Severe outcomes in unvaccinated COVID-19 cases <18 years during different variant waves in Norway

ObjectivesWe used linked individual-level data from national registries to compare the risk of severe outcomes among unvaccinated COVID-19 cases <18 years between waves of the SARS-CoV-2 Alpha, Delta and Omicron variants in Norway. MethodsOur outcomes were hospitalisation with acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C). We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable log-binomial regression, adjusting for variant wave, demographic characteristics and underlying comorbidities. ResultsWe included 10,538 Alpha (21 hospitalised with acute COVID-19, 7 MIS-C), 42,362 Delta (28 acute COVID-19, 14 MIS-C) and 82,907 Omicron wave cases (48 acute COVID-19, 7 MIS-C). The risk of hospitalisation with acute COVID-19 in cases <1 year was lower in the Delta (aRR: 0.28, 95% CI: 0.16-0.89) and Omicron wave (aRR: 0.41, 95% CI: 0.20-0.81), compared to the Alpha wave. We found no difference in the risk for this outcome for Omicron compared to Delta in any age group. The risk of MIS-C was lower in the Omicron wave compared to the Alpha (aRR: 0.09, 95% CI: 0.03-0.27) and Delta wave (aRR: 0.26, 95% CI: 0.10-0.63). ConclusionsWe found no evidence of a difference in the risk of hospitalisation due to acute COVID-19 among unvaccinated cases <18 years for Omicron compared to Delta, but a reduced risk among cases <1 year in Omicron and Delta waves, compared to Alpha. Results also suggest a decrease in the risk of MIS-C in the Omicron wave compared to the Alpha and Delta waves. Article SummaryWe compare the risk of severe outcomes in unvaccinated COVID-19 cases <18 years between waves of the SARS-CoV-2 Alpha, Delta and Omicron variant in Norway. Whats Known on This SubjectCurrently, limited evidence suggests no clear difference in the risk of severe disease outcomes among children infected with different SARS-CoV-2 variants. The risk of multisystem inflammatory syndrome in children following infection with the Omicron variant has not been quantified. What This Study AddsWe find a lower risk of hospitalisation due to acute COVID-19 among cases <1 year in the Delta and Omicron waves compared to the Alpha wave, and a lower risk of multisystem inflammatory syndrome in the Omicron wave, in Norway.

Age and product dependent vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adults in Norway: a national cohort study, July - November 2021.

BackgroundCOVID-19 vaccines have been crucial in the pandemic response and understanding changes in vaccines effectiveness is essential to guide vaccine policies. Though the Delta variant is no longer dominant, understanding vaccines effectiveness properties will provide essential knowledge to comprehend the development of the pandemic and estimate potential changes over time. MethodsIn this population-based cohort study, we estimated vaccine effectiveness against SARS-CoV-2 infections, hospitalisations, intensive care admissions, and death using Cox proportional hazard models, across different vaccine product regimens and age groups, between 15 July and 31 November 2021 (Delta variant period). Vaccine status is included as a time-varying covariate and all models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data from the entire adult Norwegian population were collated from the National Preparedness Register for COVID-19 (Beredt C19). ResultsThe overall adjusted vaccine effectiveness against infection decreased from 81.3% (confidence interval (CI): 80.7 to 81.9) in the first two to nine weeks after receiving a second dose to 8.6% (CI:4.0 to 13.1) after more than 33 weeks, compared to 98.6% (CI: 97.5 to 99.2) and 66.6% (CI: 57.9 to 73.6) against hospitalisation respectively. After the third dose (booster), the effectiveness was 75.9% (CI: 73.4 to 78.1) against infection and 95.0% (CI: 92.6 to 96.6) against hospitalisation. Spikevax or a combination of mRNA products provided the highest protection, but the vaccine effectiveness decreased with time since vaccination for all vaccine regimens. ConclusionsEven though the vaccine effectiveness against infection wanes over time, all vaccine regimens remained effective against hospitalisation after the second vaccine dose. For all vaccine regimens, a booster facilitated recovery of effectiveness. The results from this support the use of heterologous schedules, increasing flexibility in vaccination policy. Fundingno external funding

Vaccine effectiveness with BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine against reported SARS-CoV-2 Delta and Omicron infection among adolescents, Norway, August 2021 to January 2022

