COVID news and more 11/11/23

This week, COVID cases stopped their decline and are just starting to creep up again from HV.1 and newcomer HK.3. HK.3 is a descendent of XBB, so the new fall COVID vaccines should help protect against it. Biobot shows an increase in the midwest and western United States. Emergency department visits for COVID are decreasing as other respiratory viruses (RSV, influenza) are starting to increase. Influenza levels are still low, but are starting to increase. It would be a good time to get a flu vaccine and a COVID XBB.1.5 updated vaccine for protection before Thanksgiving. COVID hospitalizations have plateaued.

Figure from Biobot. Wastewater SARS-CoV-2 virus is increasing in the midwest and west.

JN.1 (BA.2.86 + L455S) is increasing by 115% per week in Paris, France and appears to have a growth advantage over other variants. The CDC has lumped together JN.1 and BA.2.86 with BA.2 for their reporting which is confusing. BA.2.86 has 33 more mutations in the spike protein than BA.2, and JN.1 has 34 mutations with the additional L455S mutation.

Figure: Kei Sato and Eric Topol

Figure: Spike mutation differences between BA.2.86 and BA.2 from Raj Rajnarayanan

A group of 212 scientists from 15 countries are working together on the COVID Moonshot, an open-science drug discovery project to try to find the best antiviral medications to fight SARS-CoV-2. Ensitrelvir, the recently approved antiviral in Japan, was identified in part from crystallographic data from the COVID Moonshot Consortium.

A new CDC report shows that Influenza vaccination coverage was 81% among Health Care Personnel (HCP) at acute care hospitals and 47% among those at nursing homes in the U.S. last year. In comparison, only 17% of HCP at acute care hospitals and 23% at nursing homes were up-to-date on COVID-19 vaccination during the 2022–23 influenza season. Improving vaccination coverage of healthcare workers can protect them and also their patients from COVID infections.

Mucosal vaccines are sprays that go directly into the nose or are inhaled into the nose, upper airways and lungs. They can cause mucosal immunity which prevents a virus from being able to enter the body. A new study from the NIH Vaccine Research Center shows again that mucosal boosters work. Virus-vectored mucosal booster vaccines (nasal or nebulized vaccine) were given to Rhesus macaques (monkeys) who had previously received 2 doses of mRNA vaccine injections. They were then challenged with a new variant (XBB.1.16). The mucosal booster vaccines had superior and durable immunity against the new and highly transmissible variant (XBB.1.16) as compared to an intramuscular booster vaccine.

Immune imprinting, also known as the “original antigenic sin”, is the theory that the immune system tends to “remember” the first antigen that it sees (i.e. the first SARS-CoV-2 virus from 2020) and continues to make antibodies for that variant instead of antibodies against new strains that may appear. A new review article looks at evidence both for and against immune imprinting in host response (antibodies) to SARS-CoV-2 and implications for booster vaccines. In another article this week, scientists evaluated different human antibodies for SARS (a.k.a. SARS-CoV-1) and SARS-CoV-2 to try to find neutralizing antibodies that would work against the entire family of sarbecoviruses. This knowledge could allow us to make a universal vaccine against all sarbecoviruses in the future.

Long COVID

“Long COVID is hard.” David Putrino recently spoke with CNN’s Dr. Sanja Gupta on his podcast about Long COVID- the symptoms, statistics, brain changes and more. Dr. Putrino relayed five tips to help people with Long COVID:

1. Rest and pace yourself https://buff.ly/3u9v3kG

2. Get evaluated for dysautonomia https://buff.ly/467sVY2

3. Mast Cell Activation Syndrome (MCAS) https://buff.ly/3uavICF

4. Breathwork- “Dysfunctional breathing and altered gas exchange is present in a majority of people with long Covid, and a daily breathwork practice can significantly improve daily symptoms. https://buff.ly/3MCfTe4

5. Reach out to others as chronic illnesses like Long COVID can be isolating. https://buff.ly/47quL7h

Many people lost their sense of smell and even their sense of taste with COVID infections early in the pandemic. A study looked at the loss of smell (anosmia) at 1, 2, and 3 years after infection and found that most people regained their sense of taste, but about 3.4% of people still had a decreased ability to smell (hyposmia) at 3 years as compared to controls. 

