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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22268602

ABSTRACT

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.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-22269406

ABSTRACT

IntroductionEarly reports showed that Omicron (BA.1) SARS-CoV-2 could be less severe. However, the magnitude of risk reduction of hospitalization and mortality of Omicron (BA.1) infections compared with Delta (B.1.617.2) is not yet clear. This study compares the risk of severe disease among patients infected with the Omicron (BA.1) variant with patients infected with Delta (B.1.617.2) variant in Portugal. MethodsWe conducted a cohort study in individuals diagnosed with SARS-CoV-2 infection between 1st and 29th December 2021. Cases were individuals with a positive PCR test notified to the national surveillance system. SARS-CoV-2 variants were classified first by whole genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure. We considered a hospitalization for all the patients admitted within the 14 days after the SARS-CoV-2 infection; after that period, they were censored. The comparison of the risk of hospitalization between Omicron (BA.1) and Delta (B.1.617.2) VOC was estimated using a Cox proportional hazards model. The mean length of stay was compared using linear regression, and the risk of death between Omicron and Delta patients was estimated with a penalized logistic regression. All models were adjusted for sex, age, previous infection, and vaccination status. ResultsWe included 15 978 participants aged 16 or more years old, 9 397 infected by Delta (B.1.617.2) and 6 581 infected with Omicron (BA.1). Within the Delta (B.1.617.2) group, 148 (1.6%) were hospitalized, and 16 (0.2%) were with the Omicron (BA.1). A total of 26 deaths were reported, all in participants with Delta (B.1.617.2) infection. Adjusted HR for hospitalization for the Omicron (BA.1) variant compared with Delta (B.1.617.2) was 0.25 (95%CI 0.15 to 0.43). The length of stay in hospital for Omicron (BA.1) patients was significantly shorter than for Delta (confounding-adjusted difference -4.0 days (95%CI -7.2 to -0.8). The odds of death were 0.14 (95% CI 0.0011 to 1.12), representing a reduction in the risk of death of 86% when infected with Omicron (BA.1) compared with Delta (B.1.617.2). ConclusionOmicron (BA.1) was associated with a 75% risk reduction of hospitalization compared with Delta (B.1.617.2) and reduced length of hospital stay.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21262020

ABSTRACT

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.

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