BackgroundCOVID-19 vaccination was recommended for adolescents in Norway since August 2021. In this population-based cohort study, we estimated the BNT162b2 vaccine effectiveness against any PCR-confirmed (symptomatic or not) SARS-CoV-2 infections caused by the Delta and Omicron variant among adolescents (12-17-years-old) in Norway from August 2021 to January 2022. MethodsUsing Cox proportional hazard models, we estimated the BNT162b2 vaccine effectiveness against any Delta and Omicron infections. Vaccine status was included as a time-varying covariate and models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data were obtained from the National Preparedness registry for COVID-19, which contains individual-level data from national health and administrative registries. FindingsVaccine effectiveness against Delta infection peaked at 68% (95%CI: 64-71%) and 62% (95%CI: 57- 66%) in days 21-48 after the first dose among 12-15-year-olds and 16-17-year-olds respectively. Among 16-17-year-olds that received two doses, vaccine effectiveness peaked at 93% (95%CI: 90-95%) in days 35-62 and declined to 84% (95%CI: 76-89%) in 63 days or more after the second dose. For both age-groups, we found no protection against Omicron infection after receiving one dose. Among 16-17-year-olds, vaccine effectiveness against Omicron infection peaked at 53% (95%CI: 43-62%) in 7-34 days after the second dose and decreased to 23% (95%CI: 3-40%) in 63 days or more after vaccination. Vaccine effectiveness decreased with time since vaccination for both variants, but waning was observed to occur faster for Omicron. InterpretationOur results suggest reduced protection from BNT162b2 vaccination against any SARS-CoV-2 infection caused by the Omicron variant compared to the Delta. In addition, waning immunity was observed to occur faster for Omicron. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during omicron dominance. FundingNo funding was received. Research in context Evidence before this studyBNT162b2 (Comirnaty, Pfizer-BioNTech) and mRNA-1273 (Spikevax, Moderna) vaccines have been approved for use in adolescents, based on results from randomized placebo-controlled trials demonstrating comparable immunogenicity and safety profile as in young adults. In addition, observational studies from Israel, the USA and England have reported high protection of BNT162b2 vaccines against SARS-CoV-2 Delta infection among adolescents. These studies also reported decrease in effectiveness with time since last vaccine dose. Evidence on the effect of an extended interval between doses, longer time since vaccination and the effect against different variants is limited. When we first planned this study in early February 2022, no data were available regarding vaccine effectiveness against SARS-CoV-2 Omicron infection among adolescents. To our knowledge when we completed this study and before submitting this article, only one study from England reported results in a preprint on vaccine effectiveness against symptomatic SARS-CoV-2 Omicron infection among adolescents. We searched for studies that evaluated vaccine efficacy or effectiveness after vaccination of adolescents during 2021-2022 in PubMed, medRxiv, bioRxiv, SSRN. We searched for studies with several variations of the primary key search terms "COVID-19", "SARS-CoV-2", and "vaccine" (including names of specific vaccines, as BNT162b2), "vaccine effectiveness", "adolescents", "children". Added value of this studyThe rapid increase in the incidence of SARS-CoV-2 infection caused by the Omicron variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines in adults but also adolescents. In this population-based cohort study, we showed that the vaccine effectiveness against Omicron is lower than against Delta infections among adolescents, including symptomatic and asymptomatic infections. We should note that evidence suggests higher rates of asymptomatic carriage for Omicron than other variants of concern. Vaccine effectiveness that includes asymptomatic cases, as in the study from England, is expected to be lower than when including symptomatic cases only. We found that one and two doses of BNT162b2 among adolescents protected well against Delta. Vaccination provided high protection against Delta infections (>91%) among Norwegian 16-17-year-olds 7-62 days after the second dose. We found no protection against Omicron SARS-CoV-2 infection after one vaccine dose, and moderate effectiveness after two doses (peaked at 53%) among the 16-17-year-olds. Moreover, waning immunity was observed to occur faster for Omicron. Implications of all the available evidenceBased on the available evidence, the vaccine effectiveness among adolescents is similar to that reported among adults, also with an extended period of 8-12 weeks between doses which was used in Norway. Protection is significantly lower against Omicron than Delta infections and immunity wanes faster against Omicron. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during omicron dominance. Policies should take into account the impact of vaccination campaigns among adolescents and their primary objective. Vaccine effectiveness should be re-evaluated when other variants appear as they might have different outcomes as shown between Delta and Omicron infections.

