Waning COVID-19 Vaccine Effectiveness for BNT162b2 and CoronaVac in Malaysia: An Observational Study

Evaluation of vaccine effectiveness over time against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) is important. Evidence on effectiveness over time for the CoronaVac vaccine is lacking despite its widespread use globally. In Malaysia, a diverse set-up of COVID-19 vaccines was rolled out nationwide, and the waning of vaccine protection is a concern. We aimed to investigate and compare waning vaccine effectiveness against COVID-19 infections, COVID-19 related ICU admission and COVID-19 related deaths for BNT162b2 and CoronaVac vaccines. In this observational study, we consolidated nationally representative data on COVID-19 vaccination and patients′ outcomes. Data on all confirmed COVID-19 cases from 1 to 30 September 2021 were used to compare vaccine effectiveness between the ′early′ group (fully vaccinated in April to June 2021) and the ′late′ group (fully vaccinated in Jul to Aug 2021). We used a negative binomial regression model to estimate vaccine effectiveness against COVID-19 infections for both ′early′ and ′late′ groups, by comparing the rates of infection for individuals vaccinated in the two different periods relative to the unvaccinated. Among confirmed COVID-19 cases, we used logistic regression to estimate and compare vaccine effectiveness against ICU admission and deaths between the two different periods. For BNT162b2, vaccine effectiveness against COVID-19 infections declined from 90.8% (95% CI 89.4, 92.0) in the late group to 79.1% (95% CI 75.8, 81.9) in the late group. Vaccine effectiveness for BNT162b2 against ICU admission and deaths were comparable between the two different periods. For CoronaVac, vaccine effectiveness waned against COVID-19 infections from 74.4% in the late group (95% CI 209 70.4, 77.8) to 30.0% (95% CI 18.4, 39.9) in the early group. It also declined significantly against ICU admission, dropping from 56.1% (95% CI 51.4, 60.2) to 29.9% (95% CI 13.9, 43.0). For deaths, however, CoronaVac′s effectiveness did not wane after three to five months of full vaccination. Vaccine effectiveness against COVID-19 infections waned after three to five months of full vaccination for both BNT162b2 and CoronaVac in Malaysia. Additionally, for CoronaVac, protection against ICU admission declined as well. Evidence on vaccine effectiveness over time informs evolving policy decisions on vaccination.

Waning Effectiveness of SARS-CoV-2 mRNA Vaccines in Older Adults: A Rapid Review

The U.S. Centers for Disease Control and Prevention (CDC) and other health agencies have recently recommended a booster dose of COVID-19 vaccines for specific vulnerable groups including adults 65 years and older. There is limited evidence whether vaccine effectiveness in older adults decreases over time, especially against severe COVID-19. We performed a rapid review of published studies available through 04 November 2021 that provide effectiveness data on mRNA vaccines approved/licensed in the United States and identified eight eligible studies which evaluated vaccine effectiveness in older adults. There is evidence of a decline in vaccine effectiveness against both SARS-CoV-2 infection and severe COVID-19 in older adults among studies which analyzed data up to July-October 2021. Our findings suggest that vaccine effectiveness diminishes in older adults, which supports the current recommendation for a booster dose in this population.

Subtype H3N2 Influenza A Viruses: An Unmet Challenge in the Western Pacific

Subtype H3N2 influenza A viruses (A(H3N2)) have been the dominant strain in some countries in the Western Pacific region since the 2009 influenza A(H1N1) pandemic. Vaccination is the most effective way to prevent influenza; however, low vaccine effectiveness has been reported in some influenza seasons, especially for A(H3N2). Antigenic mismatch introduced by egg-adaptation during vaccine production between the vaccine and circulating viral stains is one of the reasons for low vaccine effectiveness. Here we review the extent of this phenomenon, the underlying molecular mechanisms and discuss recent strategies to ameliorate this, including new vaccine platforms that may provide better protection and should be considered to reduce the impact of A(H3N2) in the Western Pacific region.

Relative Effectiveness of Cell-Cultured versus Egg-Based Seasonal Influenza Vaccines in Preventing Influenza-Related Outcomes in Subjects 18 Years Old or Older: A Systematic Review and Meta-Analysis

Avian mutations in vaccine strains obtained from embryonated eggs could impair vaccine effectiveness. We performed a systematic review and meta-analysis of the adjusted relative vaccine effectiveness (arVE) of seed cell-cultured influenza vaccines (ccIV) compared to egg-based influenza vaccines (eIV) in preventing laboratory-confirmed influenza related outcomes (IRO) or IRO by clinical codes, in subjects 18 and over. We completed the literature search in January 2021; applied exclusion criteria, evaluated risk of bias of the evidence, and performed heterogeneity, publication bias, qualitative, quantitative and sensitivity analyses. All estimates were computed using a random approach. International Prospective Register of Systematic Reviews, CRD42021228290. We identified 12 publications that reported 26 adjusted arVE results. Five publications reported 13 laboratory confirmed arVE and seven reported 13 code-ascertained arVE. Nine publications with 22 results were at low risk of bias. Heterogeneity was explained by season. We found a significant 11% (8 to 14%) adjusted arVE favoring ccIV in preventing any IRO in the 2017–2018 influenza season. The arVE was 3% (−2% to 7%) in the 2018–2019 influenza season. We found moderate evidence of a significant advantage of the ccIV in preventing IRO, compared to eIV, in a well-matched A(H3N2) predominant season.

