RECENT RISE IN COVID-19 INFECTIONS IN THE US

RECENT RISE IN COVID-19 INFECTIONS IN THE US

Dear Friends,

We hope this finds you well, and that you and your families have been able to spend time together this holiday season.

As we close on 2021, we wanted to send you an update to address the rapidly evolving conditions of the pandemic, and hopefully to help you continue to make thoughtful, balanced decisions as we approach the new year.

RECENT RISE IN COVID-19 INFECTIONS IN THE US:

Total US Deaths: Over 809,000 and increasing by an average of 1200 deaths per day.

New US Cases Per Day: 291,671 new cases were reported on 12/20/21; this is the 2nd highest single day total since the onset of the pandemic.  It is likely that these numbers markedly underestimate the actual case numbers as patients increasingly rely on home tests.  While many other countries have health systems that can easily track patient data across a broad spectrum of healthcare facilities, the US system lacks that capability.

Genomic Sequencing Data and Prevalence of Omicron: The estimated national prevalence of the Omicron variant has increased rapidly from 0.1% (week ending 11/27/21) to 73% (week ending 12/18/21), and in less than a month has replaced the Delta variant as the dominant variant.


VACCINATIONS:

US Vaccinations: 61.7% of the US population is fully vaccinated (received 2 doses of Pfizer/Moderna or 1 dose of J&J vaccine).  However, only 34% of eligible adults have received a booster.  56% of adults 65 years and older have received a booster.  Only 57% of nursing home residents and 25% of nursing home staff have received a booster.


TREATMENTS:

Oral Antiviral Medicines: Last week, the FDA provided EUA approval for 2 oral at-home antiviral medicines for the treatment of mild-moderate COVID-19 infection.

1) Paxlovid (Pfizer): Combines a new antiviral called nirmatrelvir with an older antiviral called ritonavir.

Indication: Treatment of mild-moderate COVID-19 infection in individuals 12 years and older, who have a positive COVID-19 test, are at high risk of progression to severe disease, and initiate treatment within 5 days of symptom onset.

Dose: 3 tablets twice daily for 5 days.

Mechanism: Blocks viral replication.
Benefit: The primary data supporting the EUA are from EPIC-HR, a randomized, double-blind, placebo-controlled clinical trial studying Paxlovid for the treatment of non-hospitalized symptomatic adults with a laboratory confirmed diagnosis of COVID-19 infection.  Patients were adults 18 years and older with a prespecified risk factor for progression to severe disease, or were 60 years and older regardless of prespecified chronic medical conditions.  All patients had not received a COVID-19 vaccine and had not been previously infected with COVID-19.  Paxlovid reduced the overall risk of hospitalization or death by 88%.  While the company’s lab studies show Paxlovid should be effective against the Omicron variant, the study population did not include patients infected with the Omicron variant.

Potential concerns: Impaired sense of taste, diarrhea, high blood pressure, and muscle aches.  Using Paxlovid at the same time as certain other medicines may result in potentially significant drug interactions.

Availability: Less than 65,000 treatment courses of Paxlovid will be available starting the first week of January 2022, and 265,000 treatment courses are expected to be shipped in the next month.

2) Molnupiravir (Merck): New antiviral called molnupiravir.
Indication: Treatment of mild-moderate COVID-19 infection in individuals 18 years and older, who have a positive COVID-19 test, are at high risk of progression to severe disease, initiate treatment within 5 days of symptom onset, and for whom other treatment options authorized by the FDA are not accessible or clinically appropriate.

Dose: 4 capsules taken twice daily for 5 days.

Mechanism: Introduces errors into the virus’s genetic code, which prevents the virus from replicating further.

Benefit: The primary data supporting the EUA are from MOVe-OUT, a randomized, double-blind, placebo-controlled clinical trial studying Molnupiravir for the treatment of non-hospitalized adults with mild to moderate COVID-19 at high risk for progression to severe COVID-19 and/or hospitalization.  Patients were adults 18 years and older with a prespecified chronic medical condition or at increased risk of COVID-19 infection for other reasons who had not received a COVID-19 vaccine.  Molnupiravir reduced the overall risk of hospitalization or death by 30%.

Potential concerns: Based on animal studies, Molnupiravir may cause fetal harm when administered to pregnant individuals.  Molnupiravir may cause genetic mutations in recipients, possibly increasing their risk of cancer.  Molnupiravir may also lead to the development of new COVID-19 variants.

Availability: 3 million treatment courses of Molnupiravir will be available by the end of next month.

Monoclonal Antibodies: The Regeneron and Eli Lilly monoclonal antibodies do not appear to be effective against the Omicron variant; thus, the US has stopped allocation of these antibodies.  Sotrovimab, a different monoclonal antibody developed by GSK, while retaining some efficacy against the Omicron variant, is significantly less potent against Omicron compared to previous variants.  Additionally, Sotrovimab is not widely available in the US (up to 300,000 doses are planned to be distributed by the end of January 2022).  Sotrovimab will be reserved for high-risk patients (defined as unvaccinated individuals; individuals at high-risk based upon age, comorbidities, immunosuppression).


