Mixed Oxford/Pfizer vaccine schedules generate robust immune response
Safety and Immunogenicity Report from the Com-COV Study – a Single-Blind Randomised Non-Inferiority Trial Comparing Heterologous And Homologous Prime-Boost Schedules with An Adenoviral Vectored and mRNA COVID-19 Vaccine
[Preprint.] Com-COV is a participant-blind, non-inferiority trial evaluating vaccine reactogenicity and immunogenicity. Adults ≥ 50 years, including those with well-controlled comorbidities, were randomised across eight groups to receive ChAd/ChAd, ChAd/BNT, BNT/BNT or BNT/ChAd, administered at 28- or 84-day intervals. In February 2021, 830 participants were enrolled and randomised, including 463 with a 28-day prime-boost interval whose results are reported in this paper. Participant mean age was 57.8 years, 45.8% were female, and 25.3% from ethnic minorities.The geometric mean concentration (GMC) of day 28 post-boost SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12,906 ELU/ml) was non-inferior to that in ChAd/ChAd recipients (1,392 ELU/ml) with a geometric mean ratio (GMR) of 9.2 (one-sided 97.5% CI: 7.5, ∞). In participants primed with BNT, we failed to show non-inferiority of the heterologous schedule (BNT/ChAd, GMC 7,133 ELU/ml) against the homologous schedule (BNT/BNT, GMC 14,080 ELU/ml) with a GMR of 0.51 (one-sided 97.5% CI: 0.43, ∞). Geometric mean of T cell response at 28 days post boost in the ChAd/BNT group was 185 SFC/10 6 PBMCs (spot forming cells/10 6 peripheral blood mononuclear cells) compared to 50, 80 and 99 SFC/10 6 PBMCs for ChAd/ChAd, BNT/BNT, and BNT/ChAd, respectively. There were four serious adverse events across all groups, none of which were considered related to immunisation. These data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines.
Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel — 33 U.S. Sites, January–March 2021
The first U.S. multisite test-negative design vaccine effectiveness study among health care personnel (HCP) found a single dose of Pfizer-BioNTech or Moderna COVID-19 vaccines to be 82% effective against symptomatic COVID-19 and 2 doses to be 94% effective.
Incident SARS-CoV-2 Infection among mRNA-Vaccinated and Unvaccinated Nursing Home Residents
The sample included 18,242 residents who received at least one dose of mRNA vaccine; 14,669 residents (80.4%) received the Pfizer–BioNTech vaccine, and 3573 (19.6%) received the Moderna vaccine. Of these 18,242 residents, 13,048 also received the second dose of vaccine. A total of 3990 residents were unvaccinated. The incidence of infection decreased over time among both vaccinated residents and unvaccinated residents. After receipt of the first vaccine dose, there were 822 incident cases (4.5% of vaccinated residents) within 0 to 14 days and 250 cases (1.4%) at 15 to 28 days. Among the 13,048 residents who received both doses of vaccine, there were 130 incident cases (1.0% of vaccinated residents) within 0 to 14 days after receipt of the second dose and 38 cases (0.3%) after 14 days (which included 19 cases occurring 15 to 21 days after receipt of the second dose). Among unvaccinated residents, incident cases decreased from 173 cases (4.3% of unvaccinated residents) within 0 to 14 days after the first vaccination clinic to 12 cases (0.3%) at more than 42 days after the clinic. These findings show the real-world effectiveness of the mRNA vaccines in reducing the incidence of asymptomatic and symptomatic SARS-CoV-2 infections in a vulnerable nursing home population.
COVID-19 reinfection: a rapid systematic review of case reports and case series
We undertook a rapid systematic review to identify cases infected with different genetic strains of SARS-CoV-2 confirmed by PCR and viral genome sequencing. A total of 17 cases of genetically confirmed COVID-19 reinfection were found. One immunocompromised patient had mild symptoms with the first infection but developed severe symptoms resulting in death with the second infection. Overall, 68.8% (11/16) had similar severity; 18.8% (3/16) had worse symptoms; and 12.5% (2/16) had milder symptoms with the second episode. Our case series shows that reinfection with different strains is possible, and some cases may experience more severe infections with the second episode. The findings also suggest that COVID-19 may continue to circulate even after achieving herd immunity through natural infection or vaccination, suggesting the need for longer-term transmission mitigation efforts.
Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries
We carry out a large-scale study of 506,768 SARS-CoV-2 genome isolates from patients to identify many other rapidly growing mutations on the spike (S) protein receptor-binding domain (RBD). We reveal that essentially all 100 most observed mutations strengthen the binding between the RBD and the host angiotensin-converting enzyme 2 (ACE2), indicating the virus evolves toward more infectious variants. Our comprehensive genetic analysis and protein-protein binding study show that the genetic evolution of SARS-CoV-2 on the RBD, which may be regulated by host gene editing, viral proofreading, random genetic drift, and natural selection, gives rise to more infectious variants that will potentially compromise existing vaccines and antibody therapies.