COVID news 4/22/22
Hi all,
This week’s main issues are the mask mandate repeal, Evusheld, new Omicron subvariants BA.2.12.1 and BA.5, and a newly identified phenomenon of rebound COVID infection after stopping 5 days of Paxlovid in some people.
Mask mandate
This week a federal judge in Florida with an “unqualified” rating from the American Bar Association decided that the federal mask mandate on transportation including airplanes was no longer needed despite the experts at the CDC saying that masks are still important to stop viral transmission while traveling. The repeal of the mask mandate was announced on airplanes in real time and some people cheered and took off their masks mid-flight. Other people were livid that their children under the age of 5 who are too young to be vaccinated were suddenly exposed to a plane full of maskless people as this was not their expectation before they boarded their flight.
Studies show that air is well filtered on airplanes while the flight is in the air, but the air is not filtered while people board the plane or while planes taxi on runways before departure or on arrival to the gate. So, I will definitely be wearing a KN95 mask in the airport and while on the plane and I will not eat or drink when the plane is not in flight.
Delta airlines immediately announced “COVID-19 has transitioned to an ordinary seasonal virus” which, of course, it has not, which irked many scientists.
Cases
Cases are starting to rise some, but reported case numbers are not accurate now as most people are testing at home with rapid antigen tests which are not reported to state governments.
Evusheld
There were two articles yesterday, one in the NEJM and one in Science magazine, about Evusheld, a monoclonal antibody cocktail being used as PrEP (pre-exposure prophylaxis) for immunocompromised people. The amazing thing about Evusheld is that a single dose can provide protection against Covid-19 for at least 6 months. With prophylactic Evusheld, there was a 77% reduction in symptomatic infection and 83% relative risk reduction at 6 month follow up. This is great news for immunocompromised people who can not make enough antibodies after vaccination.
Omicron Subvariants (BA.1, BA.2, BA.2.12.1, BA.4, BA.5)
BA.2.12.1, the newer subvariant of BA.2, was reported to be increasing in New York state last week. It is more contagious than BA.2 and will probably become dominant soon. The good news is that our vaccines should have similar VE (vaccine efficiency) to BA.2.12.1 as they do to BA.1 or BA.2.
BA.4 and BA.5 Omicron variants are being reported in South Africa. They have some immune evasion so unvaccinated or under vaccinated people can become reinfected with BA.4 or BA.5, but both of these subvariants are very similar to BA.2 and are expected to have similar disease severity as other Omicron subvariants.
Paxlovid and rebound COVID
This week, some people on Twitter posted that they had a rebound of their COVID infection when they finished the 5 day course of Paxlovid. Other people started chiming in with similar findings. Initially, the person is positive on RAT (rapid antigen test), they then take Paxlovid for 5 days and feel better. Their RAT tests become negative. Then, after a few days, they get a rebound in COVID symptoms and when they test, the RAT is now positive again for several days. I think that there will be more information coming out on this soon. It may be that some people will need a longer course of Paxlovid.
Finally, an article from Japan shows that vaccinated people who get a breakthrough Omicron infection that is mild or asymptomatic tend to shed virus (and be contagious) for 6 to 9 days. So much for the CDC recommendation of coming out of isolation after 5 days without taking a COVID test.
Have a great weekend.
Ruth Ann Crystal MD
Twitter: https://twitter.com/CatchTheBaby
World
United States
Note: Now that people are doing home rapid antigen tests, case numbers are not accurate and there are a lot more cases than reported.
4/22/22 Patient-Led Research Collaborative Receives $3M in Funding for Long COVID Research from Balvi, A New Fund for High-Impact COVID Projects from Ethereum Co-Founder Vitalik Buterin https://buff.ly/3k4f9zL
$2 million will be used to establish a Long COVID biomedical research fund led by patients.
4/21/22 The Guardian: Vaccinated health care worker, age 31, catches COVID twice within 20 days in Spain https://buff.ly/3k1pk8a
Whole genome sequencing showed that the patient had been infected by two different Covid variants.
Her first infection was with the Delta variant and the second was with the Omicron variant, which is known to be more infectious and can evade immunity from past infections and vaccination.
Subvariants BA.2, BA.2.12.1, BA.4 and BA.5
BA.5 in South Africa has immune evasion so reinfections may increase
4/21/22 Wash Post Opinion by Dr. Lucky Tran and Dr. Oni Blackstock:
Now’s not the time to dispense with COVID-19 precautions https://buff.ly/3MqWcDH
Lifting mask mandates on transportation is disastrous.
Some cities and states are changing their definition of COVID hospitalizations, reducing surveillance, and there is a lack of reporting of home antigen tests.
US vaccination rates are lower than other countries.
There is Long COVID sequelae including dysautonomia and there can be long term brain, heart problems, increased diabetes and blood clots one year after mild infection.
4/21/22 CDC EID: Duration of Infectious Virus Shedding by SARS-CoV-2 Omicron Variant–Infected Vaccinees https://buff.ly/36vP5KG
Japanese study of Omicron
Vaccinees with mild or asymptomatic infection shed infectious Omicron virus 6–9 days after onset or diagnosis, even after symptom resolution.
