This week, Omicron BA.2 cases are increasing in the northeastern U.S., but so far hospitalizations remain low. New York state reported an increase in subvariants BA2.12 and BA2.121 but our vaccines should protect against these as well. Some people feel that we may have a bivalent booster vaccine next fall that would include the original virus (wild type) and also mRNA from Omicron, but we will have to see the data before that happens. So far, new variants are all related to Omicron (drift).
Masks will be required on planes at least until May 2nd and the federal government has renewed the public health emergency so for now there will continue to be free testing, free vaccines and free treatments for SARS-CoV-2 in the United States. The UK has stopped free testing.
I've included a section on Long COVID articles this week. ONS data shows that 2.7% of the UK population has Long COVID. Long COVID may also account for 15% fof the 10.6 Million unfilled jobs in the United States. Other articles on Long COVID include dysautonomia, post-COVID clinics in the US, federal efforts to understand Long COVID and a podcast by Andy Slavitt with guests Akiko Iwasaki and David Putrino speaking about possible treatments for Long COVID.
Also this week, we saw a superspreader event in Washington DC at the Gridiron dinner which included many Democratic politicians. The CDC messaging about risks in different counties has been really confusing but luckily Mr. T has helped some with his helpful health comms messaging about the second booster (4th dose) and masking. Thanks Mr. T!
BA.2 cases rise significantly in the Northeastern U.S., but hospitalizations and deaths remain low
4/16/22 MedRxiv: Epidemiology of infections with SARS-CoV-2 Omicron BA.2 variant in Hong Kong, January-March 2022 https://buff.ly/3jKTahb
Hong Kong reported 12,631 confirmed COVID-19 cases and 213 deaths in the first two years of the pandemic but experienced a major wave predominantly of Omicron BA.2.2 in early 2022 with over 1.1 million reported SARS-CoV-2 infections and more than 7900 deaths.
Omicron BA.2 is just as deadly as prior variants, when infections occur in unvaccinated seniors.
4/14/22 NPR: 2 new Omicron variants (BA.2.12 and BA.2.12.1) are spreading in N.Y. and elsewhere. Here's what we know https://buff.ly/3Eg26V7
BA2.12:
Growth advantage (30% to 90% per week over BA.2).
Noted in 6 countries (Canada, UK, Australia, Israel, Luxembourg, US), but most cases are in central NY state.
BA.2 and all of its versions are expected to have a much smaller surge than BA.1.
Vaccines protect against BA.2 hospitalization and severe COVID.
4/13/22 New York State Department of Health Announces Emergence of Recently Identified, Highly Contagious Omicron Subvariants in New York and Urges Continued Vigilance Against COVID-19 https://buff.ly/3vkJmjb
Two sub-lineages of BA.2, BA.2.12 and BA.2.12.1, which potentially are contributing to increased transmission in central New York and surrounding regions.
4/14/22 FDA Coronavirus (COVID-19) Update: FDA Authorizes First COVID-19 Diagnostic Test Using Breath Samples https://buff.ly/3rvNeNh
InspectIR COVID-19 Breathalyzer instrument is about the size of a piece of carry-on luggage. The test is performed by a qualified, trained operator under the supervision of a health care provider with results in < 3 minutes.
91.2% sensitivity (the percent of positive samples the test correctly identified) and 99.3% specificity (the percent of negative samples the test correctly identified).
InspectIR expects to be able to produce approximately 100 instruments per week, which can each be used to evaluate approximately 160 samples per day.
4/14/22 San Francisco
4/14/22 Andy Slavitt Twitter thread summarizing priorities and expectations for what’s next.https://buff.ly/3vjiXm2
Priorities:
Kids 0-5
BA.2, how will it turn out here? It's been variable in Europe.
Paxlovid and test-to-treat
http://COVID.gov has made finding treatments simple
Filtration and ventilation
Long COVID treatments.
In The Bubble podcast on promising news on long-COVID treatments. With best practices from David Putrino, that he lays out here, 15-20% can fully recover & the vast majority can see 70% improvement.
Vaccines appear to reduce long COVID by 50%
Disability laws, insurance coverage, more research, more treatment sites & published clinical protocols are also important for Long COVID.
Bivalent vaccine covering Omicron & wild type (WT) possibly for this Fall given that the expectation is that continued mutations of COVID will come from the Omicron family.
Global vaccinations
Boosters in congregate care settings & for seniors
Better surveillance, testing, monitoring & data sharing
Ensuring public health remains free to the public.
