COVID-19 Science Update released: July 23, 2021 Edition 99

PEER-REVIEWED

Spike-antibody waning after second dose of BNT162b2 or ChAdOx1.external icon Shrotri et al. The Lancet (July 15, 2021).

Key findings:

• Between 21-41 days and ≥70 days after 2^nd dose, spike antibody (S-antibody) levels decreased in fully vaccinated adults by ~2-fold (BNT162b2) and ~5-fold (ChAdOx1) (Figure), regardless of sex, age, or clinical vulnerability.
  • Average S-antibody levels were higher in individuals vaccinated with BNT162b2 than ChAdOx1.
  • Women and individuals <65 years old had higher mean titers, regardless of vaccine received.
• At ≥70 days post-2^nd dose, individuals classified as clinically vulnerable who received BNT162b2 had ~25-fold higher S-antibody levels than those vaccinated with ChAdOx1.

Methods: Spike antibody levels were measured in serum from fully vaccinated, previously uninfected adults (≥18 years old, n = 552) in England and Wales. Individuals were vaccinated with either BNT162b2 (Pfizer/BioNTech) or ChAdOx1 (Oxford/AstraZeneca), and a single sample was collected 14-154 days post-2^nd dose. Limitations: Neutralization capability of the detected antibody levels is not reported.

Implications: The UK vaccination strategy of longer time interval between doses elicited antibody response, antibody levels for both BNT162b2 and ChAdOx1 vaccines, however, declined over time and there was a significant difference between vaccine types.

Figure:

Note: Box plots of antibody levels (units/mL) against SARS-CoV-2 spike glycoprotein (S-antibody) at defined timepoints after 2^nd vaccine dose in individuals with no previous infection. Median interval between 1^st and 2^nd doses was 77 days. P-values derived from non-parametric tests for trends. Permission request in process.

Association of BNT162b2 mRNA and mRNA-1273 vaccines with COVID-19 infection and hospitalization among patients with cirrhosis.external icon John et al. JAMA Internal Medicine (July 13, 2021).

Key findings:

• Among veterans with cirrhosis, a single dose of mRNA vaccine reduced SARS-CoV-2 infections by 64.8%, and hospitalizations or death by 100%, after 28 days. Two doses reduced infection by 78.6%.
• The adjusted association between vaccination and infection was significant for patients with compensated cirrhosis (adjusted hazard ratio [aHR], 0.69; 95% CI 0.54-0.89) but not for patients with decompensated cirrhosis (aHR, 0.90; 95% CI 0.62-1.30) (Figure).

Methods: Retrospective cohort study among US veterans (18 years or older) diagnosed with cirrhosis. Vaccine recipients (n = 20,037) were matched by propensity score based on age group, sex, race, alcohol use, electronic Child-Turcotte-Pugh score, and cirrhosis comorbidity score to unvaccinated controls (n = 20,037). Primary outcomes were assessed 28 days following 1^st dose and secondary outcomes 7 days after 2^nd dose. Limitations: Study only tested mRNA-based vaccines; participants were predominantly male (97.3%) and white (60.6%).

Implications: Patients with cirrhosis benefit from mRNA vaccines, although vaccine efficacy related to infection is lower than in RCTs for both mRNA-1273external icon and BNT162b2external icon . Vaccinated cirrhosis patients, especially decompensated ones, should continue practicing nonpharmaceutical interventions following vaccination.

Figure:

NOTE: Adapted from John et al. Adjusted time from receipt of 1^st dose of mRNA vaccine and COVID-19 infection or death in vaccine and control group patients with compensated cirrhosis (left) and decompensated (right). Reproduced with permission from JAMA Internal Medicine, 2021. Published online July 13, 2021. https://doi.org/10.1001/jamainternmed.2021.4325. Copyright© 2021 American Medical Association. All rights reserved.

Durable humoral and cellular immune responses 8 months after Ad26.COV2.S vaccinationexternal icon . Barouch et al. NEJM (July 14, 2021).

Key findings:

• Vaccination with a single dose of Ad26.COV2.S continued to produce humoral and cellular immunity for at least 239 days.
  • Median CD8+ T-cell responses was 0.0545%, 0.0554%, and 0.0734% on days 57, 85, and 239, respectively.
• Increased neutralization over time of SARS-CoV-2 variants, including B.1.617.2 (Delta), B.1.351 (Beta) and P.1 (Gamma) suggests maturation of B-cell responses (Figure).

Methods: Durability of humoral and cellular immune responses in experimental group receiving Ad26.COV2.S (Johnson & Johnson/Janssen) vaccination (n = 20) and placebo (n = 5) studied over 8 months. Median neutralizing antibody titers were evaluated by ELISA for the WA1/2020, D614G, B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta), P.1, B.1.429 (Epsilon), and B.1.351 (Beta) variants. Interferon-γ CD8+ and CD4+ T-cell responses were measured on days 29, 57, 71 or 85, and 239. Limitations: Small sample size.

Implications: The Ad26.COV2.S vaccine induces prolonged immune response against WA1/2020. Neutralization effects expanded against other variants over time, likely through maturation of B-cell responses.

Figure:

NOTE: Adapted from Barouch et al. Neutralizing antibody responses in all participants, according to variant. Humoral and cellular immune responses after Ad26.COV2.S vaccination. Pseudovirus neutralizing antibody titers (y-axis) against parental strain (WA1/2020), D614G, B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta), P.1 (Gamma), B.1.429 (Epsilon), and B.1.351 (Beta) on days 29 and 239. Redbarsdenote medians; horizontal dashed line indicates lower limit of quantitation. Permission request in progress.

BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israelexternal icon . Brosh-Nissimov et al. Clinical Microbiology and Infection (July 6, 2021).

Key findings:

• 96% of 152 fully vaccinated hospitalized patients with SARS-CoV-2 infections had at least 1 co-morbidity, including diabetes (73, 48%), hypertension (108, 71%), chronic renal failure (48, 32%), congestive heart failure (41, 27%), chronic lung disease (37, 24%), and cancer (36, 24%).
  • Immunosuppression was present in 40% (60) of patients, including 11% (16) with a solid organ transplant and 7% (10) on anti-CD20 therapy.
  • 38 patients had poor outcomes including 34 (22%) who died.
• Among 45 patients with available genotyping, 89% (40) were infected with B.1.1.7 (Alpha), 7% (3) with wild-type, and 4% (2) with B.1.351 (Beta) SARS-CoV-2 variants.

Methods: Multicenter retrospective cohort of 152 hospitalized patients fully vaccinated with BNT162b2 (Pfizer/BioNTech), conducted between January 18 and April 20, 2021. Breakthrough infections were identified as symptom onset, SARS-CoV-2 positive PCR test, or admission 8 days after a second dose of BNT162b2 vaccine. Patients' outcomes were either poor: requiring ventilation or in-hospital death; or favorable: not requiring ventilation or being discharged. Limitations: Study not designed to explore risk factors for vaccine failures; small cohort; patients were predominantly male and median age 71 years.

Implications: Hospitalized patients with breakthrough infections had a high burden of comorbidities and immunosuppression.

Public link

Please use the above public link if you want to share this noodl on another website.