Objectives: Convalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. Design: Open-label, parallel-arm, phase II, multicentre, randomized controlled trial. Setting: Thirty-nine public and private hospitals across India. Participants: Hospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air). Intervention: Participants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome Measure: Composite of progression to severe disease (PaO2/FiO2<100) or all-cause mortality at 28 days post-enrolment. Results: Between 22 nd April to 14 th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. Interpretation: CP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.

The apolipoprotein A1 gene polymorphism (G-75A and C+83T) was studied in 100 subjects (50 patients diagnosed with myocardial infarction and 50 healthy subjects). Serum apolipoprotein (apo) A1 and apo B levels were estimated immunoturbidometrically. Extracted DNA from blood was amplified by polymerase chain reaction, digested with MspI restriction enzyme, run on 8% polyacrylamide gel, and restriction fragment length polymorphism was studied by using a gel documentation system. Serum (mean +/- SD) apo A1 levels were significantly higher in control subjects than the study group (100.80 +/- 7.06 mg/dL [1.0 +/- 0.07 g/L] and 72.56 +/- 9.86 mg/dL [0.73 +/- 0.1 g/L], respectively; P < .0001), whereas apo B levels were significantly lower (72.12 +/- 11.32 mg/dL [0.7 +/- 0.1 g/L] and 97.45 +/- 9.04 mg/dL [1.0 +/- 0.09 g/L], respectively; P < .0001). The G allele frequency at the -75-base-pair (bp) site was higher in the study group (79%) compared with the control group (58%). The T allele frequency at the +83-bp site was higher in the study group (56%) than in the control group (32%). G at -75 bp upstream from the start of transcription and T at +83 bp in the first intron may be susceptibility alleles for myocardial infarction.

ObjectiveLarge 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.DesignSecondary 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.Setting39 public and private hospitals across India during the study period from 22 April to 14 July 2020.ParticipantsOf 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 measureFactors associated with all-cause mortality at 28 days after enrolment.ResultsThe 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.ConclusionIn 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 numberCTRI/2020/04/024775.

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As well as dengue fever (DF) and dengue haemorrhagic fever-dengue shock syndrome (DHF/DSS), other atypical manifestations of dengue virus infection have also been reported. The frequency of CNS involvement in dengue remains unknown, although isolated cases with neurological manifestations have been reported in Southeast Asia, Malaysia, Burma, Puerto Rico and India. We present two cases of encephalitis associated with DF and DHF from New Delhi, India.