COVID news 1/14/2023 (and more)

Hi all,

XBB.1.5 now represents 43% of the variants circulating in the US. We see a high level of XBB.1.5 in the northeast and while hospitalizations had initially gone up, they are actually starting to decrease now. Wastewater levels across the US are also still fairly high as seen on the CDC map, but we are starting to see more “blue dots” which represent lower levels of virus in wastewater in some communities.

A stellar review of Long COVID came out today written by three people with long COVID, Hannah Davis, Lisa McCorkell, and Julia Moore Vogel, and Dr. Eric Topol. The article reviews more than 200 articles on long COVID on topics including who gets Long COVID, what may be causing long COVID, current knowledge and misconceptions about long COVID, and some possible treatments being studied for long COVID. At least 65 million people around the world are estimated to have or had long COVID. For mild COVID infections 10% to 30% will get long COVID, 50% to 70% of hospitalized people will have long COVID and 10 to 12% of vaccinated people will get Long COVID. The most common ages for getting long COVID is between age 36 and 50 years and more than 90% of long COVID happen after mild acute COVID infections. 

Possible causes of long COVID discussed include viral reservoirs within the body after infection, immune dysregulation which sometimes can be related to reactivation of latent viruses, such as Epstein-Barr virus (EBV) or HHV-6 which can then lead to mitochondrial dysfunction. Other reasons for long COVID include an imbalance of the microbiome of the digestive system, autoantibodies, microclots in very small blood vessels and dysfunction of endothelial cells (the cells that line the blood vessels), and finally, possible malfunctioning nervous system signaling in the brainstem or the vagus nerve.

A few days ago in the British Medical Journal, an article about long COVID from Israel caused quite a stir both in the media and on Twitter. The media only reported that long COVID symptoms will resolve in a year, which while true for many, the reporting minimized that many people still will have disabling long COVID symptoms 1 year after infection. 

The BMJ article states that although there are a lot of people that have long COVID symptoms that will resolve, a significant number of people will still have difficulty breathing, brain fog, weakness, loss of smell and taste, dizziness, and cough at one year post-COVID infection. The study also showed an increase of post-COVID strep throat tonsillitis and eye infections in children. Issues with this study include that the median age of participants was quite young at 25 years old. People over age 40 had more persistent long COVID symptoms at 1 year in this study. The study did not evaluate fatigue, which is the most common symptom of long COVID, and it also failed to look at other common symptoms including post-exertional malaise, POTS, also known as postural orthostatic tachycardia syndrome, and ME/CFS. The authors reported that the study was limited by its design- a retrospective review of electronic health records- which is notorious for missing cases. So, despite the press claiming that long COVID is over based on the BMJ article, it isn’t.

Another study that came out this week shows that there’s an increased risk of long COVID after reinfections with Omicron sub variants. This study also showed that we may be able to predict who will get low long COVID by looking at low albumin levels after acute COVID infection.

Bivalent boosters offer strong protection against hospitalization and death from the newer Omicron variants. In fact, the updated booster leads to a decrease of hospitalization by 81% and a decrease in deaths by 86% in people over age 65. Eric Topol MD wrote an article this week on the bivalent boosters and how they are superior to the original vaccines against the latest variants. 

Dr. Topol also wrote an Op Ed in the Washington Post this week, stating that although we are tired of COVID,  the virus is telling the world that it is not finished with us. The article is behind a paywall, but I have included a copy of it below. Dr. Topol discusses that although we have amazing vaccines that can help protect people, the virus is still around and is still mutating to bypass our defenses. It is imperative to not to give up and become complacent. He recommends that in order to get out of this mess, we need to focus on public health measures like promoting the bivalent booster vaccines especially to seniors and by increasing genomics surveillance of the virus so that we can track new variants as they happen so that scientists can evaluate their potential and we can be ready to fight them.

