Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

Trends in Disease Severity and Health Care Utilization During the Early Omicron Variant Period Compared with Previous SARS-CoV-2 High Transmission Periods
The SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in the United States by late December 2021, leading to a surge in COVID-19 cases and associated ED visits and hospitalizations. The highest daily 7-day moving average to date of cases (798,976 daily cases during January 9–15, 2022), emergency department (ED) visits (48,238), and admissions (21,586) were reported during the Omicron period, however, the highest daily 7-day moving average of deaths (1,854) was lower than during previous periods. During the Omicron period, a maximum of 20.6% of staffed inpatient beds were in use for COVID-19 patients, 3.4 and 7.2 percentage points higher than during the winter 2020–21 and Delta periods, respectively. However, intensive care unit (ICU) bed use did not increase to the same degree: 30.4% of staffed ICU beds were in use for COVID-19 patients during the Omicron period, 0.5 percentage points lower than during the winter 2020–21 period and 1.2 percentage points higher than during the Delta period. The ratio of peak ED visits to cases (event-to-case ratios) (87 per 1,000 cases), hospital admissions (27 per 1,000 cases), and deaths (nine per 1,000 cases [lagged by 3 weeks]) during the Omicron period were lower than those observed during the winter 2020–21 (92, 68, and 16 respectively) and Delta (167, 78, and 13, respectively) periods. Further, among hospitalized COVID-19 patients from 199 U.S. hospitals, the mean length of stay and percentages who were admitted to an ICU, received invasive mechanical ventilation (IMV), and died while in the hospital were lower during the Omicron period than during previous periods. COVID-19 disease severity appears to be lower during the Omicron period than during previous periods of high transmission, likely related to higher vaccination coverage,† which reduces disease severity (4), lower virulence of the Omicron variant (3,5,6), and infection-acquired immunity (3,7). Although disease severity appears lower with the Omicron variant, the high volume of ED visits and hospitalizations can strain local health care systems in the United States, and the average daily number of deaths remains substantial.§ This underscores the importance of national emergency preparedness, specifically, hospital surge capacity and the ability to adequately staff local health care systems. In addition, being up to date on vaccination and following other recommended prevention strategies are critical to preventing infections, severe illness, or death from COVID-19.

Children and COVID19: State Level Data Report
State-level reports are the best publicly available and timely data on child COVID-19 cases in the United States. The American Academy of Pediatrics and the Children’s Hospital Association are collaborating to collect and share all publicly available data from states on child COVID-19 cases. The definition of “child” case is based on varying age ranges reported across states (see report Appendix for details and links to all data sources). COVID-19 cases among US children have reached the highest case count ever reported since the start of the pandemic. For the week ending December 30th, over 325,000 child COVID-19 cases were reported. This number is a 64% increase over the 199,000 added cases reported the week ending December 23rd and an almost doubling of case counts from the two weeks prior. Nearly 7.9 million children have tested positive for COVID-19 since the onset of the pandemic, representing over 1 in 10 US children. For the 21st week in a row child COVID-19 cases are above 100,000. Since the first week of September, there have been over 2.8 million additional child cases.

Safety, tolerability and viral kinetics during SARS-CoV-2 viral challenge
To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per protocol analysis due to seroconversion between screening and inoculation. Eighteen (53%) became infected, with viral load (VL) rising steeply and peaking at 5 days post-inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log copies/ml (median, 95% CI [8.41,9.53). Viable virus was recoverable from the nose up to 10 days post-inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected individuals, beginning 2-4 days post-inoculation. Anosmia/dysosmia developed more gradually in 12 (67%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs even in asymptomatic infection, followed by the development of serum spike-specific and neutralizing antibodies. However, lateral flow results were strongly associated with viable virus and modelling showed that twice-weekly rapid tests could diagnose infection before 70-80% of viable virus had been generated. Thus, in this first SARS-CoV-2 human challenge study, no serious safety signals were detected and the detailed characteristics of early infection and their public health implications were shown.

Veru Announces Presentation of Phase 2 Data of Sabizabulin for the Treatment of Hospitalized Severe COVID-19 Patients at High Risk for Acute Respiratory Distress Syndrome
In this study, the authors used the US Department of Veterans Affairs National Healthcare databases to build a cohort of 153,760 US veterans who survived the first 30 days of COVID-19 and two control groups: a contemporary cohort consisting of 5,637,647 users of the US Veterans Health Administration (VHA) system with no evidence of SARS-CoV-2 infection and a historical cohort (pre-dating the COVID-19 pandemic) consisting of 5,859,411 non-COVID-19-infected VHA users during 2017. These cohorts were followed longitudinally to estimate the risks and 12-month burdens of pre-specified incident cardiovascular outcomes in the overall cohort and according to care setting of the acute infection (non-hospitalized, hospitalized and admitted to intensive care). In summary, using a national cohort of people with COVID-19, study authors show that risk and 12-month burden of incident cardiovascular disease are substantial and span several cardiovascular disease categories (ischemic and non-ischemic heart disease, dysrhythmias and others). The risks and burdens of cardiovascular disease were evident even among those whose acute COVID-19 did not necessitate hospitalization. Care pathways of people who survived the acute episode of COVID-19 should include attention to cardiovascular health and disease.

