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Bivalent COVID-19 vaccines were introduced in 2022 but knowledge of their effectiveness against severe COVID-19 outcomes is currently limited. In Finnish register-based cohort analyses, we compared the risk of severe COVID-19 outcomes among those who received bivalent vaccination (exposed) between September 2022 and March 2023 to those who did not (unexposed). Among elderly aged 65–110 years, bivalent vaccination reduced the risk of hospitalisation and death due to COVID-19 in September–December 2022; the hazard ratios comparing exposed and unexposed ranged from 0.37 to 0.45 during the first 31–60 days since bivalent vaccination. However, in January–March 2023 the effect disappeared possibly indicating immune evasion of new SARS-CoV-2 variants, waning of vaccine effectiveness and increased presence of hybrid immunity. Among the chronically ill aged 18–64 years bivalent vaccination did not reduce the risk of severe COVID-19 outcomes. These results are important for developing COVID-19 vaccines and programmes worldwide.

Recently, Covid-19 vaccine effectiveness has decreased especially against mild disease due to emergence of the Delta variant and waning protection. In this register-based study among healthcare workers in Finland, the vaccine effectiveness of two-dose mRNA vaccine series against SARS-CoV-2 infection decreased from 82% (95% CI 79-85%) 14-90 days after vaccination to 53% (43-62%) after 6 months. Similar trend was observed for other series. Waning was not observed against Covid-19 hospitalization. These results facilitate decision-making of booster doses for healthcare workers.

BackgroundData on the comparative vaccine effectiveness (CVE) of the bivalent mRNA-booster vaccines containing the original SARS-CoV-2 and omicron BA.4-5 and BA.1 subvariants are limited.MethodsIn a period of BA.4-5 subvariants predominance, we estimated the CVE of the bivalent Comirnaty (Pfizer-BioNTech) and Spikevax (Moderna) BA.4-5 and BA.1 mRNA-booster vaccines given as a fourth dose in Denmark, Finland, Norway, and Sweden. From 1 July 2022 to 12 December 2022, we conducted nationwide cohort analyses using target trial emulation to compare risks of Covid-19 hospitalization and death in four-dose (second booster) with three-dose (first booster) vaccinated and between four-dose vaccinated individuals.ResultsCompared with having received three vaccine doses, receipt of a bivalent BA.4-5 booster as a fourth dose was associated with a country-combined CVE against Covid-19 hospitalization of 80.5% (95% confidence interval, 69.5% to 91.5%). The corresponding CVE for bivalent BA.1 boosters was 74.0% (68.6% to 79.4%). CVE against Covid-19 death was 77.8% (48.3% to 100%) and 80.1% (72.0% to 88.2%) for bivalent BA.4-5 and BA.1 boosters as a fourth dose, respectively. The CVE of bivalent BA.4-5 vs. BA.1 boosters were 32.3% (10.6% to 53.9%) for Covid-19 hospitalization and 12.3% (−36.1% to 60.7%) for death (the latter estimable in Denmark only).ConclusionsVaccination with bivalent BA.4-5 or BA.1 mRNA-booster vaccines as a fourth dose was associated with increased protection against Covid-19 hospitalization and death during a period of BA.4-5 predominance. Bivalent BA.4-5 boosters conferred moderately greater vaccine effectiveness against Covid-19 hospitalization compared with bivalent BA.1 boosters.

ObjectiveTo investigate the effectiveness of heterologous booster schedules with AZD1222 (Oxford-AstraZeneca, referred to as AZD), BNT162b2 (Pfizer-BioNTech, BNT), and mRNA-1273 (Moderna, MOD) vaccines compared with primary schedules and with homologous mRNA-vaccine booster schedules during a period of omicron predominance.DesignPopulation-based cohort analyses.SettingDenmark, Finland, Norway, and Sweden, 27 December 2020 to 28 February 2022.ParticipantsAdults that had received at least a primary vaccination schedule (ie, two doses) of the AZD, BNT, and/or MOD vaccines during the study period.Main outcome measuresUsing the Kaplan-Meier estimator, we compared country-specific risks of SARS-CoV-2 infection and severe COVID-19 outcomes in heterologous booster vaccinated with primary schedule vaccinated (matched analyses) and homologous booster vaccinated (weighted analyses) since emergence of omicron.ResultsHeterologous booster schedules improved protection against all outcomes compared with primary schedules, with the largest and most robust effects observed for severe COVID-19. Risk differences for documented infection ranged from -22.4% to -3.1% (comparative vaccine effectiveness [CVE] 9.7% to 60.9%; >63.2% for COVID-19 hospitalisation) across countries for AZD1BNT2BNT3 (AZD as primary dose followed by two doses of BNT) vs AZD1BNT2 and -22.2% to -3.2% (CVE 37.4% to 67.8%; >34.6% for hospitalisation) for BNT1BNT2MOD3 vs BNT1BNT2, the two most common heterologous booster schedules. Heterologous- and homologous booster schedules had comparable effectiveness. Risk differences of documented infection ranged from -0.4% to 4.4% (CVE -20.0% to 2.4%) for AZD1BNT2BNT3 vs BNT1BNT2BNT3 and -19.8% to 1.7% (CVE -14.6% to 53.8%) for BNT1BNT2MOD3 vs BNT1BNT2BNT3; for most comparisons, risk differences for severe COVID-19 outcomes were smaller than 1 per 1000 vaccinated. Previous infection followed by a booster dose conferred the greatest protection.ConclusionHeterologous booster vaccine schedules are associated with an increased protection against omicron-related COVID-19 outcomes that is comparable to that afforded by homologous booster schedules.

