There is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of ...disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity.
A prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection.
Independent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2 Relative Risk (RR) = 0.42 (95%CI: 0.34–0.52), P < 0.001, WHO outcome score >5 RR = 0.33 (95%CI: 0.21–0.50), P < 0.001, and to have had a LOS > 3 days RR = 0.84 (95%CI: 0.76–0.92), P < 0.001. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity.
We provide reassuring evidence that Omicron infection results in less serious adverse outcomes than Delta in hospitalised patients. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden and an increased admission rate of older patients with Omicron which counteracts some of the benefit arising from less severe disease.
AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.
Lower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic ...(symptom-based) case ascertainment in older (greater than or equal to 65y) as compared to younger adults (< 65y). We included adults (greater than or equal to 18y) with confirmed LRTI admitted to two acute care Trusts in Bristol, UK from 1st August 2020- 31st July 2022. Logistic regression was used to assess whether age greater than or equal to 65y reduced the probability of meeting syndromic LRTI case definitions, using patients' symptoms at admission. We also calculated relative symptom frequencies (log-odds ratios) and evaluated how symptoms were clustered across different age groups. Of 17,620 clinically confirmed LRTI cases, 8,487 (48.1%) had symptoms meeting the case definition. Compared to those not meeting the definition these cases were younger, had less severe illness and were less likely to have received a SARS-CoV-2 vaccination or to have active SARS-CoV-2 infection. Prevalence of dementia/cognitive impairment and levels of comorbidity were lower in this group. LRTI symptom profiles changed considerably with age in this hospitalised cohort. Standard screening protocols may fail to detect older and frailer cases of LRTI based on their symptoms.
Hospitalisations relating to acute respiratory deteriorations (ARD) in Interstitial Lung Disease (ILD) have poor outcomes. Factors predicting adverse outcomes are not fully understood and data ...addressing the use of illness severity scores in prognostication are limited.
To investigate the use of CURB-65 and NEWS-2 severity scores in the prediction of mortality following ARD-ILD hospitalisation, using prospective methodology and to validate previously determined cut-offs, derived from a retrospective study cohort.
A dual-centre prospective observational cohort study of all adults (≥18y) hospitalised with ARD-ILD in Bristol, UK (n = 179). Gender-Age-Physiology (GAP), CURB-65 and NEWS-2 scores were calculated for each eligible admission.
Receiver operating characteristics (ROC) curve analysis was used to quantify the strength of discrimination for NEWS-2 and CURB-65 scores. Univariable and multivariable logistic regression analyses were performed to explore the relationship between baseline severity scores and mortality.
GAP showed some merit at predicting 30-day mortality (AUC = 0.64, P = 0.015); whereas CURB-65 showed modest predictive value for in-hospital (AUC = 0.72, P < 0.001) and 90-day mortality (AUC = 0.67, P < 0.001). NEWS-2 showed higher predictive value for in-hospital (AUC = 0.80, P < 0.001) and 90-day mortality (AUC = 0.75, P < 0.001), with an optimal derived cut-off ≥6.5 found to be sensitive and specific for predicting in-hospital (83% and 63%) and 90-day (73% and 72%) mortality. In exploratory analyses, GAP score addition improved the predictive ability of NEWS-2 against 30-day mortality and CURB-65 across all time-periods.
NEWS-2 has good discriminatory value for predicting in-hospital mortality and moderate discriminatory value for predicting 90-day mortality. The optimal NEWS-2 cut-off value determined was the same as in a previous retrospective cohort, confirming the NEWS-2 score shows promise in predicting mortality following ARD-ILD hospitalisation.
•ARD-ILD is associated with high in-hospital, 30- and 90- day mortality, irrespective of cause.•NEWS-2 has high sensitivity and specificity in predicting 90d & in-hospital mortality in ARD-ILD.•CURB-65 showed high sensitivity for predicting mortality but low specificity.•CURB-65 did not add value to the NEWS-2 predictive ability.•Simple illness severity scores may support refinement of ARD-ILD management pathways.
Whilst other studies have reported the effectiveness of mRNA vaccination against hospitalisation, including emergency department or intensive care admission, few have assessed effectiveness against ...other more clinically robust indices of COVID-19 severity.
A prospective single-centre test-negative design case–control study of adults hospitalised with COVID-19 disease or other acute respiratory disease between 1 June 2021 and 20 July 2022. We assessed VE (vaccine effectiveness) against hospitalisation, length of stay LOS >3 days, WHO COVID Score >5 and supplementary oxygen FiO2 (fraction inspired oxygen) >28%, conducting regression analyses controlling for age, gender, index of multiple deprivation, Charlson comorbidity index, time, and community infection prevalence.
935 controls and 546 cases were hospitalised during the Delta period, with 721 controls and 372 cases hospitalised during the Omicron study period. Two-dose BNT162b2 was associated with VE 82.5% 95% confidence interval 76.2%–87.2% against hospitalisation following Delta infection, 63.3% 26.9–81.8%, 58.5% 24.8–77.3%, and 51.5% 16.7–72.1% against LOS >3 days, WHO COVID Score >5, and requirement for FiO2 >28% respectively. Three-dose BNT162b2 protection against hospitalisation with Omicron infection was 30.9% 5.9–49.3%, with sensitivity analyses ranging from 28.8–72.6%. Protection against LOS >3 days, WHO COVID Score >5 and requirement for FiO2 >28% was 56.1% 20.6–76.5%, 58.8% 31.2–75.8%, and 41.5% −0.4–66.3%, respectively. In the UK, BNT162b2 was prioritised for high-risk individuals and those aged >75 years. In the latter group we found a higher estimate of VE against hospitalisation of 47.2% 16.8–66.6%.
