Coronavirus COVID-19 Update for July 6, 2021

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Clinical Reports

Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic — United States, March–April 2021
Increases in mental health conditions have been documented among the general population and health care workers during the COVID-19 pandemic; however, data on public health workers are limited. Among 26,174 surveyed state, tribal, local, and territorial public health workers, 53.0% reported symptoms of at least one mental health condition in the past 2 weeks. Symptoms were more prevalent among those who were unable to take time off or worked ≥41 hours per week. Implementing prevention and control practices that eliminate, reduce, and manage factors that cause or contribute to public health workers’ poor mental health might improve mental health outcomes during emergencies.
By Now, Burnout Is a Given

The pandemic has stripped our emotional reserves even further, laying bare our unique physical,

social, and emotional vulnerabilities.
Confronting Our Next National Health Disaster — Long-Haul Covid
The Centers for Disease Control and Prevention (CDC) estimates that more than 114 million Americans had been infected with Covid-19 through March 2021. Factoring in new infections in unvaccinated people, more than 15 million cases of long Covid can conservatibely be expected to result from this pandemic. And though data are still emerging, the average age of patients with long Covid is about 40, which means that the majority are in their prime working years. Given these demographics, long Covid is likely to cast a long shadow on our health care system and economic recovery.

Antiviral Therapeutics and Vaccines

Serum Neutralizing Activity of mRNA-1273 against SARS-CoV-2 Variants
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has led to growing concerns over increased transmissibility and the ability of some variants to partially escape immunity. Sera from participants immunized on a prime-boost schedule with the mRNA-1273 COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants, including variants of concern (VOCs) and variants of interest (VOIs), compared to neutralization of the wild-type SARS-CoV-2 virus (designated as D614G). Results showed minimal effects on neutralization titers against the B.1.1.7 (Alpha) variant (1.2-fold reduction compared with D614G); other VOCs such as B.1.351 (Beta, including B.1.351-v1, B.1.351-v2, and B.1.351-v3), B.1.617.2 (Delta), and P.1 (Gamma) showed decreased neutralization titers ranging from 2.1-fold to 8.4-fold reductions compared with D614G, although all remained susceptible to mRNA-1273–elicited serum neutralization.
Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection
Data from a randomized efficacy trial of ChAdOx1 nCoV-19 (AZD1222) vaccine in the UK was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Anti-spike and anti-RBD IgG by multiplex immunoassay, pseudovirus and live neutralizing antibody at 28 days after the second dose were measured in infected and non-infected vaccine recipients. Weighted generalized additive models for binary data were applied to symptomatic and asymptomatic SARS-CoV-2 infection data from ChAdOx1 nCoV-19 recipients. Cubic spline smoothed log antibody levels, and weights were applied to account for potential selection bias in sample processing. Models were adjusted for baseline risk of exposure to SARS-CoV-2 infection. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Vaccine efficacy of 80% against primary symptomatic COVID-19 was achieved with an antibody level of 40923 (95% CI: 16748, 125017) and 63383 (95% CI: 16903, not computed (NC)) for anti-spike and anti-RBD, and 185 (95% CI: NC, NC) and 247 (95% CI: 101, NC) for pseudo- and live-neutralisation assays respectively. Antibody responses did not correlate with overall protection against asymptomatic infection. Correlates of protection can be used to bridge to new populations using validated assays. The data can be used to extrapolate efficacy estimates for new vaccines where large efficacy trials cannot be conducted. More work is needed to assess correlates for emerging variants.
Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial
To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. Immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) was determined when administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). A phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralization assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69–112·99) to 3684·87 BAU/mL (3429·87–3958·83). The interventional:control ratio was 77·69 (95% CI 59·57–101·32) for RBD protein and 36·41 (29·31–45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported. BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile.

Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine rollout has coincided with the spread of variants of concern. Whether single-dose vaccination, with or without prior infection, confers cross-protective immunity to variants was investigated in this study. T and B cell responses after first-dose vaccination with the Pfizer/BioNTech messenger RNA vaccine BNT162b2 were analyzed in health care workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody-secreting memory B cell response to the spike protein, and neutralizing antibodies effective against variants B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated, or unchanged T cell responses, depending on human leukocyte antigen (HLA) polymorphisms. Single-dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.

SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA)-based vaccines are ~95% effective in preventing coronavirus disease 2019. The dynamics of antibody secreting plasmablasts (PBs) and germinal centre (GC) B cells induced by these vaccines in humans remain unclear. Authors examined antigen-specific B cell responses in peripheral blood (n=41) and draining lymph nodes (LNs) in 14 individuals who received two doses of BNT162b2, an mRNA-based vaccine encoding full-length SARS-CoV-2 spike (S) gene. Circulating IgG- and IgA-secreting PBs targeting the S protein peaked one week after the second immunization then declined, becoming undetectable three weeks later. These PB responses preceded maximal levels of serum anti-S binding and neutralizing antibodies to an early circulating SARS-CoV-2 strain as well as emerging variants, especially in individuals previously infected with SARS-CoV-2, who produced the most robust serologic responses. By examining fine needle aspirates (FNAs) of draining axillary LNs, GC B cells that bound S protein in all participants sampled after primary immunization were identified. Remarkably, high frequencies of S-binding GC B cells and PBs were sustained in these draining LNs for at least twelve weeks after the booster immunization. S-binding GC B cell-derived monoclonal antibodies predominantly targeted the receptor binding domain of the S protein, with fewer clones binding to the N-terminal domain or to epitopes shared with the S proteins of the human betacoronaviruses OC43 and HKU1. The latter cross-reactive B cell clones had higher levels of somatic hypermutation compared to those that only recognized SARS-CoV-2 S protein, suggesting a memory B cell origin. These studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent GC B cell response, enabling the generation of robust humoral immunity.

Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine
In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-μg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline. A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant.

Emergency Use Authorization for Actemra (Tocilizumab) for Treatment of COVID-19
The EUA authorizes Actemra (tocilizumab), manufactured by Genentech, for emergency use by healthcare providers for the treatment of COVID-19 in hospitalized adults and pediatric patients (2 years of age and older) who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Epidemiology

Effect of Vaccination on Household Transmission of SARS-CoV-2 in England
Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevents infection and reduces the severity of coronavirus disease 2019 (Covid-19) in vaccinated persons. Authors investigated whether vaccination would reduce transmission in the household setting in the context of postvaccination infection. Data from the Household Transmission Evaluation Dataset (HOSTED), which has information on all laboratory-confirmed cases of Covid-19 in England and in which data on all persons sharing the same address are linked. Between January 4 and February 28, 2021, there were 960,765 household contacts of unvaccinated index patients, and there were 96,898 secondary cases of Covid-19 (10.1%). Overall, the likelihood of household transmission was approximately 40 to 50% lower in households of index patients who had been vaccinated 21 days or more before testing positive than in households of unvaccinated index patients; the findings were similar for the two vaccines. Most of the vaccinated index patients in our data set (93%) had received only the first dose of vaccine. Assessment of infection risks among household contacts according to the timing of vaccination of the index patient showed protective effects when the vaccine had been administered at least 14 days before the positive test

Basic Virology

Human Behavior During the Pandemic Is More Important Than Any Covid Variant
News headlines and health experts on social media are sounding the alarm over another variant of the coronavirus, this time Delta, claiming it is much more contagious and perhaps more lethal than any other variant seen so far. It’s easy to understand why: New variants of the virus continue to emerge, and cases are rising in many countries. But whether new variants pose a unique or substantial risk is still unknown, and as virologists, we are concerned that misunderstanding variants and the risk they pose can cause confusion and panic.