Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

Severe Respiratory Illnesses Associated with Rhinoviruses and/or Enteroviruses Including EV-D68 – Multistate, 2022
Healthcare providers and hospitals in several regions of the United States notified the Centers for Disease Control and Prevention (CDC) during August 2022 about increases in pediatric hospitalizations in patients with severe respiratory illness who also tested positive for rhinovirus (RV) and/or enterovirus (EV). RVs and EVs can have clinically similar presentations and are indistinguishable from one another on multiplex assays often used in clinical settings. Upon further typing, some specimens have been positive for enterovirus D68 (EV-D68). Concurrently, pediatric acute respiratory illness sentinel surveillance sites are reporting a higher proportion of EV-D68 positivity in children who are RV/EV positive compared to previous years. Although it primarily causes acute respiratory illness, EV-D68 has been associated with acute flaccid myelitis (AFM), a rare but serious neurologic complication involving limb weakness.
Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae
The diagnosis of post-acute sequelae of COVID-19 (PASC) poses an ongoing medical challenge. To identify biomarkers associated with PASC, researchers analyzed plasma samples collected from PASC and COVID-19 patients to quantify viral antigens and inflammatory markers. Researchers detect SARS-CoV-2 spike predominantly in PASC patients up to 12 months post-diagnosis.
Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: A systematic review
Although COVID-19 vaccination decreases the risk of severe illness, it is unclear whether vaccine administration may impact the prevalence of long-COVID. The aim of this systematic review is to investigate the association between COVID-19 vaccination and long-COVID symptomatology. From 2584 studies identified, 11 peer-reviewed studies and six preprints were included. The methodological quality of 82% (n=14/17) studies was high. Six studies (n=17,256,654 individuals) investigated the impact of vaccines before acute SARS-CoV-2 infection (vaccine-infection-long-COVID design). Overall, vaccination was associated with reduced risks or odds of long-COVID, with preliminary evidence suggesting that two doses are more effective than one dose. Eleven studies (n=36,736 COVID-19 survivors) investigated changes in long-COVID symptoms after vaccination (infection-long-COVID-vaccine design). Seven articles showed an improvement in long-COVID symptoms at least one dose post-vaccination, while four studies reported no change or worsening in long-COVID symptoms after vaccination. Low level of evidence (grade III, case-controls, cohort studies) suggests that vaccination before SARS-CoV-2 infection could reduce the risk of subsequent long-COVID. The impact of vaccination in people with existing long-COVID symptoms is still controversial, with some data showing changes in symptoms and others did not. These assumptions are limited to those vaccines used in the studies.