This week, two sources (here and here) show that convalescent plasma can help vulnerable immunocompromised people fight a COVID infection. The monoclonal antibody drugs that exist no longer work against the newest Omicron sub variants such as XBB .1.5, but convalescent plasma from vaccinated people who had a breakthrough Omicron infection can.  Vaccinated people who had a breakthrough COVID infection often have a diverse amount of antibodies in their blood that can attack even the newest variants. This gives hope to immunocompromised people such as those with leukemias or other conditions.

Many people find out that they have COVID by doing a home rapid antigen test. However, these COVID cases are not reported anywhere and this important data is lost. Reporting your home test results at MakeMyTestCount.org can help public health professionals see where the virus is spreading. One only needs to report their test results with their age and zip code. Also regarding home COVID tests, some of the free COVID tests mailed to people from the government will be expiring soon. You can look up the expiration dates on the box of the home tests and you can check to see if the expiration date was extended on the FDA website.

Have a good weekend,

Ruth Ann Crystal MD

Other news:

1/11/23 From JPM Week: Trends That Life Science Experts Are Watching in 2023 - MedCity News https://buff.ly/3GBOTri

1/5/23 Nature: Circulating microparticle proteins predict pregnancies complicated by placenta accreta spectrum https://buff.ly/3CFwBVc

• Using plasma sampled at a median of 26 weeks’ gestation, five circulating microparticle (CMP) proteins distinguished placenta accreta spectrum (PAS)  from controls with a mean area under the curve (AUC) of 0.83. For a separate sample taken at a median of 35 weeks’ gestation, the mean AUC was 0.78. 

• The researchers “identified five second-trimester CMPs and four third-trimester CMPs that could be used to detect placenta accreta.” 

1/12/23 CNN: Monterey Peninsula could become an island as epic flooding engulfs California cities. And more rain is on the way  https://buff.ly/3iAQplD

• This happened in 1995 after flooding and could happen again with the next storm.

Are gas stoves bad for your health? Here's why the federal government is considering new safety regulations https://buff.ly/3iDubPV

COVID news:

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

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

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

United States:

US Hospitalizations are high but just starting to decrease for people age 70+:

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

Wastewater Monitoring:

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

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

US wastewater virus levels are just starting to decrease.

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

In the last 52 weeks:

Make Your Test Count:

https://makemytestcount.org/

You can report the results of your home COVID test to help public health personnel follow virus spread and trends. 

• Your name and personal info is not given. They collect just your age and zip code.

• h/t Dr. Virmani (thanks)

Amazing review of Long COVID by 3 Long COVID patients- Hannah Davis, Lisa McCorkell, Julia Moore Vogel- and Dr. Eric Topol. 

Review of more that 200 articles on Long COVID on the topics of who has Long COVID, what causes Long COVID (pathophysiology) present knowledge and misconceptions and how to treat it.

1/13/23 Nature Reviews: Long COVID: major findings, mechanisms and recommendations https://buff.ly/3Xc3FvZ or rdcu.be/c3m45

• At least 65 million individuals around the world have long COVID.

• The incidence is estimated at 10–30% of non-hospitalized cases, 50–70% of hospitalized cases, and 10–12% of vaccinated cases. 

• The highest percentage of diagnoses between the ages of 36 and 50 years, and most long COVID cases happen after a mild COVID infection.

• Hypotheses for the pathogenesis of Long COVID: 

  • Persistent viral reservoirs of SARS-CoV-2 in tissues

  • Immune dysregulation with or without reactivation of underlying viruses

    • Reactivated viruses include EBV and HHV-6 which may cause mitochondrial dysfunction.

  • Microbiome imbalance

  • Autoimmunity and priming of the immune system from molecular mimicry

  • Microvascular blood clotting with endothelial dysfunction

  • Dysfunctional signaling in the brainstem and/or vagus nerve

• Around half of people with long COVID meet the criteria for ME/CFS postexertional malaise.

