COVID News 5/13/22
Hi all,
Cases are going up in the Northeast and the Great Lakes regions as well as in the Bay Area in California. The CDC has very confusing messaging regarding risk levels. Below, you'll see one CDC map shows "transmission risk'' and the other shows "community risk" which equates to the number of hospital beds that are still available. You need to know about both, but transmission risk is important to let you know if you should wear masks and avoid indoor events if possible.
Here in the Bay Area, wastewater viral levels are increasing significantly and positivity rates are high. Test positivity rate is 9% in San Francisco county, 6.4% in San Mateo county and 5.6% in Santa Clara county. If you haven't gotten your latest booster, I would get it now. Also, we should wear masks indoors.
If you do get infected with COVID, many people now qualify for treatment with Paxlovid pills. Supply is ample in most places but you do need a prescription. Here is a searchable database that shows which pharmacies have Paxlovid, Molnupirvir and which hospitals have Evusheld and other monoclonal antibodies:
https://covid-19-therapeutics-locator-dhhs.hub.arcgis.com/
Then click on the blue banner to put in your location and what medication you are searching for.
There are several online telemedicine companies including Hello Alpha that can write you a prescription for Paxlovid depending on the medications that you take and whether you have kidney disease.
Regarding Paxlovid, about 1-2% of people may get a rebound COVID infection a few days after finishing the prescription. If you have symptoms again, take a COVID home antigen test. If it is positive, you are contagious and can infect others so you should isolate until the antigen tests are negative. According to a few case reports, most people with rebound COVID after Paxlovid have mild disease.
North Korea was able to avoid SARS-CoV-2 infection until now. Yesterday, over 350,000 cases of "fever" that happened 2 weeks ago were reported in North Korea. Unfortunately, the country does not have many tests for COVID so they are following fevers and symptoms. No one in North Korea is vaccinated as the government refused to accept vaccines from the WHO COVAX program.
This week, there are many different articles putting together the pieces on Long COVID or PASC. A study from China of people who had a COVID infection in early 2020, most of those who got long COVID still have at least one symptom such as fatigue 2 years later. Many of these patients were able to return to work by 2 years however.
Impaired exercise intolerance from Long COVID may be related to ongoing microclots, possibly of fibrin amyloid, that block capillaries and inhibit the transport of oxygen to tissues. Other articles show ghost viral fragments in the gut which may be improved with either vaccination or perhaps even Paxlovid treatment. Here at Stanford, doctors in the post-COVID clinic did have a 47 year old patient who significantly improved after Paxlovid. But, that is just one patient and clinical trials are needed before Paxlovid is used for Long COVID. Congress gave the NIH more than $1 Billion to study Long COVID, but the RECOVER trial is moving slowly with recruitment. As of early May, only 2,600 Long COVID patients out of the 40,000 needed have been recruited. It will be especially important to include people of color and low income patients in clinical trials as they have been affected by COVID and Long COVID more.
Have a good weekend (and don't forget your masks).
Ruth Ann Crystal MD
Twitter: https://twitter.com/CatchTheBaby
h/t @EricTopol
World
United States
CDC messaging is confusing. “Transmission” vs. “Community Risk Level”.
Transmission Map shows cases, test positivity rates and risk of getting infected.
Community Risk Map shows if there are hospital beds available for sick patients.
CDC Transmission Map (cases + test positivity rates): https://covid.cdc.gov/covid-data-tracker/#county-view?list=&data-type=Risk
CDC “Community Risk” level which is how many hospital beds are available now.
The messaging is confusing.
5/12/22 California data: https://covid19.ca.gov/state-dashboard/#todays-update
California statewide: 16 cases per 100K, 4.1% test positivity
San Francisco county: 36.2 cases per 100K, 9.0% positivity (up 1.1% in 7 days)
Santa Clara county: 29.7 cases per 100K, 5.6% test positivity
San Mateo county: 31.4 cases per 100K, 6.4% test positivity
Santa Cruz county: 33.7 cases per 100K, 3.3% test positivity
Los Angeles county: 18.8 cases per 100K, 1.9% test positivity
Wastewater virus levels:
5/10/22 Palo Alto Online: Santa Clara County COVID cases surpass height of Delta surge https://buff.ly/3Pv3CIv
COVID-19 cases are rising again in Santa Clara County and hospitalizations are also on the rise.
