COVID news 2/25/23

This week XBB.1.5 makes up 85% of cases in the United States, but hospitalizations and deaths are decreasing despite this variant being so contagious. Reported cases are high in Arizona, but wastewater shows that there are also increased amounts of SARS-CoV-2 virus in the San Francisco Bay Area, Nebraska, the Carolinas and Alabama this week. Regarding wastewater, taking an extra 3 minutes to test airplane toilet wastewater from more than 80 international flights into JFK airport in August and September 2022 showed that 81% of these samples were positive for SARS-CoV-2 and all were Omicron subvariants. Authors reported that “aircraft wastewater monitoring can provide a complementary early warning system for the detection of SARS-CoV-2 variants and other pathogens of public health concern.”

Antiviral therapies

Shionogi Pharmaceutical in Japan reported that data from their Phase 2/3 studies on antiviral drug Ensitrelvir was successful in treating acute COVID infection, was safe and may decrease long COVID as well. The drug does not contain ritonavir like Paxlovid does, so it would not have the same drug-drug interactions as Paxlovid. An article this week in JAMA summarizes the most important drug-drug interactions for Paxlovid. However, I find that the University of Liverpool COVID-19 drug checker is easiest to use to check these interactions..

A new randomized, placebo-controlled trial found that Ivermectin given at high doses and for long duration did not show any benefit in treating COVID infection. A follow up editorial to this study asks the question- is it ethical to continue spending time and money on 10 more planned clinical trials of Ivermectin when many randomized clinical studies have proven that it does not work? Could time and resources be “better invested in examining other questions?”

Long COVID

Trisha Greenhalgh’s group in England just published an article on how to evaluate and treat people who get tachycardia (rapid heart beat) when standing in a condition called POTS. Included is an infographic summarizing the workup and treatment of POTS for primary care providers.

A new study shows that inflammation from COVID infection may cause damage to calcium channels in the heart which can lead to heart arrhythmias and heart failure. Prior studies show that COVID can also damage calcium channels in the brain causing Alzheimer's-like dementia symptoms. New onset neurogenic stuttering associated with cognitive difficulties was reported in 2 patients with Long COVID. The stuttering improved gradually and was thought to be due to a slowed metabolism of (pre)frontal and sensorimotor brain regions.

COVID and Long COVID can affect different groups differently. MD Anderson reports that 60% of their cancer patients reported Long COVID symptoms lasting about 7 to 14 months after infection. A retrospective cohort study from New York shows racial and ethnic disparities in post-acute sequelae of COVID (PASC or Long COVID). Hospitalized black people had higher risks of diabetes and headaches post-acute infection and hospitalized hispanic people had increased risks of headaches and shortness of breath as compared to hospitalized white people. Non-hospitalized black people were found to have higher risk of pulmonary embolism and diabetes post-COVID infection and non-hospitalized hispanic people had more headaches and chest pain when compared to non-hospitalized white people with COVID.  

On Twitter, Dr. Raven Baxter reminds us that if someone tests positive for COVID on a home test, it is important to get an official PCR test from a healthcare provider for documentation. If that person develops Long COVID in the future, having the official COVID test is helpful for getting into Long COVID clinics and possibly can help with disability insurance as well.

NPR featured the stories of people with Long COVID. They also discussed Long COVID with Dr. Putrino of Mount Sinai in New York who said:

“We understand very clearly that this [long COVID] is not a psychological illness… The immune system has become very dysregulated as a result of the virus, and it's leading to these highly debilitating symptoms…We need the public to understand that dying is not your only risk of serious life-changing effects from having an acute COVID infection."

Vaccines

This week, an article showed that vaccination against COVID-19 is associated with a lower risk of heart attacks, strokes, and other cardiovascular issues in people who were infected with SARS-CoV-2. The CDC reported that people of all ages have less risk of death from COVID if they have been vaccinated. Fifty international leaders in vaccine technology worked with CIDRAP at the University of Minnesota to make an extensive report on how to improve vaccines against coronaviruses.

In non-COVID news this week, two human cases of bird flu in Cambodia are being investigated by the WHO. An 11 year old girl died of H5N1 avian flu in a village in Cambodia and her father tested positive but is asymptomatic. Human-to-human transmission of H5N1 avian flu is rare, but it is being examined. It is more likely that they were infected through contact with infected birds. If you see a dead bird, do not touch it. Call animal services instead so that they can test it.