4/20/22 ACIP Presentation Slides | Immunization Practices | CDC https://buff.ly/38cyYCt
4/20/22 CDC presentation by Ruth Link-Gelles, PhD, MPH :
COVID-19 Vaccine Effectiveness during Omicron https://buff.ly/3OotMvL
4/20/22 NEJM: Intramuscular Evusheld AZD7442 (Tixagevimab–Cilgavimab) for Prevention of Covid-19 https://buff.ly/3xIG2S0
RCT COVID prevention trial,
n = 3460 in the AZD7442 group and n = 1737 in the placebo group.
Nov 2020 to March 2021.
Evusheld AZD7442 is a combo of two neutralizing monoclonal antibodies (tixagevimab and cilgavimab) derived from B cells obtained from persons infected with SARS-CoV-2.
Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days.
Although Covid-19 vaccines are highly effective, immunocompromised people may not make enough antibodies after Covid-19 vaccination.
A single dose of Evusheld AZD7442 could provide protection against Covid-19 for at least 6 months. At 9 months, these antibodies were still detected.
The complementary binding of tixagevimab and cilgavimab to distinct regions of the viral spike protein receptor-binding domain presents a barrier to virus escape.
With prophylactic Evusheld, there was a 77% reduction in symptomatic infection and 83% RR reduction at 6 month follow up.
Five cases of severe or critical Covid-19 and two Covid-19–related deaths occurred, all in the placebo group. None in the Evusheld group.
4/20/22 Science: The SARS-CoV-2 monoclonal antibody combination, Evusheld AZD7442, is protective in nonhuman primates and has an extended half-life in humans https://buff.ly/3v0hiTf
Evusheld AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct, nonoverlapping epitopes on the spike protein receptor binding domain to neutralize SARS-CoV-2.
Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and reduce effector functions.
A single injection of these antibodies provides durable protection at 6+ months.
About 1 to 2% of serum AZD7442 was detected in nasal mucosa, a site of SARS-CoV-2 infection.
4/20/22 NBC: Vaccines, antibodies, antivirals: How some immunocompromised can cut Covid risk https://buff.ly/3K0ymwY
2.7% of US adults are immunocompromised including organ transplant recipients, certain cancer patients and people with HIV or other conditions that impair the immune system.
Evusheld is a monoclonal antibody cocktail to prevent Covid in immunocompromised people.
Evusheld is 83% effective against symptomatic illness over six months.
Paxlovid: “a bit of a tricky point, because you’ll have to hold some of your medication for your autoimmune diseases so you can be on Paxlovid even for a brief period of time.”
4/20/22 MedRxiV: Three-dose mRNA-1273 vaccination schedule: sufficient antibody response in majority of immunocompromised hematology patients https://buff.ly/385Regt
In immunocompromised hematology patients, a 3rd dose of Moderna mRNA-1273 led to antibody levels similar to healthy controls after 2 doses.
Exceptions: Less response or no response to 3rd dose seen with:
Rituximab
CD19-directed CAR-T recipients
Chronic lymphocytic leukemia patients on Ibrutinib.
B cell lymphoma patients and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.
4/20/22 Science: An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses https://buff.ly/3EywjyT
To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody "10-40" that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo.
4/19/22 CDC MMWR: Hospitalizations of Children Aged 5–11 Years with COVID-19, March 2020 to Feb 2022 https://buff.ly/3JSW269
Kids aged 5–11 years became eligible for COVID-19 vaccination November 2021.
Black children represented the largest group of unvaccinated children.
Children with diabetes and obesity were more likely to experience severe COVID-19.
4/19/22 FT: Scientists urge China to replace its faltering Covid vaccines https://buff.ly/3uZFky1
Sinovac and Sinopharm are inactivated virus vaccines and had about 60% VE against COVID before Omicron became the dominant variant.
People over age 60 who had received 2 doses of Sinovac were 3x more likely to die of COVID-19 compared with people who had received 2 doses of Pfizer vaccine.
3 doses of Sinovac are needed to reduce deaths.
In China, only 57% of people over age 60 have received a 3rd dose.
A Brazil study showed that CoronaVac booster (3rd dose) gave little protection but adding a booster of Pfizer mRNA vaccine protected against severe disease for at least 3 months.
A Yale University study showed that people that received 2 doses of inactivated virus vaccines like Sinovac may need 2 additional boosters (dose 3 and dose 4) of mRNA vaccine to have the same protection as 3 doses of Pfizer mRNA vaccine.
2 Sinovac + 2 mRNA boosters = 2 Pfizer mRNA + 1 mRNA booster
Inactivated virus vaccines tend not to stimulate CD8 T cells well so long term protection may not be reliable without the addition of mRNA boosters.
4/19/22 The Guardian: Vaccines are no match for Long Covid. Treating it is science's next great challenge | Danny Altmann https://buff.ly/3uP4KxX
Vaccines decrease Long COVID by half, but when you apply this to the huge waves – 3.5 million people infected at a given time – each 3.5 million cases becomes another 175,000 people with long Covid.