Milder disease trajectory among COVID-19 patients hospitalised with the SARS-CoV-2 Omicron variant compared with the Delta variant in Norway

Using individual-level national registry data, we conducted a cohort study to estimate differences in the length of hospital stay, and risk of admission to an intensive care unit and in-hospital death among patients infected with the SARS-CoV-2 Omicron variant, compared to patients infected with Delta variant in Norway. We included 409 (38%) patients infected with Omicron and 666 (62%) infected with Delta who were hospitalised with COVID-19 as the main cause of hospitalisation between 6 December 2021 and 6 February 2022. Omicron patients had a 48% lower risk of intensive care admission (aHR: 0.52, 95%CI: 0.34-0.80) and a 56% lower risk of in-hospital death (aHR: 0.44, 95%CI: 0.24-0.79) compared to Delta patients. Omicron patients had a shorter length of stay (with or without ICU stay) compared to Delta patients in the age groups from 18-79 years and those who had at least completed their primary vaccination. This supports growing evidence of reduced disease severity among hospitalised Omicron patients compared with Delta patients.

Age and product dependent vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adults in Norway: a national cohort study, January to September 2021.

BackgroundSARS-CoV-2 vaccines show high effectiveness against infection and (severe) disease. However, few studies estimate population level vaccine effectiveness against multiple COVID-19 outcomes, by age and including homologous and heterologous vaccine regimens. MethodsUsing Cox proportional hazard models on data from 4 293 544 individuals (99% of Norwegian adults), we estimated overall, age-, and product-specific vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, ICU admission and death in Norway, using data from national registries. Vaccine status was included as time-dependent variable and we adjusted for sex, pre-existing medical conditions, country of birth, county of residence, and crowded living conditions. FindingsAdjusted vaccine effectiveness among fully vaccinated is 72{middle dot}1% (71{middle dot}2-73{middle dot}0) against SARS-CoV-2 infection, 92{middle dot}9% (91{middle dot}2-94{middle dot}2) against hospitalisation, 95{middle dot}5% (92{middle dot}6-97{middle dot}2) against ICU admission, and 88{middle dot}0% (82{middle dot}5-91{middle dot}8) against death. Among partially vaccinated, the effectiveness is 24{middle dot}3% (22{middle dot}3-26{middle dot}2) against infection and 82{middle dot}7% (77{middle dot}7-86{middle dot}6) against hospitalisation. Vaccine effectiveness against infection is 84{middle dot}7% (83{middle dot}1-86{middle dot}1) for heterologous mRNA vaccine regimens, 78{middle dot}3% (76{middle dot}8-79{middle dot}7) for Spikevax (Moderna; mRNA-1273), 69{middle dot}7% (68{middle dot}6-70{middle dot}8) for Comirnaty (Pfizer/BioNTech; BNT162b2), and 60{middle dot}7% (57{middle dot}5-63{middle dot}6) for Vaxzevria (AstraZeneca; ChAdOx nCoV-19; AZD1222) with a mRNA dose among fully vaccinated. InterpretationWe demonstrate good protection against SARS-CoV-2 infection and severe disease in fully vaccinated, including heterologous vaccine regimens, which could facilitate rapid immunization. Partially vaccinated were less likely to get severe disease than unvaccinated, though protection against infection was not as high, which could be essential in making vaccine prioritisation policies especially when availability is limited. FundingNorwegian Institute of Public Health, Helse Bergen Health Trust

No difference in risk of hospitalisation between reported cases of the SARS-CoV-2 Delta variant and Alpha variant in Norway