Antiviral Therapeutics and Vaccines

FDA to discuss request authorization for the Pfizer COVID-19 Vaccine for use in children 6 months-4 years
On February 1, 2022, the FDA announced it will convene its Vaccines and Related Biological Products Advisory Committee (VRBPAC) on February 15, 2022, to discuss the request for emergency use authorization (EUA) of two 3-µg doses of the Pfizer-BioNTech COVID-19 Vaccine for use in children 6 months through 4 years of age. The announcement followed the initiation of a rolling submission by Pfizer and BioNTech on the same day, seeking to amend the current EUA to include children in this age group. The submission is based on the totality of data on the safety, tolerability, immunogenicity, and available efficacy of two doses of the Pfizer-BioNTech COVID-19 Vaccine in clinical trials that include approximately 8300 enrolled children between the ages of 6 months and 12 years. The companies expect to complete the submission of data to the FDA in the coming days.

mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron
Study authors had the following findings that highlight two important factors that will impact management of this pandemic. The first is the design of the vaccine and whether it should be changed based on the currently circulating variant. At present, boosting with mRNA-1273 provides robust increases in neutralizing antibodies and appears to be sufficient to prevent severe disease after exposure from all known variants. Variant-matched vaccines may be preferable in the future if new variants were to emerge that were even further antigenically distant such that cross-reactive epitopes are rendered ineffective or if there were differences in the durability of neutralizing antibody titers elicited by different boosts. Second, as neutralizing antibody titers wane with time, their ability to serve as a surrogate for vaccine efficacy or to predict clinical outcomes against severe disease after infection with VOC may become diminished. Thus, the determination of when to administer a boost may depend on the recall capacity of the underlying memory B cell population. These considerations will become clear as human clinical data are made available.

Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2
The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, study authors evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. The results show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. Study authors further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Study findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC.

Perceived COVID-19 vaccine effectiveness, acceptance, and drivers of vaccination decision-making among the general adult population: A global survey of 20 countries
The purpose of this study was to determine the characteristics that influence perceptions of COVID-19 vaccine efficacy, acceptability, hesitancy and decision making to take vaccine among general adult populations in a variety of socioeconomic and cultural contexts. Study authors conducted an online cross-sectional study in 20 countries across four continents from February to May 2021. A total of 10,477 participants were included in the analyses with a mean age of 36±14.3 years. The findings revealed the prevalence of perceptions towards COVID-19 vaccine’s effectiveness (78.8%), acceptance (81.8%), hesitancy (47.2%), and drivers of vaccination decision-making (convenience [73.3%], health providers’ advice [81.8%], and costs [57.0%]). Most participants believed that vaccination would effectively control and prevent COVID-19, and they would take vaccinations upon availability. Determinant factors found in this study are critical and should be considered as essential elements in developing COVID-19 vaccination campaigns to boost vaccination uptake in the populations.

Epidemiology

Science Brief: Transmission of SARS-CoV-2 in K-12 Schools and Early Care and Education Programs – Updated
ARS-CoV-2 transmission in the community is correlated with the amount of infections in schools. When community rates of COVID-19 are high, there is an increased likelihood that SARS-CoV-2 will be introduced to, and potentially transmitted within, a school or ECE setting. Evidence to date suggests that when prevention strategies are layered and implemented with fidelity, transmission within schools and ECE programs can be limited. Information on transmission patterns following the uptake of COVID-19 vaccines and the experiences of schools as they use different mixes of effective prevention strategies to address COVID-19 will help refine guidance. Reducing SARS-CoV-2 transmission in schools and ECE programs is a shared responsibility. Schools and ECE programs can limit transmission by layering the following effective prevention strategies. Implementing the following strategies is particularly important in areas with moderate, substantial, or high transmission rates and low vaccination coverage, and to protect people who are not fully
- Promoting COVID-19 vaccination for those eligible
- Consistent and correct use of masks by people who are not fully vaccinated
- Physical distancing among people who are not fully vaccinated
- Screening testing in K-12 schools
- Improving ventilation
- Handwashing and respiratory etiquette
- Staying home when sick and getting tested
- Testing and contact tracing in combination with isolation and quarantine, including Test to Stay as appropriate
- Routine cleaning with disinfection under certain conditions.
Effectiveness of Face Mask or Respirator Use in Indoor Public Settings for Prevention of SARS-CoV-2 Infection — California, February–December 2021
The use of face masks or respirators (N95/KN95) is recommended to reduce transmission of SARS-CoV-2, the virus that causes COVID-19. Well-fitting face masks and respirators effectively filter virus-sized particles in laboratory conditions but few studies have assessed their real-world effectiveness in preventing acquisition of SARS-CoV-2 infection. In this study, authors report results of a test-negative design case-control study that enrolled randomly selected California residents who had received a test result for SARS-CoV-2 during February 18–December 1, 2021. Face mask or respirator use was assessed among 652 case-participants (residents who had received positive test results for SARS-CoV-2) and 1,176 matched control-participants (residents who had received negative test results for SARS-CoV-2) who self-reported being in indoor public settings during the 2 weeks preceding testing and who reported no known contact with anyone with confirmed or suspected SARS-CoV-2 infection during this time. Study authors found that always using a face mask or respirator in indoor public settings was associated with lower adjusted odds of a positive test result compared with never wearing a face mask or respirator in these settings (adjusted odds ratio [aOR] = 0.44; 95% CI = 0.24–0.82).
- Wearing an N95/KN95 respirator (aOR = 0.17; 95% CI = 0.05–0.64) statistically significant
- wearing a surgical mask (aOR = 0.34; 95% CI = 0.13–0.90) statistically significant
- Wearing a cloth mask (aOR = 0.44; 95% CI = 0.17–1.17) was not statistically significant.