In an interview with Medscape, Dr. Ziyad Al-Aly recently summarized some of the data on Long COVID. Long COVID is not uncommon. Second and third infections increase the risk of Long COVID, but vaccination can help to decrease the risk somewhat. Long COVID has become a chronic disease for many and at this point, there is no cure for Long COVID. Treatments now focus on managing symptoms. Long COVID is a complex disease and is often multisystemic. It can be different for each person affected, although there are several phenotypes. 

A small case series from Yale shows that 8 patients treated IVIG for 9 months had significant improvement of post-COVID Small Fiber Neuropathy. This is initial evidence that small fiber neuropathy (SFN) may respond to IVIG and is linked with neurovascular dysregulation and dysautonomia. A larger clinical trial is needed.

In people with Long COVID from the first pandemic wave who were initially immunonaive to SARS-CoV-2, blood CD4+ T cell count levels independently correlate with Long COVID fatigue severity, regardless of the initial disease severity. Although non-hospitalized patients had fewer organ complications, they did have comparable levels of fatigue, depression, anxiety, and overall quality of life impairment. Elevated activated B cells and exhausted T cells may suggest persistent SARS-CoV-2 antigen per Dr. Iwasaki in a past tweet thread.

A new meta-analysis of 13 studies shows that pre-existing asthma or allergic rhinitis may increase the risk of Long COVID. In response to this article, Dr. Blitshteyn of the Dysautonomia Clinic posted that “this meta-analysis confirms my clinical observation that pre-existing allergies, asthma or other features of mast cell hyperactivity may be risk factors for Long Covid. Another probable risk factor is joint hypermobility syndrome that may be undiagnosed. Finally, in our paper early in the pandemic describing the first and largest case series of POTS and other autonomic disorders after Covid, some patients with Long Covid had a history of concussion, migraine and minor autonomic symptoms, such as dizziness or palpitations, before Covid.”

There are different types of Long COVID. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious disease with symptoms of exhaustion, post-exertional malaise (severe fatigue or illness after trying to do common activities), cognitive dysfunction (brain fog), sleep problems and pain. There is an ME/CFS type of Long COVID that is more common in younger women and is seen more often after a mild COVID infection.

But, there are other Long COVID subtypes such as those people who initially have a severe initial COVID infection requiring hospitalization. These Long COVID patients tend to be older and male. A new study from China looks at Long COVID after severe COVID infection requiring hospitalization, studying plasma proteins at 6-months, 1-year, and 2-years. The proteomic results showed 4 types of biologic pathways affected: 1) cell–matrix interactions and cytoskeletal remodeling and hypertrophic cardiomyopathy, 2) immune responses related to the complement and coagulation cascade and cholesterol, 3) Fc receptor signaling, and 4) neuron generation and differentiation.

NIH funding for Long Covid research has run out and there are still no approved treatments for the millions of people with Long COVID. On Tuesday November 14th, people with Long COVID and their allies will be calling their congressional representatives to demand a Long COVID Moonshot with annual funding of $1 Billion for research, including clinical trials, on Long COVID. They are also asking for support for 3 bills to support educating healthcare providers about Long COVID and the establishment of Long COVID clinics. If interested, you can call on November 14th or you can email your senators and representatives now. Easy instructions on what to do are available at https://longcovidmoonshot.com/

In an interview with Dr. Emily Mendenhall posted yesterday, Dr. Fauci relayed how important it is to fund research on postviral diseases like ME/CFS and Long COVID. He recommended stable multi-year funding for Long COVID research which aligns with what people with Long COVID are asking for with the Long COVID Moonshot.

