We are in a surge. The CDC is urging people to wear masks indoors and for those over age 50 to get their latest boosters. There are more people aged 70+ that are hospitalized now than there were during the Delta variant wave. Wastewater virus levels are now higher than prior waves, with the exception of the Omicron BA.1 wave. You can't tell by the fact that many people are no longer wearing masks in stores and in airplanes, but 96% of U.S. counties are now in the CDC substantial or high risk categories for viral transmission.
BA.2.12.1 is now the dominant variant in the United States. New studies show that BA.4/5, which was dominant in South Africa, has more immune evasion than BA.2.12.1, so it may outcompete BA.2.12.1. Prior BA.1 or BA.2 infection in unvaccinated people does not protect against BA.4/5. The serum of triple vaccinated people with 3 doses of AstraZeneca or 3 doses of Pfizer has less neutralization of BA.4/5 than of BA.1 and BA.2. Similarly, serum from vaccinated people who had breakthrough infections (BTI) with BA.1 show significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron breakthrough infections with BA.4/5.
In real world studies, Paxlovid and Molnupiravir were found to significantly lower risks of disease progression and all-cause mortality, in addition to achieving low viral load faster, than their respective matched controls for people hospitalized with BA.2 infections. The CDC now recommends re-isolation if COVID recurs after taking Pfizer's pill Paxlovid. Relapse of infection after Paxlovid appears to be more common with Omicron infections.
There are several articles this week about monoclonal antibodies discovered in the blood of vaccinated people who got a breakthrough infection (BTI) with Omicron. These monoclonal antibodies can neutralize all variants. In fact, the human monoclonal antibody called 10-40 which was isolated from an individual with a prior SARS-CoV-2 infection, can broadly neutralize several variants of SARS-CoV-2, SARS-CoV, and other coronaviruses. We would be smart to focus time and money on making new monoclonal antibody drugs like we previously focused on vaccine development with the Operation Warp Speed program.
Long COVID: This week there was an article on a Veteran's Administration study of almost 34,000 breakthrough infections (BTIs) pre-Omicron showed that vaccination reduced Long COVID by only 15% and not 50% like previous studies have shown. In this study, vaccinated people with BTI had 44% lower risk of death than unvaccinated people, but still had increased death compared to people who never got COVID. Being vaccinated appeared to reduce the risk of lung and blood clot disorders, but did little to protect against most other Long COVID problems (neurological issues, gastrointestinal symptoms, kidney failure). While the study population contained a range of ages and racial and ethnic backgrounds, it did skew older, Whiter and more male than the United States as a whole.
A separate article from the CDC shows that from March 2020–November 2021, 1 in 5 people age 18 to 64 who got COVID developed Long COVID sequelae, as did 1 in 4 people age 65+.
Travel: As predicted, Delta airlines now has to cut 100 flights a day due to employee sickness. Most flight attendants are no longer wearing masks and unsurprisingly they are getting COVID which is affecting staffing of flights. If you don't want to get COVID while traveling, it will be important to wear a mask indoors, and especially when you are in an airplane or other transportation. SARS-CoV-2 variants have become increasingly more contagious.
Early data reported this week in children aged 6 months to 5 years shows that three doses of the 3 mcg Pfizer vaccine showed 80% vaccine efficiency against symptomatic infections during the Omicron wave. Hopefully, the FDA will approve the vaccine soon for this age group.
Finally, there are two other public health issues in the news- Monkeypox for which I am including a summary sheet, and gun violence which is unfortunately very timely given the devastating shooting at an elementary school in Uvalde, Texas this week. Katelyn Jetelina wrote an excellent article on how we can successfully tackle gun violence, like we have smoking or motor vehicle accidents, using public health interventions.
Have a great holiday weekend (and don't forget to bring your mask).
Less than 4% of Americans live in a county that is not classified by @CDCgov as a substantial or high transmission area.
In 6 weeks, from 23% High transmission to 91%.
CDC “Community Risk” based on available hospital beds
Last week - 17% of people lived in high level areas, 45% in medium or high.
Now, nearly 1 in 4 people live in a "high" level area.
5/27/22 Who could have predicted this?
5/27/22 CBS: White House touts efforts to expand COVID test-to-treat sites amid latest wave https://buff.ly/39ZVuiG
White House officials introduce new models for Paxlovid distribution to expand access.
New "test-to-treat" sites will open in Rhode Island, Minnesota, New York and Illinois.
Overall, the pace of new COVID-19 hospitalizations has accelerated for more than a month, especially among Americans ages 70 and older – the age group most vulnerable to severe disease and death.
In several regions, the pace of new hospitalizations among these oldest Americans is now several times higher than even the worst days of the Delta variant surge last year.
The Omicron Variants:
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SUMMARY OF OMICRON SUBVARIANTS:
BA.1 = The Original Omicron (November 2021 to February 2022)
BA.2
More symptoms than BA.1
Prior BA.1 infection does not protect against BA.2
Antiviral pills work against BA.2. Hazard ratios (HR):
Monoclonal antibody that works against BA.2.12.1: Bebtelovimab
Like BA.4/5, BA.2.12.1 replicates more in lung cells than BA.2.
