Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID
Study authors analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. They captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average. Among 17 patients (mean age 43.3 years, 69% female, 94% Caucasian, and 19% Latino), 59% had ≥1 test interpretation confirming neuropathy. These included 63% (10/16) of skin biopsies, 17% (2/12) of electrodiagnostic tests and 50% (4/8) of autonomic function tests. One patient was diagnosed with critical illness axonal neuropathy and another with multifocal demyelinating neuropathy 3 weeks after mild COVID, and ≥10 received small-fiber neuropathy diagnoses. Longitudinal improvement averaged 52%, although none reported complete resolution. For treatment, 65% (11/17) received immunotherapies (corticosteroids and/or IV immunoglobulins). Among evaluated patients with long COVID, prolonged, often disabling, small-fiber neuropathy after mild SARS-CoV-2 was most common, beginning within 1 month of COVID-19 onset. Various evidence suggested infection-triggered immune dysregulation as a common mechanism. Various long COVID symptoms overlap with those of small-fiber polyneuropathy (SFN). Hence, we prospectively analyzed a cross-section of patients with long COVID evaluated for incident neuropathy. Among 17 patients with SARS-CoV-2 onset between February 21, 2020, and January 19, 2021, treated in 10 states/territories, 16 had mild COVID. The one with severe COVID (1 month stay in intensive care with ventilatory support) had electrodiagnostically confirmed sensorimotor polyneuropathy ascribed to critical care illness in addition to SFN. Medical histories and comprehensive blood screening (not shown) identified none with conventional neuropathy risks nor evidence of systemic dysimmunity. Imaging of the brain or spine, if performed, was unrevealing.
Development and validation of SCOPE score: a clinical score to predict progression of COVID-19 pneumonia to severe respiratory failure
In this study, authors looked at D-dimers, CRP, Ferritin, IL-6 and based on levels a certain number of points between 0-3 were assigned were assigned per biomarker. Having a score or 6 or more was predictive of progression to severe respiratory failure or death within 14 days.