In non-COVID news, private equity firms are buying up nursing homes (and medical practices) with penny-pinching mandates that can be very dangerous for patients. Because they are not publicly traded companies, private equity firms are effectively invisible to investors, the media, and to regulators.  A tuberculosis outbreak has been linked to the California Grand Casino in Pacheco, California. Fruit puree pouches for children (WanaBana and other brands) have been recalled because they may be tainted with lead. 

The CDC has warned of a 755% increase in congenital syphilis from 2012 to 2021. Syphilis transferred from a pregnant individual to their fetus can lead to stillbirth, miscarriage, or neonatal death, blindness, deafness, developmental delay, or bone abnormalities. Routine prenatal care includes testing for syphilis and Bicillin is an effective treatment. Better outreach could help women get early prenatal care which is important to reduce the rate of congenital syphilis.

Liv Boeree warned in her recent TED talk about artificial intelligence (AI) and the dangers of the “Moloch's trap” of unhealthy competition. The astrophysicist turned professional poker player turned science communicator gives advice on how to avoid this trap. Tens of thousands of ancient coins dating back to the 4th century were found off the coast of Sardinia. Kenya declared a surprise public holiday on November 13th for a national campaign to plant 15 billion trees to combat climate change. 

Happy Veterans Day and thank you to all veterans for your service. 

Have a great rest of your weekend,

Ruth Ann Crystal MD

COVID news:

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

Variants in locations around the globe:

https://outbreak.info/

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

Weekly ED visits for respiratory illnesses, by age and disease: https://www.cdc.gov/ncird/surveillance/respiratory-illnesses/index.html

Influenza:

Walgreens positivity rate: https://www.walgreens.com/businesssolutions/covid-19-index.jsp

US Wastewater Monitoring:

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

*** This map is probably not accurate because of the Biobot contracting lawsuit.

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

California wastewater level updates:

–Wastewater SCAN:

https://data.wastewaterscan.org/

  California statewide view https://buff.ly/3YObiul
Sewer Coronavirus Alert Network (SCAN) project by Stanford University: 

JP Weiland: https://twitter.com/JPWeiland

JN.1 growth in Paris, France area: 

---

Via Eric Topol MD

Variants

11/3/23 BioRxiv (Sato lab): Virological characteristics of the SARS-CoV-2 BA.2.86 variant https://buff.ly/3QtXxgn

• The original BA.2.86 has lower growth than BA.2 and its lower pathogenicity appears to be due to its decreased replication capacity. 

Figure from Sato lab with annotations by E. Topol

Treatments

11/10/23 Science: Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors https://buff.ly/3SuCrBm

• Scientists from around the world worked together and crowdsourced ideas to accelerate antiviral drug discovery against SARS-CoV-2.

• "The COVID Moonshot project, a fully open-science drug discovery campaign to identify, synthesize, and test inhibitors against the SARS-CoV-2 main protease, a key antiviral target."

• The recently approved antiviral ensitrelvir was identified in part based on crystallographic data from the COVID Moonshot Consortium. 

Vaccines

11/10/23 CDC MMWR: Influenza and Up-to-Date COVID-19 Vaccination Coverage Among Health Care Personnel (HCP) https://buff.ly/3u9hFNA

• During the 2022–23 influenza season:

  • Influenza vaccination coverage was 81% among HCP at acute care hospitals and 47% among those at nursing homes.

  • Up-to-date COVID-19 vaccination coverage was 17% among HCP at acute care hospitals and 23% among those at nursing homes. 

11/8/23 BioRxiV: Mucosal Adenoviral-vectored Vaccine Boosting Durably Prevents XBB.1.16 Infection in Nonhuman Primates https://buff.ly/40w7pLm

• Virus-vectored mucosal booster vaccines (nasal or nebulized vaccine) were given to Rhesus macaques (monkeys) who had previously received 2 doses of mRNA im vaccine. They were then challenged with a new variant (XBB.1.16). 

• The mucosal booster vaccines had superior and durable immunity against the new and highly transmissible variant (XBB.1.16) as compared to an intramuscular booster vaccine.