Antiviral Therapeutics and Vaccines

Effects of Vaccination and Previous Infection on Omicron Infections in Children
Both the BNT162b2 vaccine and previous infection were found to confer considerable immunity against omicron infection and protection against hospitalization and death. The rapid decline in protection against omicron infection that was conferred by vaccination and previous infection provides support for booster vaccination.
COVID-19-Associated Hospitalizations Among Vaccinated and Unvaccinated Adults 18 Years or Older in 13 US States, January 2021 to April 2022
In this cross-sectional study of US adults hospitalized with COVID-19 during January 2022 to April 2022 (during Omicron variant predominance), COVID-19-associated hospitalization rates were 10.5 times higher in unvaccinated persons and 2.5 times higher in vaccinated persons with no booster dose, respectively, compared with those who had received a booster dose. Compared with unvaccinated hospitalized persons, vaccinated hospitalized persons were more likely to be older and have more underlying medical conditions. The study results suggest that COVID-19 vaccines are strongly associated with prevention of serious COVID-19 illness.
Effectiveness of COVID-19 vaccines over time prior to Omicron emergence in Ontario, Canada
Researchers used the test-negative study design to estimate vaccine effectiveness (VE) against any SARS-CoV-2 infection, symptomatic infection, and severe outcomes (COVID-19-related hospitalizations or death) by time since second dose of any combination of BNT162b2, mRNA-1273, and ChAdOx1 between 11 January and 21 November 2021 for subgroups based on patient and vaccine characteristics. They included 261,360 test-positive cases (of any SARS-CoV-2 lineage) and 2,783,699 individuals as test-negative controls. VE of two mRNA vaccine doses decreased from 90% (95%CI, 90-90%) 7-59 days after the second dose to 75% (95%CI, 72-78%) after ≥240 days against infection, from 94% (95%CI, 84-95%) to 87% (95%CI, 85-89%) against symptomatic infection, and remained stable (98% [95%CI, 97-98%] to 98% [95%CI, 96-99%])against severe outcomes. Similar trends were seen with heterologous ChAdOx1 and mRNA vaccine schedules. VE estimates for dosing intervals <35 days were lower than for longer intervals (e.g., VE of two mRNA vaccines against symptomatic infection at 120-179 days was 86% [95%CI, 85-88%] for dosing intervals <35 days, 92% [95%CI, 91-93%] for 35-55 days, and 91% [95%CI, 90-92%] for ≥56 days), but when stratified by age group and subperiod, there were no differences between dosing intervals. Prior to Omicron emergence, VE of any two-dose primary series, including heterologous schedules and varying dosing intervals, decreased over time against any infection and symptomatic infection but remained high against severe outcomes.
Nasal IgA wanes 9 months after hospitalization with COVID-19 and is not induced by subsequent vaccination
Plasma and nasosorption samples were prospectively collected from 446 adults hospitalized for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralization data. Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months. Nasal and plasma anti-S IgG remained elevated for at least 12 months with high plasma neutralizing titres against all variants. Of 180 with complete data, 160 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal. Samples 12 months after admission showed no association between nasal IgA and plasma IgG responses, indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defense against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.
Resistance of SARS-CoV-2 Omicron Subvariant BA.4.6 to Antibody Neutralization
SARS-CoV-2 Omicron subvariants BA.4.6, BA.4.7, and BA.5.9 have recently emerged, and BA.4.6 appears to be expanding even in the presence of BA.5 that is globally dominant. Compared to BA.5, these new subvariants harbor a mutation at R346 residue in the spike glycoprotein, raising concerns for further antibody evasion. Researchers compared the viral receptor binding affinity of the new Omicron subvariants with BA.5 by surface plasmon resonance. Researchers also performed VSV-based pseudovirus neutralization assays to evaluate their antigenic properties using sera from individuals who received three doses of a COVID-19 mRNA vaccine (boosted) and patients with BA.1 or BA.2 breakthrough infection, as well as using a panel of 23 monoclonal antibodies (mAbs). Compared to the BA.5 subvariant, BA.4.6, BA.4.7, and BA.5.9 showed similar binding affinities to hACE2 and exhibited similar resistance profiles to boosted and BA.1 breakthrough sera, but BA.4.6 was slightly but significantly more resistant than BA.5 to BA.2 breakthrough sera. Moreover, BA.4.6, BA.4.7, and BA.5.9 showed heightened resistance over to a class of mAbs due to R346T/S/I mutation. Notably, the authorized combination of tixagevimab and cilgavimab completely lost neutralizing activity against these three subvariants. The loss of activity of tixagevimab and cilgavimab against BA.4.6 leaves us with bebtelovimab as the only therapeutic mAb that has retained potent activity against all circulating forms of SARS-CoV-2. As the virus continues to evolve, our arsenal of authorized mAbs may soon be depleted, thereby jeopardizing the wellbeing of millions of immunocompromised persons who cannot robustly respond to COVID-19 vaccines.

Epidemiology

Detection of a Highly Divergent Type 3 Vaccine-Derived Poliovirus in a Child with a Severe Primary Immunodeficiency Disorder — Chongqing, China, 2022.
Surveillance of acute flaccid paralysis (AFP) and wastewater (environmental) are critical to polio eradication efforts. Children with primary immunodeficiency disorders (PIDs) can excrete vaccine-derived polioviruses (VDPVs), which can hamper eradication efforts. In March 2022, a type 3 VDPV was detected in stool specimens from an infant with PID who was hospitalized in Children’s Hospital of Chongqing Medical University, China. Surveillance for poliovirus in PID patients has increased detection of immunodeficiency-related (iVDPV) cases. Integrated systematic poliovirus surveillance, including AFP, environmental, and iVDPV surveillance, is critical to the detection and containment of all polioviruses and achievement of global polio eradication.