- The durability of immunity against reinfection by SARS-CoV-2: a comparative evolutionary study
Among the most consequential unknowns of the devastating COVID-19 pandemic are the durability of immunity and time to likely reinfection. There are limited direct data on SARS-CoV-2 long-term immune responses and reinfection. The aim of this study is to use data on the durability of immunity among evolutionarily close coronavirus relatives of SARS-CoV-2 to estimate times to reinfection by a comparative evolutionary analysis of related viruses SARS-CoV, MERS-CoV, human coronavirus (HCoV)-229E, HCoV-OC43, and HCoV-NL63. Phylogenetic analyses of the S, M, and ORF1b genes were conducted to reconstruct a maximum-likelihood molecular phylogeny of human-infecting coronaviruses. This phylogeny enabled comparative analyses of peak-normalised nucleocapsid protein, spike protein, and whole-virus lysate IgG antibody optical density levels, in conjunction with reinfection data on endemic human-infecting coronaviruses. Ancestral and descendent states analyses were done to estimate the expected declines in antibody levels over time, the probabilities of reinfection based on antibody level, and the anticipated times to reinfection after recovery under conditions of endemic transmission for SARS-CoV-2, as well as the other human-infecting coronaviruses. Antibody optical density data for six human-infecting coronaviruses was obtained, extending from 128 days to 28 years after infection between 1984 and 2020. These data provided a means to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5·1 years after peak antibody response, with a median of 16 months. This protection is less than half the duration revealed for the endemic coronaviruses circulating among humans (5–95% quantiles 15 months to 10 years for HCoV-OC43, 31 months to 12 years for HCoV-NL63, and 16 months to 12 years for HCoV-229E). For SARS-CoV, the 5–95% quantiles were 4 months to 6 years, whereas the 95% quantiles for MERS-CoV were inconsistent by dataset. The timeframe for reinfection is fundamental to numerous aspects of public health decision making. As the COVID-19 pandemic continues, reinfection is likely to become increasingly common. Maintaining public health measures that curb transmission—including among individuals who were previously infected with SARS-CoV-2—coupled with persistent efforts to accelerate vaccination worldwide is critical to the prevention of COVID-19 morbidity and mortality.
- IVIG Compared to IVIG Plus Infliximab in Multisystem Inflammatory Syndrome in Children
No abstract available for this study.
- AZD7442 request for Emergency Use Authorization for COVID-19 prophylaxis filed in US
AstraZeneca has submitted a request to the US Food and Drug Administration (FDA) for an Emergency Use Authorization (EUA) for AZD7442, its long-acting antibody (LAAB) combination, for prophylaxis of symptomatic COVID-19. If granted, AZD7442 would be the first LAAB to receive an EUA for COVID-19 prevention. It is the first LAAB with Phase III data demonstrating a statistically significant reduction in the risk of developing symptomatic COVID-19 compared to placebo. In August, 2021, AstraZeneca announced high-level results from the PROVENT pre-exposure prophylaxis trial which showed AZD7442 reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval (CI): 46, 90), compared to placebo. Importantly, the trial population included people with co-morbidities and who may be in need of additional protection from SARS-CoV-2 infection. Greater than 75% of participants in PROVENT presented with co-morbidities associated with an increased risk of severe disease or a reduced immune response to vaccination. The trial accrued 25 cases of symptomatic COVID-19 at the primary analysis. AZD7442 was well-tolerated. The EUA request filing includes safety and efficacy data from the PROVENT and STORM CHASER Phase III trials and the Phase I trial.
- Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine
The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose. AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults.
- Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study
Vaccine effectiveness studies have not differentiated the effect of the delta (B.1.617.2) variant and potential waning immunity in observed reductions in effectiveness against SARS-CoV-2 infections. Authors aimed to evaluate overall and variant-specific effectiveness of BNT162b2 (tozinameran, Pfizer–BioNTech) against SARS-CoV-2 infections and COVID-19-related hospital admissions by time since vaccination among members of a large US health-care system. In this retrospective cohort study, electronic health records of individuals (≥12 years) who were members of the health-care organisation Kaiser Permanente Southern California (CA, USA),were analyzed to assess BNT162b2 vaccine effectiveness against SARS-CoV-2 infections and COVID-19-related hospital admissions for up to 6 months. Participants were required to have 1 year or more previous membership of the organisation. Outcomes comprised SARS-CoV-2 PCR-positive tests and COVID-19-related hospital admissions. Effectiveness calculations were based on hazard ratios from adjusted Cox models. Between Dec 14, 2020, and Aug 8, 2021, of 4 920 549 individuals assessed for eligibility, were included 3 436 957 (median age 45 years [IQR 29–61]; 1 799 395 [52·4%] female and 1 637 394 [47·6%] male). For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95% CI 72–74) and against COVID-19-related hospital admissions was 90% (89–92). Effectiveness against infections declined from 88% (95% CI 86–89) during the first month after full vaccination to 47% (43–51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85–97]) but declined to 53% [39–65] after 4 months. Effectiveness against other (non-delta) variants the first month after full vaccination was also high at 97% (95% CI 95–99), but waned to 67% (45–80) at 4–5 months. Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84–96]) up to 6 months. The results provide support for high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the delta variant escaping vaccine protection.
- Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study
Merck and Ridgeback Biotherapeutics today announced that molnupiravir (MK-4482, EIDD-2801), an investigational oral antiviral medicine, significantly reduced the risk of hospitalization or death at a planned interim analysis of the Phase 3 MOVe-OUT trial in at risk, non-hospitalized adult patients with mild-to-moderate COVID-19. At the interim analysis, molnupiravir reduced the risk of hospitalization or death by approximately 50%; 7.3% of patients who received molnupiravir were either hospitalized or died through Day 29 following randomization (28/385), compared with 14.1% of placebo-treated patients (53/377); p=0.0012. Through Day 29, no deaths were reported in patients who received molnupiravir, as compared to 8 deaths in patients who received placebo. At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. Food and Drug Administration (FDA), recruitment into the study is being stopped early due to these positive results. Merck plans to submit an application for Emergency Use Authorization (EUA) to the U.S. FDA as soon as possible based on these findings and plans to submit marketing applications to other regulatory bodies worldwide.
- Optimal Time Identified for Monoclonal Antibody Infusions in Patients With COVID-19
Patients with mild –or moderate COVID-19 who received a monoclonal antibody (mAb) infusion within the first 5 days of symptom onset experienced decreased disease progression compared with those who received the infusion after 6 or more days, according to results of a single-center retrospective case-control study presented at IDWeek, held virtually from September 29 to October 3, 2021. Investigators performed a risk factor analysis on the composite outcome of subsequent evaluation of patients with SARS-CoV-2 infection who hospitalized or admitted to the emergency department (ED) and treated with mAbs between December 2020 and May 2021. Authors performed multivariate and univariate analyses to find significant variables. Following mAb treatment, 31 (10.8%) patients required treatment in the ED or hospitalization due to disease progression. Patients who received early (days 1-5 of symptom onset) mAb infusion had a decreased risk for disease progression compared with those who received late (days 6-12 of symptom onset) mAb infusion (6.1% vs 13.2%; P =.048). Of 21 patients who received mAb infusion between days 1 and 3 following symptom onset, none experienced disease progression. Patients with certain comorbidities were more likely to have disease progression, including those with congestive heart failure (P =.038), cirrhosis (P =.012), chronic kidney disease (CKD) (P =.001), and hypertension (P =.021). No differences in disease progression were observed in regard to sex, ethnicity, BMI, or symptoms between the treatment groups. A multivariate analysis showed an increased risk for disease progression among patients with cirrhosis (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and CKD (OR, 2.6; 95% CI, 1.0-6.4); however, early mAb infusion was found to decrease the risk for disease progression (OR, 0.38; 95% CI, 0.14-1.0).
- Coronavirus (COVID-19) Update: FDA Authorizes Additional OTC Home Test to Increase Access to Rapid Testing for Consumers
The U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the ACON Laboratories Flowflex COVID-19 Home Test, an over-the-counter (OTC) COVID-19 antigen test, which adds to the growing list of tests that can be used at home without a prescription. This action highlights our continued commitment to increasing the availability of appropriately accurate and reliable OTC tests to meet public health needs and increase access to testing for consumers. This authorization for the ACON Laboratories Flowflex COVID-19 Home Test should significantly increase the availability of rapid, at-home tests and is expected to double rapid at-home testing capacity in the U.S. over the next several weeks. By years end, the manufacturer plans to produce more than 100 million tests per month, and this number will rise to 200 million per month by February 2022.