In medical innovation news, two stroke patients regained the use of their hand and arm using epidural stimulation. Columbia University scientists successfully grew new skin in the shape of a human hand for easier skin grafting than standard engineered skin grafts. In microbiome news, scientists discovered four enzymes made by gut bacteria that are related to 5-ASA (mesalamine) treatment failure in people with Ulcerative Colitis. I have also included a link to my favorite medical conference on mind-blowing innovation called NextMed Health.

Have a good weekend,

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

Non-COVID news:

My favorite medical conference, NextMed Health, is happening March 13 to 16 at the iconic Hotel Del Coronado near San Diego. https://buff.ly/3XMnB88

• NextMed Health (previously Exponential Medicine) focuses on mind-blowing new technology and innovation in health and medicine. The people are amazing too. At dinner, I have sat with an astronaut, health designers and a surgeon who teaches physicians around the world using VR during surgeries. It’s a phenomenal place to learn about the future of medicine.

2/24/23 NBC: The World Health Organization is investigating bird flu cases in Cambodia https://buff.ly/3Z0kyKX

• The WHO is investigating two human cases of bird flu in Cambodia, after an 11-year-old girl died this week and her father also tested positive for the H5N1 strain.

• It’s not yet known if the girl’s father was infected through human-to-human transmission, or through contact with infected birds or animals. Human-to-human transmission is rare with avian flu. 

2/21/23 USA Today: 'New frontier' in therapy helps 2 stroke patients move again – and gives hope for many more https://buff.ly/3EtiLWx

• This is the first time epidural stimulation “has been used to restore arm and hand movements to people immobilized by stroke.” 

2/23/23 Nature Medicine: Gut microbial metabolism of 5-ASA diminishes its clinical efficacy in inflammatory bowel disease https://buff.ly/3EzQM7V

Commentary: 2/23/23 Nature Medicine: Secrets of microbiota drug metabolism https://buff.ly/3KAbPen

• Enteric coated 5-ASA (mesalamine) is a standard initial treatment to maintain mild and moderate Ulcerative Colitis in remission. 

• Four enzymes made by gut microbiome (bacteria) predict 5-ASA treatment failure. 

2/14/23 NIH: Engineering skin grafts for complex body parts https://buff.ly/3XXp4ZE

• Columbia University scientists successfully grew new skin in the shape of a human hand that was also stronger than standard engineered skin grafts.

• The new technology has the potential to help heal burns and other damage to complex body parts with less trauma and scarring. 

A bioengineered glove of human skin created for grafting. Alberto Pappalardo and Hasan Erbil Abaci / Columbia University Vagelos College of Physicians and Surgeons

2/14/23 Man facing jail over theft of almost 200,000 Cadbury Creme Eggs https://buff.ly/3YJ2QLE

• He tried driving away with the Cadbury eggs in a tractor but was caught.

COVID news:

World: https://medriva.com/charts/world-monitor.php

USA: https://medriva.com/charts/usa-monitor.php

https://www.nytimes.com/interactive/2021/us/covid-cases.html

US hospitalizations:

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

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

• XBB.1.5 is now 85% of new COVID cases in the US

Wastewater Monitoring:

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

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

Last 6 months of wastewater virus in LA county:

2/23/23 Los Angeles County cases per Dept of Public Health:

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

Bay Area wastewater virus levels:

COVID NYC: https://www.nyc.gov/site/doh/covid/covid-19-data.page

2/24/23 BMJ by Trisha Greenhalgh: Orthostatic tachycardia after covid-19 https://buff.ly/3Y5Qxbj

• POTS (postural orthostatic tachycardia syndrome) can cause tachycardia on standing or minimal exertion may occur after covid-19 and may cause substantial functional impairment.

• Article summarizes key steps for diagnosis and treatment for primary care physicians including testing for autonomic dysfunction.

From the IDSA and COVID-19 Real-Time Learning Network (RTLN) (or @RealTimeCOVID19 on Twitter)

• Summary of COVID prevention and treatment recommendations for Immunocompromised people, including those with HIV, cancer, transplants, etc.

  • Oral and intravenous antiviral drugs

• Convalescent plasma from Omicron era

  

Molnupiravir should be removed from this infographic since it does not work (i.e. does not reduce hospitalizations or deaths) and it causes mutations in the SARS-CoV-2 virus.

