SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal

BackgroundIn a context of multiple Omicron lineages circulation, it is relevant to clarify the effect of vaccination and previous infections on the risk of infection and severe post-infection outcomes. MethodsUsing electronic health records and SARS-CoV-2 laboratory surveillance data, we conducted a case-case and a cohort study covering the period of Omicron BA.2/BA.5 lineage replacement in Portugal, to compare vaccine effectiveness of complete primary and booster dose against infection, COVID-19 hospitalization, and mortality. Variant classification was performed through whole-genome sequencing (WGS) or Spike Gene Target Failure (SGTF). FindingsBetween April 25 and June 10, 2022, within a total of 27702 collected samples, 55.5% were classified as BA.2 and the remaining as BA.5. We observed no evidence of reduced vaccine effectiveness for the primary complete vaccination (OR=1.07, CI95%:0.93-1.23) or booster dose vaccination (OR=0.96, CI95%:0.84-1.09) against BA.5 infection compared with BA.2. The protection against reinfection was inferior in BA.5 cases when compared with BA.2 (OR=1.44; CI95%:1.30-1.60). Among those infected with BA.5, booster vaccination was associated with 77% and 88% of reduction in risk of COVID-19 hospitalization and death, respectively, while higher risk reduction was found for BA.2 cases, with 93% and 94%, respectively. InterpretationThis study shows that the SARS-CoV-2 Omicron BA.5 lineage is associated with higher odds of reinfection compared with Omicron BA.2, regardless of the vaccination status. Although less effective compared with BA.2, COVID-19 booster vaccination still offers substantial protection against severe outcomes following BA.5 infection.

B.1.617.2 SARS-CoV-2 (Delta) variant is associated with increased risk of hospitalization and death compared with B.1.1.7 SARS-CoV-2 (Alpha) variant

IntroductionThe B.1.617.2 variant (Delta) was associated with increased transmissibility and lower vaccine effectiveness than the B.1.1.7 variant (Alpha). However, the effect of the B.1.617.2 variant on disease severity remains unclear. This study aims to assess whether infection with the B.1.617.2 variant was associated with a higher risk of serious illness, compared with other co-circulating variants, measured through hospitalization and death by COVID-19 in Portugal. MethodsWe conducted a matched cohort study in adult individuals diagnosed with SARS-CoV-2/COVID-19 infection between March 29 and August 1, 2021. Cases were individuals with a positive PCR test notified to the surveillance system. SARS-CoV-2 variants were classified first by genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure. Delta (B.1.617.2) and Alpha (B.1.1.7) cases were matched on the week of diagnosis at a 1 to k ratio (k being the maximum number of unexposed available in that week) to maximize the inclusion of unexposed, using the nearest-neighbor algorithm. The hazard risk and 95% confidence intervals of hospitalization and death among those infected with the Delta (B.1.617.2) variant vs. Alpha (B.1.1.7) was estimated using a Cox proportional hazards model, adjusting for confounding for sex, age, and vaccination status. ResultsA total of 2,778 cases were included in the study. Of the total, 1 742 (68%) were identified as B.1.617.2 variant cases and 3 629 (32%) as B.1.1.7 variant. Within the B.1.1.7 variant cases 106 (2.9%) were hospitalized, and 110 (6.3%) within the B.1.617.2 variant cases. A total of 29 deaths were reported, 8 (0.2%) in patients infected with B.1.1.7 variant and 21 (1.2%) in patients with the B.1.617.2 variant. The confounding adjusted risk of hospitalization, in persons infected with the B.1.617.2 variant was 2.44 (95%CI 1.85; 3.20) times higher than the risk of hospitalization among B.1.1.7 variant cases, and the confounding-adjusted risk of death for B.1.617.2 variant cases was 5.20 (95%CI 2.20; 12.29) times higher than the risk of death in patients infected by B.1.1.7 variant. ConclusionThe B.1.617.2 variant is associated with an increased risk of hospitalization and death compared with the B.1.1.7 variant.

Delta variant and mRNA Covid-19 vaccines effectiveness: higher odds of vaccine infection breakthroughs

BackgroundThe SARS-CoV-2 Delta variant (B.1.617.2), initially identified in India, has become predominant in several countries, including Portugal. Few studies have compared the effectiveness of mRNA vaccines against Delta versus Alpha variant of concern (VOC) and estimated variant-specific viral loads in vaccine infection breakthroughs cases. In the context of Delta dominance, this information is critical to inform decision-makers regarding the planning of restrictions and vaccination roll-out. MethodsWe developed a case-case study to compare mRNA vaccines effectiveness against Delta (B.1.617.2) versus Alpha (B.1.1.7) variants. We used RT-PCR positive cases notified to the National Surveillance System between 17th of May and 4th of July 2021 (week 20 to 26) and information about demographics and vaccination status through the electronic vaccination register. Whole-genome sequencing (WGS) or spike (S) gene target failure (SGTF) data were used to classify SARS-CoV-2 variants. The odds of vaccinated individuals to become infected (odds of vaccine infection breakthrough) in Delta cases compared to Alpha SARS-CoV-2 cases was estimated by conditional logistic regression adjusted for age group, sex, and matched by the week of diagnosis. As a surrogate of viral load, mean RT-PCR Ct values were stratified and compared between vaccine status and VOC. ResultsOf the 2 097 SARS-CoV-2 RT-PCR positive cases included in the analysis, 966 (46.1%) were classified with WGS and 1131 (53.9%) with SGTF. Individuals infected with the Delta variant were more frequently vaccinated 162 (12%) than individuals infected with the Alpha variant 38 (5%). We report a statistically significant higher odds of vaccine infection breakthrough for partial (OR=1.70; CI95% 1.18 to 2.47) and complete vaccination (OR=1.96; CI95% 1.22 to 3.14) in the Delta cases when compared to the Alpha cases, suggesting lower mRNA vaccine effectiveness against Delta cases. On our secondary analysis, we observed lower mean Ct values for the Delta VOC cases versus Alpha, regardless the vaccination status. Additionally, the Delta variant cases revealed a Ct-value mean increase of 2.24 (CI95% 0.85 to 3.64) between unvaccinated and fully vaccinated breakthrough cases contrasting with 4.49 (CI95% 2.07 to 6.91) in the Alpha VOC, suggesting a lower impact of vaccine on viral load of Delta cases. ConclusionsWe found significantly higher odds of vaccine infection breakthrough in Delta cases when compared to Alpha cases, suggesting lower effectiveness of the mRNA vaccines in preventing infection with the Delta variant. Additionally, the vaccine breakthrough cases are estimated to be of higher mean Ct values, suggesting higher infectiousness with the Delta variant infection. These findings can help decision-makers weigh on the application or lifting of control measures and adjusting vaccine roll-out depending on the predominance of the Delta variant and the coverage of partial and complete mRNA vaccination.