Article Text

Original research
Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial
  1. Joy John Mammen1,
  2. Snehil Kumar1,
  3. Lovely Thomas2,
  4. Gunjan Kumar3,
  5. Anand Zachariah4,
  6. Lakshmanan Jeyaseelan5,
  7. John Victor Peter2,
  8. Anup Agarwal3,
  9. Aparna Mukherjee3,
  10. Pranab Chatterjee6,
  11. Tarun Bhatnagar7,
  12. Jess Elizabeth Rasalam1,
  13. Binila Chacko2,
  14. Thenmozhi Mani5,
  15. Melvin Joy5,
  16. Priscilla Rupali8,
  17. Malathi Murugesan9,
  18. Dolly Daniel1,
  19. B Latha10,
  20. Sunita Bundas11,
  21. Vivek Kumar12,
  22. Ravi Dosi13,
  23. Janakkumar R Khambholja14,
  24. Rosemarie de Souza15,
  25. B Thrilok Chander16,
  26. Shalini Bahadur17,
  27. Simmi Dube18,
  28. Amit Suri19,
  29. Aikaj Jindal20,
  30. Om Shrivastav21,
  31. Vijay Barge22,
  32. Archana Bajpayee23,
  33. Pankaj Malhotra24,
  34. Neha Singh25,
  35. Muralidhar Tambe26,
  36. Nimisha Sharma27,
  37. Shreepad Bhat28,
  38. Ram S Kaulgud29,
  39. Anil Gurtoo30,
  40. D Himanshu Reddy31,
  41. Kamlesh Upadhyay32,
  42. Ashish Jain33,
  43. Tinkal C Patel34,
  44. Irfan Nagori35,
  45. Pramod R Jha36,
  46. K V Sreedhar Babu37,
  47. C Aparna38,
  48. Sunil Jodharam Panjwani39,
  49. M Natarajan40,
  50. Milind Baldi41,
  51. Vrushali Khirid Khadke42,
  52. Seema Dua43,
  53. Ravindraa Singh44,
  54. Ashish Sharma45,
  55. Jayashree Sharma46,
  56. Yojana A Gokhale47,
  57. Pragya D Yadav48,
  58. Gajanan Sapkal49,
  59. Himanshu Kaushal50,
  60. V Saravana Kumar51
  1. 1Transfusion Medicine and Immunohaematology, Christian Medical College and Hospital Vellore, Vellore, Tamil Nadu, India
  2. 2Medical Intensive Care Unit, Christian Medical College and Hospital Vellore, Vellore, Tamil Nadu, India
  3. 3Clinical Trials and Health Systems Research Unit, ICMR, New Delhi, Delhi, India
  4. 4Medicine, Christian Medical College and Hospital Vellore, Vellore, Tamil Nadu, India
  5. 5Biostatistics, Christian Medical College and Hospital Vellore, Vellore, Tamil Nadu, India
  6. 6Translational Global Health Policy and Research Cell, ICMR, New Delhi, Delhi, India
  7. 7ICMR School of Public Health, National Institute of Epidemiology, Chennai, Tamil Nadu, India
  8. 8Infectious Diseases, Christian Medical College and Hospital Vellore, Vellore, Tamil Nadu, India
  9. 9Hospital Infection Control Committee, Christian Medical College and Hospital Vellore, Vellore, Tamil Nadu, India
  10. 10Transfusion Medicine, Madras Medical College, Chennai, Tamil Nadu, India
  11. 11Transfusion Medicine, SMS Medical College and Hospital, Jaipur, Rajasthan, India
  12. 12Critical Care, Sir HN Reliance Foundation Hospital and Research Centre, Mumbai, Maharashtra, India
  13. 13Respiratory Medicine, Sri Aurobindo Institute of Medical Sciences, Indore, Madhya Pradesh, India
  14. 14Internal Medicine, Smt NHL Municipal Medical College, Ahmedabad, Gujarat, India
  15. 15Department of Medicine, BYL Nair Charitable Hospital, Mumbai, India
  16. 16Internal Medicine, Gandhi Medical College and Hospital, Secunderabad-Padmarao Nagar, Telangana, India
  17. 17Pathology, Government Institute of Medical Sciences, Noida, Uttar Pradesh, India
  18. 18Internal Medicine, Gandhi Medical College Bhopal, Bhopal, Madhya Pradesh, India
  19. 19Pulmonary Medicine, Atal Bihari Vajpayee Institute of Medical Sciences and Ram Manohar Lohia Hospital, New Delhi, Delhi, India
  20. 20Transfusion Medicine, Satguru Partap Singh Hospitals, Ludhiana, Punjab, India
  21. 21Infectious Diseases, Kasturba Hospital for Infectious Diseases, Mumbai, Maharashtra, India
  22. 22Medicine, RCSM Government Medical College, Kolhapur, Maharashtra, India
  23. 23Transfusion Medicine, AIIMS Jodhpur, Jodhpur, Rajasthan, India
  24. 24Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India
  25. 25Transfusion Medicine, AIIMS Patna, Patna, Bihar, India
  26. 26Department of Community Medicine, B J Government Medical College, Pune, Maharashtra, India
  27. 27Transfusion Medicine, ESIC Medical College and Hospital Faridabad, Faridabad, Haryana, India
  28. 28Internal Medicine, Smt Kashibai Navale Medical College and General Hospital, Pune, Maharashtra, India
  29. 29Internal Medicine, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India
  30. 30Internal Medicine, Lady Hardinge Medical College, New Delhi, Delhi, India
  31. 31Internal Medicine, King George Medical College, Lucknow, Uttar Pradesh, India
  32. 32Internal Medicine, Byramjee Jeejeebhoy Medical College, Ahmedabad, Gujarat, India
  33. 33Respiratory Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
  34. 34Internal Medicine, Government Medical College, Surat, Gujarat, India
  35. 35Medicine, GMERS Medical College Gotri Vadodara, Vadodara, Gujarat, India
  36. 36Internal Medicine, Sumandeep Vidyapeeth University, Vadodara, Gujarat, India
  37. 37Transfusion Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
  38. 38Pathology, Kurnool Medical College, Kurnool, Andhra Pradesh, India
  39. 39Internal Medicine, Government Medical College, Bhavnagar, Gujarat, India
  40. 40Internal Medicine, Madurai Medical College, Madurai, Tamil Nadu, India
  41. 41Internal Medicine, Mahatma Gandhi Memorial Medical College, Indore, Madhya Pradesh, UK
  42. 42Interventional Pulmonology, Poona Hospital and Research Centre, Pune, Maharashtra, India
  43. 43Transfusion Medicine, Super Speciality Paediatric Hospital and Teaching Hospital, Noida, Uttar Pradesh, India
  44. 44Transfusion Medicine, Aditya Birla Memorial Hospital, Pune, Maharashtra, India
  45. 45Medicine, R D Gardi Medical College, Ujjain, Madhya Pradesh, India
  46. 46Transfusion Medicine, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
  47. 47Internal Medicine, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, Maharashtra, India
  48. 48Maximum Containment Laboratory, ICMR, National Institute of Virology, Pune, Maharashtra, India
  49. 49Diagnostic Virology Group, ICMR, National Institute of Virology, Pune, Maharashtra, India
  50. 50Human Influenza Group, ICMR, National Institute of Virology, Pune, Maharashtra, India
  51. 51Epidemiology and Biostatistics Division, National Institute of Epidemiology, Chennai, Tamil Nadu, India
  1. Correspondence to Dr Joy John Mammen; joymammen{at}cmcvellore.ac.in

