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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.
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IntroductionInformation on vaccine effectiveness and viral loads in a context of novel variants of concern (VOC) emergence is of key importance to inform public health policies. This study aimed to estimate a measure of comparative vaccine effectiveness between Omicron (BA.1) and Delta (B.1.617.2 and sub-lineages) VOC according to vaccination exposure (primary or booster) and time since primary vaccination and to compare cycle threshold (Ct) values between Omicron and Delta VOC infections according to the vaccination status as an indirect measure of viral load. MethodsWe developed a case-case study using data on RT-PCR SARS-CoV-2 positive cases notified in Portugal during weeks 49-51 2021. The odds of vaccination in Omicron cases were compared to Delta using logistic regression adjusted for age group, sex, region and week of diagnosis and laboratory of origin. RT-PCR Ct values were compared by vaccination status and variant using linear regression model. ResultsHigher odds of vaccination were observed in cases infected by Omicron (BA.1) VOC compared to Delta (B.1.617.2) VOC cases for both complete primary vaccination (OR=2.1; CI 95% :1.8 to 2.4) and booster dose (OR= 5.2; CI 95%: 3.1 to 8.8), indicating vaccine effectiveness reduction against Omicron. No differences in distribution of Ct-values between these two VOC were observed for any vaccination exposure categories. ConclusionConsistent lower VE was observed against Omicron infection. Complete primary vaccination may not be protective against SARS-CoV-2 infection in regions where Omicron variant is dominant, but a massive rollout of booster vaccination campaign can contribute to reduce SARS-CoV-2 incidence in the population.
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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.
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IntroductionHealthcare workers (HCW) were amongst the first prioritized for COVID-19 vaccination but data on COVID-19 vaccine effectiveness among HCW is still limited. This study aims to estimate the COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 symptomatic infection among HCW from Portuguese hospitals. MethodsIn this prospective cohort study, we analysed data from HCW (all professional categories) from two central hospitals in the Lisbon and Tagus Valley and Centre regions of mainland Portugal between December 2020 and November 2021. VE against symptomatic SARS-CoV-2 infection was estimated as one minus the confounder adjusted hazard ratios by Cox models considering age group, sex, presence of chronic disease and occupational exposure to patients diagnosed with COVID-19 as adjustment variables. ResultsDuring the 11 months of follow up, the 2213 HCW contributed a total of 1950 person-years at risk and 171 SARS-CoV-2 events occurred. The COVID-19 incidence rate for unvaccinated HCW was 348.7 per 1000 person-years while for fully vaccinated HCW was 43.0 per 1000 person-years. We observed a VE against symptomatic SARS-CoV-2 infection of 73.9% (95% CI: 26.2-90.8%) for complete vaccination status. ConclusionThis cohort study found a high COVID-19 VE against symptomatic SARS-CoV-2 infection in Portuguese HCW, which is in concordance with previous studies from other countries. Monitoring of VE in this HCW cohort continues during the winter 2021/2022 to evaluate potential VE decay and booster vaccine effect.