Prioritisation of elderly people in COVID-19 vaccination campaigns aimed at reducing severe outcomes in this group. Using EU/EEA surveillance and vaccination uptake, we estimated the risk ratio of case, hospitalisation and death notifications in people 80 years and older compared with 25–59-year-olds. Highest impact was observed for full vaccination uptake 80% or higher with reductions in notification rates of cases up to 65% (IRR: 0.35; 95% CI: 0.13–0.99), hospitalisations up to 78% (IRR: 0.22; 95% CI: 0.13–0.37) and deaths up to 84% (IRR: 0.16; 95% CI: 0.13–0.20).

The gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is reverse transcription (RT)-PCR from a nasopharyngeal swab specimen (NPS). Its collection involves close contact between patients and health care workers, requiring a significant amount of workforce and putting them at risk of infection. We evaluated self-collection of alternative specimens and compared their sensitivity and cycle threshold (CT) values to those of NPS. We visited acute coronavirus disease 2019 (COVID-19) outpatients to collect concomitant NPS and gargle specimens and had patients self-collect gargle and either sputum or spit specimens the next morning. We included 40 patients and collected 40 concomitant NPS and gargle specimens, as well as 40 gargle, 22 spit, and 16 sputum specimens the next day (2 patients could not produce sputum). All specimens were as sensitive as NPS. Gargle specimens had a sensitivity of 0.97 (95% confidence interval [CI], 0.92 to 1.00), whether collected concomitantly with NPS or the next morning. Next-morning spit and sputum specimens showed sensitivities of 1.00 (95% CI, 1.00 to 1.00) and 0.94 (95% CI, 0.87 to 1.00]), respectively. The gargle specimens had significantly higher mean CT values of 29.89 (standard deviation [SD], 4.63; P < 0.001) and 29.25 (SD, 3.99; P < 0.001) when collected concomitantly and the next morning, respectively, compared to NPS (22.07 [SD, 4.63]). CT values obtained with spit (23.51 [SD, 4.57]; P = 0.11) and sputum (25.82 [SD, 9.21]; P = 0.28) specimens were close to those of NPS. All alternative specimen collection methods were as sensitive as NPS, but spit collection appeared more promising, with a low CT value and ease of collection. Our findings warrant further investigation. IMPORTANCE Control of the COVID-19 pandemic relies heavily on a test-trace-isolate strategy. The most commonly used specimen for diagnosis of SARS-CoV-2 infection is a nasopharyngeal swab. However, this method is quite uncomfortable for the patient, requires specific equipment (nose swabs and containers), and requires close proximity to health care workers, putting them at risk of infection. Developing alternative sampling strategies could decrease the burden for health care workers, help overcome potential shortages of equipment, and improve acceptability of testing by reducing patient discomfort. publishedVersion

BackgroundIn Finland, both mRNA and adenovirus vector (AdV) Covid-19 vaccines have been used after the vaccination campaign started on December 27, 2020. Vaccination of the elderly and chronically ill was prioritized and the interval between doses set to 12 weeks. The objective of this interim analysis was to evaluate first and second dose vaccine effectiveness (VE) in a real-world setting.MethodsDuring the first 5 months of the campaign, a register-based cohort study was conducted in the Finnish elderly aged 70+ years and those aged 16–69 years with medical conditions predisposing to severe Covid-19 (chronically ill). Using Cox regression, VE against SARS-CoV-2 infection and Covid-19 hospitalization was estimated comparing the hazard in the vaccinated with that in the unvaccinated.ResultsThe cohorts included 901092 elderly (89% vaccinated) and 774526 chronically ill (69% vaccinated) individuals. Three weeks after the first dose, mRNA VE against infection was 45% (95% confidence interval, 36–53%) and 40% (26–51%) in elderly and chronically ill; mRNA VE against hospitalization was 63% (49–74%) and 82% (56–93%). In chronically ill, AdV VE was 42% (32–50) and 62% (42– 75%) against infection and hospitalization, respectively. One week after the second dose, mRNA VE against infection was 75% (65–82%) and 77% (65–85%) in elderly and chronically ill; mRNA VE against hospitalization was 93% (70–98%) and 90% (29–99%).ConclusionsCovid-19 vaccines protect against SARS-CoV-2 infection and Covid-19 hospitalization. A single dose provides moderate protection in elderly and chronically ill, although 2 doses are clearly superior.summaryThis register-based cohort study demonstrates that Covid-19 vaccines protect against SARS-CoV-2 infection and Covid-19 hospitalization among Finnish elderly and chronically ill. Vaccine effectiveness against hospitalization was moderate after 1 dose and increased to ≥90% after 2 doses.