- Multicomponent Strategies to Prevent SARS-CoV-2 Transmission — Nine Overnight Youth Summer Camps, United States, June–August 2021
Previous studies have demonstrated the importance of prevention strategies to reduce SARS-CoV-2 transmission in overnight camps. During June–August 2021, a total of 7,173 campers and staff members attended nine U.S. overnight camps that implemented multiple prevention strategies including high vaccination coverage (>93% among eligible persons aged ≥12 years); prearrival and frequent screening testing (38,059 tests); and additional concomitant prevention measures. Nine laboratory-confirmed COVID-19 cases and no secondary infections were detected. Implementation of high vaccination coverage coupled with multiple prevention strategies is critical to averting COVID-19 outbreaks in congregate settings, including overnight camps. These findings highlight important guiding principles for school and youth-based COVID-19 prevention protocols.
- COVID-19 Outbreaks at Youth Summer Camps — Louisiana, June–July 2021
According to sequencing data reported by CDC, the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, has been the predominant lineage circulating in Louisiana since the week of June 20, 2021. In Louisiana, the increased spread of the Delta variant corresponded with the start of the state’s fourth and largest increase in average daily COVID-19 incidence to date. This report describes COVID-19 outbreaks in Louisiana youth summer camps as the Delta variant became the predominant lineage during June–July 2021. The increased number of outbreaks and cases observed in Louisiana youth summer camps in 2021 compared with the previous year coincided with the widespread circulation of the highly transmissible Delta variant. This period also coincided with apparent underutilization of preventive measures such as vaccination, masking, and physical distancing. Multicomponent prevention measures, including vaccination of all eligible adults and adolescents, wearing masks indoors, regular screening testing, physical distancing and cohorting, and increasing ventilation can help prevent transmission of SARS-CoV-2 in settings with youths who cannot be vaccinated
- The impact of SARS-CoV-2 vaccination on Alpha & Delta variant transmission
Pre-Delta, vaccination reduced transmission of SARS-CoV-2 from individuals infected despite vaccination, potentially via reducing viral loads. While vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated individuals infected with Delta question how much vaccination prevents onward transmission. Authors performed a retrospective observational cohort study of contacts of SARS-CoV-2-infected index cases using contact testing data from England. Multivariable logistic regression was used to investigate the impact of index case and contact vaccination on transmission, and how this varies with Alpha and Delta variants (classified using S-gene detection/calendar trends) and time since second vaccination. 51,798/139,164(37.2%) contacts tested were PCR-positive. Two doses of BNT162b2 or ChAdOx1 vaccines in Alpha variant index cases independently reduced PCR-positivity in contacts (aOR, adjusted odds ratio vs. unvaccinated=0.18[95%CI 0.12-0.29] and 0.37[0.22-0.63] respectively). The Delta variant attenuated vaccine-associated reductions in transmission: two BNT162b2 doses reduced Delta transmission (aOR=0.35[0.26-0.48]), more than ChAdOx1 (aOR=0.64[0.57-0.72]; heterogeneity p<0.001). Variation in viral load (Ct values) explained only a modest proportion of vaccine-associated transmission reductions. Transmission reductions declined over time since second vaccination, for Delta reaching similar levels to unvaccinated individuals by 12 weeks for ChAdOx1 and attenuating substantially for BNT162b2. Protection from vaccination in contacts also declined in the 3 months after second vaccination.Vaccination reduces transmission of Delta, but by less than the Alpha variant. The impact of vaccination decreased over time. Factors other than PCR-measured viral load are important in vaccine-associated transmission reductions. Booster vaccinations may help control transmission together with preventing infections.
World Health Organization (WHO)
Novel Coronavirus (COVID-19) Situation from World Health Organization (WHO)
Johns Hopkins University (JHU)
Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at JHU
COVID-19 in US and Canada
1Point3Acres Real-Time Coronavirus (COVID-19) Updates in US and Canada with Credible Sources
Genomic Epidemiology COVID-19
Genomic Epidemiology of (COVID-19) Maintained by the Nextstrain team, enabled by data from GISAID.