Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial

Mammen, Joy John; Kumar, Snehil; Thomas, Lovely; Kumar, Gunjan; Zachariah, Anand; Jeyaseelan, Lakshmanan; Peter, John Victor; Agarwal, Anup; Mukherjee, Aparna; Chatterjee, Pranab; Bhatnagar, Tarun; Rasalam, Jess Elizabeth; Chacko, Binila; Mani, Thenmozhi; Joy, Melvin; Rupali, Priscilla; Murugesan, Malathi; Daniel, Dolly; Latha, B; Bundas, Sunita; Kumar, Vivek; Dosi, Ravi; Khambholja, Janakkumar R; de Souza, Rosemarie; Chander, B Thrilok; Bahadur, Shalini; Dube, Simmi; Suri, Amit; Jindal, Aikaj; Shrivastav, Om; Barge, Vijay; Bajpayee, Archana; Malhotra, Pankaj; Singh, Neha; Tambe, Muralidhar; Sharma, Nimisha; Bhat, Shreepad; Kaulgud, Ram S; Gurtoo, Anil; Reddy, D Himanshu; Upadhyay, Kamlesh; Jain, Ashish; Patel, Tinkal C; Nagori, Irfan; Jha, Pramod R; Babu, K V Sreedhar; Aparna, C; Panjwani, Sunil Jodharam; Natarajan, M; Baldi, Milind; Khadke, Vrushali Khirid; Dua, Seema; Singh, Ravindraa; Sharma, Ashish; Sharma, Jayashree; Gokhale, Yojana A; Yadav, Pragya D; Sapkal, Gajanan; Kaushal, Himanshu; Kumar, V Saravana

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), PaO(2)/FiO(2) 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.