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

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.

Patient trajectories among hospitalised COVID-19 patients vaccinated with an mRNA vaccine in Norway: a register-based cohort study (preprint)

Objectives With most of the Norwegian population vaccinated against COVID-19, an increasing number and proportion of COVID-19 related hospitalisations are occurring among vaccinated patients. To support patient management and capacity planning in hospitals, we estimated the length of stay (LoS) in hospital and odds of intensive care (ICU) admission and in-hospital mortality among COVID-19 patients [≥]18 years who had been vaccinated with an mRNA vaccine, compared to unvaccinated patients. Methods Using national registry data, we conducted a cohort study on SARS-CoV-2 positive patients hospitalised in Norway between 1 February and 30 September 2021, with COVID-19 as the main cause of hospitalisation. We used a Cox proportional hazards model to examine the association between vaccination status and LoS. We used logistic regression to examine the association between vaccination status and ICU admission and in-hospital mortality. Results We included 2,361 patients, including 70 (3%) partially vaccinated and 183 (8%) fully vaccinated. Fully vaccinated patients 18-79 years had a shorter LoS in hospital overall (adjusted hazard ratio for discharge: 1.35, 95%CI: 1.07-1.72), and lower odds of ICU admission (adjusted odds ratio: 0.57, 95%CI: 0.33-0.96). Similar estimates were observed when collectively analysing partially and fully vaccinated patients. We observed no difference in the LoS for patients not admitted to ICU, nor odds of in-hospital death between vaccinated and unvaccinated patients. Conclusions Vaccinated patients hospitalised with COVID-19 in Norway have a shorter LoS and lower odds of ICU admission than unvaccinated patients. These findings can support patient management and ongoing capacity planning in hospitals.

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

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

Gut microbiota alterations in patients with persistent respiratory dysfunction three months after severe COVID-19 (preprint)

ObjectiveAlthough COVID-19 is primarily a respiratory infection, mounting evidence suggests that the GI tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and could be related to long-term respiratory dysfunction is unknown. DesignFrom the NOR-Solidarity trial (n=181), plasma was collected during hospital admission and after three months, and analyzed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring diffusing capacity of the lungs for carbon monoxide (DLCO), and rectal swabs for gut microbiota analyses were collected (n= 97) and analysed by sequencing of the 16S rRNA gene. ResultsGut microbiota diversity was reduced in COVID-19 patients with persistent respiratory dysfunction, defined as DLCO below lower limit of normal three months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Flavonifractor and Veillonella, the latter potentially being linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2/fiO2-(P/F-ratio)<26.6 kPa. LBP levels remained elevated during and after hospitalization, and was associated with low-grade inflammation and persistent respiratory dysfunction after three months. ConclusionPersistent respiratory dysfunction after COVID-19 is associated with reduced biodiversity and gut microbiota alterations, along with persistently elevated LBP levels. Our results point to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID. Summary boxO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIMounting evidence suggests that the gastrointestinal tract is involved in the pathogenesis of COVID-19, with the putative SARS-CoV-2 receptor ACE 2 ubiquitously expressed in the gut. C_LIO_LIIn severe COVID-19, the gut-blood barrier is compromised, and leakage of microbial products, such as lipopolysaccharides (LPS), could affect the hosts response to COVID-19 infection. C_LIO_LICOVID-19 patients exhibit an altered gut microbiota composition, which has been related to disease severity. However, it is currently not known whether dysbiosis or gut barrier dysfunction persist long-term after hospitalization, or whether microbiota-related mechanisms could be related to persistent pulmonary dysfunction. C_LI What are the new findings?O_LICOVID-19 patients with persistent respiratory dysfunction after three months had a lower microbial diversity and an altered gut microbiota composition at the same time point. C_LIO_LIThe microbiota alterations included reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Veillonella and Flavonifractor. C_LIO_LIDuring hospitalization, increased plasma levels of LBP were strongly associated with respiratory failure. C_LIO_LILBP levels remained elevated during and after hospitalization, and associated significantly with persistent respiratory dysfunction at three-month follow-up. C_LI How might it impact on clinical practice in the foreseeable future?Our findings point to a potential gut-lung axis in relation not only to respiratory failure during hospitalization, but also to long-term COVID-19 morbidity. Further studies on gut microbiota composition and gut barrier dysfunction as potential treatment targets and/or disease severity biomarkers in relation to long-term pulmonary dysfunction and long COVID are warranted.

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

ABSTRACT Background The 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. Methods Using 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. Results We 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. Conclusions B.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.