2/24/23 CDC MMWR: Aircraft Toilet Wastewater Surveillance, JFK airport, NYC, August–September 2022 https://buff.ly/3EzaH70

• Wastewater tested from >80 international flights (from UK, Netherlands, France) arriving to JFK Airport in NYC.

• Sampling added an extra 3 minutes to normal aircraft maintenance times.

• 81% of wastewater samples were positive for COVID. All were Omicron subvariants.

• “Aircraft wastewater monitoring can provide a complementary early warning system for the detection of SARS-CoV-2 variants and other pathogens of public health concern.”

2/24/23 CDC MMWR: Pre Departure COVID testing requirement for international flights to the US was associated with 52% lower post-arrival SARS-CoV-2 positivity. https://buff.ly/3ImlrGK

• March 20–September 3, 2022

NEW Anti-viral Ensitrelvir: 

Shionogi: Ensitrelvir for mild-to-moderate COVID-19: Phase 3 part of Phase 2/3 study

https://buff.ly/3EAAImi

2/22/23 Shionogi Presents Pivotal Ensitrelvir Fumaric Acid Phase 3 Data and Exploratory Long COVID Data at CROI https://buff.ly/3kpDrYI

Standing up quickly with POTS feels like many check engine lights going off all at once.

2/7/23 eLIFE (MD Anderson): Long COVID in cancer patients: preponderance of symptoms in majority of patients over a long time period. https://buff.ly/3xy5gkQ

• Cancer patients who got COVID infection May 2020 to Sept 2020 followed until 2021.

• 60% of cancer patients reported long COVID symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis.

• The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia and gastro-intestinal symptoms.

2/22/23 Nature: Assessing the impact of one million COVID-19 deaths in America: economic and life expectancy losses https://buff.ly/3IQMWK0

• Impact of COVID in the United States through May 2022:

  • >1 Million deaths

  • Reduced life expectancy by 3+ years

  • Economic welfare losses of $3.57 trillion

  • Calculations do not include many people disabled by Long COVID

2/21/23 Annals of Internal Medicine: Symptom and Viral Rebound in Untreated SARS-CoV-2 Infection https://buff.ly/3ImnlXY

• RCT. N = 563 untreated outpatients with mild to moderate COVID-19 who did not take Paxlovid, mostly unvaccinated, pre-Omicron.

• Rebound without Paxlovid is higher than expected:

  • 26% rebound of symptoms

  • 31% viral rebound

  • 13% high level of virus rebound.

  • 3% had symptoms and high level viral rebound.

• Most symptom and viral rebound events were transient: 89% of symptom rebound and 95% of viral rebound events occurred at only a single time point before improving.

2/21/23 Vaccine: A Research and Development (R&D) Roadmap for Broadly Protective Coronavirus Vaccines: A Pandemic Preparedness Strategy https://buff.ly/3St8eR5

• Funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation.

• Led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts.

2/23 CDC: https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status

• Vaccination reduces COVID deaths for all ages:

2/21/23 NBC news: Covid can cause heart problems. Here's how the virus may do its damage. https://buff.ly/3SaF21a

• Inflammation from COVID infection can cause damage to calcium channels in the heart which keeps them open too long. This can lead to irregular heartbeats, some fatal, and heart failure.

• Damage to calcium channels was seen in both human heart autopsies and in mice studies.

• Past studies have shown that COVID can also damage calcium channels in the brain causing Alzheimer's-like dementia symptoms.

FYI- If you get a COVID infection, make sure to get an official PCR test from a healthcare provider. If you get Long COVID, you will need this.

2/20/23 Eurekalert: COVID-19 vaccination linked to fewer cardiac events https://buff.ly/3XVRBi2

• Vaccination against COVID-19 is associated with fewer heart attacks, strokes, and other cardiovascular issues among people who were infected with SARS-CoV-2

2/20/23 JACC: Impact of Vaccination on Major Adverse Cardiovascular Events (MACE) in Patients With COVID-19 Infection https://buff.ly/419Esoi

• Partial and complete vaccination is associated with a lower risk of MACE (major adverse cardiac events) after SARS-CoV-2 infection.

2/20/23 JAMA: Safely Prescribing Nirmatrelvir and Ritonavir (Paxlovid)—Avoiding Drug-Drug Interactions https://buff.ly/3EnJ9kV

• Teachable moment on how to avoid Paxlovid drug-drug interactions by either reducing the dose or holding the other drug in patients at high risk for complications from COVID.

• Risk ratings:

  • C (monitor therapy), 

  • D (consider drug modification) 

  • X (avoid combination). 