In the UK, these waves have disproportionately affected primary and secondary schools, and many of the new sufferers are children.
A team at the University of Toronto followed up patients with persistent symptoms after infection during the 2003 SARS outbreak. Many of these showed little recovery several years later. If this trend were extrapolated to our current Omicron wave, the effects on education, the workforce and healthcare provision would be huge.
Some current UK research programmes:
Stimulate-ICP trial at University College hospital
A clinical trial at Oxford University is investigating whether a drug called AXA1125 can treat fatigue and muscle weakness.
Airplanes and masks
4/18/22 AP: Florida judge voids US mask mandate for planes, other travel https://buff.ly/3vvxaMz
U.S. District Judge Kathryn Kimball Mizelle in Tampa, an appointee of former President Donald Trump, said CDC failed to justify masks and did not follow proper rulemaking procedures that left it fatally flawed.
“This is obviously a disappointing decision,” White House press secretary Jen Psaki told reporters. “The CDC is recommending wearing a mask on public transit.”
The CDC had recently extended the mask mandate, which was set to expire Monday, until May 3 to allow more time to study the BA.2 omicron subvariant.
The federal mask requirement for travelers was the target of months of lobbying from the airlines, which sought to kill it. The carriers argued that effective air filters on modern planes make transmission of the virus during a flight highly unlikely.
However, the air filters are not on while people board planes or when they idle on the tarmac.
9/10/20 American Bar Association (ABA): Federal judicial nominee Kathryn Kimball Mizelle lacks enough experience, ABA says in letter explaining 'not qualified' rating https://buff.ly/3rCYkAh
4/18/22 CBS: Hundreds of Overseas Flights Canceled After Mask Rules Dropped https://buff.ly/3vt3RdJ
In Europe, when mask mandates were dropped, airlines had to cancel hundreds of flights because their employees got COVID and they could not staff the flights.
4/19/22
4/21/22 Katelyn Jetelina blog: SARS-CoV-2 transmission on planes https://buff.ly/3L5op2p
Airlines have good air filtration systems, but they are not on during boarding or while the plane is taxiing.
SARS-CoV-2 is spread through aerosols and droplets.
Aerosols are picked up by filtration, droplets by masks.
Proximity to an infected person matters.
People tend to move a lot on long plane flights.
4/20/22
4/19/22 NY Times: Americans Over 60 Should Get Second Booster (4th dose), Official Says https://buff.ly/3Ek8F9n
Americans over 60 should get a second booster shot of a coronavirus vaccine, Dr. Ashish K. Jha, the new White House Covid-19 response coordinator, said on Sunday, citing “pretty compelling” new data from Israel indicating that a fourth shot significantly reduced infections and deaths among older people there.
4/18/22 Fierce Pharma (h/t Ritu Lal): Could Pfizer's Paxlovid or other antivirals help cure long COVID? https://buff.ly/3EFRbnO
Two women in the U.S. who have shook off their lingering long-haul symptoms after going on a standard five-day regimen of Pfizer’s oral antiviral Paxlovid.
Pfizer is not testing Paxlovid against long COVID, a company spokesperson said. But two ongoing studies of the treatment involving more than 4,000 patients could provide “us with relevant data to help inform future studies.
4/17/22 Bob Wachter on how he is making decisions on what activities to do now:
7) My biggest worry is that of Long Covid (LC), which I now think of in two fairly distinct buckets:
a. Prolonged symptoms, including fatigue and brain fog, that last for many months. From the (confusing) literature, I estimate the probability of symptomatic LC from an Omicron infection in a fully vaxxed person is ~5%.
b. Increasing the risk of bad non-Covid outcomes over time.
Recent studies have shown increased risk of heart attacks & strokes, of diabetes, of brain shrinkage, and of blood clots.
It’s hard to translate that to my own personal risk, since there are no long-term studies of 1-year outcomes of Omicron infections in fully vaxxed people (Omicron hasn’t been around long enough).
But it is this long-term and uncertain LC risk that is my main motivation to try to avoid infection, even if the likelihood of a severe outcome from an acute case isn’t very high, and the likelihood of symptomatic LC in a fully vaxxed person is real but fairly low.
(If I’d already had Covid, these concerns about LC would also motivate me to try to avoid another infection.)
Rebound COVID after Paxlovid
4/18/22 Dr. Paul Sax: Newly noted phenomenon where virus rebounds after 5 days of Paxlovid, people get symptoms again and rapid Ag tests become positive again.
The FDA EUA did describe this phenomenon (rebound COVID after Paxlovid)on page 22 https://www.fda.gov/media/155194/download
4/21/22 The Boston Globe: A puzzling phenomenon: Patients report a rebound of COVID-19 symptoms after taking the antiviral Paxlovid https://buff.ly/3MnFwwC
Their symptoms rebound and they become positive again on rapid antigen tests.
I couldn’t read the whole article because of the paywall.
–
Reinfections again and again may not be so benign.
FYI- FEMA COVID-19 Funeral Assistance https://buff.ly/3k982Y5
Passover in the time of COVID:
