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.

Aim: To study the efficacy of intravenous vitamin C in management of moderate and severe COVID-19. Objective: To determine the efficacy of intravenous vitamin C in reducing in-hospital mortality in moderate and severe cases of COVID-19. Design: Parallel, double-blinded randomized controlled trial with placebo. Ethical clearance was obtained from the institutional ethics committee, AIIMS Patna. The trial was registered with the Clinical Trials Registry – India (registration number- CTRI/2020/11/029230.) Setting: A tertiary care centre in Bihar, India Participants: All patients above the age of 18 years both males and females, admitted in ICU with a diagnosis of moderate and severe COVID-19 (on the basis of a positive reverse transcriptase polymerase chain reaction (RT–PCR) report) at our facility during the study period (01/10/2020–31/12/2020) not having any of the exclusion criteria. Intervention: The patients in the intervention arm were given 1 gram (2 ampoules of 2 ml each containing 500 mg of vitamin C mixed in 100 ml normal saline) intravenous vitamin C 8 hourly for four days. The patients in the placebo arm received similar looking ampoules (2 ampoules of 2 ml sterile water for injection mixed in 100 ml normal saline) intravenously 8 hourly for four days. The rest of the treatment was given as per the standard operating procedure (SOP) of the institute with adjustments as per treating team’s judgement. Outcome Measures: Primary outcome was reduction in in-hospital mortality. Secondary outcomes were improvement in qSOFA score, pO2/fiO2 ratio, fall in inflammatory markers, need for mechanical ventilation and vasopressors. Results: Regarding primary outcome, 10 (33.3%) patients died in intervention group compared to 13 (43.3%) in placebo. Worth noting from baseline characteristics is that 86.7% in intervention arm were of severe category compared to 66.7% severe category patients in placebo group. Though number of severe cases were more in intervention arm there has been comparatively less mortality in this group. Regarding secondary outcomes, amongst 30 patients in vitamin C group, 11 (36.7%) required invasive mechanical ventilation compared to 14 (46.7%) out of 30 in placebo group but the difference was not statistically significant. Although there were a greater number of moderate cases in placebo group, invasive ventilation requirement (and NIV requirement) was more in this group, thus it could be considered that vitamin C might have a role in reducing the severity of disease. The need for vasopressor therapy was higher in intervention arm 33.3% compared to 26.7% in placebo but not significant statistically. The secondary outcomes of the study such as improvement in organ failure score (qSOFA Score), fall in level of inflammatory markers, improvement in respiratory index (pO2/fiO2 ratio), need...

A bstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the cardiovascular system at many levels. It initially infects endothelial cells, inducing marked endothelial damage and inflammation. However, there was no empirical evidence of functional compromise of arterial walls. Aims and objective Our primary objective was to study functional arterial damage in coronavirus disease 2019 (COVID-19) and establish the noninvasive measurement of arterial stiffness as an independent marker of disease severity. Materials and methods We recorded the arterial stiffness of 23 mild, 21 moderate, and 20 severe COVID-19 patients grouped on the latest National Institute of Health (NIH) severity criteria. We observed arterial stiffness of COVID-19 patients with standard parameters like noninvasive estimated carotid–femoral pulse wave velocity (cfPWV), age-normalized increase in cfPWV (ANI_cfPWV), age-normalized increase in aortic augmentation pressure (ANI_AugP), and heart rate-normalized augmentation index (HRN_ AIx). All the parameters were also corrected for statistically significant confounding factors. Results Moderate and severe COVID-19 patients have extremely significantly elevated arterial stiffness than mild patients. In mild patients, cfPWV (829.1 ± 139.2 cm/second) was significantly lower than both moderate (1067 ± 152.5 cm/second, p <0.0001) and severe (1416 ± 253.9 cm/second, p <0.0001) patients. ANI_cfPWV in moderate and severe patients was significantly higher than mild patients (mild: 101.2 ± 126.1 cm/second; moderate: 279 ± 114.4 cm/second; severe: 580.1 ± 216.4 cm/second; intergroup p <0.0001). The results even after correction for significant confounding factors did not show any considerable change in the increasing trend of arterial stiffness. Conclusion This study establishes the functional deterioration of arteries in proportion to the severity of COVID-19. How to cite this article Kumar N, Kumar S, Kumar A, Bhushan D, Kumar A, Kumar A, et al. The COSEVAST Study Outcome: Evidence of COVID-19 Severity Proportionate to Surge in Arterial Stiffness. Indian J Crit Care Med 2021;25(10):1113–1119.

BackgroundTreatment for coronavirus disease 2019 (COVID-19) pneumonia remains largely supportive till date and multiple clinical trials took place within the short span of time to evaluate the role of investigational therapies. The anti-inflammatory effect of low dose whole lung radiation in treating pneumonia has been documented earlier. This clinical trial analyzed the effect of low dose radiation therapy (LDRT) in a moderately affected COVID-19 pneumonia patient cohort and has evaluated its effect in stopping the conversion of moderate disease into severe disease.MethodsPatients with moderate COVID-19 pneumonia as characterized by the Ministry of Health and Family Welfare (MOHFW), Government of India, were randomized (1:1) to low dose whole lung radiation versus no radiation. All treatment of patients was concurrently being given as per institutional protocol. Patients were followed up with clinical and laboratory parameters monitored on Days 1, 3, 7, and 14. Computed tomography scan (CT scan) of thorax was performed on Days 1 and 7. Patients were evaluated for conversion of moderate into severe disease as per National Early Warning Score-2 (NEWS-2 score) as the primary end point. The secondary endpoints included changes in ratio between peripheral capillary oxygen saturation and fraction of inspired oxygen (SpO2/FiO2), biochemical markers, 25-point CT severity score, and radiation induced acute pulmonary toxicities.FindingsAt the interim analysis, there were seven patients in the radiation arm and six in the control. A whole lung LDRT improved the outcome of SpO2/FiO2 at Day 3; however it did not convert into a statistically significant improvement for the NEWS-2 score. The serum levels of LDH, CRP, Ferritin and D-dimer were significantly reduced on 14 days in the LDRT arm in comparison to the baseline value but were not significant between the two groups.InterpretationLDRT seems to have the potential to prevent moderate COVID-19 pneumonia from a deteriorating to severe category. However, further randomized clinical trial with an adequate number of such patients is warranted to establish the definitive role of LDRT in the management of COVID-19 pneumonia.FundingAn intramural research project bearing code: I-27/621, was sanctioned from the All India Institute of Medical Sciences, Patna, India.Clinical Trial RegistrationClinical Trials Registry-India (CTRI/2021/06/033912, 25th May 2021) ctri.nic.in/Clinicaltrials/login.php

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