BNT162b2 vaccination results in risk reductions for hospitalisation and multiple patient outcomes following Delta and Omicron COVID-19 infection, particularly in older adults. BNT162b2 remains effective against severe SARS-CoV-2 disease.
AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.
Background: Whilst other studies have reported the effectiveness of mRNA vaccination against hospitalisation, including emergency department or intensive care admission, few have assessed ...effectiveness against other more clinically robust indices of COVID-19 severity. Methods: A prospective single-centre test-negative design case–control study of adults hospitalised with COVID-19 disease or other acute respiratory disease between 1 June 2021 and 20 July 2022. We assessed VE (vaccine effectiveness) against hospitalisation, length of stay LOS >3 days, WHO COVID Score >5 and supplementary oxygen FiO2 (fraction inspired oxygen) >28%, conducting regression analyses controlling for age, gender, index of multiple deprivation, Charlson comorbidity index, time, and community infection prevalence. Findings: 935 controls and 546 cases were hospitalised during the Delta period, with 721 controls and 372 cases hospitalised during the Omicron study period. Two-dose BNT162b2 was associated with VE 82.5% 95% confidence interval 76.2%–87.2% against hospitalisation following Delta infection, 63.3% 26.9–81.8%, 58.5% 24.8–77.3%, and 51.5% 16.7–72.1% against LOS >3 days, WHO COVID Score >5, and requirement for FiO2 >28% respectively. Three-dose BNT162b2 protection against hospitalisation with Omicron infection was 30.9% 5.9–49.3%, with sensitivity analyses ranging from 28.8–72.6%. Protection against LOS >3 days, WHO COVID Score >5 and requirement for FiO2 >28% was 56.1% 20.6–76.5%, 58.8% 31.2–75.8%, and 41.5% −0.4–66.3%, respectively. In the UK, BNT162b2 was prioritised for high-risk individuals and those aged >75 years. In the latter group we found a higher estimate of VE against hospitalisation of 47.2% 16.8–66.6%. Interpretation: BNT162b2 vaccination results in risk reductions for hospitalisation and multiple patient outcomes following Delta and Omicron COVID-19 infection, particularly in older adults. BNT162b2 remains effective against severe SARS-CoV-2 disease. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.
Background: There is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing ...severity of disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity. Methods: A prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection. Findings: Independent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2 Relative Risk (RR) = 0.42 (95%CI: 0.34–0.52), P < 0.001, WHO outcome score >5 RR = 0.33 (95%CI: 0.21–0.50), P < 0.001, and to have had a LOS > 3 days RR = 0.84 (95%CI: 0.76–0.92), P < 0.001. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Interpretation: We provide reassuring evidence that Omicron infection results in less serious adverse outcomes than Delta in hospitalised patients. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden and an increased admission rate of older patients with Omicron which counteracts some of the benefit arising from less severe disease. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.
The regulation of Rubisco activity was investigated under high, constant photosynthetic photon flux density during the diurnal phases of Crassulacean acid metabolism in Kalanchoë daigremontiana Hamet ...et Perr. During phase I, a significant period of nocturnal, C4-mediated CO2 fixation was observed, with the generated malic acid being decarboxylated the following day (phase III). Two periods of daytime atmospheric CO2 fixation occurred at the beginning (phase II, $\text{C}_{4}-\text{C}_{3}$ carboxylation) and end (phase IV, C3-C4 carboxylation) of the day. During the 1st h of the photoperiod, when phosphoenolpyruvate carboxylase was still active, the highest rates of atmospheric CO2 uptake were observed, coincident with the lowest rates of electron transport and minimal Rubisco activity. Over the next 1 to 2 h of phase II, carbamylation increased rapidly during an initial period of decarboxylation. Maximal carbamylation (70%-80%) was reached 2 h into phase III and was maintained under conditions of elevated CO2 resulting from malic acid decarboxylation. Initial and total Rubisco activity increased throughout phase III, with maximal activity achieved 9 h into the photoperiod at the beginning of phase IV, as atmospheric CO2 uptake recommenced. We suggest that the increased enzyme activity supports assimilation under CO2-limited conditions at the start of phase IV. The data indicate that Rubisco activity is modulated in-line with intracellular CO2 supply during the daytime phases of Crassulacean acid metabolism.
The regulation of Rubisco activity was investigated under high, constant photosynthetic photon flux density during the diurnal phases of Crassulacean acid metabolism in
Kalanchoë daigremontiana
Hamet ...et Perr. During phase I, a significant period of nocturnal, C
4
-mediated CO
2
fixation was observed, with the generated malic acid being decarboxylated the following day (phase III). Two periods of daytime atmospheric CO
2
fixation occurred at the beginning (phase II, C
4
–C
3
carboxylation) and end (phase IV, C
3
–C
4
carboxylation) of the day. During the 1st h of the photoperiod, when phospho
enol
pyruvate carboxylase was still active, the highest rates of atmospheric CO
2
uptake were observed, coincident with the lowest rates of electron transport and minimal Rubisco activity. Over the next 1 to 2 h of phase II, carbamylation increased rapidly during an initial period of decarboxylation. Maximal carbamylation (70%–80%) was reached 2 h into phase III and was maintained under conditions of elevated CO
2
resulting from malic acid decarboxylation. Initial and total Rubisco activity increased throughout phase III, with maximal activity achieved 9 h into the photoperiod at the beginning of phase IV, as atmospheric CO
2
uptake recommenced. We suggest that the increased enzyme activity supports assimilation under CO
2
-limited conditions at the start of phase IV. The data indicate that Rubisco activity is modulated in-line with intracellular CO
2
supply during the daytime phases of Crassulacean acid metabolism.