Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

COVID-19–Associated Hospitalizations Among Adults During SARS-CoV-2 Delta and Omicron Variant Predominance, by Race/Ethnicity and Vaccination Status — COVID-NET, 14 States, July 2021–January 2022
During the Omicron-predominant period, weekly COVID-19–associated hospitalization rates (hospitalizations per 100,000 adults) peaked at 38.4, compared with 15.5 during Delta predominance. Hospitalization rates during peak Omicron circulation (January 2022) among unvaccinated adults remained 12 times the rates among vaccinated adults who received booster or additional doses and four times the rates among adults who received a primary series, but no booster or additional dose. During the Omicron-predominant period, peak hospitalization rates among non-Hispanic Black (Black) adults were nearly four times the rate of non-Hispanic White (White) adults and was the highest rate observed among any racial and ethnic group during the pandemic.
Intrinsic Severity of SARS-CoV-2 Omicron BA.2 in Uninfected, Unvaccinated Children: A Population-Based, Case-Control Study on Hospital Complications
This was a population-based study retrieved data from the HK territory-wide CDARS database of hospitalizations in all public hospitals and compared severe outcomes of the Omicron BA.2-dominant fifth wave (5 to 28 February 2022, n=1147), prior SARS-CoV-2 variants (1 January 2020 to 1 November 2021, n=737), and influenza and parainfluenza (1 January 2015 to 31 December 2019, n=32212 and n=16423, respectively) in children 0-11 years old. Outcomes included fatalities, paediatric intensive care unit (PICU) admissions and neurological and respiratory complications. They reported a higher in-hospital case fatality rate than other SARS-CoV-2 variants. PICU admission was higher for Omicron than other SARS-CoV-2 variants (OR=18.50, 95% CI 2.42-140.70, p=0.005). The proportion with neurological complications was 14.91% (171 out of 1,147) for Omicron. The intrinsic severity of Omicron BA.2 is not mild as evident by the fatality and severe complications of the uninfected and unvaccinated children.
SARS-CoV-2 Placentitis and Intraparenchymal Thrombohematomas Among COVID-19 Infections in Pregnancy
This was a study that examined placental pathology and perinatal outcomes in a series of SARS-CoV-2 placentitis cases before and during the Delta wave. At MGH, all SARS-CoV-2 exposed placentas were fully pathologically examined. Forty-seven cases of SARS-CoV-2 placentitis were identified by histopathologic criteria. In all cases, the placentitis was diffuse (>50% involvement). (62%), had multiple intraparenchymal thrombohematomas. Of these, 21 (72%) were stillbirths. Seventeen of the 18 placentas without thrombohematomas were livebirths (94%). Viral variants was identified in 8 cases: 3 Delta (2 stillbirths with thrombohematomas, 1 livebirth without thrombohematomas), 2 Alpha, and 3 other strains, all livebirths without thrombohematomas. In 2 cases the ultrasound documenting fetal demise demonstrated multiple large maternal lakes with echogenic rims. All patients but 1 were unvaccinated. The vaccinated patient had a PCR-confirmed infection 7 weeks prior to delivery and was subsequently vaccinated once. Her term livebirth was without thrombohematomas.
De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report
In this report, authors present a case of an immunocompromised patient with an acquired B-cell deficiency who developed an indolent, protracted course of SARS-CoV-2 infection (COVID-19). They were treated with Remdesivir therapy which alleviated symptoms and produced a transient virologic response, but the course was complicated by recrudescence of high-grade viral shedding. Whole genome sequencing identified a mutation, E802D, in the nsp12 RNA-dependent RNA polymerase, which was not present in pre-treatment specimens. In vitro experiments demonstrated that the mutation conferred a ~6-fold increase in remdesivir IC₅₀but resulted in a fitness cost in the absence of remdesivir. Sustained clinical and virologic response was achieved after treatment with casirivimab-imdevimab

Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomized controlled trial (COVERAGE)
The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59–68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3–5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%–18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4–21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms.
Effectiveness and safety of pulse oximetry in remote patient monitoring of patients with COVID-19: a systematic review
This review suggests that the use of pulse oximetry as a monitoring tool for patients at home with COVID-19 helped to triage patients on the basis of their SpO₂concentrations, detect the risk of deterioration, and promote patient safety. It was suggested that this was potentially cost-effective and did suggest consideration of assessment of post-exertional pulse ox readings with concern that some patients can have a rapid decrease.
Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19A Randomized Clinical Trial
This was a study that examined if antiplatelet therapy administered to critically ill patients with COVID-19 improved organ support–free days (a composite end point of in-hospital mortality and duration of intensive care unit–based respiratory or cardiovascular support) up to day 21. In this bayesian randomized clinical trial that included 1557 patients, antiplatelet therapy with either aspirin or a P2Y12 inhibitor, compared with no antiplatelet therapy, resulted in a 95.7% posterior probability of futility with regard to the odds of improvement in organ support–free days within 21 days. Among critically ill patients with COVID-19, there was a low likelihood that treatment with an antiplatelet agent provided improvement in organ support–free days within 21 days.

