COVID-19 Update #116 for 1/4/2022

NIH recommend that nonhospitalized patients with mild to moderate COVID-19 who are at high risk of disease progression, be treated with (in order of preference): 

1. Nirmatrelvir 300 mg with ritonavir 100 mg orally twice daily for 5 days and initiated within 5 days of symptom onset in patients at least 12 years old, who weigh at least 40 Kg. The patient’s current drugs should be reviewed for drug interactions using data provided from NIH.
2. A single dose of Sotrovimab 500 mg administered within 10 days of symptom onset in patients at least 12 years old who weigh at least 40 Kg. Bamlanivimab plus etesevimab or casirivimab plus imdevimab can be used in areas with a low incidence of the Omicron variant.
3. Remdesivir 200 mg IV on Day 1, followed by remdesivir 100 mg IV daily on Days 2 and 3, initiated within seven days of symptom onset in in patients at least 12 years old, who weigh at least 40 Kg.
4. Molnupiravir 800 mg orally twice daily for 5 days, initiated within 5 days of symptom onset in patients at least 18 years and only when none of the above options can be used. Molnupiravir is not recommended in pregnant patients due to concerns for fetal toxicity, but the drug can be considered if none of the other recommended treatments are available. Molnupiravir has not been tested in vaccinated patients.

Current treatment recommendations from NIH are organized by severity of disease in an easy-to-use graphic.

• Hospitalized patients requiring supplemental oxygen, but not high flow oxygen or ventilation should receive remdesivir, dexamethasone plus remdesivir or dexamethasone alone. Baricitinib or tocilizumab should be added for patients with increasing oxygen requirement and systemic inflammation.
• Hospitalized patients requiring high-flow oxygen or non-invasive ventilation should receive dexamethasone or remdesivir plus dexamethasone. Baricitinib or tocilizumab should be added for patients with increasing oxygen requirement and systemic inflammation.
• Hospitalized patients requiring mechanical ventilation or ECMO should receive dexamethasone. Tocilizumab should be added in patients within 24-hours of being admitted to an ICU. If tocilizumab is not available, sarilumab can be used.

COVID-19 Vaccines
 
The FDA expanded the EUA for the Pfizer-BioNTech COVID-19 Vaccine to allow for a single booster dose for patients 12 through 15 years of age. Boosters for all patients 12 years and older can now be given as soon as five months after completion of primary series. Patients who are 5 through 11 years, who have undergone solid organ transplantation or are immunocompromised to an equivalent level are also now eligible for a booster dose. The interval between the primary series and a booster dose remains unchanged at six months for the Moderna COVID-19 vaccine and two months for the J&J vaccine.
 
South African researchers examined the results of 133,437 COVID-19 PCR tests and found the effectiveness of the Pfizer-BioNTech COVID-19 vaccine to be 70% after two doses in preventing hospitalizations for COVID-19 during a period when Omicron variant was the dominant strain compared to 93% when the Delta variant was the dominant strain.
 
In a second study, South African researchers compared the COVID-19 neutralization ability for the Beta, Delta, and Omicron variants with serum from 20 patents that had received two vaccinations with the Pfizer-BioNTech COVID-19 vaccine to a group of 20 patients that had received three injections. The researchers found that a third dose of the vaccine increased neutralization efficiency by a factor of 100 against the Omicron variant, but neutralization was lower by a factor of four against the omicron variant compared to the delta variant.
 
Rockefeller University researchers tested plasma from a variety of patients and found that recovered COVID-19 patients and patients that had received a third (booster) vaccination had enhanced protection against the Omicron variant.
 
CDC researchers reviewed data from VAERS and V-Safe voluntarily surveillance systems for children ages 5 to 11 years from 11/3/2021 to 12/19/2021. The researchers found the most common adverse reactions were injection site pain, fatigue and headache. ADR were mostly mild, and few cases of myocarditis were reported. It was estimated that 8.7 million doses were given during this time period to children 5 to 11 years.

A retrospective analysis of maternal and umbilical cord blood samples from 1,359 vaccinated pregnant women found that COVID-19 immunization before and throughout pregnancy resulted in detectable antibodies at delivery. The highest maternal and umbilical cord antibody levels were found in mothers who had received a complete vaccination course, had a prior history of COVID-19, or received a third-trimester booster dose.
 
COVID-19 Antibodies
 
The FDA issued an emergency use authorization (EUA) for convalescent plasma, on 8/23/2020, for the treatment of hospitalized patients with COVID-19. The original EUA was granted for any convalescent plasma product collected at FDA registered blood establishments. In February 2021, the FDA narrowed the EUA to high-antibody-titer convalescent plasma. The FDA no longer authorizes the use of plasma with low SARS-CoV-2 antibody titers. In December 2021, the FDA narrowed the EUA to treatment of COVID-19 in inpatients or outpatients who have an immunosuppressive disease or who are receiving immunosuppressive treatment. Fact sheets have been created for health care providers and patients. The Fact Sheet for HCPs has been revised to reflect the changes in the EUA. The documents include dosing instructions and potential adverse effects, such as allergic reactions, transfusion-associated circulatory overload, and transfusion associated lung injury, as well as the potential for transfusion-transmitted infections.
 
COVID-19 Anti-Inflammatories
 
Kiniksa Pharmaceuticals announced that in a 29-day, 582 patient, Phase II/III trial (NCT0444746), treatment with mavrilimumab did not decrease the percentage of patients that required mechanical ventilation or died compared to placebo in patients with severe COVID-19 pneumonia and systemic hyperinflammation.