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BackgroundUsing data from electronic health registries, this study intended to estimate the COVID-19 vaccine effectiveness in the population aged 65 years and more, against symptomatic infection, COVID-19 related hospitalizations and deaths, overall and by time since complete vaccination. MethodsWe stablished a cohort of individuals aged 65 and more years old, resident in Portugal mainland, using the National Health Service unique identifier User number to link eight electronic health registries. Outcomes included were symptomatic SARS-CoV-2 infections, COVID-19 related hospitalizations or deaths. The exposures of interest were the mRNA vaccines (Cominarty or Spikevax) and the viral vector Vaxzevria vaccine. Complete scheme vaccine effectiveness (VE) was estimated as one minus the confounder adjusted hazard ratio, for each outcome, estimated by time-dependent Cox regression with time dependent vaccine exposure. ResultsFor the cohort of individuals aged 65-79 years, complete scheme VE against symptomatic infection varied between 43% (Vaxzevria) and 65% (mRNA vaccines). This estimate was slightly lower in the [≥]80 year cohort (53% for mRNA vaccines. VE against COVID-19 hospitalization varied between 89% (95%CI: 52-94) for Vaxzevria and 95% (95%CI: 93-97) for mRNA vaccines for the cohort aged 65-79 years and was 76% (95%CI: 67-83) for mRNA vaccines in the [≥]80 year cohort. High VE against COVID-19 related deaths were estimated, for both vaccine types, 95% and 81% for the 65-79 years and the [≥]80 year cohort, respectively. We observed a significant waning of VE against symptomatic infection, with VE estimates reaching approximately 34% for both vaccine types and cohorts. Significant waning was observed for the COVID-19 hospitalizations in the [≥]80 year cohort (decay from 83% 14-41 days to 63% 124 days after mRNA second dose). No significant waning effect was observed for COVID-19 related deaths in the period of follow-up of either cohorts. ConclusionsIn a population with a high risk of SARS-CoV-2 complications, we observed higher overall VE estimates against more severe outcomes for both age cohorts when compared to symptomatic infections. Considering the analysis of VE according to time since complete vaccination, the results showed a waning effect for both age cohorts in symptomatic infection and COVID-19 hospitalization for the 80 and more yo cohort.
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Vaccination is considered the most important measure to control the COVID-19 pandemic. Extensive follow-up studies with distinct vaccines and populations are able to promote robust and reliable data to better understand the effectiveness of this pharmacologic strategy. In this sense, we present data regarding binding and neutralizing antibodies throughout time, from vaccinated and previously infected (PI) health care workers (HCW) in Portugal. We analyzed serum samples of 132 HCW, vaccinated and with previous SARS-CoV-2 infection. Samples were collected before vaccination (baseline, M1), at second dose vaccine uptake (M2), and 25-70 days (M3) and 150-210 days (M4) after the second dose for vaccinated individuals. The IgG (anti-RBD/S) antibody geometric mean titer found on vaccinated HCW at M2 (814.7 AU/ml; 95% CI 649.8-1021.5) were significantly higher than those found on PI HCW at recruitment (M1) (252.6 AU/ml; 95% CI 108.7 - 587.1), and the neutralizing antibodies (nAb) were similar between these groups, 93.2 UI/ml (95% CI 73.2-118.5) vs. 84.1 UI/ml (95% CI 40.4-155.9), respectively. We detected about 10-fold higher IgG (anti-RBD/S) antibodies titers in M3 when compared with M2, with a slightly but significant decrease in titers from 36 days after the second dose vaccine uptake. The increase of nAb titers were correlated with IgG (anti-RBD/S) antibodies titers, however, contrasting to IgG (anti-RBD/S) antibodies titers, we did not detect a decrease in nAb titer from 36 days after a second vaccine dose uptake. At M4, was observed a decrease of 8-fold in binding IgG (anti-RBD/S) and nAb. No significant differences in antibody titers were observed by sex, age or chronic diseases. Our results suggest that IgG (anti-RBD/S) antibodies titers and nAb titers could be correlated, but ongoing follow up of the cohort, is required to better understand this correlation, and the duration of the immune response.
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BackgroundWe used electronic health registries to estimate the mRNA vaccine effectiveness (VE) against COVID-19 hospitalizations and deaths in older adults. MethodsWe established a cohort of individuals aged 65 and more years, resident in Portugal mainland through data linkage of eight national health registries. For each outcome, VE was computed as one minus the confounder-adjusted hazard ratio, estimated by time-dependent Cox regression. ResultsVE against COVID-19 hospitalization [≥]14 days after the second dose was 94% (95%CI 88 to 97) for age-group 65-79 years old (yo) and 82% (95%CI 72 to 89) for [≥]80 yo. VE against COVID-19 related deaths [≥] 14 days after second dose was 96% (95%CI 92 to 98) for age-group 65-79 yo and 81% (95%CI 74 to 87), for [≥]80 yo individuals. No evidence of VE waning was observed after 98 days of second dose uptake. ConclusionsmRNA vaccine effectiveness was high for the prevention of hospitalizations and deaths in age-group 65-79 yo and [≥]80 yo with a complete vaccination scheme, even after 98 days of second dose uptake.
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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.