"What we're seeing now is similar to what we were seeing in mid-February, and it's more than what we were seeing at the height of the delta surge." Dr Cody said.
All of our sewersheds show an uptick.
Dr. Cody recommends wearing masks indoors, getting vaccines and boosters and testing if exposed or you have symptoms.
To buy high quality, trusted masks:
5/13/22 Cell Immunity: Antibody-Mediated Neutralization of SARS-CoV-2 https://buff.ly/3yy9wT3
Comprehensive review of SARS-CoV-2 neutralizing antibodies with a focus on their clinical application for vaccine design as well as antibody-mediated therapies.
5/13/22 Science: Detecting anti–SARS-CoV-2 antibodies in urine samples: A noninvasive and sensitive way to assay COVID-19 immune conversion from infection https://buff.ly/3wb1q0P
A simpler way to diagnose prior COVID infection with urine based ELISA was developed using recombinant SARS-CoV-2 nucleocapsid protein.
5/12/22 CNN: North Korea announces first Covid deaths amid 'explosive' outbreak https://buff.ly/3FIw19f
>350,000 cases reported and 6 deaths reported by North Korean state media in a country of about 25 Million.
North Korea rejected millions of doses of AstraZeneca and Sinovac vaccines offered by the WHO-led COVAX program and is not believed to have received any Covid vaccinations.
5/11/22 NEJM: Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age https://buff.ly/3L7aAQf
Moderna RCT in kids age 6 to 11
Two 50-μg doses of the Moderna mRNA-1273 vaccine were found to be safe and effective (88% efficacy) in inducing immune responses and preventing Covid-19 symptomatic infections in children 6 to 11 years of age during the Delta wave.
5/11/22 5/11/22 STAT news: Telehealth aims to crack open Paxlovid's prescription bottleneck https://buff.ly/3L4POAY
Massachusetts and NYC have telemedicine services in place.
Hello Alpha, Truepill, Carbon Health, Plush Care and other telemedicine companies offer appointments so that patients can get a prescription for Paxlovid or Molnupirvir.
Bright.md, a StartX company, has enabled Paxlovid as a prescribable option on its asynchronous telehealth platform, which is deployed at large health systems nationwide.
5/11/ 22 CNN: Why Covid-19 vaccine boosters may be more important than ever https://buff.ly/3N5LN0A
Everyone age 12+ is eligible for a booster (3rd dose) but less than half of eligible Americans have gotten it.
The second booster (4th dose) is authorized for people 50+, along with those who are 12+ who are moderately to severely immunocompromised, but only 10 million people have gotten it.
Immunity can wane over time and boosters are needed for protection.
5/11/22 BioRxiV: Imprinted antibody responses against SARS-CoV-2 Omicron sublineages and discovery of a pan-variant neutralizing antibody https://buff.ly/3NbnZIJ
Most monoclonal antibodies (mAbs) do not neutralize BA.1, BA.2, BA.2.12.1, BA.3, BA.4 and BA.5 well.
Vessler lab discovered a new mAb called S2X324 that neutralizes all SARS-CoV-2 variants ultrapotently, including BA.1, BA.2.12.1, BA.2, BA.3, BA.4 and BA.5.
5/12/22 Lancet (China): Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study https://buff.ly/37CEhuZ
2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan to May 2020.
At 6 months, 68% had at least one Long COVID symptom and 55% still had at least one COVID symptom at 2 years, with fatigue or muscle weakness always being the most frequent.
Survivors with long COVID symptoms at 2 years had lower quality of life, worse exercise capacity, more mental health issues, and increased health-care use.
Those with initial respiratory support in hospital had reduced lung function as compared to controls.
5/11/22 Nature: Coronavirus ‘ghosts’ found lingering in the gut https://buff.ly/3L4pvdV
Scientists are studying whether long COVID could be linked to persistent immune response to viral fragments found in the body months after initial infection.