Abstract

Objective Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma.

Design Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease.

Setting 39 public and private hospitals across India during the study period from 22 April to 14 July 2020.

Participants Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed.

Primary outcome measure Factors associated with all-cause mortality at 28 days after enrolment.

Results The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3–7) and non-survivors (4 days; IQR 3–6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64–7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65–27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14–5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44–4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60–5.45, p=0.001) were significantly associated with death.

Conclusion In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death.

Trial registration number CTRI/2020/04/024775.

  • COVID-19
  • public health
  • adult intensive & critical care

Data availability statement

Data are available upon reasonable request. Data will be made available, upon request, and must be accompanied by a brief proposal outlining the analysis plan. A signed data access agreement might be needed to ensure data safety and compliance with national rules about data sharing.

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Data availability statement

Data are available upon reasonable request. Data will be made available, upon request, and must be accompanied by a brief proposal outlining the analysis plan. A signed data access agreement might be needed to ensure data safety and compliance with national rules about data sharing.

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Footnotes

  • Twitter @tarunb20

  • Contributors All the authors contributed equally in the study and the specific contributions are mentioned in the manuscript. Study design: JJM, LJ, JVP. Clinical management: SK, LT, AZ, JER, BC, BL, SBu, VK, RD, JRK, RdS, BTC, SBa, SDub, ASu, AJi, OS, VB, AB, PM, NSi, MT, NSh, SBh, RSK, AG, DHR, KU, AJa, TCP, IN, PRJ, KVSB, CA, SJP, MN, MB, VKK, SDua, RS, AS, JS, YAG. Data collection: JJM, SK, LT, AZ, AA, AM, GK, PC, TB, JER, PR, MM, BC, BL, SBu, VK, RD, JRK, RdS, BTC, SBa, SDub, ASu, AJi, OS, VB, AB, PM, NSi, MT, NSh, SBh, RSK, AG, DHR, KU, AJa, TCP, IN, PRJ, KVSB, CA, SJP, MN, MB, VKK, SDua, RS, ASh, JS, YAG, PDY, GS, HK, VSK. Data analysis: JJM, SK, LJ, TM, MJ, PR, MM, DD, JVP. Data interpretation: JJM, SK, AZ, LJ, JER, TM, MJ, DD, JVP. Manuscript writing: JJM, SK, LT, AZ, LJ, JER, BC, TM, MJ, PR, MM, DD, JVP, AA, AM, GK, HK, PC, TB. Study administration: JJM, BC, JVP, AA, AM, GK, HK, PC, TB.

  • Funding The funding source for the primary study was ICMR (RFC No ECD/NTF/20/2020-21/Covid, 23 July 2020).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.