Development and validation of the 4C Deterioration model for adults hospitalised with COVID-19

Rk, Gupta; A, Ho; Ab, Docherty; Knight,; Smeden, Maarten van; Abubakar, Ibrahim; Lipman, Marc; Quartagno, Matteo; Pius, Riinu; Buchan, Iain; Carson, Gail; Tm, Drake; Dunning, Jake; Fairfield, Cameron J; Gamble, Carrol; Ca, Green; Halpin, Sophie; He, Hardwick; Ka, Holden; Pw, Horby; Jackson, Clare; Ka, Mclean; Merson, Laura; Nguyen-Van-Tam, Jonathan S.; Norman, Lisa; Pl, Olliaro; Pritchard, Mark G; Cd, Russell; Scott-Brown, James; Ca, Shaw; Azimullah, Sheikh; Solomon, Tom; Sudlow, Cathie; Ov, Swann; Turtle, Lance; Openshaw, Peter; Jk, Baillie; Semple, Malcolm G; Noursadeghi, Mahdad

doi:10.1101/2020.10.09.20209957

Cited by 32 publications

(33 citation statements)

References 36 publications

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“…Decreased abundance of ILCs with increasing age and male sex ( Table S4 and Figure S3 ) may therefore explain why morbidity and mortality associated with SARS-CoV-2 infection is worse in males and more severe with older age 1 – 6 , 8 , 61 . This conclusion is also supported by the association reported here between ILC abundance, odds of hospitalization, length of stay in the hospital, and levels of the markers of COVID-19 severity, CRP, ESR, and D-dimer 9 , 72 – 74 ( Table 3 ).…”

Section: Resultssupporting

confidence: 85%

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Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection

Silverstein

Wang

Manickas-Hill

et al. 2021

Preprint

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BACKGROUNDRisk of severe coronavirus disease 2019 (COVID-19) increases with age, is greater in males, and is associated with decreased numbers of blood lymphoid cells. Though the reasons for these robust associations are unclear, effects of age and sex on innate and adaptive lymphoid subsets, including on homeostatic innate lymphoid cells (ILCs) implicated in disease tolerance, may underlie the effects of age and sex on COVID-19 morbidity and mortality.METHODSFlow cytometry was used to quantitate subsets of blood lymphoid cells from people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comparing those hospitalized with severe COVID-19 (n=40) and those treated as outpatients for less severe disease (n=51). 86 healthy individuals served as controls. The relationship between abundance of specific blood lymphoid cell types, age, sex, hospitalization, duration of hospitalization, and elevation of blood markers for systemic inflammation, was determined using multiple regression.RESULTSAfter accounting for effects of age and sex, hospitalization for COVID-19 was associated with 1.78-fold fewer ILCs (95%CI: 2.34–1.36; p = 4.55 x 10−5) and 2.31-fold fewer CD16+ natural killer (NK) cells (95%CI: 3.1–1.71; p = 1.04 x 10−7), when compared to uninfected controls. Among people infected with SARS-CoV-2, the odds ratio for hospitalization, adjusted for age, sex, and duration of symptoms, was 0.413 (95%CI: 0.197–0.724; p = 0.00691) for every 2-fold increase in ILCs. In addition, higher ILC abundance was associated with less time spent in the hospital and lower levels of blood markers associated with COVID-19 severity: each two-fold increase in ILC abundance was associated with a 9.38 day decrease in duration of hospital stay (95% CI: 15.76–3.01; p= 0.0054), and decrease in blood C-reactive protein (CRP) by 46.29 mg/L (95% CI: 71.34–21.24; p = 6.25 x 10−4), erythrocyte sedimentation rate (ESR) by 11.04 mm/h (95% CI: 21.94–0.13; p = 0.047), and the fibrin degradation product D-dimer by 1098.52 ng/mL (95% CI: 1932.84–264.19; p = 0.011).CONCLUSIONSBoth ILCs and NK cells were depleted in the blood of people hospitalized for severe COVID-19, but, among lymphoid cell subsets, only ILC abundance was independently associated with the need for hospitalization, duration of hospital stay, and severity of inflammation. These results indicate that, by promoting disease tolerance, homeostatic ILCs protect against morbidity and mortality in SARS-CoV-2 infection, and suggest that reduction in the number of ILCs with age and in males accounts for the increased risk of severe COVID-19 in these demographic groups.

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Section: Resultssupporting

confidence: 85%

“…The risk of disease severity in people infected with SARS-CoV-2 increases with age and is greater for men than for women 1 – 9 . Similar trends exist in people infected with SARS-CoV 10 – 12 or MERS-CoV 13 , and have been observed in laboratory animals challenged with SARS-CoV or SARS-CoV-2 14 , 15 .…”

Section: Introductionmentioning

confidence: 99%

Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection

Silverstein

Wang

Manickas-Hill

et al. 2021

Preprint

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“…Given the remarkable increase in the availability of COVID-19 predictive models, we expect the derivation of our score will be helpful in triage settings with similarities to our institution; however, extensive external validation and calibration studies are required to evaluate its performance in a triage prior to clinical utilization [17]. Given the conducted sensitivity analyses, we do not currently recommend the use of our score for in-hospital clinical deterioration, which could be assessed with other available tools after due external validation [18]. Underlying factors which explain the pathogenesis of severe COVID-19 complications have been extensively studied [19,20].…”

Section: Plos Onementioning

confidence: 99%

Validation and repurposing of the MSL-COVID-19 score for prediction of severe COVID-19 using simple clinical predictors in a triage setting: The Nutri-CoV score

et al. 2020

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Background During the COVID-19 pandemic, risk stratification has been used to decide patient eligibility for inpatient, critical and domiciliary care. Here, we sought to validate the MSL-COVID-19 score, originally developed to predict COVID-19 mortality in Mexicans. Also, an adaptation of the formula is proposed for the prediction of COVID-19 severity in a triage setting (Nutri-CoV). Methods We included patients evaluated from March 16th to August 17th, 2020 at the Instituto Nacional de Ciencias Médicas y Nutrición, defining severe COVID-19 as a composite of death, ICU admission or requirement for intubation (n = 3,007). We validated MSL-COVID-19 for prediction of mortality and severe disease. Using Elastic Net Cox regression, we trained (n = 1,831) and validated (n = 1,176) a model for prediction of severe COVID-19 using MSL-COVID-19 along with clinical assessments obtained at a triage setting. Results The variables included in MSL-COVID-19 are: pneumonia, early onset type 2 diabetes, age > 65 years, chronic kidney disease, any form of immunosuppression, COPD, obesity, diabetes, and age <40 years. MSL-COVID-19 had good performance to predict COVID-19 mortality (c-statistic = 0.722, 95%CI 0.690–0.753) and severity (c-statistic = 0.777, 95%CI 0.753–0.801). The Nutri-CoV score includes the MSL-COVID-19 plus respiratory rate, and pulse oximetry. This tool had better performance in both training (c-statistic = 0.797, 95%CI 0.765–0.826) and validation cohorts (c-statistic = 0.772, 95%CI 0.0.745–0.800) compared to other severity scores. Conclusions MSL-COVID-19 predicts inpatient COVID-19 lethality. The Nutri-CoV score is an adaptation of MSL-COVID-19 to be used in a triage environment. Both scores have been deployed as web-based tools for clinical use in a triage setting.

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“…In The Lancet Respiratory Medicine , Gupta and colleagues describe the 4C Deterioration model, which can be used at hospital admission to estimate the risk of death or requirement for ventilatory support or critical care. 1 …”

mentioning

confidence: 99%