5/11/22 Blood Advances: Impaired exercise capacity in post-COVID syndrome (PASC): the role of VWF-ADAMTS13 axis https://buff.ly/3M8BqZL
Like with acute COVID infection, some patients with PACS have a hypercoagulable state.
55% of Long COVID (PACS) patients with impaired exercise capacity had a raised VWF(Ag):ADAMTS13 ratio ≥1.5.
Factor VIII was elevated in 26% and Von Willebrand Factor (VWF) Antigen was increased in 18% of PACS patients.
There may be an ongoing microvascular/endothelial dysfunction in some PACS patients which may be helped with antithrombotic therapy.
5/11/22 BioRxiV: Persistent serum protein signatures define an inflammatory subset of Long COVID https://buff.ly/3vYxipr
Serum proteome studied in longitudinal samples from 55 PASC patients.
There is a subset of PASC with distinct signatures of persistent inflammation.
Type II interferon signaling and canonical NF-κB signaling (particularly associated with TNF), were the most differentially enriched pathways.
5/11/22 Research Square: Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) https://buff.ly/3w2Dxso
n = 845 South African Long COVID/PASC patients
Blood samples from 80 patients were analyzed, and show the presence of significant fibrin amyloid microclots and platelet pathology in all cases.
Fibrin amyloid microclots that block capillaries and inhibit the transport of oxygen to tissues, accompanied by platelet hyperactivation, may cause the symptoms of Long COVID/PASC.
5/11/22 5/11/22 Grid News: The U.S. has had the most COVID cases in the world. Why isn’t it doing more to study Long COVID? https://buff.ly/3w23J6n
Congress gave the NIH more than $1 Billion to study Long COVID, but the RECOVER trial is moving too slowly with recruiting patients.
As of early May, 2,600 people out of the 40,000 needed have been recruited.
It is important to include people of color and those with low incomes in the study as they are affected more by COVID and Long COVID.
Between 7.7 and 23 million people in the U.S. have long COVID.
The UK is doing a similar study but has enrolled patients more easily because of their national health system.
5/10/22 5/10/22 Open Forum Infectious Diseases: The protective effect of covid-19 vaccination on post-acute sequelae of covid-19 (PASC): a multicenter study from a large national health research network https://buff.ly/3Fz8h7q
1,578,719 patients with confirmed COVID-19 were identified and 1.6% (n = 25,225) completed vaccination.
Data suggest that COVID-19 vaccine is protective against:
post-acute sequelae of SARS-CoV-2 (PASC) symptoms (Long COVID)
new onset of health conditions:
hypertension with relative risk RR of 0.33,
diabetes RR 0.28,
heart disease RR 0.35 and
death RR 0.21
5/10/22 Medpage Today: Do COVID Vaccines Stave Off New Medical Conditions? https://buff.ly/3smDS6Y
Large study finds risk of new onset hypertension, diabetes, and heart disease were lower among vaccinated patients with breakthrough infection versus those with COVID who were unvaccinated.
5/10/22 The Atlantic: Is Paxlovid The Promising Treatment for Long COVID We’re Not Even Trying? https://buff.ly/38eRIBI
There are a handful of post-Paxlovid improvement stories now emerging that echo what other long-haulers felt with the vaccines.
Studies are needed as there is little data whether or not Paxlovid could help.
5/10/22 Research Square (Stanford): Case Report of Breakthrough Long COVID and the Use of Nirmatrelvir-Ritonavir (Paxlovid) https://buff.ly/3N6IXIx
Post-Acute Sequelae of COVID (PASC), or long COVID
A previously healthy 47 year-old vaccinated woman was evaluated at our post-COVID clinic for 7 months of PASC symptoms after breakthrough infection. When she was treated with Paxlovid for a possible new COVID infection, her PASC symptoms resolved.
5/9/22 IDSA: Management of Drug Interactions With Nirmatrelvir/Ritonavir (Paxlovid):
Resource for Clinicians https://buff.ly/3KXOnUD
Among the top 100 prescribed drugs, only two have interactions so severe that nirmatrelvir/ ritonavir should be avoided altogether: rivaroxaban (Xarelto) and salmeterol (Serevent Diskus).