ObjectivesTo estimate the risk of hospitalisation among reported cases of the Delta-variant of SARS-CoV-2 compared to the Alpha variant in Norway. We also estimated the risk of hospitalisation by vaccination status. MethodsWe conducted a cohort study on laboratory-confirmed cases of SARS-CoV-2 in Norway, diagnosed between 3 May and 15 August 2021. We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable binomial regression, accounting for variant, vaccination status, demographic characteristics, week of sampling and underlying comorbidities. ResultsWe included 7,977 cases of Delta and 12,078 cases of Alpha. Overall, 347 (1.7%) cases were hospitalised. The aRR of hospitalisation for Delta compared to Alpha was 0.97 (95%CI 0.76-1.23). Partially vaccinated cases had a 72% reduced risk of hospitalisation (95%CI 59%-82%), and fully vaccinated cases had a 76% reduced risk (95%CI 61%-85%), compared to unvaccinated cases. ConclusionsWe found no difference in the risk of hospitalisation for Delta cases compared to Alpha cases in Norway. Further research from a wide variety of settings is needed to better understand the association between the Delta variant and severe disease. Our results support the notion that partially and fully vaccinated persons are highly protected against hospitalisation with COVID-19. HighlightsO_LIThe SARS-CoV-2 Delta variant has dominated in Norway since July 2021 C_LIO_LIThere was no difference in the risk of hospitalisation for Delta cases compared to Alpha C_LIO_LIPartially and fully vaccinated cases had >70% decreased risk of hospitalisation C_LI

Trajectories of hospitalisation for patients infected with SARS-CoV-2 variant B.1.1.7 in Norway, December 2020 - April 2021

BackgroundThe SARS-CoV-2 variant of concern (VOC) B.1.1.7 has spread worldwide and has been associated with increased risk of severe disease. Studies on patient trajectories and outcomes among hospitalised patients infected with B.1.1.7 are essential for hospital capacity planning. MethodsUsing linked individual-level data from national registries, we conducted a cohort study on cases of SARS-CoV-2 in Norway hospitalised between 21 December 2020 and 25 April 2021. We calculated adjusted hazard ratios using survival analysis to examine the association between B.1.1.7 and time from symptom onset to hospitalisation, and length of stay (LoS) in hospital and an intensive care unit compared to non-VOC. We calculated adjusted odds ratios using logistic regression to examine the association between B.1.1.7 and mortality (up to 30 days post discharge) compared to non-VOC. ResultsWe included 946 B.1.1.7 patients and 157 non-VOC. The crude median time from symptom onset to hospitalisation was 8 days (IQR: 5-10) for B.1.1.7 and 8 days (IQR: 4-11) for non-VOC. The crude median LoS in hospital was 5.0 days (IQR: 2.6-10.0) for B.1.1.7 patients and 5.1 days (IQR: 2.5-9.9) for non-VOC. Fifty-four (6%) B.1.1.7 patients died, compared to 14 (9%) non-VOC. There was no difference in the unadjusted or adjusted estimates of our outcome measures for B.1.1.7 and non-VOC patients. ConclusionsB.1.1.7 does not appear to influence hospitalised patient trajectories, compared to non-VOC. These findings, along with the success of ongoing vaccination programmes, are encouraging for ongoing capacity planning in the hospital sector.

COVID-19 among immigrants in Norway, notified infections, related hospitalizations and associated mortality: A register-based study.

Aim: Research concerning COVID-19 among immigrants is limited. We present epidemiological data for all notified cases of COVID-19 among the 17 largest immigrant groups in Norway, and related hospitalizations and mortality. Methods: We used data on all notified COVID-19 cases in Norway up to 18 October 2020, and associated hospitalizations and mortality, from the emergency preparedness register (including Norwegian Surveillance System for Communicable Diseases) set up by The Norwegian Institute of Public Health to handle the pandemic. We report numbers and rates per 100,000 people for notified COVID-19 cases, and related hospitalizations and mortality in the 17 largest immigrant groups in Norway, crude and with age adjustment. Results: The notification, hospitalization and mortality rates per 100,000 were 251, 21 and five, respectively, for non-immigrants; 567, 62 and four among immigrants; 408, 27 and two, respectively, for immigrants from Europe, North-America and Oceania; and 773, 106 and six, respectively for immigrants from Africa, Asia and South America. The notification rate was highest among immigrants from Somalia (2057), Pakistan (1868) and Iraq (1616). Differences between immigrants and non-immigrants increased when adjusting for age, especially for mortality. Immigrants had a high number of hospitalizations relative to notified cases compared to non-immigrants. Although the overall COVID-19 notification rate was higher in Oslo than outside of Oslo, the notification rate among immigrants compared to non-immigrants was not higher in Oslo than outside. Conclusions: We observed a higher COVID-19 notification rate in immigrants compared to non-immigrants and much higher hospitalization rate, with major differences between different immigrant groups. Somali-, Pakistani- and Iraqi-born immigrants had especially high rates.