PREVENTION THROUGH VACCINATION IS THE BEST TREATMENT:

Omicron Infection Is Less Severe for Vaccinated or Previously Infected

A new study evaluating the health records of 5.4 million people in Scotland found the risk of hospitalization with COVID-19 was two-thirds lower with infection with the Omicron variant, compared to infection with the Delta variant.  Of note, Scotland has very high vaccination rates (84% of individuals 12 years and older have received 2 doses of vaccine and 57% have received a third dose).

A separate South African study found people infected with the Omicron variant were 70-80% less likely to need hospitalization, compared to people infected with earlier variants including the Delta variant.  This study also showed that patients who were hospitalized with the Omicron variant were less likely to need intensive care, compared to patients who were hospitalized with other variants.  Of note, some of this risk reduction is likely due to high population immunity from previous infection.

While recent UK data suggest that the risk of hospitalization with the Omicron variant is 60% lower than with previous variants, it is only ~10% lower than the Delta variant for individuals who are unvaccinated or have not been previously infected, highlighting the protection that persists against the Omicron variant from vaccination or previous infection.

 

Long-acting Monoclonal Antibody for Prevention of COVID-19 Infection (for Immunocompromised Individuals): 

Earlier this month, the FDA provided EUA approval for a long-acting monoclonal antibody (Evusheld, AstraZeneca) for the prevention of COVID-19 infection.

Indication: Prevention of COVID-19 infection in individuals 12 years and older, who: 1) have moderate to severely compromised immune systems due to a medical condition or due to taking immunosuppressive medications and may not mount an adequate immune response to COVID-19 vaccination; or 2) history of severe adverse reactions to a COVID-19 vaccine and/or component(s) of those vaccines, therefore vaccination with an available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended.

Dose: One dose of Evusheld, administered as 2 separate consecutive intramuscular injections, may be effective for pre-exposure prevention for 6 months.

Benefit: The primary data supporting the EUA are from PROVENT, a randomized, double-blind, placebo-controlled clinical trial in adults older than 59 years or with a prespecified chronic medical condition or at increased risk of COVID-19 infection for other reasons who had not received a COVID-19 vaccine and did not have a history of prior COVID-19 infection.  Evusheld reduced the risk of developing COVID-19 infection by 77%.  While the company’s lab studies show Evusheld retains activity against the Omicron variant, the trial was conducted before the Omicron variant.

Potential concerns: Serious cardiac adverse events were infrequent but more trial participants had serious cardiac adverse events (such as heart attacks) after receiving Evusheld compared to placebo.  These participants all had risk factors for cardiac disease or a history of cardiovascular disease before participating in the clinical trial.

Availability: The US government, which is the sole distributor of the drug, has contracted for only enough doses to treat 700,000 people.


ARGUMENT FOR BOOSTERS: SIGNIFICANT BENEFITS AGAINST OMICRON

An Israeli study showed that individuals who received their second vaccine dose 5-6 months ago have almost no neutralization ability against the Omicron variant.  However, the booster dose provides significant protection by increasing neutralization against the Omicron variant by about 100-fold.  In real world data this translates to ~70% protection against symptomatic disease.  Recent data suggest that this additional protection may start to decline 2-3 months after the booster dose.

 

THE NEXT MONTHH:
Retired NIH Director Dr. Francis Collins recently predicted a peak of up to 1 million new US cases per day.  Early analysis from South Africa suggests the peak in daily case numbers may come in about 4 weeks.

While geographic areas with higher vaccination rates will experience a lower ratio of hospitalizations to cases, areas of the country with lower vaccination rates may be overwhelmed particularly as high proportions of health care workers are infected and unable to provide care.  Because recent data suggest that additional protection provided by boosters may start to decline 2-3 months after the booster dose, additional booster doses may be recommended.

QUARANTINE AFTER EXPOSURE: Fully vaccinated, asymptomatic individuals do not need to quarantine after an exposure but should be tested 5-7 days after exposure even if asymptomatic.  They should wear a mask indoors until receiving a negative test on day 5 or for 14 days after exposure.  Asymptomatic but infected individuals can definitely infect other individuals.  Vaccinated individuals are vulnerable to breakthrough infections with the Omicron variant and therefore should be particularly careful around individuals who are high-risk for severe COVID-19 infection.

Definition of an exposure: The CDC definition of an exposure is being within 6 feet of someone who has COVID-19 for a cumulative total of 15 minutes or more over a 24-hour period.  Because of Omicron’s increased transmissibility, significant exposure likely occurs beyond 6 feet and over a shorter duration of time.

ISOLATION AFTER POSITIVE COVID-19 TEST: For asymptomatic COVID-19 infections, isolation should continue for 10 days after a positive test.  For symptomatic COVID-19 infections, isolation should continue for 10 days after symptoms started.


INFLUENZA: Early studies suggest the flu vaccine may have reduced efficacy this year due to a mismatch between this year’s flu vaccine and the H3N2 strain of influenza that is currently circulating.


RECOMMENDATIONS:

The Omicron variant has proved to be impressively transmissible independent of boosters.  Unless one eliminates all social interaction, it will not be possible to decrease the risk of infection to zero.  If you are recently vaccinated or boosted, you should have very good protection against significant illness.  To minimize infection risk, we would emphasize distancing, N95 masking, and ventilation (all still commonly underutilized).  A balanced plan will consider our own personal health status and the health status of our whole community.

We are thinking about each of you as we ring in the new year, and wish you and your families a healthy and happy 2022.

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