• 27.1% of SARS-CoV-1 infection survivors in one study met the criteria for ME/CFS diagnosis 4 years after onset 

• Long COVID research has shown: 

  • mitochondrial dysfunction

  • endothelial dysfunction, 

  • cerebral blood flow abnormalities and metabolic changes, 

  • extensive neuroinflammation, 

  • reactivated herpes viruses (EBV, HHV-6) 

  • deformed red blood cells

  • Microclots and hyperactivated platelets seen in long COVID and ME/CFS.

  • Dysautonomia, particularly POTS, is commonly comorbid with ME/CFS.

    • POTS is associated with G protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies, platelet storage pool deficiency, small fiber neuropathy and other neuropathologies. 

1/10/23 Time Magazine written by Dr. R. Glatter and Dr. P. Papadakos: 

The Coming Collapse of the U.S. Health Care System https://buff.ly/3XuLKjM

• Must read article

• Doctors, nurses and other health care staff are exhausted from pandemic stress and difficult work conditions, by nearby hospital closures, increasing staff shortages, and by temporary locum workers who make 2x to 3x their salary but who are not around long enough to work with others as a team.

1/12/23 CNN: Study shows convalescent plasma works for immune-compromised Covid-19 patients, but it can be hard to find  https://buff.ly/3XkqXzA

Great slides by Drs. Michael Joyner and Arturo Casadevall:

Convalescent Plasma from vaccinated people with breakthrough COVID infections can help immunocompromised people, especially those with hematologic malignancies, and protects against the newest Omicron subvariants.

FYI:

Carbon Health study is recruiting patients testing giving an extra 5 days of Paxlovid for Paxlovid rebound.

Criteria: Must live in the Los Angeles area, be age 18+, have completed a Paxlovid course with rebound symptoms within 14 days, still within 48 hours of first rebound symptom.

For more information, email paxlovidstudy@carbonhealth.com.

-There is time & effort compensation of up to $1300 for involvement.

1/12/23 Hospitalizations are just starting to descend in the northeastern US.

1/12/23 Nature Aging: Impaired CD4+ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination https://buff.ly/3W6GAJU

• Older adults make fewer CD4+ T cells after the first dose of vaccine.

• This can result in lower helper T cytokines, even after the second dose of vaccine, thereby lowering humoral (antibody) and cellular immunity and reducing systemic reactogenicity. 

• Enhancing CD4+ T cell response following the first dose is key to improving vaccine efficacy in older adults. 

1/11/23 STAT news: What's standing in the way of wastewater data becoming a more mainstream public health tool https://buff.ly/3Qtmzw1

• "the truth is in the toilets." 

1/11/23 NBC news: Some newly mailed Covid tests from the government expire soon — even with extensions https://buff.ly/3vWFRAm

• The FDA extended the shelf life of iHealth Covid tests by six months this summer, but many kits still expire in February, and some have already. 

• To find out when a Covid test really expires — factoring in the extension period — people can look up the manufacturer and test name on the FDA website.  

1/11/23 Dr. Claire Taylor’s tweet thread on COVID, Long Covid and endothelial inflammation

“Psychological intervention will not cure long Covid.  We need rapid adaptive trials with anti-virals, immune modulators, anti-coagulants and statins.”

The following article has been used to minimize Long COVID in the media, but it has limitations and actually shows that many people do have Long COVID symptoms at 1 year. See all of the comments from Twitter.

1/11/23 BMJ: Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study https://buff.ly/3Ztq4GI

• Retrospective EHR cohort study in Israel of mild COVID infections with the original virus, Alpha variant or Delta variant. (Not Omicron).

• Cohort with median age of 25 years. 

• In people who had Long COVID symptoms after mild COVID in the pre-Omicron era:

  • Most were symptomatic for 6 months after infection and then decreased thereafter. But, major symptoms of difficulty breathing, cognitive impairment and weakness were present at 1 year. 

  • Children had more risk of strep throat and conjunctivitis.

  • Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea.

• “Anosmia and dysgeusia, concentration and memory impairment, dyspnoea, weakness, streptococcal tonsillitis, and dizziness were still reported more frequently in infected patients a year after infection, indicating long lasting symptoms.” 

