Directions of change in intrinsic case severity across successive SARS-CoV-2 variant waves have been inconsistent.

OBJECTIVES: To determine how the intrinsic severity of successively dominant SARS-CoV-2 variants changed over the course of the pandemic. METHODS: A retrospective cohort analysis in the NHS Greater Glasgow and Clyde (NHS GGC) Health Board. All sequenced non-nosocomial adult COVID-19 cases in NHS GGC with relevant SARS-CoV-2 lineages (B.1.177/Alpha, Alpha/Delta, AY.4.2 Delta/non-AY.4.2 Delta, non-AY.4.2 Delta/Omicron, and BA.1 Omicron/BA.2 Omicron) during analysis periods were included. Outcome measures were hospital admission, ICU admission, or death within 28 days of positive COVID-19 test. We report the cumulative odds ratio; the ratio of the odds that an individual experiences a severity event of a given level vs all lower severity levels for the resident and the replacement variant after adjustment. RESULTS: After adjustment for covariates, the cumulative odds ratio was 1.51 (95% CI: 1.08-2.11) for Alpha versus B.1.177, 2.09 (95% CI: 1.42-3.08) for Delta versus Alpha, 0.99 (95% CI: 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta, 0.49 (95% CI: 0.22-1.06) for Omicron versus non-AY.4.2 Delta, and 0.86 (95% CI: 0.68-1.09) for BA.2 Omicron versus BA.1 Omicron. CONCLUSIONS: The direction of change in intrinsic severity between successively emerging SARS-CoV-2 variants was inconsistent, reminding us that the intrinsic severity of future SARS-CoV-2 variants remains uncertain.

The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis.

OBJECTIVES: The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this. METHODS: In this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death. RESULTS: Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants). CONCLUSIONS: The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.

Is there an association between central vein stenosis and line infection in patients with tunnelled central venous catheters (TCVCs)?

PURPOSE: Central vein stenosis (CVS) and line infection are well-recognized complications of tunnelled central venous catheters (TCVCs) in patients on haemodialysis. The aim of this study was to evaluate any relationship between CVS and line infection. METHODS: Analysis of 500 consecutive patients undergoing TCVC insertion was undertaken. Data were collected on patient demographics, details of line insertion and duration, culture-proven bacteraemia and presence of symptomatic CVS. Logistic regression analysis was used to determine risk factors for CVS and bacteraemia. RESULTS: Mean patient age was 59.0 years (range: 17-93). Mean number of catheter days was 961.1 ± 57.6 per TCVC; 39.4% of TCVCs were associated with culture-proven bacteraemia and 23.6% developed symptomatic CVS. Bacteraemia and CVS were inevitable complications of all TCVCs. The time to symptomatic CVS was longer in patients with bacteraemia than without (1230.91 ± 101.29 vs. 677.49 ± 61.59 days, p<0.001). Patients who had early infection within 90 days of TCVC insertion were less likely to develop CVS (5.9% vs. 22.8%, p<0.001). There was no difference in the bacteraemia rate per 1,000 catheter days between patients with and without CVS (2.62 ± 1.41 vs. 2.35 ± 0.51; p = 0.98). Number of line days (odds ratio (OR) 1.02, p = 0.003), age (OR 1.04, p = 0.04) and culture-proven line infection (OR 0.59, p = 0.014) were all independently associated with CVS. CONCLUSIONS: Our results suggest that early line infection may be protective against CVS. Alternatively, there may be two distinct predisposition states for CVS and line infection. Further studies are needed to confirm our association and investigate causation.