Household secondary attack rates of SARS-CoV-2 by variant and vaccination status: an updated systematic review and meta-analysis

We previously reported a household secondary attack rate (SAR) for SARS-CoV-2 of 18.9% through June 17, 2021. To examine how emerging variants and increased vaccination have affected transmission rates, we searched PubMed from June 18, 2021, through January 7, 2022. Meta-analyses used generalized linear mixed models to obtain SAR estimates and 95%CI, disaggregated by several covariates. SARs were used to estimate vaccine effectiveness based on the transmission probability for susceptibility (VE_S,p), infectiousness (VE_I,p), and total vaccine effectiveness (VE_T,p). Household SAR for 27 studies with midpoints in 2021 was 35.8% (95%CI, 30.6%-41.3%), compared to 15.7% (95%CI, 13.3%-18.4%) for 62 studies with midpoints through April 2020. Household SARs were 38.0% (95%CI, 36.0%-40.0%), 30.8% (95%CI, 23.5%-39.3%), and 22.5% (95%CI, 18.6%-26.8%) for Alpha, Delta, and Beta, respectively. VE_I,p, VE_S,p, and VE_T,p were 56.6% (95%CI, 28.7%-73.6%), 70.3% (95%CI, 59.3%-78.4%), and 86.8% (95%CI, 76.7%-92.5%) for full vaccination, and 27.5% (95%CI, -6.4%-50.7%), 43.9% (95%CI, 21.8%-59.7%), and 59.9% (95%CI, 34.4%-75.5%) for partial vaccination, respectively. Household contacts exposed to Alpha or Delta are at increased risk of infection compared to the original wild-type strain. Vaccination reduced susceptibility to infection and transmission to others.

A systematic review of methodological approaches for evaluating real-world effectiveness of COVID-19 vaccines: Advising resource-constrained settings

Real-world effectiveness studies are important for monitoring performance of COVID-19 vaccination programmes and informing COVID-19 prevention and control policies. We aimed to synthesise methodological approaches used in COVID-19 vaccine effectiveness studies, in order to evaluate which approaches are most appropriate to implement in low- and middle-income countries (LMICs). For this rapid systematic review, we searched PubMed and Scopus for articles published from inception to July 7, 2021, without language restrictions. We included any type of peer-reviewed observational study measuring COVID-19 vaccine effectiveness, for any population. We excluded randomised control trials and modelling studies. All data used in the analysis were extracted from included papers. We used a standardised data extraction form, modified from STrengthening the Reporting of OBservational studies in Epidemiology (STROBE). Study quality was assessed using the REal Life EVidence AssessmeNt Tool (RELEVANT) tool. This study is registered with PROSPERO, CRD42021264658. Our search identified 3,327 studies, of which 42 were eligible for analysis. Most studies (97.5%) were conducted in high-income countries and the majority assessed mRNA vaccines (78% mRNA only, 17% mRNA and viral vector, 2.5% viral vector, 2.5% inactivated vaccine). Thirty-five of the studies (83%) used a cohort study design. Across studies, short follow-up time and limited assessment and mitigation of potential confounders, including previous SARS-CoV-2 infection and healthcare seeking behaviour, were major limitations. This review summarises methodological approaches for evaluating real-world effectiveness of COVID-19 vaccines and highlights the lack of such studies in LMICs, as well as the importance of context-specific vaccine effectiveness data. Further research in LMICs will refine guidance for conducting real-world COVID-19 vaccine effectiveness studies in resource-constrained settings.

Systematic review and meta-analysis of COVID-19 vaccines safety, tolerability, and efficacy among HIV-infected patients

Objective To conduct a comprehensive systematic review and meta-analysis of all recommended SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) vaccines in people living with HIV (PLWH), as well as an overview of the safety, tolerability, and efficacy of the vaccines in PLWH. Methods We searched six databases, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Medline, Medrxiv, Global research on COVID-19 database, and Google Scholar for studies investigating the effects of SARS-CoV-2 vaccines on PLWH. Results of the association were summarised by SARS-CoV-2 IgG seroconversion and level, vaccines efficacy and tolerability. A meta-analysis was performed for studies, using random-effects model and a pooled RR with 95% CI was reported. Results Twenty-three of the 1052 studies screened met the inclusion criteria. The review included 28, 246 participants among whom 79.55% (22,469/28, 246) were PLWH with median CD4 >=200 cells/mm3. The pooled estimate of SARS-CoV-2 IgG seroconversion and positive neutralizing antibodies after the second vaccination dose between PLWH vs HIV negative were RR 0.95 (95%CI: 0.92 to 0.99, P = 0.006) and 0.88 (95%CI: 0.82 to 0.95, P = 0.0007), respectively. The mean difference of IgG antibodies level (BAU/ml) was found higher in mRNA vaccines MD -1444.97 (95%CI: -1871.39 to -1018.55). PLWH with CD4 less than 500 cells/mm3 had 15% risk reduction of neutralizing antibodies response compared to those with CD4>=500 cells/mm3 (P = 0.003). The SARS-CoV-2 vaccine effectiveness was 65% (95%CI: 56% to 72%, P <0.001) among vaccinated compared to unvaccinated PLWH. PLWH with CD4 count <350 cells/mm3 had lower vaccine effectiveness compared to CD4 count >=350 cells/mm3 with 59% vs 72%, respectively. Vaccine tolerability was the same between PLWH and HIV negatives. Conclusion According to our findings, PLWH with CD4>=200 cells/mm3 had lower immunogenicity and antigenicity in COVID-19 vaccines than HIV negatives. Additional doses of SARS-CoV-2 vaccination are needful in PLWH.

