Coronavirus COVID-19 Update for December 27, 2021

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Clinical Reports

Children and COVID-19: State Data Report
A joint report from the American Academy of Pediatrics and the Children’s Hospital Association. Summary of publicly reported data from 49 states, NYC, DC, PR, and GU Version: 12/16/21. The numbers in this report represent cumulative counts since states began reporting. The data are based on how public agencies collect, categorize and post information. All data reported by state/local health departments are preliminary and subject to change and reporting may change over time. Notably, in the summer of 2021, some states have revised cases counts previously reported, begun reporting less frequently, or dropped metrics previously reported. For example, due to several changes on their dashboards and the data currently available, AL, NE, and TX data in this report are not current (cumulative data through 7/29/21, 6/24/21, and 8/26/21 respectively). Readers should consider these factors. States may have additional information on their web sites.
Duration of SARS-CoV-2 Natural Immunity and Protection against the Delta Variant: A Retrospective Cohort Study
Infection with SARS-CoV-2 has been shown to be highly protective against reinfection and symptomatic disease. However, effectiveness against the highly transmissible Delta variant and duration of natural immunity remain unknown. This retrospective cohort study included 325,157 patients tested for coronavirus disease 2019 (COVID-19) via polymerase chain reaction (PCR) from 09 March 2020 to 31 December 2020 (Delta variant analysis) and 152,656 patients tested from 09 March 2020 to 30 August 2020 (long-term effectiveness analysis) with subsequent testing through 09 September 2021. The primary outcome was reinfection, defined as a positive PCR test >90 days after initial positive test. Among 325,157 patients tested before 31 December 2020, 50,327 (15.5%) tested positive. After 01 July 2021 (Delta dominant period), 40 (0.08%) of the initially positive and 1,494 (0.5%) of the initially negative patients tested positive. Protection of prior infection against reinfection with Delta was 85.4% (95% CI, 80.0-89.3). For the long-term effectiveness analysis, among 152,656 patients tested before 30 August 2020, 11,186 (7.3%) tested positive. After at least 90 days, 81 (0.7%) of the initially positive patients and 7,167 (5.1%) of the initially negative patients tested positive. Overall protection of previous infection was 85.7% (95% CI, 82.2-88.5) and lasted up to 13 months. Patients over age 65 had slightly lower protection. SARS-CoV-2 infection is highly protective against reinfection with the Delta variant. Immunity from prior infection lasts for at least 13 months. Countries facing vaccine shortages should consider delaying vaccinations for previously infected patients to increase access.
Quarantine and Isolation
Quarantine if you have been in close contact (within 6 feet of someone for a cumulative total of 15 minutes or more over a 24-hour period) with someone who has COVID-19, unless you have been fully vaccinated. People who are fully vaccinated do NOT need to quarantine after contact with someone who had COVID-19 unless they have symptoms. However, fully vaccinated people should get tested 5-7 days after their exposure, even if they don’t have symptoms and wear a mask indoors in public for 14 days following exposure or until their test result is negative. Isolation is used to separate people infected with COVID-19 from those who are not infected. People who are in isolation should stay home until it’s safe for them to be around others. At home, anyone sick or infected should separate from others, stay in a specific “sick room” or area, and use a separate bathroom (if available). To calculate your 10 full day isolation period, day 0 is your first day of symptoms. Day 1 is the first full day after your symptoms developed. If you test positive for COVID-19 and never develop symptoms, day 0 is the day of your positive viral test (based on the date you were tested) and day 1 is the first full day after your positive test. If you develop symptoms after testing positive, your 10-day isolation period must start over. Day 0 is your first day of symptoms. Day 1 is the first full day after your symptoms developed.

Antiviral Therapeutics and Vaccines

Frequently Asked Questions on the Emergency Use Authorization for Paxlovid for Treatment of COVID-19
This EUA authorizes the emergency use of the unapproved product Paxlovid (nirmatrelvir co-packaged with ritonavir) for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. Paxlovid is not approved for any use, including for the treatment of COVID-19. Paxlovid is not authorized:

for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19.
for pre-exposure or post-exposure prophylaxis for prevention of COVID-19.
for use longer than five consecutive days.