BA.4/5
L452R mutation in spike
More immune evasion than BA.2.12.1 so may outcompete.
Prior BA.1 or BA.2 infection in unvaccinated does not protect against BA.4/5.
Triple vaccinees (3 doses) of AstraZeneca or Pfizer have less neutralization of BA.4/5 than BA.1 and BA.2.
Serum from vaccinated people who had breakthrough infections (BTI) with BA.1 has significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.
More pathogenic than BA.2 in hamster model
Like BA.2.12.1, BA.4/5 replicates more in lung cells than BA.2.
Antigenically distinct to BA.1.
Monoclonal antibody that works against BA.4/5: Bebtelovimab
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5/26/22 BioRxiV (Kei Sato lab): Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5https://buff.ly/3sZDZpu
Immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5.
BA.2.12.1 and BA.4/BA.5 all have enhanced replication in lung cells compared to BA.2 and BA.4/5 is more fusogenic than BA.2.
BA.4/5 is more pathogenic than BA.2 in hamsters.
Mutations of L452 residue of spike protein:
BA.2.12.1 (L452Q)
BA.4/BA.5 (L452R)
The risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2.
5/26/22 BioRxiV: SARS-CoV-2 Omicron BA.2.12.1, BA.4, and BA.5 subvariants evolved to extend antibody evasion https://buff.ly/3lOQwrM
The immune evasion is more extensive for BA.4/5 than for BA.2.12.1 variant, raising the possibility that the former can out-compete the latter.
Only one monoclonal antibody Bebtelovimab has full potency against BA.2.12.1, BA.4/BA.5 Omicron subvariants.
5/26/22 BioRxiV: Distinct antigenic properties of the SARS-CoV-2 Omicron lineages BA.4 and BA.5https://buff.ly/39VgtTE
Vacinees have a similar ability to neutralize BA.1, BA.2 and BA.4/BA.5.
Prior infection with BA.2 or, in particular, BA.1, in unvaccinated people poorly neutralized BA.4/BA.5.
Breakthrough infection with Omicron in vaccinees leads to a broad neutralizing response against the new variants.
The sensitivity of BA.4/BA.5 to neutralization by therapeutic monoclonal antibodies was similar to that of BA.2.
These data suggest BA.4/BA.5 are antigenically distinct from BA.1 and, to a lesser extent, BA.2.
5/26/22 NEJM: Effectiveness of Homologous and Heterologous Covid-19 Boosters against Omicron https://buff.ly/3lK8cop
January 2 and March 23, 2022
The J&J vaccine plus 1 mRNA shot had similar protection as 3 mRNA vaccine shots against symptomatic Omicron infections.
5/26/22 Cell: Humoral and cellular immune memory to four COVID-19 vaccineshttps://buff.ly/3aqlvrL
Head-to-head comparison of immune response, both antibody and cellular, for 4 vaccines: Moderna, Pfizer, J&J (Ad26 COV2S), Novovax.
Antibody wanes in response to mRNA vaccines, but memory T and B cells are comparatively stable.
5/26/22 Science: An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses including SARS-CoV-2 and its variants https://buff.ly/3EywjyT
Human monoclonal antibody, 10-40, isolated from an individual with a prior SARS-CoV-2 infection, can broadly neutralize several variants of SARS-CoV-2, SARS-CoV, and other coronaviruses.
This class of common CDRH3 motifs may be important to elicit for effective pan-sarbecovirus vaccines.
5/26/22 Reuters: U.S. CDC recommends re-isolation if COVID recurs after taking Pfizer's pill Paxlovidhttps://buff.ly/39Z5b12
Patients with COVID rebound after Paxlovid can end their re-isolation period after five full days if there is no fever for 24 hours and symptoms improve, but such patients should wear a mask for a total of 10 days after rebound symptoms begin.
5/26/22 Washington Post: Vaccines may not prevent many symptoms of long COVID, V.A. study suggests https://buff.ly/3NARlAd
Previous studies showed that vaccination may decrease the risk of Long COVID by 50%. This pre-Omicron study from the V.A. showed that vaccination greatly reduces the risk of death or serious illness, but Long COVID is only decreased by 15% in V.A. patients. Being vaccinated appeared to reduce the risk of lung and blood clot disorders, but did little to protect against most other Long COVID problems (neurological issues, gastrointestinal symptoms, kidney failure, etc.)
Veterans Affairs analyzed records from nearly 34,000 people in the U.S. who experienced breakthrough infections. Before Omicron.
While the study population contained a wide range of ages and racial and ethnic backgrounds, it did skew older, Whiter and more male than the United States as a whole.
Koralnik and his colleagues found that vaccination did not appear to have a positive or negative impact on Long COVID cognitive function or fatigue. https://buff.ly/3PNkZnZ
US Department of Veterans Affairs national healthcare databases cohort of 33,940 individuals with COVID BreakThrough Infection (BTI) after vaccination, compared to 13 million controls
Compared to unvaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66) and post-acute sequelae (HR = 0.85).