COVID-19 vaccination breakthrough infections in a real-world setting: Using community reporters to evaluate vaccine effectiveness

Background COVID-19 has highlighted the need for new methods of pharmacovigilance. Here we use community volunteers to obtain systematic information on vaccine effectiveness and the nature and severity of breakthrough infections. Methods Between December 15, 2020 to September 16, 2021, 10,412 unpaid community-based participants reported the following information to an on-line registry: COVID-19 test results, vaccination (Pfizer, Moderna, or Johnson & Johnson), COVID-19 symptoms and perceived severity using a 4-point scale. COVID-19 infections were described for those who were 1) fully vaccinated, 2) partially vaccinated (received first of two dose vaccines or were <14 days post-final dose), or 3) unvaccinated. Results Of 8,554 who were vaccinated, COVID-19 infections were reported by 74 (1.0%) of those who were fully vaccinated and 198 (2.3%) of those who were partially vaccinated. Among the 74 participants who reported a breakthrough infection after full vaccination, the median time to reported positive test result was 104.5 days (Interquartile range: 77-135 days), with no difference among vaccine manufactures. One quarter (25.7%) of breakthrough infections in the fully vaccinated cases were asymptomatic. More than 97% of fully vaccinated participants reported no moderate/severe symptoms compared to 89.3% of the unvaccinated cases; and only 1.4% of fully vaccinated participants reported experiencing at least 3 moderate to severe symptoms compared to 7.8% in the unvaccinated. Conclusion Person-generated health data, also referred to as patient-reported outcomes, is a useful resource for quantifying breakthrough infections and their severity, showing here that fully vaccinated participants report no or very mild COVID-19 symptoms.

Evaluating the Impact of SARS-CoV-2 Variants on the COVID-19 Epidemic and Social Restoration in the United States: A Mathematical Modelling Study

Background: Multiple SARS-CoV-2 variants are still rampant across the United States (US). We aimed to evaluate the impact of vaccination scale-up and potential reduction in the vaccination effectiveness on the COVID-19 epidemic and social restoration in the US.Methods: We extended a published compartmental model and calibrated the model to the latest US COVID-19 data. We estimated the vaccine effectiveness against the variant and evaluated the impact of a potential reduction in vaccine effectiveness on the epidemics. We explored the epidemic trends under different levels of social restoration.Results: We estimated the overall existing vaccine effectiveness against the variant as 88.5% (95% CI: 87.4–89.5%) with the vaccination coverage of 70% by the end of August, 2021. With this vaccine effectiveness and coverage, there would be 498,972 (109,998–885,947) cumulative infections and 15,443 (3,828–27,057) deaths nationwide over the next 12 months, of which 95.0% infections and 93.3% deaths were caused by the variant. Complete social restoration at 60, 65, 70% vaccination coverage would increase cumulative infections to 1.6 (0.2–2.9) million 0.7 (0.1–1.2) million, and 511,159 (110,578–911,740), respectively. At same time it would increase cumulative deaths to 39,040 (5,509–72,570), 19,562 (3,873–35,250), 15,739 (3,841–27,638), respectively. However, if the vaccine effectiveness were reduced to 75%, 50% or 25% due to new SARS-CoV-2 variants, there would be 667,075 (130,682–1,203,468), 1.7 (0.2–3.2) million, 19.0 (5.3–32.7) million new infections and 19,249 (4,281–34,217), 42,265 (5,081–79,448), 426,860 (117,229–736,490) cumulative deaths to occur over the next 12 months. Further, social restoration at a lower vaccination coverage would lead to even greater secondary outbreaks.Conclusion: Current COVID-19 vaccines remain effective against the SARS-CoV-2 variant, and 70% vaccination coverage would be sufficient to restore social activities to a pre-pandemic level. Further reduction in vaccine effectiveness against SARS-CoV-2 variants would result in a potential surge of the epidemic. Multiple measures, including public health interventions, vaccination scale-up and development of a new vaccine booster, should be integrated to counter the new challenges of new SARS-CoV-2 variants.