Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings
Arjun Chandna, Raman Mahajan, Priyanka Gautam, Lazaro Mwandigha, Karthik Gunasekaran, Divendu Bhusan, Arthur T L Cheung, Nicholas Day, Sabine Dittrich, Arjen Dondorp, Tulasi Geevar, Srinivasa R Ghattamaneni, Samreen Hussain, Carolina Jimenez, Rohini Karthikeyan, Sanjeev Kumar, Shiril Kumar, Vikash Kumar, Debasree Kundu, Ankita Lakshmanan, Abi Manesh, Chonticha Menggred, Mahesh Moorthy, Jennifer Osborn, Melissa Richard-Greenblatt, Sadhana Sharma, Veena K Singh, Vikash K Singh, Javvad Suri, Shuichi Suzuki, Jaruwan Tubprasert, Paul Turner, Annavi M G Villanueva, Naomi Waithira, Pragya Kumar, George M Varghese, Constantinos Koshiaris, Yoel Lubell, Sakib Burza, Arjun Chandna, Raman Mahajan, Priyanka Gautam, Lazaro Mwandigha, Karthik Gunasekaran, Divendu Bhusan, Arthur T L Cheung, Nicholas Day, Sabine Dittrich, Arjen Dondorp, Tulasi Geevar, Srinivasa R Ghattamaneni, Samreen Hussain, Carolina Jimenez, Rohini Karthikeyan, Sanjeev Kumar, Shiril Kumar, Vikash Kumar, Debasree Kundu, Ankita Lakshmanan, Abi Manesh, Chonticha Menggred, Mahesh Moorthy, Jennifer Osborn, Melissa Richard-Greenblatt, Sadhana Sharma, Veena K Singh, Vikash K Singh, Javvad Suri, Shuichi Suzuki, Jaruwan Tubprasert, Paul Turner, Annavi M G Villanueva, Naomi Waithira, Pragya Kumar, George M Varghese, Constantinos Koshiaris, Yoel Lubell, Sakib Burza
Abstract
Background: In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed.
Methods: We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort.
Results: In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72-0.74) and calibration (calibration slopes: 1.01-1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone.
Conclusions: We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.
Trial registration: ClinicalTrials.gov NCT04441372.
Keywords: COVID-19; LMIC; low- and middle-income country; prognostic model; triage.
© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.
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References
- Ritchie H, Mathieu E, Rodes-Guirao L, et al. . Coronavirus pandemic (COVID-19)—vaccinations. 2020. Available at: . Accessed 21 December 2021.
- Truelove S, Abrahim O, Altare C, et al. . The potential impact of COVID-19 in refugee camps in Bangladesh and beyond: a modeling study. PLoS Med 2020; 17:e1003144.
- Malik MA. Fragility and challenges of health systems in pandemic: early lessons from India’s second wave of coronavirus disease 2019 (COVID-19). Glob Health J 2022; 6:44–9.
- Silva S, Pena L.. Collapse of the public health system and the emergence of new variants during the second wave of the COVID-19 pandemic in Brazil. One Health 2021; 13:100287.
- Serpa Neto A, Checkley W, Sivakorn C, et al. . Pragmatic recommendations for the management of acute respiratory failure and mechanical ventilation in patients with COVID-19 in low- and middle-income countries. Am J Trop Med Hyg 2021; 104:60–71.
- World. Health Organization. Living Guidance for Clinical Management of COVID-19 (version 2). 2021. Available at: . Accessed 4 April 2022.
- Barros LM, Pigoga JL, Chea S, et al. . Pragmatic recommendations for identification and triage of patients with COVID-19 disease in low- and middle-income countries. Am J Trop Med Hyg 2021; 104:3–11.
- Wynants L, Van Calster B, Collins GS, et al. . Prediction models for diagnosis and prognosis of COVID-19: systematic review and critical appraisal. BMJ 2020; 369:m1328.
- Schultz MJ, Gebremariam TH, Park C, et al. . Pragmatic recommendations for the use of diagnostic testing and prognostic models in hospitalized patients with severe COVID-19 in low- and middle-income countries. Am J Trop Med Hyg 2021; 104:34–47.
- Prieto-Alhambra D, Ballo E, Coma E, et al. . Filling the gaps in the characterization of the clinical management of COVID-19: 30-day hospital admission and fatality rates in a cohort of 118 150 cases diagnosed in outpatient settings in Spain. Int J Epidemiol 2021; 49:1930–9.
- Ji D, Zhang D, Xu J, et al. . Prediction for progression risk in patients with COVID-19 pneumonia: the CALL score. Clin Infect Dis 2020; 71:1393–9.
- Wei W, Sivapalasingam S, Mellis S, Geba GP, Jalbert JJ.. A retrospective study of COVID-19-related urgent medical visits and hospitalizations after outpatient COVID-19 diagnosis in the US. Adv Ther 2021; 38:3185–202.
- Chang MC, Park YK, Kim BO, Park D.. Risk factors for disease progression in COVID-19 patients. BMC Infect Dis 2020; 20:445.