Concerns with the BMJ Israeli study above:

• Retrospective study that relied only on EHR records may confound conclusions.

• Per Dr.Deepti Gurdasani, the researchers looked at specific diagnostic codes recorded in the health records. Only structured data was used (data entered specifically as coded by clinicians) - 'free text' - letters etc. were not used. In general, this approach will miss diagnoses.

• Israeli diagnosis codes are not the same as are used in the US, so it may be hard to compare.

• Study did not look at fatigue which is the most common symptom of Long COVID, unless it was coded under “weakness”.

• Median age was 25 years old. People aged 41 to 60 had worse outcomes.

• Pre-Omicron study.

• Did not look at major disabling Long COVID conditions such as PEM, POTS, ME/CFS as Dr. Verduzco-Gutierrez states.

• Major symptoms still present at 1 year:

  • dyspnea (difficulty breathing), cognitive impairment (brain fog) and weakness,  anosmia and dysgeusia (loss of smell and taste), dizziness and cough.

Reference to this article: 1/12/2023 CNN: Long Covid resolves within year for many with mild Covid, study says https://buff.ly/3Qyv6O9

Dr. Deepti Gurdasani summary of this Long COVID study:

Summary:

• This is a study only of 'mild' COVID in mostly young people - showing increased risk of several symptoms post-COVID lasting up to 1 year. The burden of these even in young people is non-trivial. 

• Also an increased risk of post-COVID strep tonsillitis in children.

• This needs to be interpreted within the limitations of the study- the primary one being that it's based on medical records which generally under ascertain long COVID symptoms. And low power to look at vascular outcomes in this age group.

• I'm hearing this study has been used to minimize long COVID in the media- the study doesn't seem to reflect the reporting though, & the authors have been quite cautious given the limitations.

1/10/23 Eric Topol’s summary of studies on the bivalent booster and the newer variants.https://buff.ly/3QDKbhw

• While the bivalent booster broadens immunity and works better than the original monovalent boosters for inducing antibodies against BQ.1.1 and the XBB variants (2 to 6x increased neutralizing antibodies against XBB).

• 

1/11/23 ABC: COVID was the leading cause of law enforcement deaths in 2022 for 3rd year in a row: Report https://buff.ly/3CNnpOn

1/9/23 STAT news: ‘I want people to see us’: A writer gives voice to long Covid and mothering from bed https://buff.ly/3CG9utB

• Long COVID Myalgic Encephalomyelitis 

1/9/23 Nature Neuroscience: Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate https://buff.ly/3XmqkWi

• One or two doses of a modified vaccinia virus Ankara (MVA) vector expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) given to transgenic mice conferred full protection against SARS-CoV-2 cerebral infection, preventing virus replication in all areas of the brain and its associated damage.

1/8/23 Eric Topol MD Op Ed in Wash Post: The coronavirus is speaking. It’s saying it’s not done with us. https://buff.ly/3imCzTZ

• XBB.1.5 is rapidly spreading in the northeastern US and is now seen in Europe and Asian countries.

• Spikes in hospitalizations seen with XBB.1.5 are concerning. 

• People 65+ who got the bivalent booster are 80% less likely to be hospitalized. 

• Genomic surveillance of the virus is down 90%, but the virus keeps changing to challenge our immune systems.

• “We are all tired, but we are up against a force that isn’t.”

1/5/23 MedRxiV: SARS-CoV-2 Reinfection is Preceded by Unique Biomarkers and Related to Initial Infection Timing and Severity: an N3C RECOVER EHR-Based Cohort Study  https://buff.ly/3wfnvuJ

• EHR data from the N3C Data Enclave as part of the NIH RECOVER Initiative. 

• 1,597,490 adults from 38 healthcare facilities.

• Omicron variant (November 01, 2021-March 11, 2022)

• Omicron BA variant (March 12, 2022-August 01, 2022) 

• Reinfection is most common in the Omicron epoch.