Antiviral Therapeutics and Vaccines

Moderna announces its COVID-19 vaccine Phase 2/3 Study in Children 6 months to under 6 years has successfully met its primary endpoint
Two 25 μg doses of mRNA-1273 in participants 6 months to under 6 years met primary endpoint with robust neutralizing antibody titers similar to adults mRNA-1273 was generally well tolerated in this age group Although not a primary endpoint, statistically significant vaccine efficacy was observed during the Omicron wave that was consistent with the lower two-dose effectiveness against Omicron seen in adults. Moderna is moving forward with global regulatory submissions for mRNA-1273 for primary vaccination of children 6 months to under 6 years of age. Additionally, Moderna has initiated a submission to the FDA for emergency use authorization of mRNA-1273 in children 6 to under 12 years of age; mRNA-1273 is approved for use in this age group in Europe, Canada and Australia.
Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains
New preclinical authentic ‘live’ virus data from Washington University School of Medicine demonstrated that Evusheld(tixagevimab co-packaged with cilgavimab) retains potent neutralising activity against the emerging and highly transmissible Omicron SARS-CoV-2 BA.2 subvariant. The data also showed that Evusheld retains activity against Omicron BA.1 and BA.1.1. In addition, in vivo (live organism) data generated using mice infected with Omicron BA.1, BA.1.1 and BA.2 demonstrated that Evusheld significantly reduced the viral burden and limited inflammation in the lungs for all three subvariants. SARS-CoV-2 viral load is associated with increased disease severity and mortality as well as post-COVID conditions (long COVID).The study used a transgenic mouse model to evaluate Evusheld in pre-exposure prophylaxis (prevention) of COVID-19, similar to how Evusheld is used in the clinic. These are the first in vivo data evaluating Evusheld’s efficacy against the Omicron variants versus previous in vitro neutralising activity assays in cultured cells.

Diagnostics

Predictive value of isolated symptoms for diagnosis of SARS-CoV-2 infection in children tested during peak circulation of the delta variant
Study authors evaluated children presenting for SARS-CoV-2 testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with one versus ≥2 symptoms, and to examine the predictive capability of isolated symptoms. Participants ≤ 18 years presenting for clinical SARS-CoV-2 molecular testing in six sites in urban/suburban/rural Georgia (July-October, 2021; delta variant predominant) were queried about individual symptoms. Participants were classified into three groups: asymptomatic, one symptom only, or ≥2 symptoms. SARS-CoV-2 test results and clinical characteristics of the three groups were compared. Sensitivity, specificity, and positive/negative predictive values (PPV/NPV) for isolated symptoms were calculated by fitting a saturated Poisson model. Of 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting one symptom (n=82; OR=6.00, 95% CI: 2.70-13.33) and children reporting ≥2 symptoms (n=365; OR=5.25: 2.66-10.38) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n=155), but they were not significantly different from each other (OR=0.88: 0.52-1.49). Sensitivity/PPV were highest for isolated fever (33%/57%), cough (25%/32%), and sore throat (21%/45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity/PPV of isolated congestion/rhinorrhea were 8%/9%. With high delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered highest predictive value.

Epidemiology

Comparison of Trials Using Ivermectin for COVID-19 Between Regions With High and Low Prevalence of StrongyloidiasisA Meta-analysis
The study evaluated whether prevalence of strongyloidiasis interacts with the relative risk (RR) of mortality in ivermectin trials for the treatment of COVID-19. In this meta-analysis of 12 randomized clinical trials involving 3901 patients, favorable mortality results were limited to trials in high-prevalence regions, with no evidence that ivermectin had a mortality benefit in low-prevalence regions. Meta-regression found an association between the regional prevalence of strongyloidiasis and risk of mortality, with a decrease in RR of 39% for each 5% increase in strongyloidiasis prevalence. Evidence supports that strongyloidiasis prevalence interacts with the RR of mortality in ivermectin trial results; no evidence was found to suggest ivermectin has any role in preventing mortality in patients with COVID-19 in regions where strongyloidiasis is not endemic.
Sustained high prevalence of COVID-19 deaths from a systematic post-mortem study in Lusaka, Zambia: one year later
From 1,118 enrolled decedents, COVID-19 was detected among 32.0% (358/1,116). Researchers observed three waves of transmission that peaked in July 2020, January 2021, and ∼June 2021 (end of surveillance). These were dominated by the AE.1 lineage and the Beta and Delta variants, respectively. During peak transmission, COVID-19 was detected in ∼90% of all deaths. Roughly four COVID-19 deaths occurred in the community for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths and overall, only ∼10% of COVID-19+ deaths were identified in life. COVID-19 had a devastating impact in Lusaka. COVID-19+ deaths occurred in all age groups and was the leading cause of death during peak transmission periods. Testing was rarely done for the vast majority of COVID-19 deaths that occurred in the community, yielding a substantial undercount.