• Paxlovid (nirmatrelvir-ritonavir) contains a CYP3A4 inhibitor, a prescriber should be vigilant to check for interactions.

C: monitor therapy

D: modify therapy

X: avoid combination of these drugs

A: Hold apixaban if dose is 2.5 mg twice daily

Remember that you can check drug-drug interactions for Paxlovid on the University of Liverpool website below:

1/17/23 California COVID-19 Therapeutics Provider Warmline 1-866-268-4322 (COVID-CA)

• Monday through Friday, 6 a.m. – 5 p.m.

Clinician Favorite Online Resources:

• Liverpool COVID-19 Drug Interaction Checker (for Paxlovid): https://www.covid19-druginteractions.org/checker

• NIH COVID-19 Treatment Guidelines COVID-19 Treatment Guidelines (nih.gov)

2/20/23 JAMA: Higher-Dose Ivermectin vs Placebo and Time to Sustained Recovery in Outpatients With COVID-19 https://buff.ly/3KmTIs5

• Double-blind, randomized, placebo-controlled platform trial in 2022 (Omicron)

• Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 μg/kg daily for 6 days did not improve time to recovery. 

2/20/23 JAMA: Managing Persistent Uncertainty in the Ethics of Clinical Research https://buff.ly/3KlcK1U

• Ethics of continuing to run more than 10 clinical trials on Ivermectin, or any treatment, that already has many randomized trials showing no benefit.

• Clinical equipoise - the ethics of randomizing participants to receive forms of medical treatment that are known to be worse than an available alternative.

2/19/23

2/16/23 NPR with Dr. Putrino: People living with long COVID explain how the disease changed their lives https://buff.ly/3Yx8vVn

"We understand very clearly that this is not a psychological illness. This is not a psychosomatic illness. This is an illness that has been caused by the body responding to a previously unknown virus. The immune system has become very dysregulated as a result of the virus, and it's leading to these highly debilitating symptoms.

I'm really optimistic that we have the potential to close in on some biomarkers and some therapies for people with long COVID. But we need much more attention to the problem. We need the public to understand that dying is not your only risk of serious life-changing effects from having an acute COVID infection."

2/16/23 Journal of General Internal Medicine: Racial/Ethnic Disparities in Post-acute Sequelae (Long COVID) of SARS-CoV-2 Infection in New York: an EHR-Based Cohort Study from the RECOVER Program https://buff.ly/3IpH3SF

• PASC, Long COVID retrospective cohort study

• Hospitalized patients:

  • Hospitalized Black patients had higher odds of being diagnosed with diabetes and headaches after COVID infection than hospitalized white patients.

  • Hospitalized Hispanic patients had higher odds of headaches and dyspnea than hospitalized white patients.

• Non-hospitalized patients: 

  • Black patients had higher odds of being diagnosed with pulmonary embolism and diabetes, but lower odds of encephalopathy compared to white patients.

  • Hispanic patients had higher odds of being diagnosed with headaches and chest pain but lower odds of encephalopathy compared to white patients. 

2/15/23 JAMA: Association of Post–COVID-19 Condition Symptoms and Employment Status in the United States https://buff.ly/3k5q4Nn

• N = 9679 people with post–COVID-19 condition (PCC, aka.Long COVID or PASC)

• The mean age was 38.8, 63% women and 70.0% were White.

• Individuals with PCC (Long COVID) are less likely to be working full time or to be working at all.

• The presence of cognitive symptoms was associated with diminished likelihood of working full time. Reinfections can increase the risk of Long COVID.

2/13/23 J Speech Language Hearing Research: Stuttering-Like Dysfluencies as a Consequence of Long COVID https://buff.ly/3ExkDxu

• Two patients with neurogenic stuttering and cognitive difficulties for 4-5 months after COVID, with gradual improvement and near-to-complete recovery.

• Neurogenic stuttering may be a consequence of a "slowed" metabolism of (pre)frontal and sensorimotor brain regions. 

2/10/23 BMJ: As a doctor with long covid, I feel abandoned by the NHS https://buff.ly/3Ixjwk5

This week junior doctors in the UK have announced a 3 day strike.

2/16/23 @GosiaGasperoPhD on masks

2/17/23 Fox News: Two Idaho lawmakers introduce legislation to criminalize giving out certain COVID-19 vaccines (mRNA vaccines) https://buff.ly/3YN1QXe