For $75/American, all of these priorities mentioned can all be funded.
The United States renewed the COVID-19 public health emergency, allowing millions of Americans to keep getting free tests, vaccines and treatments for at least three more months.
4/13/22 NEJM: Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting in Israel https://buff.ly/3jDG0SZ
182,122 matched pairs (3 doses vs 4 doses) age 60+
Compared to 3 doses (control), 4th dose VE against Omicron up to day 30 showed significant increased protection from death, hospitalization, severe disease, symptomatic infection through 30d.
Compared to 3 doses (control), 4th dose VE against Omicron protected:
52% any Omicron breakthrough infection
61% symptomatic Omicron breakthrough infection
72% hospitalization
64% severe disease
76% death
4/13/22 Cell: Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infectionhttps://buff.ly/3uFFGtt
Approximately half of COVID-19 patients shed fecal RNA in the week after infection.
Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at and after 4 months, 13% continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% shed at 7 months.
The GI tract may be infected after the respiratory infection has cleared.
Presence of fecal SARS-CoV-2 RNA is associated with gastrointestinal symptoms of abdominal pain, nausea, vomiting.
Despite pressure from airlines and industry groups, the Biden administration extended the requirement to wear masks while traveling on public transportation through May 3.
4/13/22 Science: Population-level implications of the Israeli booster campaign to curtail COVID-19 resurgence https://buff.ly/3E9wn7W
"The vast benefits of vaccinating younger age groups that are not at a high risk of developing severe disease but play an important role in transmission."
4/13/22 NEJM by Paul Sax MD: Should We Prescribe Paxlovid to Low-Risk COVID-19 Patients? https://buff.ly/3Odix9h
Dr. Sax’s own view? Given sufficient supply — and we’re not there yet — I’d certainly recommend nirmatrelvir/r even for low-risk symptomatic people.
The safe and reliable activity against all variants
The substantial reduction in viral load, the most of any drug tested to date in a 5 day oral regimen.
Paxlovid may shorten viral replication and the impact on secondary transmission could be enormous.
4/13/22 BioRxiV: Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variantshttps://buff.ly/3uE5qpP
SARS-CoV-2 WA1 and Delta infect some olfactory neurons in addition to sustentacular cells.
Delta invades the submucosa, while Omicron stays more in the sinonasal epithelium.
The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon is more pronounced in younger hosts.
These variant tropisms may be why Omicron leads to less loss of smell (ansomia) than Delta and the original virus.
4/13/22 JAMA: Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients With COVID-19 https://buff.ly/3vgoxpb
April 2020 to Sept 2021 (pre-Omicron)
Axon and microvascular pathology was worse in patients with COVID-19 with smell alterations than those with intact smell but was not associated with clinical severity, timing of infection, or presence of virus.
COVID-19 infection is associated with axon injuries and microvasculopathy in olfactory tissue.
4/13/22 Science: SARS-CoV-2 spike protein–induced cell fusionactivates the cGAS-STING pathway and the interferon response https://buff.ly/3EksJZ9
The cell fusion–dependent activation of the cGAS-STING-IFN pathway (i.e. via syncytial or fused pneumocytes) may contribute to the excessive inflammatory response seen in the lungs of patients with severe COVID-19.
4/9/22 Annals of Clinical and Translational Neurology: Prevalence and patterns of symptoms of Dysautonomia in patients with Long COVID syndrome: A cross‐sectional study https://buff.ly/3uEjcc7
Symptoms of dysautonomia are common in long-COVID syndrome.
The most common COMPASS-31 affected domains of dysautonomia are gastrointestinal (92%), secretomotor (76%), orthostatic intolerance (74%), and pupillomotor (68%).
There is a positive correlation between orthostatic intolerance domain score and patients' age.
2/9/22 Becker's Hospital Review: 66 hospitals, health systems that have launched Post-COVID-19 clinicshttps://buff.ly/36br4Zp
Long COVID, PASC
4/10/22 FT: Long Covid: the invisible public health crisis fuelling labour shortageshttps://buff.ly/3LVUv0Q
ONS: 2.7% of the UK population are experiencing Long COVID (symptoms persisting for more than four weeks after COVID-19, mostly in people age 35 to 49.
Lazell-Fairman is one of an estimated 100-million people worldwide suffering from long COVID, a debilitating condition where COVID symptoms linger for 12 weeks or more, frequently leaving them unable to return to their previous working lives.
