A phase 2 single center open label randomised control trial for convalescent plasma therapy in patients with severe COVID-19.

A single center open label phase 2 randomised control trial (Clinical Trial Registry of India No. CTRI/2020/05/025209) was done to assess clinical and immunological benefits of passive immunization using convalescent plasma therapy. At the Infectious Diseases and Beleghata General Hospital in Kolkata, India, 80 patients hospitalized with severe COVID-19 disease and fulfilling the inclusion criteria (aged more than 18 years, with either mild ARDS having PaO2/FiO2 200-300 or moderate ARDS having PaO2/FiO2 100-200, not on mechanical ventilation) were recruited and randomized into either standard of care (SOC) arm (N = 40) or the convalescent plasma therapy (CPT) arm (N = 40). Primary outcomes were all-cause mortality by day 30 of enrolment and immunological correlates of response to therapy if any, for which plasma abundance of a large panel of cytokines was quantitated before and after intervention to assess the effect of CPT on the systemic hyper-inflammation encountered in these patients. The secondary outcomes were recovery from ARDS and time taken to negative viral RNA PCR as well as to report any adverse reaction to plasma therapy. Transfused convalescent plasma was characterized in terms of its neutralizing antibody content as well as proteome. The trial was completed and it was found that primary outcome of all-cause mortality was not significantly different among severe COVID-19 patients with ARDS randomized to two treatment arms (Mantel-Haenszel Hazard Ratio 0.6731, 95% confidence interval 0.3010-1.505, with a P value of 0.3424 on Mantel-Cox Log-rank test). No adverse effect was reported with CPT. In severe COVID-19 patients with mild or moderate ARDS no significant clinical benefit was registered in this clinical trial with convalescent plasma therapy in terms of prespecified outcomes.

Plasma Gradient of Soluble Urokinase-Type Plasminogen Activator Receptor Is Linked to Pathogenic Plasma Proteome and Immune Transcriptome and Stratifies Outcomes in Severe COVID-19.

Disease caused by SARS-CoV-2 coronavirus (COVID-19) led to significant morbidity and mortality worldwide. A systemic hyper-inflammation characterizes severe COVID-19 disease, often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. Flow cytometry and next-generation sequencing were done on peripheral blood cells and urokinase-type plasminogen activator receptor (suPAR), and cytokines were measured from and mass spectrometry-based proteomics was done on plasma samples from an Indian cohort of COVID-19 patients. Publicly available single-cell RNA sequencing data were analyzed for validation of primary data. Statistical analyses were performed to validate risk stratification. We report here higher plasma abundance of suPAR, expressed by an abnormally expanded myeloid cell population, in severe COVID-19 patients with ARDS. The plasma suPAR level was found to be linked to a characteristic plasma proteome, associated with coagulation disorders and complement activation. Receiver operator characteristic curve analysis to predict mortality identified a cutoff value of suPAR at 1,996.809 pg/ml (odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower-than-cutoff suPAR levels were associated with a differential expression of the immune transcriptome as well as favorable clinical outcomes, in terms of both survival benefit (hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus, we identified suPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.

Nature and Dimensions of Systemic Hyperinflammation and its Attenuation by Convalescent Plasma in Severe COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to severe disease with acute respiratory distress syndrome (ARDS) and associated systemic hyperinflammation. METHODS: First, to characterize key cytokines and their dynamics in this hyperinflammatory condition, we assessed abundance and correlative expression of a panel of 48 cytokines in patients progressing to ARDS as compared to patients with mild disease. Then, in an ongoing randomized controlled trial of convalescent plasma therapy (CPT), we analyzed rapid effects of CPT on the systemic cytokine dynamics as a correlate for the level of hypoxia experienced by the patients. RESULTS: We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content. CONCLUSIONS: Neutralizing antibodies, as well as reductions in circulating interleukin-6 and interferon-γ-inducible protein 10, contributed to marked rapid reductions in hypoxia in response to CPT. CLINICAL TRIAL REGISTRY OF INDIA: CTRI/2020/05/025209. http://www.ctri.nic.in/.

Profile of Patients with Allergic Rhinitis (AR): A Clinic Based Cross-Sectional Study from Kolkata, India.

BACKGROUND: Allergic Rhinitis (AR) though quite common in India, does not receive its due importance as it deserves. AIM OF THE STUDY: To identify the demographic and clinical profile of the patients with AR and to find the association of pre-dominant disease symptoms with common allergens, type and severity of the disease and other co-morbidities. SETTINGS AND DESIGN: This clinic-based cross-sectional, observational study was conducted among adult patients presenting with signs and symptoms suggestive of AR. METHODS AND MATERIAL: Consecutive 548 patients were initially screened for possible cases of AR by proper history taking and physical examination and confirmation was done by a battery of investigations, including modified skin prick test. A total of 462 patients who were finally diagnosed with AR were included in the study. Categorization of these patients was done following Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. Pulmonary function tests and X-ray/CT-scan of the para-nasal sinuses were done to confirm the presence of bronchial asthma and sinusitis, respectively. STATISTICAL ANALYSIS USED: Data were analyzed by Statistical Package for Social Scientists (SPSS version 10). Z-test was applied to compare between two rates, at 5% level of significance. RESULTS: Proportion of "blockers" was found to be much higher than that of "sneezers-runners" (64.1% vs. 35.9%). "Blockers" had significantly more sensitization to polyvalent house dust, house dust mites and fungi (p < 0.05), while, "sneezers-runners" had more sensitization to pollens (p < 0.05). Significantly more "blockers" had "moderate/severe persistent" and "mild persistent" types of the disease (p < 0.05), while "mild intermittent" and moderate/severe intermittent" type of disease were significantly more common among "sneezers-runners" (p < 0.05). Both bronchial asthma and sinusitis were significantly more common among the "blockers" (p < 0.05). CONCLUSION: It can be concluded from the present study that the clinical profiles of the two main categories of AR namely "sneezers-runners" and "blockers" were distinct from each other. This knowledge can be useful to physicians at all levels for better management of patients with AR.

Systemic Sclerosis Presenting with Simultaneous Retinal Vasculitis in One Eye and Optic Neuritis in the other along with Severe Immune Haemolytic Anaemia.

Systemic Sclerosis (SSc) is a connective tissue disorder which involves multiple systems in a chronic progressive manner. Micro-angiopathic haemolytic anaemia is a distinguished feature of "scleroderma renal crisis", which is manifested by severe hypertension, a rapidly progressing renal dysfunction and hyperreninaemia and is seen in patients with an early, diffuse form of the disease. A nervous system involvement is rare, though entrapment neuropathies have been reported. Who presented with a sequential loss of vision in both eyes; due to retinal vasculitis in right eye and optic nerve demyelination in the left eye. She also had severe Coombs' negative haemolytic anaemia in absence of any renal dysfunction or hypertension. Both the ophthalmologic and the haematologic manifestations are very rare and both responded well to oral prednisolone therapy.