Antiviral Therapeutics and Vaccines

Effectiveness of the BNT162b2 vaccine among children 5-11 and 12-17 years in New York after the Emergence of the Omicron Variant
The objective of this study was to estimate BNT162b2 vaccine effectiveness against COVID cases and hospitalizations among children 5-11 years and 12-17 years during December, 2021 and January, 2022. From December 13, 2021 to January 30, 2022, among 852,384 fully-vaccinated children 12-17 years and 365,502 children 5-11 years, vaccine effectiveness against cases declined from 66% (95% CI: 64%, 67%) to 51% (95% CI: 48%, 54%) for those 12-17 years and from 68% (95% CI: 63%, 72%) to 12% (95% CI: 6%, 16%) for those 5-11 years. During the January 24-30 week, vaccine effectiveness for children 11 years was 11% (95%CI -3%, 23%) and for those age 12 was 67% (95% CI: 62%, 71%). Vaccine effectiveness against hospitalization declined changed from 85% (95% CI: 63%, 95%) to 73% (95% CI: 53%, 87%) for children 12-17 years, and from 100% (95% CI: -189%, 100%) to 48% (95% CI: -12%, 75%) for those 5-11 years. Among children newly fully-vaccinated December 13, 2021 to January 2, 2022, vaccine effectiveness against cases within two weeks of full vaccination for children 12-17 years was 76% (95% CI: 71%, 81%) and by 28-34 days it was 56% (95% CI: 43%, 63%). For children 5-11, vaccine effectiveness against cases declined from 65% (95% CI: 62%, 68%) to 12% (95% CI: 8%, 16%) by 28-34 days. In the Omicron era, the effectiveness against cases of BNT162b2 declined rapidly for children, particularly those 5-11 years. However, vaccination of children 5-11 years was protective against severe disease and is recommended. These results highlight the potential need to study alternative vaccine dosing for children and the continued importance layered protections, including mask wearing, to prevent infection and transmission.
Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5–17 Years — VISION Network
Two doses of Pfizer-BioNTech vaccine provided protection against COVID-19 in persons aged 12–17 years during Delta predominance, but data during Omicron predominance and among children aged 5–11 years are lacking. Two doses protect against COVID-19–associated emergency department and urgent care encounters among children and adolescents. However, vaccine effectiveness (VE) was lower during Omicron predominance and decreased with time since vaccination; a booster dose restored VE to 81% among adolescents aged 16–17 years. Overall, 2-dose VE against COVID-19–associated hospitalization was 73%–94%. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations, including a booster dose for those aged 12–17 years.
The Impact of COVID-19 Monoclonal Antibody Therapy on Progression to Hospitalization in A Population with a High Percentage of the SARS-CoV-2 Alpha Variant
Several investigational monoclonal antibody (mAb) therapies have Emergency Use Authorizations (EUA) for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). In well-designed randomized clinical trials (RCTs), mAb therapies have demonstrated a reduction in the progression to hospitalization and death in high-risk individuals. This study assessed the real-world efficacy of treatment with mAb therapy during a time with a high percentage of the Alpha variant circulating. We performed a prospective study looking at the progression to hospitalization in a high-risk treatment population that qualified for mAb therapy under the current EUA and that consented to have their viral isolates undergo whole genome sequencing (WGS) to assess for the presence of genetic variants. A total of 125 patients consented to participate and ultimately 81 participants that both had obtainable sequence data and completed follow-up were included in the final analysis. Based on the risk profile of these participants we anticipated a >10% hospitalization without therapy and a 70-80% reduction based on prior RCTs. Five of the 81 patients (6%) were hospitalized despite monoclonal antibody therapy. The most common variant was Alpha (n=66, 81%), followed by other unknown variants (n=6, 7%), Iota (n=3, 4%), Epsilon (n=2, 2%), Gamma (n=2, 2%), and no variant detected (n=2, 2%). Monitoring of the local variants, proper procurement decisions regarding specific mAb treatment effective against circulating variants and following real world efficacy has the potential to positively impact the use of mAb therapies. Future studies are needed to assess the efficacy of different mAb treatment results in real world settings with various SARS-CoV-2 variants, various treatment delays and various populations.

Diagnostics

Comparison of Rapid Antigen Tests′ Performance between Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) Variants of SARS-CoV-2: Secondary Analysis from a Serial Home Self-Testing Study
There is a need to understand the performance of rapid antigen tests (Ag-RDT) for detection of the Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) SARS-CoV-2 variants. Participants without any symptoms were enrolled from October 18, 2021 to January 24, 2022 and performed Ag-RDT and RT-PCR tests every 48 hours for 15 days. This study represents a non-pre-specified analysis in which we sought to determine if sensitivity of Ag-RDT differed in participants with Delta compared to Omicron variant. Participants who were positive on RT-PCR on the first day of the testing period were excluded. Delta and Omicron variants were defined based on sequencing and date of first RT-PCR positive result (RT-PCR+). From the 7,349 participants enrolled in the parent study, 5,506 met the eligibility criteria for this analysis. A total of 153 participants were RT-PCR+ (61 Delta, 92 Omicron); among this group, 36 (23.5%) tested Ag-RDT+ on the same day and 36 (23.5%) tested Ag-RDT+ within 48 hours as first RT-PCR+. The differences in sensitivity between variants were not statistically significant (same-day: Delta 16.4% [95% CI: 8.2-28.1] vs Omicron 28.2% [95% CI: 19.4-38.6]; and 48-hours: Delta 45.9% [33.1-59.2] vs. Omicron 60.9% [50.1-70.9]). This trend continued among the 86 participants who had consecutive RT-PCR+ result (48-hour sensitivity: Delta 79.3% [60.3-92.1] vs. Omicron: 89.5% [78.5-96.0]). Conversely, the 38 participants who had an isolated RT-PCR+ remained consistently negative on Ag-RDT, regardless of the variant. The performance of Ag-RDT is not inferior among individuals infected with the SARS-CoV-2 Omicron variant as compared to the Delta variant. The improvement in sensitivity of Ag-RDT noted with serial testing is consistent between Delta and Omicron variant. Performance of Ag-RDT varies based on duration of RT-PCR+ results and more studies are needed to understand the clinical and public health significance of individuals who are RT-PCR+ for less than 48 hours.