One study by the Brookings Institution in January speculated that long COVID could potentially account for upwards of 15% of the 10.6 million unfilled jobs in the U.S.
“We are talking about … people who are in the prime of their lives, who are also at the prime of their earning potential.”
4/5/22 NBC: Biden expands federal efforts to understand, treat Long Covid https://buff.ly/3ro0bca
Researchers believe that as many as 23 million Americans continue to suffer from long Covid symptoms, which include chronic pain, persistent dizziness and memory loss.
In The Bubble podcast on promising news on long-COVID treatments. With best practices from David Putrino, that he lays out here, 15-20% can fully recover & the vast majority can see 70% improvement.
In depth review of organ systems affected by Long COVID (PASC) with many helpful links for Long COVID patients.
4/12/22 Nature via John Chi: Can drugs reduce the risk of long COVID? What scientists know so far https://buff.ly/3M6qGdI
Vaccination appears to reduce the risk of long COVID by about half among those who become infected after vaccination.
Long COVID often happens after mild or asymptomatic infections.
There are ongoing clinical trials to test whether antiviral drugs molnupiravir and Paxlovid could decrease Long COVID risk.
A large UK-based trial called HEAL-COVID is testing 2 cardiovascular drugs in hospitalized patients: apixaban, an anticoagulant and atorvastatin, a cholesterol-lowering medication thought to reduce inflammation in blood vessels.
Cases of BA.2 are rising in the Northeast & likely Florida. But cases are growing faster than it appears as the large number of at-home tests increases.
35,000 daily cases used to represent 100,000 actual cases. Today, they represent 200,000-300,000.
Most are predicting that BA.2 will cause some real outbreaks, but will not overly tax the health care system and burn out rather quickly.
The layers of immunity, pre-existing BA.1.1 prevalence & availability of a 4th booster for high risk people are all abating factors.
As BA.2 is fading in Europe, we are seeing new progressive variants emerge— BA.4 and BA.5.
But the fact that the next variants are coming from omicron is a positive sign.
It gives us insight into the big question which is described by some as drift vs shift.
“Drift” is when variants show a progression of new variants off of the last one.
“Shift” represents new variants coming from a completely different lineage— as omicron was after delta.
The “drift” world is far more predictable. Vaccine development is easier & more linear & prior protection from infection is much better.
Prior versions & the current version of omicron seem to be highly protective against BA.4 & 5, for example.
The more time that passes, the less likely it may be to see an antigenic shift.
4/11/22 NY Times: The Home Test Is Negative, but Could I Still Have Covid? https://buff.ly/3Ky9ayY
The harder your immune system is working to tamp down the virus, particularly an immune system supercharged by vaccine antibodies, the more likely you are to get an early negative result on a rapid test, even if you’re infected.
“If you test negative and you have symptoms, don’t assume you’re negative. Assume that the virus has not had an opportunity to grow up yet. The symptoms might mean your immune system is just triggering a very early warning.” Michael Mina
“When you have symptoms, the tests are really ‘rule-in’ tests. I think of those two days when I was so symptomatic. I had one positive test and five negative tests. There was only one moment in there where I was more infectious.”
“When the test is new, it has a six-month expiration,” Dr. Mina said. “But once you get to six months, the F.D.A. may extend it" because of new data.
In January, the F.D.A. extended the shelf life of the BinaxNOW test to 15 months, from 12 months, so many people can just add another three months to the expiration listed on their box.
“The reality is that these tests are very, very stable,” Dr. Mina said. “My expectation is that most of them, if not all of them, eventually will have a two-year expiration date at least. If the control line is showing up and it’s within 18 to 24 months of the manufacture date, you should assume the test is working.”
4/11/22 NY Times: New Drug Slashed Deaths Among Patients With Severe Covid, Maker Claims https://buff.ly/3vi4l6y
Sabizabulin reduced deaths among hospitalized Covid-19 patients so drastically in a clinical trial that independent safety monitors recommended stopping it early, officials at Veru Inc., the drug’s maker, said.
The data have not yet been published or peer-reviewed.
4/11/22 BBC: England’s Queen Elizabeth reveals Covid in February has left her 'very tired and exhausted' https://buff.ly/3jtKD23
4/11/22 Nature: SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cellshttps://buff.ly/3jqRaus
Repeated SARS-CoV-2 antigen exposure from infection and/or vaccines does not lead to an exhausted T cell phenotype.
Breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory.
Calculate your risk of COVID for different activities in your location: https://mycovidrisk.app/
4/10/22 IDSA: Health equity articles providing data on the significant impacts that bias and racism have on COVID-related patient care. https://buff.ly/3KteW4I
4/10/22 CNN: New York City Mayor Eric Adams tests positive for Covid-19, spokesperson says https://buff.ly/3JpEWg1
"He is also going to immediately begin taking the antiviral medications offered for free to New York City residents and encourages all New Yorkers eligible for these medications to take them as well."
He was at the Gridiron dinner in Washington DC. April 2nd and has been at many events since then unmasked.
4/11/22 MedRxiV: A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Amelioration of Loss of Smell and Tastehttps://buff.ly/3jshNix
June 2020 to April 2021 (Wuhan OG virus and Alpha), we conducted a randomized, double-blind, placebo-controlled phase 2 trial.
The camostat group had more rapid resolution of COVID-19 symptoms and amelioration of the loss of taste and smell.
Camostat compared to placebo was not associated with reduction in nasopharyngeal SARS-COV-2 viral load.
4/11/22 Nature Genetics : Understanding COVID-19 through genome-wide association studies https://buff.ly/3v6kfRc
Summary of the known genomic loci that are associated with both risk and protection for SARS-CoV-2.
In places like China and in older buildings in Spain, infected air can flow from one apartment to another.
3/11/22 El Pais: Coronavirus- How infected air can flow from one apartment to another https://buff.ly/3uqd9YH
Great interactive graphics showing how older buildings in Spain have air flow from one apartment to another through communal ducts.
In Spain, the bathrooms of older buildings are connected through communal ducts that allow aerosol exchanges. Although not common, it is suspected that transmission may occur in specific circumstances
7/2020 International Journal of Civil Engineering and Technology: Why China Stinks. Deficiencies in Plumbing and Ventilation Systems in China. https://buff.ly/3LS6NXU
Offensive odors (and viruses) can enter apartments through sewage lines that are not properly sealed, the lack of P-traps in plumbing fixtures, and through vents that connect apartments.
4/10/22 MedPage Today reports on American Academy of Neurology (AAN) abstract: Persistent Brain Fog After Mild COVID Infection Tied to CSF Markershttps://buff.ly/3v96Vf1
13 participants with cognitive issues and 5 controls with no cognitive symptoms after COVID, median age 40 years old. CSF was collected 10 months after the first COVID symptoms.
Higher level of CSF levels of C-reactive protein (P=0.004) and serum amyloid A (P=0.001) in long COVID patients with cognitive symptoms compared with COVID patients who experienced no cognitive changes after infection.
CSF immune activation markers IP-10, IL-8, and immunovascular markers VEGF-C and VEGFR-1 also trended higher.
Inflammation within the brain and immunovascular dysregulation via endothelial dysfunction and activation may contribute to this executive function disorder.
"People have difficulty retrieving names and words or holding onto and manipulating information, or difficulties with slow processing speed."
4/10/22 Scott Gottlieb (former FDA Commissioner) speaks about the US:
4/10/22
China had a zero-COVID policy and therefore has little immunity from prior infection.
In the US, the CDC has had poor messaging about county level risks:
4/10/22 Nature: Infectious viral load (VL) in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2 https://buff.ly/37D41GY
2 doses of mRNA vaccine significantly reduced infectious VL for Delta breakthrough cases compared to unvaccinated individuals.
For Omicron breakthrough cases, reduced infectious VL was only observed in boosted (3 doses) but not with 2 doses compared to unvaccinated subjects.
These findings indicate that vaccines may lower transmission risk and therefore have a public health benefit beyond the individual protection from severe disease.
4/10/22 NBC: 67 attendees of high profile D.C. Gridiron dinner test positive for Covid https://buff.ly/3usQ9bC
Agriculture Secretary Tom Vilsack, Attorney General Merrick Garland and Commerce Secretary Gina Raimondo are among the positive.
Vice President Kamala Harris' communications director Jamal Simmons, first lady Jill Biden’s press secretary Michael LaRosa and Valerie Biden Owens, President Joe Biden’s sister were also among guests who later tested positive following the event.
House Speaker Nancy Pelosi, D-Calif., who did not attend the dinner, also tested positive last week after spending time with President Joe Biden and Vice President Kamala Harris.
