracker/index.html#trends_weeklyhospitaladmissions_7dayeddiagnosed_00

NEW Benjy Renton and Jeremy Faust: Inside Medicine COVID-19 Metrics Dashboard https://buff.ly/3s36yop

US Wastewater Monitoring:

CDC Wastewater Monitor https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance

Wastewater from NWSS and Biobot in a US map format:

https://iowacovid19tracker.org/

Biobot: https://biobot.io/data/

Sewer Coronavirus Alert Network (SCAN) project by Stanford University: 

In the last 12 weeks

San Francisco

8/9/23 CNN: New variant EG.5 is on the rise as Covid-19 cases and hospitalizations go up https://buff.ly/3DRuZHY

• EG.5 is a descendant of the XBB strain of the Omicron family.

• EG.5 = XBB.1.9.2 + mutation at 465.

• Beyond the US, EG.5 is growing quickly in Ireland, France, the UK, Japan and China. The World Health Organization upgraded its status on Wednesday from a variant under monitoring to a variant of interest. 

8/11/23 CDC MMWR: Long COVID and Significant Activity Limitation Among Adults, by Age — United States, June 1–13, 2022, to June 7–19, 2023 https://buff.ly/3QBqg4z

• All U.S. adults: After an initial decline (7.5% down to 6.0% of all US adults), prevalence plateaued beginning January 2023.

• Adults with prior COVID infection: Long COVID prevalence decreased from 18.9% to 11.0% where it stabilized .

• One quarter of adults (26.4%) with long COVID report significant activity limitations. 

All US adults (with or without prior COVID infection):

US adults with prior COVID infection:

8/10/23 AP: COVID-19 took a toll on heart health and doctors are still grappling with how to help https://buff.ly/44YFrJA

• “We’re about to exit this pandemic as even a sicker nation” because of COVID-related heart problems like heart attacks, arrhythmias and blood clots, said Washington University’s Dr. Ziyad Al-Aly.

8/9/23 STAT news: Study mapping how SARS-CoV-2 disrupts mitochondria suggests a cause for Long Covid https://buff.ly/3YtXpBe

• See the paper from Sci Transl Med below

• “What I think this paper does is cement the case for mitochondria as being one of the root causes of long Covid...at least in some people,” Eric Topol MD.

• “The virus inhibited mitochondrial genes that produce proteins critical for making energy. And by turning down that production, SARS-CoV-2 forced the cell to use an alternative approach that it then hijacked to make more virus — much as cancer cells do to promote their own growth.”

• The virus disrupted mitochondrial genes, especially in the heart, liver, and kidneys. 

The article referred to in STAT news:

8/9/23 Sci Transl Med: Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts https://buff.ly/3YwltUb

• Study in people and then in 2 animal models (mice and rats) to confirm.

• With SARS-CoV-2 infection, the virus causes mitochondrial dysfunction and induction of glycolysis leading to the deployment of antiviral immune defenses.

• Even after the virus was cleared, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired.

• "Therapies that enhance mitochondrial function [such as the mTOR inhibitor rapamycin per Eric Topol MD], minimize mROS, and block mtDNA release potentially could reduce the more severe symptoms of acute SARS-CoV-2 infection and mitigate the symptoms of Long Covid."

  • Sirolimus (Rapamune, Rapamycin)- immunosuppressant for transplant patients

Original article: 8/10/23 Een leven zonder postcovid ietsje dichterbij? Amsterdamse wetenschappers zitten op een spoor https://buff.ly/45l4B4U

• Google translation of article from Dutch to English

• Article in the Lancet written by these scientists:

7/26/23 Lancet: Prolonged indoleamine 2,3-dioxygenase-2 (IDO2) activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection (PASC, Long COVID) https://buff.ly/3OQbBRM

• IDO2 is expressed and active in peripheral blood mononuclear cells (PBMC) and in brain tissue from PASC patients, long after SARS-CoV-2 infection.