• “Our study provides a template for the development of mucosal vaccines that limit infection and transmission against respiratory pathogens.” 

11/6/23 Nature Microbiology: Immune imprinting and next-generation coronavirus vaccines https://buff.ly/467mpAk

• Review article that looks at evidence for and against immune imprinting in host response (antibodies) to SARS-CoV-2 and implications for booster vaccines.

11/3/23 Immunity: Dissecting the intricacies of human antibody responses to SARS-CoV-1 and SARS-CoV-2 infection https://buff.ly/3QKwsXR

• Evaluating human antibodies for SARS-1 and SARS-2 and trying to find neutralizing antibodies that work against the family of sarbecoviruses so that we could make a universal vaccine in the future.

Long COVID

“Long COVID is hard” is a new article from Dr. Sanjay Gupta of CNN. 

11/9/23 CNN: Long Covid is hard — here are five tips to help https://buff.ly/3Qvyaeq

1. Rest and pace yourself

2. Get evaluated for dysautonomia

3. Mast cells

4. Breathwork- “Dysfunctional breathing and altered gas exchange is present in a majority of people with long Covid, and a daily breathwork practice can significantly improve daily symptoms.

5. Reach out- Chronic illness like Long COVID can be very isolating.

Links:

• Pacing — Long COVID Physio https://buff.ly/3u9v3kG

• Dysautonomia International https://buff.ly/467sVY2

• Mast Cell Activation Syndrome (MCAS) https://buff.ly/3uavICF

• Breathing Pattern Disorder — Long COVID Physio https://buff.ly/3MCfTe4

• Social Connection and Physical Health — Social Creatures https://buff.ly/47quL7h

11/9/23 JAMA: Loss of Smell 3 Years After COVID-19 https://buff.ly/40MWTjb

• The 3-year prevalence of measured olfactory dysfunction (hyposmia and anosmia) and gustatory dysfunction (GD) associated with SARS-CoV-2 infection.

11/6/23 Medscape: Second Infection Hikes Long COVID Risk: Expert Q&A with Ziyad Al-Aly, MD https://buff.ly/49H4FiD

• Long COVID is not uncommon. Second and third infections increase the risk of LC. Vaccination can help to decrease the risk.

• Long COVID has become a chronic disease for many; most people don't recover from LC.

• Long COVID is complex and is not the same for everyone.

• Long COVID is multisystemic and can be different for each person affected.

• "they may have different manifestations, various health trajectories, and different outcomes."

• "Management at this point is really managing the symptoms. We don't have a treatment for it; we don't have a cure for it." 

Article refers to this paper by Z. Al-Aly and colleagues:

8/21/23 Nature Medicine (Ziyad Al-Aly, MD): Postacute sequelae of COVID-19 at 2 years https://buff.ly/45gYC1y

• 3 year study of 138,000 veterans.

• "People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition." 

11/8/23 MedRxiV (Yale): Small Fiber Neuropathy after COVID-19: A Key to Long COVID https://buff.ly/47567cM

• Case series (n = 16 ) of new onset small fiber neuropathy (SFN) after COVID-19.

• 8 patients treated with 9.5 months of IVIG had significant improvement of SFN symptoms.

  • IVIG to treat post-infectious small fiber neuropathy. 

• This small study shows initial evidence that small fiber neuropathy (SFN) responds to IVIG and is linked with neurovascular dysregulation and dysautonomia. A larger clinical trial is needed.

• SFN has been linked to both ME/CFS and POTS.

11/4/23 Infection: Blood T cell phenotypes correlate with fatigue severity in post-acute sequelae of COVID-19 (PASC, Long COVID) https://buff.ly/3Qx9CBD

• In people with Long COVID from the first pandemic wave who were initially immunonaive to SARS-CoV-2, blood CD4+ T cell counts independently correlated with Long COVID fatigue severity , regardless of the initial disease severity.