Includes list of drugs that may need to be reduced or stopped.
5/9/22 Helpful: FDA Paxlovid Patient Eligibility Screening Checklist Tool for Prescribers
5/9/22 Healio: Prevalence of Gestational Diabetes increases by almost 40% during COVID-19 pandemic https://buff.ly/38ebWvd
“This also spurs the question of what exactly may be causing these increased rates, whether it is COVID-19 directly or the effects of the quarantine.”
5/9/22 Bob Wachter MD tweet thread
He talks about his 64 year old wife giving a writing conference, 4 doses vaccinated (2 + 2 boosters), mostly masked but not always (especially when eating), and now she has COVID. Polls about what to do.
South Africa, BA.4 and BA.5
31% positivity rate
Omicron BA.4 and BA.5 are antigenic distinct from BA.1 as other variants were from each other.
5/8/22 Science: Interferon therapy shows striking results against COVID-19 https://buff.ly/3FmYeSZ
RCT, 1900 mostly vaccinated high risk people in Brazil
Single injection of PegInterferon Lambda given within 7 days of symptoms reduced hospitalization and ER visits by 50%.
5/8/22 Cell: SARS-CoV-2 Omicron sublineages show comparable cell entry but differential neutralization by therapeutic (monoclonal) antibodies https://buff.ly/3FqnuHY
Sotrovimab: low sensitivity to BA.2, but high sensitivity to BA.1 and BA.3 (and BA.4 and BA.5 in Japanese in vitro study below)
Cilgavimab: low sensitivity to BA.1, but high sensitivity to BA.2 and BA.3
Evusheld = Cilgavimab + Tixagevimab
All sublineages were comparably and efficiently neutralized by antibodies induced by Pfizer BNT162b2 booster vaccination after previous two-dose homologous or heterologous vaccination.
Collectively, the Omicron sublineages show comparable cell entry and neutralization by vaccine-induced antibodies but differ in susceptibility to therapeutic antibodies.
Remember from last week:
5/4/22 BioRxiV: Sensitivity of novel SARS-CoV-2 Omicron subvariants, BA.2.11, BA.2.12.1, BA.4 and BA.5 to therapeutic monoclonal antibodies https://buff.ly/3kDURNS
Although Sotrovimab was ~20-fold less antiviral against BA.2 than the parental virus, the Omicron subvariants bearing L452R substitution including BA.2.11 and BA.4/5 were more sensitive to Sotrovimab than BA.2.
Cilgavimab is antiviral against BA.2.
BA.4/5 exhibits 30x higher resistance to Cilgavimab compared to BA.2.
The L452R/Q substitution rendered ~2-5-fold resistance to Cilgavimab.
Evusheld (PrEP) is a combo of Tixagevimab and Cilgavimab.
5/8/22 Nature (Sigal lab) Omicron infection enhances Delta antibody immunity in vaccinated persons https://buff.ly/3kK8CuB
Omicron BA.1 infection offers limited cross protection with other variants.
Omicron BA.1 plus vaccination is protective against Delta and other variants.
5/8/22 BioRxiV (Iwasaki, Yale): SARS-CoV-2 variants do not evolve to promote further escape from MHC-I recognition https://buff.ly/3PatGIp
Ancestral virus WA1 and VOCs both down regulate MHC I on host T cells.
In contrast, VOCs appear to better prevent interferon-stimulated gene (ISG) expression than the ancestral WA1 strain.
The virus is evolving to better suppress innate antiviral control (interferons) but not CD8 T-mediated control.
5/8/22 Omicron: increased transmissibility and decreased pathogenicity https://buff.ly/3MSCMaM
Why is Omicron more transmissible, but causes less severe disease than Delta?
5/7/22 NY Times: The White House, warning of a fall COVID surge, plans for how to provide vaccines if there’s no more COVID aid. https://buff.ly/3LOwJ7b
The White House has been asking Congress for $22.5 billion in emergency aid to continue responding to the pandemic, but Republicans have insisted on a much lower number.