- Guo Y, Liu Y, Lu J, et al. . Development and validation of an early warning score (EWAS) for predicting clinical deterioration in patients with coronavirus disease 2019. medRxiv [Preprint]. April 21, 2020. [cited 2022 Apr 4]. Available from: 10.1101/2020.04.17.20064691
- Higuchi T, Nishida T, Iwahashi H, et al. . Early clinical factors predicting the development of critical disease in Japanese patients with COVID-19: a single-center, retrospective, observational study. J Med Virol 2021; 93:2141–8.
- Shi J, Li Y, Zhou X, et al. . Lactate dehydrogenase and susceptibility to deterioration of mild COVID-19 patients: a multicenter nested case-control study. BMC Med 2020; 18:168.
- Sun Q, Qiu H, Huang M, Yang Y.. Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province. Ann Intensive Care 2020; 10:33.
- Collins GS, Reitsma JB, Altman DG, Moons KG.. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. Ann Intern Med 2015; 162:55–63.
- Marshall JC, Murthy S, Diaz J, et al. . A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 2020; 20:e192–e7.
- Wayne MT, Weng W, O’Malley M, et al. . Variation in COVID-19 disease severity at hospital admission over time and across hospitals: a multi-institution cohort of Michigan hospitals. Medicine (Baltim) 2021; 100:e27265.
- Lambden S, Laterre PF, Levy MM, Francois B.. The SOFA score-development, utility and challenges of accurate assessment in clinical trials. Crit Care 2019; 23:374.
- Grissom CK, Brown SM, Kuttler KG, et al. . A modified sequential organ failure assessment score for critical care triage. Disaster Med Public Health Prep 2010; 4:277–84.
- Gupta RK, Harrison EM, Ho A, et al. . Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study. Lancet Respirat Med 2021; 9:349–59.
- European Union. Horizon 2020: Technology readiness levels (TRL); Extract from Part 19—Commission Decision C(2014)4995. 2020. Available at: . Accessed 4 April 2022.
- Cen Y, Chen X, Shen Y, et al. . Risk factors for disease progression in patients with mild to moderate coronavirus disease 2019-a multi-centre observational study. Clin Microbiol Infect 2020; 26:1242–7.
- Luo X, Zhou W, Yan X, et al. . Prognostic value of C-reactive protein in patients with coronavirus 2019. Clin Infect Dis 2020; 71:2174–9.
- Del Valle DM, Kim-Schulze S, Huang HH, et al. . An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 2020; 26:1636–43.
- Van Singer M, Brahier T, Ngai M, et al. . COVID-19 risk stratification algorithms based on sTREM-1 and IL-6 in emergency department. J Allergy Clin Immunol 2021; 147:99–106.e4.
- Rovina N, Akinosoglou K, Eugen-Olsen J, Hayek S, Reiser J, Giamarellos-Bourboulis EJ.. Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia. Crit Care 2020; 24:187.
- Leligdowicz A, Conroy AL, Hawkes M, et al. . Validation of two multiplex platforms to quantify circulating markers of inflammation and endothelial injury in severe infection. PLoS One 2017; 12:e0175130.
- Riley RD, Ensor J, Snell KIE, et al. . Calculating the sample size required for developing a clinical prediction model. BMJ 2020; 368:m441.
- Vickers AJ, Elkin EB.. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 2006; 26:565–74.
- International. Severe Acute Respiratory Infection Consoritum (ISARIC). Clinical data collection—the COVID-19 case report forms (CRFs). 2021. Available at: . Accessed 4 April 2022.
- Wheeler I, Price C, Sitch A, et al. . Early warning scores generated in developed healthcare settings are not sufficient at predicting early mortality in Blantyre, Malawi: a prospective cohort study. PLoS One 2013; 8:e59830.
- RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397:1637–45.
- Webb BJ, Peltan ID, Jensen P, et al. . Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study. Lancet Rheumatol 2020; 2:e754–63.
- Eugen-Olsen J, Altintas I, Tingleff J, et al. . Low levels of the prognostic biomarker suPAR are predictive of mild outcome in patients with symptoms of COVID-19—a prospective cohort study. medRxiv [Preprint]. June 20, 2020. [cited 2022 Apr 4]. Available from: 10.1101/2020.05.27.20114678
- Kyriazopoulou E, Poulakou G, Milionis H, et al. . Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. Nat Med 2021; 27:1752–60.
- World Health Organization. Fifteen African countries hit 10% COVID-19 vaccination goal. 2021. Available at: . Accessed 8 November 2021.
- Hogan AB, Winskill P, Watson O, et al. Report 33: modelling the allocation and impact of a COVID-19 vaccine. Imperial College London (25-09-2020). 2020.
- Sendagire C, Lipnick MS, Kizito S, et al. . Feasibility of the modified sequential organ function assessment score in a resource-constrained setting: a prospective observational study. BMC Anesthesiol 2017; 17:12.
- McHugh LC, Snyder K, Yager TD.. The effect of uncertainty in patient classification on diagnostic performance estimations. PLoS One 2019; 14:e0217146.
- RECOVERY Collaborative Group. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2022; 399:665–76.
- RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet 2021; 397:2049–59.
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