Vaccinated people with BTI had 44% less death and 15% less Long COVID than unvaccinated people, but still had increased death and PASC compared to people who never got COVID.
Measures for the prevention of breakthrough infections are needed to most optimally reduce the risk of the long-term health consequences of SARS-CoV-2 infection.
Eric Topol MD:
For the common, non-severe breakthrough infections, the risks are still increased during 6-month follow-up for multiple outcomes.
This is a really important paper because it looks at risk of long covid and other post covid impacts (e.g. on kidneys, heart etc) in vaccinated people who get Covid BTIs and shows that risk is still very much there.
5/25/22 CDC MMWR: Post–COVID Conditions Among Adult COVID-19 Survivors Aged 18–64 and ≥65 Years, United States, March 2020–November 2021 https://buff.ly/3PGs3m9
A retrospective matched cohort design was used to analyze EHRs during March 2020–November 2021.
Inpatient, emergency department, or outpatient settings EHR reviewed.
Independent of age, COVID-19 survivors have twice the risk for developing pulmonary embolism or respiratory conditions.
High frequency of PASC/Long COVID:
Age 18-64 years: 1 in 5 had Long COVID condition
Age 65+: 1 in 4 had Long COVID condition
5/25/22 MedRxiV: Variant-specific symptoms of COVID-19 among 1,542,510 people in England https://buff.ly/3Gla4xm
Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1.
5/25/22 BioRxiV (Oxford): Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum https://buff.ly/3Gl2K50
BA.4/5 shows reduced neutralization by serum (immune escape) from triple AZ or Pfizer vaccinated individuals compared to BA.1 and BA.2.
Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.
5/24/22 NY Times: Omicron BA.2.12.1, has become the dominant form among new U.S. virus cases. https://buff.ly/3GezzQS
BA.2121 made up 58% of US cases as of 5/21/22.
Hospitalizations have increased 28% over the last 2 weeks.
NYC is on "high COVID alert" because of increased cases and hospitalizations.
People should wear masks indoors in high transmission areas per Dr Ashish Jha, and all people over age 50 should get a booster if it has been 4 months since their last shot.
The United States has had over 1 million COVID deaths.
5/23/22 The Hill: Early study shows Pfizer COVID vaccine 80% effective in youngest children https://buff.ly/3MB7Yf7
In children aged 6 months to 5 years, three doses of the Pfizer vaccine showed 80% VE during the Omicron wave.
3 doses of 3 mcg each.
Pfizer-BioNTech Press Release: Children 6 Months to Under 5 Years of Age Following Third Dose https://buff.ly/38PLwQC
from CNBC
5/23/22 JAMA: Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms https://buff.ly/3Pxc5e9
In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation.
Neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity.
Neurologic symptoms are clinically significant in COVID-19 and viral components (like the nucleocapsid antigen) can contribute to CNS immune responses without direct viral invasion of the central nervous system.
5/23/22 MedRxiV: Real-world effectiveness of Molnupiravir and Paxlovid (nirmatrelvir/ritonavir) among COVID-19 inpatients during Hong Kong's Omicron BA.2 wave: an observational study https://buff.ly/3lAdXoC
First real world study of Molnupiravir and Paxlovid during the Omicron BA.2 wave in Hong Kong in hospitalized patients not requiring oxygen on admission vs. controls.
Molnupiravir or Paxlovid were associated with significantly lower risks of disease progression and all-cause mortality, in addition to achieving low viral load faster than their respective matched controls for BA.2 infections.
Length of hospital stay: Paxlovid users had shorter stays
Viral load decreased faster in those who had taken Molnupiravir or Paxlovid
5/23/22 Lancet: Impact of the Use of Oral Antiviral Agents on the Risk of Hospitalisation in Community COVID-19 Patients https://buff.ly/3yYHAb0
Hong Kong. Non-hospitalised COVID-19 patients. Feb to March 2021.
93,883 patients, 83,154 no meds, 5,808 Molnupiravir, and 4,921 Paxlovid
Paxlovid but not Molnupiravir reduced hospitalisation in real-world COVID-19 patients.
5/23/22 New Study Points to Longer Duration of Axillary Lymphadenopathy After COVID-19 Vaccinehttps://buff.ly/3MGVxyx
While COVID-19 vaccine clinical trials noted that post-vaccine axillary lymphadenopathy lasted for 1 to 10 days, breast ultrasound research found a mean resolution of 127 days after a first vaccine dose.
5/23/22 Nature: Multisystem involvement is common in post-COVID-19 syndrome https://buff.ly/3sV5v7m
A prospective clinical study evaluating patients 28–60 days after hospitalization for COVID-19 reveals increased cardio-renal inflammation, reduced lung function and poorer self-reported clinical outcomes in patients relative to that in controls.
5/22/22 Cell: Potent cross-reactive antibodies following Omicron breakthrough in vaccinees https://buff.ly/3yRFjyl
Identification and structural analysis of 27 potent RBD-binding monoclonal antibodies (mAbs) isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection show that these antibodies can broadly neutralize VOCs.
The CDC previously said that the booster was an option, but now they urge all people over age 50 to get a booster because of recent increases in COVID hospitalizations.
