COVID news 1/20/23

Hi all,

XBB.1.5 comprised 43% of cases last week in the United States and now represents 49% of reported U.S. COVID cases. In the northeastern U.S., XBB.1.5 is now at 85% of cases. Wastewater SARS-CoV-2 virus levels are still high in many parts of the country, but are starting to decrease in more areas as seen by blue dots on the CDC map here.

Long COVID:

Last week, three Long COVID patients- Hannah Davis, Lisa McCorkell, Julia Moore Vogel- and Dr. Eric Topol published an outstanding review in Nature of over 200 articles on Long COVID. This week, the NPR Morning Edition spoke with Dr. Eric Topol about what they found.

An important Long COVID, a.k.a. PSC or PASC, study came out this week where researchers were actually able to watch in real time the blood from Long COVID patients form microclots in a new microfluidic assay. The assay had one channel coated with collagen and the other coated with VWF A3 antibodies. The blood from Long COVID patients made clots, but the blood from controls did not. Long Covid is indeed a clotting disease. Patients in the study were on average almost 2 years out from their acute COVID infection, but their blood still was hypercoagulable. In addition, the microclots that formed in the blood of the Long COVID patients had a different geometric shape than typical blood clots. The hypercoagulable blood in the Long COVID patients was found to be related to an increase in the VWF(Ag):ADAMTS13 ratio and thrombin generation but not in α2-antiplasmin levels. 

In other long Covid news this week, a small study showed that brain fog and muscular pain in Long COVID patients was associated with a longer time to clearance of the virus in the respiratory system during the original acute infection. Another study showed among unvaccinated participants, vaccination after COVID infection reduced Long COVID symptoms by 41% across multiple organ systems.

The Washington Post reported that pacing strategies can help reduce the severe fatigue of Long COVID. Pacing is an “activity management” strategy, which requires people to carefully limit their daily activities including scaling back on mundane tasks that most people take for granted. Pacing techniques have been helpful for ME/CFS patients for years.

McKinsey Consulting wrote an article on the 1 billion days of work lost in the US to COVID. Workers' illness (acute Covid infections and long Covid), caregiver responsibilities for children and seniors who are sick and compliance with isolation guidelines led to many workdays lost. They calculated that COVID reduced the availability of the US workforce by 2.6% in 2022 and that we should plan for workforce issues in the foreseeable future. 

In a Twitter thread by Charlos, he discussed how the medical profession does not accept new ideas easily despite the evidence because of the “Semmelweis Reflex” and how it is important to think outside the box with COVID, and especially with Long COVID, as many are suffering. 

Pregnancy:

An article came out this week showing that a SARS-CoV-2 infection in pregnancy increases the risk of maternal death by 7.7 fold, increases risks of pneumonia by 23.5 fold, increased risk of clotting diseases by 5.5 fold and also increases the chances of babies being born prematurely and/or being admitted to the neonatal intensive care unit (NICU) by about a factor of 2 to 3. It is extremely important that pregnant people be vaccinated against COVID, as a Covid infection can be deadly in pregnancy.

Bivalent Booster:

Several articles this week came out, showing that the bivalent booster is better at fighting the newer subvariants, such as BQ 1.1 and XBB.1.5. One article showed that people made 10 times the amount of neutralizing antibodies against the new subvariants after being boosted with the bivalent vaccine mRNA vaccine. Another study used mathematical modeling to show that getting the bivalent booster about every six months would be best to prevent COVID infections. So far, we have not heard from the CDC as to when we should be getting our next bivalent booster, although it has been at least five months since the last booster for many people.

Disinformation and Myths:

Epidemiologist Katelyn Jetelina wrote two different articles this week that were very interesting. The first was on debunking myths about COVID vaccines and sudden death, and the second article was on the science and business of COVID-19 disinformation spreading during the pandemic. I was unaware that there is a “disinformation dozen” of websites that spread disinformation using a very specific protocol. Why would someone want to spread disinformation? Because they make money off of traffic coming to their websites, where they explain their theories using convoluted logic, starting with a small kernel of truth that has been distorted and taken out of context to prove their points, even though they are false. As Jetelina says, “It’s [disinformation] a public health and biosecurity threat. And we need to treat it like one.” 

Have a good weekend,

Ruth Ann Crystal MD

Other news:

1/20/23 Stanford Daily (Lauren Koong): Stanford researchers claim to create ‘Theranos that works’ https://buff.ly/3D2FlVo

• Genetics department chair and senior author Michael Snyder said his lab has combined a microsampling device with multi-omnic technology, a biological analysis approach, to measure thousands of molecules from 10 microliters of blood (about a single drop). 

1/16/23 The rules, laws, and policy digital health needs to know to stay ahead this year https://buff.ly/3weVPFX

• Interoperability, Patient Access, Trusted Exchange, EHR, Prior Authorization, Price Transparency, etc. discussed.

1/18/23 Nature: Functional T cells are capable of supernumerary cell division and longevity - Nature https://buff.ly/3GZ3kps

"These observations provide a model to better understand memory cell differentiation, exhaustion, cancer and aging, and show that functionally competent T cells can retain the potential for extraordinary population expansion and longevity well beyond their organismal lifespan."

COVID news: 

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

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

United States reported cases and hospitalizations:

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

US reported cases

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

https://ourworldindata.org/coronavirus

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

XBB.1.5 in purple

Wastewater Monitoring:

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

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

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

For Health Care Providers:

1/17/23 CDPH Launches COVID-19 Therapeutics Provider Warmline

California COVID Therapeutics and Testing Free Warmline for health care providers

• 1-866-268-4322 (COVID-CA)

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

• For questions regarding drug-drug interactions or any other clinical challenges.

• 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)

1/20/23 NPR: As the pandemic enters its 4th year, there's still much to learn about long COVID https://buff.ly/3j0aC4m

1/20/23 Katelyn Jetelina: The science (and business) behind COVID-19 disinformation. And what to do about it. https://buff.ly/3ZUosWW

• Excellent overview of disinformation including use of social media, presenting a kernel of truth laced with information gaps, how to recognize it and what we can do.

• "The disinformation dozen" peddle their misinformation on their websites because it makes money for them.

1/19/23 The Atlantic: Trying to Stop Long COVID Before It Even Starts https://buff.ly/3HiCr1d

• Paxlovid can decrease Long COVID by 26% in one study.

• Metformin taken during acute infection may decrease long COVID by 42% in people with high BMI.

1/19/23 MedRxiV (Johns Hopkins): Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection https://buff.ly/3HeMft7

• n = 73 adults with mild COVID

• Serial PCR tests and COVID symptom diary

• Brain fog and muscle pain at 90+ days post-acute COVID infection are associated with longer time to clearance of SARS–CoV–2 RNA from the upper respiratory tract in the initial infection.

1/19/23 CV Research (Hong Kong): Association of COVID-19 with short- and long-term risk of cardiovascular disease and mortality: a prospective cohort in UK Biobank https://buff.ly/3WqlC95

• A prospective cohort of patients with COVID-19 infection between 16 March 2020 and 30 November 2020 (pre-vaccination) was identified from UK Biobank, and followed for up to 18 months was compared to controls.

• COVID infection increased risk of cardiovascular disease (1.4x) and death (5x risk) for more than 18 months after infection as compared to uninfected people.

1/19/23 Nature Reviews Bioengineering: Lateral flow test engineering and lessons learned from COVID-19 https://buff.ly/3QOECgl 

• Review of Lateral Flow Tests (LFTs), “the heroes of the pandemic” and future considerations.

• Home rapid antigen tests for COVID.

1/18/23 JAMA: COVID-19 Symptoms 6 Months After Onset and the Role of Vaccination for SARS-CoV-2 Infection https://buff.ly/3IZy2le

• Unvaccinated people with COVID-19 were more likely to seek medical care for diabetes, pulmonary, neurological, and mental health–related illness for at least 6 months after onset compared with their pre-COVID baseline health care use patterns.

However, among unvaccinated participants, vaccination after COVID infection reduced Long COVID symptoms by 41% across multiple organ systems.

1/18/23 NEJM: Substantial Neutralization Escape by SARS-CoV-2 Omicron Variants BQ.1.1 and XBB.1 https://buff.ly/3iOV3wn

1/18/23 Nature Reviews: SARS-CoV-2 variant biology: immune escape, transmission and fitness https://buff.ly/3XqbzlG

• The authors discuss the mutations of SARS-CoV-2 variants, the impact of mutations on virus infectivity and transmissibility, and SARS-CoV-2 evolution in the context of immunity. 

1/17/23 Katelyn Jetelina and Kristen Panthagani, MD, PhD: 

COVID-19 vaccines and sudden deaths: Separating fact from fiction https://buff.ly/3ksJECX

• A great article that debunks many of the myths on COVID vaccines and deaths.

• COVID-19 vaccines have always been safer than infection.

• To be very clear: We have more evidence than for any other vaccine or disease in the history of humans that the benefits of COVID-19 vaccines greatly outweigh the risks.  

1/17/23 BioRxiV: Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants https://buff.ly/3CXYhEE

• Bivalent booster is better than the original monovalent vaccination at protecting against the new variants such as XBB.1.5.

• Enhanced memory B cell response and cross-immunity to other subvariants noted.

1/17/23 BioRxiV (Shan-Lu Liu): Extraordinary Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1 and CA.3.1 Variants https://buff.ly/3XHrprW

• XBB.1.5, CH.1.1 and CA.3.1 variants almost completely escape from neutralizing antibodies stimulated by three doses of mRNA vaccine, but were neutralized by a bivalent booster. 

• XBB.1.5 has higher infectivity.

  • Notably, the spike proteins of XBB.1.5, CH.1.1, and CA.3.1 all exhibited increased fusogenicity compared to BA.2.

1/17/22 MedRxiV: Long-term cardiac symptoms following COVID-19: a systematic review and meta-analysis https://buff.ly/3J0JQUo

• Meta-analysis showed that the proportion of continued chest pain was 10.1% and arrhythmia was 9.8%.

• "There is a wide spectrum of long-term cardiac symptoms following COVID-19. Findings of existing studies are strongly related to study quality, size and design, underscoring the need for high-quality epidemiologic studies to characterize these symptoms and understand their etiology." 

1/17/23 UK Office for National Statistics (ONS), COVID-19 latest insights https://buff.ly/3m8cRll

1/16/23 BMJ Global Health: Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis https://buff.ly/3ZAlzKF

• SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction.

• Pregnant people with SARS-CoV-2 infection had:

  • 7.7x increased risk of maternal death

  • 3.8x risk of admission to intensive care unit 

  • 15.2x risk of needing mechanical ventilation

  • 5.5x risk of receiving any critical care

  • 23.5x risk of pneumonia 

  • 5.5x risk of thromboembolic disease (blood clots in legs, lungs, etc)

• Newborn babies born to people with SARS-CoV-2 infection were:

  • 1.9x more likely to be admitted to the neonatal intensive care unit (NICU)

  • 1.7x more likely to be born preterm or

  • 2.9x more likely to be born moderately preterm

  • 1.2x more likely to be born low birth weight

  • Infection was not linked to stillbirth.

Long COVID is a clotting disease.

New microfluidic assay showed in 21 people with Long COVID (PSC, PASC) their blood is HYPERCOAGULABLE associated with an increase in VWF(Ag):ADAMTS13 ratio and thrombin generation but not elevated α2-antiplasmin. https://buff.ly/3IZOZvJ

1/2023 J of Thrombosis and Haemostasis: Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome https://buff.ly/3IZOZvJ

• Microclot formation (thrombogenicity) was studied in 21 people with PCS (PACS or Long COVID) using a microfluidic assay. 

  • Assay channels were coated with collagen or an antibody to VWF A3.

• Significant increase in platelet binding on both collagen and anti-VWF A3 microchannels in patients with PCS compared with that in controls, which positively correlated with VWF antigen (Ag) levels, the VWF(Ag):ADAMTS13 ratio (on anti-VWF A3), and inversely correlated with ADAMTS13 activity (on collagen). 

• α(2)-Antiplasmin levels were normal in 89.5% of patients. 

• Together, these data present, for the first time, a dynamic assay showing a prothrombotic tendency in patients with PASC for almost 2 years. 

• Our results confirm a hypercoagulable state in patients with PCS related to an increase in VWF(Ag):ADAMTS13 ratio and thrombin generation but not in α2-antiplasmin levels. 

1/16/23 Washington Post: For long covid fatigue, a strategy called ‘pacing’ helps, but at a cost https://buff.ly/3ZTs8Iv

• Extreme fatigue experienced by many long covid patients has a name: myalgic encephalomyelitis (ME/CFS), a condition previously known as chronic fatigue syndrome. 

• About half of people with long covid have developed ME/CFS.

• Pacing is an “activity management” strategy, which requires people to carefully limit their daily activities, reduce their energy expenditure and track their symptoms. 

• It often requires scaling back on mundane tasks that most people take for granted.

Pre-COVID study of ME/CFS:

2014 J of Translational Medicine: Inability of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients to reproduce VO2peak indicates functional impairment https://buff.ly/3QMugNP

• Post exertional malaise

• 22 people with ME/CFS, researchers tested people’s capacity for activity by measuring oxygen intake and how hard they could pedal while they pushed themselves on a stationary bicycle.

• Participants cycled to the point of exhaustion, then repeated the exercise test 24 hours later. 

• On the second test, the researchers found the participants could not match the performance they had put in the day before, even when putting in maximum effort. And their bodies’ ability to use oxygen and deliver it to cells had declined significantly. 

Twitter thread by Charlos on how the medical profession does not accept new ideas easily despite the evidence because of the “Semmelweis Reflex” and how it is important to think outside the box with COVID and especially Long COVID as many are suffering. 

1/13/23 Update: The WHO recommends masking irrespective of the local epidemiological situation, given the current spread of the COVID-19 globally. https://t.co/lPfYfyfc7D 

• Masks are recommended for "anyone in a crowded, enclosed, or poorly ventilated space." 

1/13/23 CDC MMWR: Bivalent Booster Doses Among Children Aged 5–11 Years Are  Shown To Be Safe https://buff.ly/3CTV1dp

1/12/23 Clinical Microbiology and Infection (Saudi Arabia):  A Systematic Review of Trials Currently Investigating Therapeutic Modalities for Post-Acute COVID-19 Syndrome and Registered on World Health Organization International Clinical Trials Platform https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(23)00009-5/fulltext#%20

• Search of clinical trials was conducted up to the 16th of September 2022 using the COVID-19 section of the World Health Organization (WHO) Internal Clinical Trials Registry Platform. 

• “We identified 388 registered trials with a high degree of heterogeneity exploring 144 unique interventions for PACS. Most target general alleviation of symptoms.  

• The definition of PACS illustrated by the trials was variable and primary outcomes were often non-system-specific and not standardized." 

1/9/23 McKinsey: One billion days lost: How COVID-19 is hurting the US workforce https://buff.ly/3CZ59Sk

• COVID reduced the availability of the US workforce by 2.6% in 2022—a burden on productivity that could last for years. 

• COVID continues to exert a brake on the US economy through work days lost to worker illness (acute COVID infections and Long COVID), caregivers’ responsibilities for children and seniors, and compliance with isolation guidelines. 

1/6/23 Al-Aly in Lancet: Risks and burdens of incident dyslipidaemia in long COVID: a cohort study https://buff.ly/3HaHoJt

• One year after COVID infections, lipids (cholesterol) can be elevated and should be checked so that they can be treated if needed.

1/5/23 J Med Virology: Infection by SARS‐CoV‐2 with alternate frequencies of mRNA vaccine boosting https://buff.ly/3IYaRb1

• Mathematical modeling predicts that getting a booster mRNA vaccine every 6 months should be best to prevent COVID infections. 

• "Instituting regular, population-wide booster vaccination updated to predominant variants has the potential to substantially forestall—and with global, widespread uptake, eliminate—COVID-19."

1/2023 J Am Coll Cardiol: PCSK9 Inhibition During the Acute Inflammatory Stage of SARS-CoV-2 Infection https://buff.ly/3GQsOp9

• Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. 

• PCSK9 inhibitors may have a role in dampening vascular inflammation to improve outcomes in severe acute COVID-19 by affecting circulating interleukin (IL)-6 levels after treatment.