PFIZER AND BIONTECH PROVIDE UPDATE ON ONGOING STUDIES OF COVID-19 VACCINE
BioNTech SE (Nasdaq: BNTX) today shared that following a routine review by the external independent Data Monitoring Committee (DMC), the companies will amend the clinical study evaluating the safety, tolerability, and immunogenicity of the Pfizer-BioNTech COVID-19 Vaccine in children 6 months to under 5 years of age. The study will now include evaluating a third dose of 3 µg at least two months after the second dose of the two-dose series to provide high levels of protection in this young age group. While the study is ongoing and remains blinded, a pre-specified immunogenicity analysis was conducted on a subset of the study population one month following the second dose. Compared to the 16- to 25-year-old population in which high efficacy was demonstrated, non-inferiority was met for the 6- to 24-month-old population but not for the 2- to under 5-year-old population in this analysis. No safety concerns were identified and the 3 µg dose demonstrated a favorable safety profile in children 6 months to under 5 years of age. The decision to evaluate a third dose of 3 µg for children 6 months to under 5 years of age reflects the companies’ commitment to carefully select the right dose to maximize the risk-benefit profile. If the three-dose study is successful, Pfizer and BioNTech expect to submit data to regulators to support an Emergency Use Authorization (EUA) for children 6 months to under 5 years of age in the first half of 2022.Pfizer and BioNTech also plan to evaluate a third dose of the 10 µg formulation in children 5 to under 12 years of age. Furthermore, the companies have initiated a low dose sub-study of a third dose of 10 µg or 30 µg in approximately 600 adolescents aged 12- to 17, to assess safety and immunogenicity. These updates were informed by the effectiveness data for three doses of the vaccine for people 16 years and older, and the early laboratory data observed with Delta and other variants of concern, including Omicron, which suggest that people vaccinated with three doses of a COVID- 19 vaccine may have a higher degree of protection. These changes have been endorsed by and agreed upon with the U.S. Food and Drug Administration.
CDC Endorses ACIP’s Updated COVID-19 Vaccine Recommendations
CDC is endorsing updated recommendations made by the Advisory Committee on Immunization Practices (ACIP) for the prevention of COVID-19, expressing a clinical preference for individuals to receive an mRNA COVID-19 vaccine over Johnson & Johnson’s COVID-19 vaccine. ACIP’s unanimous recommendation followed a robust discussion of the latest evidence on vaccine effectiveness, vaccine safety and rare adverse events, and consideration of the U.S. vaccine supply. The U.S. supply of mRNA vaccines is abundant – with nearly 100 million doses in the field for immediate use. This updated CDC recommendation follows similar recommendations from other countries, including Canada and the United Kingdom. Given the current state of the pandemic both here and around the world, the ACIP reaffirmed that receiving any vaccine is better than being unvaccinated. Individuals who are unable or unwilling to receive an mRNA vaccine will continue to have access to Johnson & Johnson’s COVID-19 vaccine.
Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection
Breakthrough infections after vaccination against SARS-CoV-2 are increasingly reported, possibly due to waning of vaccine-induced antibody levels. Moreover, emerging variants of concern with diminished susceptibility to vaccine-induced antibodies are responsible for most new cases. Studies have focused on determining the rate of vaccine breakthrough based on antibody levels after standard vaccination practices. Authors assessed antibody levels and variant cross-neutralization after breakthrough infection. Results of this study showed substantial boosting of humoral immunity after breakthrough infection, despite predominantly mild disease. Boosting was most notable for IgA, possibly due to the differences in route of exposure between vaccination and natural infection. In addition, breakthrough sera demonstrated improved variant cross-neutralization, and Delta breakthrough infections in particular exhibited improved potency against Delta vs WA1, suggesting that the protective immune response may be broadened through development of variant boosters with antigenic inserts matching the emerging SARS-CoV-2 variants.
Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients
We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. arly treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19.
Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021. A total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions. Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic.

Diagnostics

Evaluation of Test to Stay Strategy on Secondary and Tertiary Transmission of SARS-CoV-2 in K–12 Schools — Lake County, Illinois, August 9–October 29, 2021
COVID-19 transmission within K–12 schools can remain low with implementation of multiple, concurrent prevention strategies.During fall 2021, 90 Lake County, Illinois, schools implemented Test to Stay (TTS), permitting eligible close contacts with masked COVID-19 exposures to remain in school. Secondary transmission among TTS participants was 1.5%; no tertiary transmission was observed among school-based contacts; however, tertiary cases were identified among household contacts. Implementation of TTS preserved up to 8,152 in-person learning days. Although vaccination remains the leading recommendation to protect against COVID-19, TTS allows close contacts to remain in the classroom as an alternative to home quarantine.

Evaluation of a Test to Stay Strategy in Transitional Kindergarten Through Grade 12 Schools — Los Angeles County, California, August 16–October 31, 2021
Los Angeles County Department of Public Health permits Test to Stay (TTS) as a COVID-19 quarantine strategy that allows students with school exposures to remain in school if both infected and exposed persons wore masks. One in five LAC public schools adopted TTS. In TTS schools, student case rates did not increase, and tertiary transmission was not identified. A higher percentage of disadvantaged schools did not implement TTS. TTS does not appear to increase transmission risk in public schools and might greatly reduce loss of in-person school days. Implementation requires resources that might be currently unavailable for some schools. Vaccination remains the leading recommendation to protect against COVID-19; TTS allows students with a school exposure to remain in the classroom as an alternative to home quarantine.