Epidemiology

Global, regional, and national minimum estimates of children affected by COVID-19-associated orphanhood and caregiver death, by age and family circumstance up to Oct 31, 2021: an updated modelling study
In the 6 months following our estimates from March 1, 2020, to April 30, 2021, the proliferation of new coronavirus variants, updated mortality data, and disparities in vaccine access increased the amount of children experiencing COVID-19-associated orphanhood. To inform responses, researchers aimed to model the increases in numbers of children affected by COVID-19-associated orphanhood and caregiver death, as well as the cumulative orphanhood age-group distribution and circumstance (maternal or paternal orphanhood). The number of children affected by COVID-19-associated orphanhood and caregiver death is estimated to have increased by 90·0% (95% CrI 89·7–90·4) from April 30 to Oct 31, 2021, from 2 737 300 (95% CrI 1 976 100–2 987 000) to 5 200 300 (3 619 400–5 731 400). Between March 1, 2020, and Oct 31, 2021, 491, 300 (95% CrI 485 100–497 900) children aged 0–4 years, 736 800 (726 900–746 500) children aged 5–9 years, and 2 146 700 (2 120 900–2 174 200) children aged 10–17 years are estimated to have experienced COVID-19-associated orphanhood. Globally, 76·5% (95% CrI 76·3–76·7) of children were paternal orphans, whereas 23·5% (23·3–23·7) were maternal orphans. In each age group and region, the prevalence of paternal orphanhood exceeded that of maternal orphanhood. Researchers findings show that numbers of children affected by COVID-19-associated orphanhood and caregiver death almost doubled in 6 months compared with the amount after the first 14 months of the pandemic. Over the entire 20-month period, 5·0 million COVID-19 deaths meant that 5·2 million children lost a parent or caregiver. The data on children's ages and circumstances should support pandemic response planning for children globally.
Risk of Long Covid in people infected with SARS-CoV-2 after two doses of a COVID-19 vaccine: community-based, matched cohort study.
It is unclear whether receiving two COVID-19 vaccinations before SARS-CoV-2 infection reduces the risk of developing Long Covid symptoms. Study authors examined whether the likelihood of symptoms 12 weeks after infection differed by vaccination status. Study authors included COVID-19 Infection Survey participants aged 18-69 years who tested positive for SARS-CoV-2 between 26 April 2020 and 30 November 2021; we excluded participants who, before their first test-confirmed infection, had suspected COVID-19 or Long Covid symptoms, or were single-vaccinated. Participants who were double-vaccinated ≥14 days before infection were 1:1 propensity-score matched, based on socio-demographic characteristics and time from infection to follow-up for Long Covid, to those unvaccinated at time of infection. They estimated adjusted odds ratios (aOR) of Long Covid symptoms ≥12 weeks post-infection, comparing double-vaccinated with unvaccinated (reference group) participants. The study sample comprised 3,090 double-vaccinated participants (mean age 49 years, 54% female, 92% white, median follow-up from infection 96 days) and matched control participants. Long Covid symptoms were reported by 294 double-vaccinated participants (prevalence 9.5%) compared with 452 unvaccinated participants (14.6%), corresponding to an aOR for Long Covid symptoms of 0.59 (95% CI: 0.50 to 0.69). There was no evidence of heterogeneity by adenovirus vector versus messenger ribonucleic acid vaccines (p=0.25). COVID-19 vaccination is associated with reduced risk of Long Covid, emphasizing the need for public health initiatives to increase population-level vaccine uptake. Longer follow-up is needed, as is the assessment of further vaccine doses and the Omicron variant.