• Non-hospitalized patients had fewer organ complications, they had comparable levels of fatigue, depression, anxiety, and overall quality of life impairment. 

11/8/23 Allergic diseases as risk factors for Long‐COVID symptoms: Systematic review of prospective cohort studies https://buff.ly/46ZXq3k

• Meta-analysis of 13 studies shows that pre-existing asthma or allergic rhinitis may increase the risk of Long COVID.

https://twitter.com/dysclinic/status/1722686244532912148

Long COVID Moonshot: https://longcovidmoonshot.com/

People will be calling their representatives on November 14th to demand $1B in annual research for Long COVID.

11/10/23 Scientific American (Mendenhall): What Tony Fauci Told Me About Long COVID and Other Postviral Illnesses https://buff.ly/3QU7i9d

• “Fauci emphasized to me how important it is to do more research on postviral syndromes and, specifically, on how long COVID affects people differently.”

• "But the key, he said, would be the kind of long-range, multiple-year funding that isn’t necessarily dependent on a result for renewal—the type of funding that has existed in the past where so long as the work was good, he said, the researcher’s job would be safe. We talked about how current funding structures don’t really support this kind of open-ended research." 

Long COVID after severe COVID infection requiring hospitalization:

12/2023 Lancet (China): Probing long COVID through a proteomic lens: a comprehensive two-year longitudinal cohort study of hospitalised survivors https://buff.ly/3FLufoP

• Cohort study of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. 63% were male.

• Proteomic of plasma samples from hospitalized COVID-19 survivors at 6-month, 1-year, and 2-year after symptom onset and age and sex matched healthy controls.

• The results indicated four major recovery modes of biological processes and pathways related to:

  • 1. Cell–matrix interactions and cytoskeletal remodeling and hypertrophic cardiomyopathy

  • 2. Immune response, complement and coagulation cascade, and cholesterol.

  • 3. Fc receptor signaling 

  • 4. Neuron generation and differentiation

8 Nov 2023 Le Parisien: Covid long : pourquoi cette maladie doit être mieux reconnue et prise en charge https://buff.ly/46b1NHw

Non-COVID news:

10/30/23 The Atlantic: The Secretive Industry (Private-Equity) Devouring the U.S. Economy https://buff.ly/3FDgwjL

11/6/23 People: Tuberculosis Outbreak Linked to California Casino Prompts Bay Area Health Officials to Encourage Testing https://buff.ly/461LOvA

• 11 individuals linked to the California Grand Casino, in Pacheco, California, tested positive for tuberculosis.

11/6/23 CNN: Emergency room visits for firearm injuries among children doubled during the pandemic https://buff.ly/3MA5VKh

11/5/23 AP: More fruit pouches for kids are being recalled because of illnesses that are linked to lead https://buff.ly/3u59dig

10/2023 TED Talk: Liv Boeree: The deadly trap that could create an AI catastrophe https://buff.ly/3SEs26l

• Moloch's trap of unhealthy competition and what to do to fight it. Excellent talk on the future of AI from an astrophysicist turned professional poker player turned science communicator.

11/4/23 AP: Tens of thousands of ancient coins have been found off Sardinia. They may be spoils of a shipwreck https://buff.ly/3SyHm4a

• The coins date to the first half of the 4th century. 

11/7/23 AP: Kenya declares a surprise public holiday on November 13th for a national campaign to plant 15 billion trees to combat climate change https://buff.ly/3QMlu48

11/7/23 CDC: Preventing Congenital Syphilis https://buff.ly/3u4bn1z.

• From 2012–2021, congenital syphilis cases increased 755%.

• Congenital syphilis can lead to stillbirth, miscarriage, or neonatal death, blindness, deafness, developmental delay, or bone abnormalities.

• People of color are affected more. Social determinants of health pose barriers to prenatal care which includes testing for syphilis.

• “They don’t have a car or health insurance, they have a job or caretaking responsibilities, or they struggle to find a provider who speaks their language.” https://buff.ly/40ruXkF