• IDO2 expression is driven by the aryl hydrocarbon receptor (AHR) and coincides with reduced mitochondrial functioning and autophagy. 

• SARS-CoV-2 infection induces IDO2 expression, but resulting pathology appears related to the specific kynurenine breakdown products that are generated.

• All PASC patients experienced an increase in plasma xanthurenic acid levels, while only some patients exhibited significantly elevated levels of 3-hydroxy anthranilic acid. 

• In vitro, IDO2 expression was stopped by an AHR antagonist.

Diagnostics 2019 (A. Kashi, Ron Davis, Rob Phair): The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS https://buff.ly/451uMO9

• Figure 2. Diagram of the kinetic model of the IDO metabolic trap.

Kynurenine Pathway - Enamine https://buff.ly/3DSDF0U

8/9/23 MedRxiV: Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave - Australia, 2022 https://buff.ly/456BPWa

• 94% received >= 3 vaccine doses

• 18.2% (n=2,130) had Long COVID. Female sex, being 50-69 years of age, pre-existing health issues, residing in a rural or remote area, and receiving fewer vaccine doses were significant independent predictors of Long COVID (p < 0.05). 

• Persons with Long COVID reported a median of 6 symptoms, most commonly fatigue (70.6%) and difficulty concentrating (59.6%);

• 17.9% of people with Long COVID reported reducing/discontinuing work/study. 

8/9/23 Washington Post: Novelist Madeline Miller: Long COVID has derailed my life. Make no mistake: It could yours, too. https://buff.ly/3DLevkJ

• Free version without paywall: https://buff.ly/3s2KJp1

• Very well written article on living with Long COVID.

• “Because the truth is that however immortal we feel, we are all just one infection away from a new life.” 

8/9/23 Clinical Infectious Disease: Remdesivir reduced mortality in immunocompromised patients hospitalized for COVID-19 across variant waves: Findings from routine clinical practice. https://buff.ly/3OSPlae

• Prompt initiation of remdesivir in immunocompromised patients hospitalized for COVID-19 is associated with significant survival benefit across all variant waves.

8/9/23 Cell (Ertuk lab): Distinct molecular profiles of skull bone marrow in health and neurological disorders https://buff.ly/3OSNEto

• Bone marrow across the body is different in different bones suggesting localized functions for different bones.

  • The Skull has a unique molecular profile and may help diagnosing, monitoring, and treating brain diseases.

• Skull Calvaria cells have a distinct profile that is relevant to brain pathologies.

• Structural details of human skull-meninges connections shown in amazing 3D videos in the article.

• TSPO-PET imaging of human skulls can show neuroinflammation in the brain.

• This group showed in April 2023 how SARS-CoV-2 invades the skull bone marrow leading to inflammation which then affects the brain tissue:

  • SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19 https://buff.ly/453SXM6)

8/9/23 MedRxiV (UK): Diabetes following SARS-CoV-2 infection: Incidence, persistence, and implications of COVID-19 vaccination. A cohort study of fifteen million people. https://buff.ly/3OQxAbh

• Study of 15 million people.

• People who were hospitalized with a COVID infection have a higher incidence of Type 2 Diabetes than non-hospitalized people.

• COVID vaccination markedly reduced the incidence of Type 2 Diabetes after COVID infection as compared to unvaccinated people.

Michael Mina on the present wave(let):

https://twitter.com/michaelmina_lab/status/1688995002297339904

8/2/23 Medscape: Long COVID Disability Court Battles Just 'Tip of Iceberg' https://buff.ly/3E5YZQF

• The Social Security Administration said it has received about 52,000 disability claims tied to SARS-CoV-2 infections, which represents 1% of all applications.

• "With this system, they deny two thirds of initial applications, then people who appeal get denied almost 90% of the time, and then they can appeal before a judge," said Kevin LaPorte, a Social Security disability attorney.

• Article details how to document Long COVID symptoms, etc.