  • Lower albumin levels after initial COVID-19 infection and leading up to reinfection. 

• Major findings:

  • The severity of SARS-CoV-2 reinfections was similar to those of the initial infection.  

  • Long COVID diagnoses also occurred in a shorter time frame for infections or reinfections during the Omicron epoch.

  • There was an increase in Long COVID diagnoses noted with reinfections with more recent variants (i.e. Omicron subvariant BA epoch). 

1/5/23 Reuters: NIH launches pilot COVID telehealth program https://buff.ly/3ZqMatg

• The U.S. National Institutes of Health (NIH) on Thursday launched a virtual program via eMed aimed at making antiviral treatments for COVID-19 available at home for those who test positive. 

1/5/23 The Conversation: 90% of Long COVID stemmed from mild cases of COVID-19, according to a new multicountry study https://buff.ly/3vOkKA8

• Patients who were hospitalized for COVID-19 had a greater risk of developing long COVID, but because there are so many more people who had milder disease, 90% of people with Long COVID initially had a mild infection.

• Among all people with long COVID, our study found that nearly one out of every seven were still experiencing these symptoms a year later, and researchers don’t yet know how many of these cases may become chronic.

• After developing Long COVID, however, the typical person experienced symptoms including fatigue, shortness of breath and cognitive problems such as brain fog – or a combination of these – that affected daily functioning. 

  • These symptoms had an impact on health as severe as the long-term effects of traumatic brain injury. 

  • Our study also found that women have twice the risk of men and four times the risk of children for developing long COVID. 

• Many people affected by Long COVID are of working age. If disabled, they may be unable to work thus losing their income and housing. This could also affect these people being able to care for their children. In addition, this could affect the workforce.

Authors refer to this study: 10/10/22 JAMA: Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters After COVID-19 https://buff.ly/3T7pg73

• Post Infection fatigue syndrome was seen in the 1918 Influenza A (H1N1) pandemic, after SARS-CoV-1 infections in 2003 and after the Ebola epidemic in West Africa in 2014. 

• Similar symptoms have been reported after other viral infections including the Epstein-Barr virus, mononucleosis, and dengue as well as after non viral infections such as Q fever, Lyme disease, and giardiasis. 

1/3/23 Lancet preprint: Effectiveness of the Bivalent mRNA Vaccine in Preventing Severe COVID-19 Outcomes: An Observational Cohort Study https://buff.ly/3Zps6HR

• n = 622,701 participants

• Participants age 65+ who received the bivalent booster vaccine had lower hospitalization and mortality rates due to Covid-19 than non-recipients up to 70 days after vaccination. 

  • 81% reduction of hospitalizations

  • 86% reduction of deaths 

12/27/22 JAMA: Effect of COVID-19 Vaccine Messaging Platforms in Emergency Departments on Vaccine Acceptance and Uptake https://buff.ly/3XiYDNX

• COVID vaccine messaging platform (a 4-minute video, informational flyer and script for face-to-face ED clinician messaging) in the Emergency Department lead to:

  • significantly higher vaccine acceptance (25.8% vs 12.0%)

  • significantly higher receipt of vaccine within 30 days (25.8% vs 12.0%)

• Latinx persons and participants without primary care physicians responded the most. 

1/8/23 Nature Reviews: MIS-C: myths have been debunked, but mysteries remain  https://buff.ly/3k1u2pN

• Although coronary artery dilation is associated with both multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease, there is currently no evidence of long-term coronary artery damage in MIS-C.

• The incidence and severity of MIS-C declined during the Omicron wave.

12/26/22 MedRxiV (Australia): Comparative effectiveness of four COVID-19 vaccines, BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection https://buff.ly/3vXdt0U

• Ancestral strain mRNA vaccines are more effective against SARS-CoV-2 Omicron infection than viral vector (AstraZeneca) and protein subunit (Novavax) vaccines.