NEW Benjy Renton and Jeremy Faust: Inside Medicine COVID-19 Metrics Dashboard https://buff.ly/3s36yop

8/6/23 Eric Topol MD: The Virus is Learning New Tricks and We Humans Keep Falling Behind https://buff.ly/44XFPbk

• Very helpful article

• Dr. Topol discusses EG.5 and the FLip mutations and how they affect our ability to fight off a COVID infection in 2023. 

• The Fall boosters for XBB.1.5 would protect us, but they are taking too long to make.

8/5/23 Tweet thread from Yunlong Cao on the latest variants

• EG.5 = XBB + F456L, now 35% worldwide

• FLip = XBB + F456L + L455F, 2% worldwide, but increasing quickly in Brazil and Spain

Mutation advantages: 

1) F456L evades serum antibody neutralization, even after XBB infection. 

2) FLip L455F+F456L combo shows both antibody evasion and stronger ACE2 binding.

.

"we anticipate there being a new COVID booster available probably in the early October time frame." Dr. Mandy Cohen, CDC director on NPR 8/1/23 https://buff.ly/3OtCucU.

8/5/23 Make sure you get the right test :-)

7/4/23 British Medical Association (BMA): First major survey of doctors with Long Covid reveals debilitating impact on health, life and work https://buff.ly/3JIMlKm

Key findings include:

• 54% of UK doctors believe they got COVID infection during the first wave in 2020. Few had access to PPE. 77% believe they got COVID on the job taking care of patients.

• Doctors had a wide range of symptoms.

• 60% of doctors with Long COVID had difficulty carrying out their day-to-day activities.

• Half of doctors said that they were not referred to an NHS Long COVID clinic. Of those who were referred, 65% of doctors did not feel they had a thorough work up of their Long COVID at the NHS Long COVID clinic.

9/2023 Seminars in Immunology (Petter Brodin): Immune responses to SARS-CoV-2 infection and vaccination in children https://buff.ly/45aE9Le

8/1/23 Angiogenesis: VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in (pulmonary) long COVID patients https://buff.ly/47dEI97

• 137 PASC patients, mostly male (68%), with a median age of 55 years.

• VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement.

• VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms. 

Other news:

8/4/23 FDA Approves First Oral Treatment for Postpartum Depression https://buff.ly/3OLDMBv

• Zurzuvae (zuranolone), the first oral medication indicated to treat postpartum depression (PPD).

8/8/23 Nature: Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice https://buff.ly/440EGhO

• A step towards making a vaccine for humans against Epstein -Barr Virus (EBV).

8/8/23 NBC: Weight loss drug Wegovy (semaglutide) shown to cut risk of stroke and heart attacks by 20%, company says in press release https://buff.ly/449er9e

• n = 17, 604 people age 45+ with obesity or overweight 

8/9/23 CNN: Daily sugar-sweetened drinks like soda or fruit drinks linked to liver problems in older women, report finds https://buff.ly/3KBfyr0

• Women who drank at least one sugar-sweetened beverage a day were 1.75 times as likely to be diagnosed with liver cancer and 2.5 times as likely to die from chronic liver disease.

• Artificially sweetened drinks did not increase risk of liver problems.

8/5/23 CBS: Legionnaires' disease deaths possibly linked to spa in Richmond, California https://buff.ly/3QGXkYW

• The spa did not have a permit for the hot tub.

8/10/23 Science: Engineered bacteria detect tumor DNA https://buff.ly/3saY2Us

YouTube video: Engineering bacteria to detect tumour DNA https://buff.ly/3OPE7Dk

8/10/23 Maui residents come to aid of communities suffering amid wildfire tragedies https://buff.ly/453ZaHX 

• Since the two roads to Western Maui are still closed, people brought supplies of diapers, food, water, and generators on their boats to people in the Lahaina area.

Donate to the Hawaii Community Foundation here:  https://www.hawaiicommunityfoundation.org/maui-strong