Nature and dimensions of the cytokine storm and its attenuation by convalescent plasma in severe COVID-19

Bandopadhyay, Purbita; D’Rozario, Ranit; Lahiri, Abhishake; Sarif, Jafar; Ray, Yogiraj; Paul, Shekhar Ranjan; Roy, Rammohan; Maiti, Rajsekhar; Chaudhuri, Kausik; Bagchi, Sougata; Maiti, Ayan; Parwez, Md. Masoom; Sarkar, Biswanath Sharma; Roy, Devlina; Chakraborty, Rahul; Vasudevan, Janani Srinivasa; Sharma, Sachin; Biswas, Durba; Maiti, Chikam; Saha, Bibhuti; Bhattacharya, Partha Pratim; Pandey, Rajesh; Chatterjee, Shilpak; Paul, Sandip; Ganguly, Dipyaman

doi:10.1101/2020.09.21.20199109

Cited by 20 publications

(20 citation statements)

References 14 publications

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“…The severe COVID-19 patients have been found by previous studies to experience a systemic immune hyper-activation characterized by a cytokine storm. We had previously reported nature and dimension of the cytokine storm in a fraction of these patients, comparing them to patients suffering from mild COVID-19 disease (Bandopadhyay et al, 2020). On measuring plasma abundance of a panel of 48 cytokines in patients from both arms we found that correlative nature and magnitude of the individual components of the cytokine storm were not notably different at T1 in a correlative network analysis (Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

Clinical and immunological benefits of convalescent plasma therapy in severe COVID-19: insights from a single center open label randomised control trial

Ray

Paul²,

Bandopadhyay

et al. 2020

Preprint

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IntroductionA single center open label phase II randomised control trial was done to assess the pathogen and host-intrinsic factors influencing clinical and immunological benefits of passive immunization using convalescent plasma therapy (CPT), in addition to standard of care (SOC) therapy in severe COVID-19 patients, as compared to patients only on SOC therapy.MethodsConvalescent plasma was collected from patients recovered from COVID-19 following a screening protocol which also included measuring plasma anti SARS-CoV2 spike IgG content. Retrospectively, neutralizing antibody content was measured and proteome was characterized by LC-MS/MS for all convalescent plasma units that were transfused to patients. Severe COVID-19 patients with evidence for acute respiratory distress syndrome (ARDS) with PaO2/FiO2 ratio 100-300 (moderate ARDS) were recruited and randomised into two parallel arms of SOC and CPT, N=40 in each arm. Peripheral blood samples were collected on the day of enrolment (T1) followed by day3/4 (T2) and day 7 (T3). RT-PCR and sequencing was done for SARS-CoV2 RNA isolated from nasopharyngeal swabs collected at T1. A panel of cytokines and neutralizing antibody content were measured in plasma at all three timepoints. Patients were followed up for 30 days post-admission to assess the primary outcomes of all cause mortality and immunological correlates for clinical benefits.ResultsWhile across all age-groups no statistically significant clinical benefit was registered for patients in the CPT arm, significant immediate mitigation of hypoxia, reduction in hospital stay as well as survival benefit was recorded in severe COVID-19 patients with ARDS aged less than 67 years receiving convalescent plasma therapy. In addition to its neutralizing antibody content a prominent effect of convalescent plasma on attenuation of systemic cytokine levels possibly contributed to its benefits.ConclusionPrecise targeting of severe COVID-19 patients is necessary for reaping the clinical benefits of convalescent plasma therapy.Clinical trial registrationClinical Trial Registry of India No. CTRI/2020/05/025209

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Section: Resultsmentioning

confidence: 99%

Clinical and immunological benefits of convalescent plasma therapy in severe COVID-19: insights from a single center open label randomised control trial

Ray

Paul²,

Bandopadhyay

et al. 2020

Preprint

Self Cite

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“…In addition, convalescent plasma transfusion is associated with reductions in inflammatory markers, such as chemokines, cytokines and C-reactive protein. 44,57 Concomitant reductions in inflammation and improved gas exchange may underlie the reductions in oxygen requirements associated with convalescent plasma, even in critically ill patients. These findings provide mechanistic evidence for the reduction in mortality observed in patients receiving convalescent plasma.…”

Section: Resultsmentioning

confidence: 99%

Evidence favouring the efficacy of convalescent plasma for COVID-19 therapy

Joyner

Klassen

Senefeld

et al. 2020

Preprint

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To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from randomized clinical trials, matched control, and case-series studies. Fixed-effects analyses demontrated that hospitalized COVID-19 patients transfused with convalescent plasma exhibited a ã57% reduction in mortality rate (13%) compared to matched-patients receiving standard treatments (25%; OR: 0.43, P < 0.001). These data provide evidence favouring the efficacy of human convalescent plasma as a therapeutic agent in hospitalized COVID-19 patients.

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“…• Patients treated with CCP manifest reduced inflammatory markers [35][36][37] that can lead to host damage. 38 • Research has identified nine places where plasma affects the cascade of inflammation to the benefit of treated patients 39 .…”

Section: Discussionmentioning

confidence: 99%

Convalescent Plasma Use in the United States was inversely correlated with COVID-19 Mortality: Did Plasma Hesitancy cost lives?

Casadevall

Dragotakes

Johnson

et al. 2021

Preprint

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The US Food and Drug Administration (FDA) authorized treatment of hospitalized COVID-19 patients with Convalescent Plasma (CCP) via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to the use of CCP in some 500,000 patients during the first year of the pandemic. We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data over the course of the year. CCP usage per admission peaked after issuance of the EUA, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, following reports of randomized controlled trials that failed to show clear benefit from CCP, usage/admissions declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (Pearson correlation coefficient of -0.5176 with P = 0.00242) between CCP usage/hospital admission and deaths occurring two weeks after admission, and this finding was robust to examination of deaths taking place one, two or three weeks after admission. Changes in the number of hospital admissions, prevalence of variants, and age of patients could not explain these findings. We estimate that the retreat from CCP usage, a phenomenon we termed plasma hesitancy, might have resulted in 29,000 to 36,000 excess deaths in the period from mid-November 2020 to February 2021. These results highlight the need for additional studies to ascertain the variables associated with efficacy and/or provide other explanations for the robust relationships observed in this study.

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Nature and dimensions of the cytokine storm and its attenuation by convalescent plasma in severe COVID-19

Cited by 20 publications

References 14 publications

Clinical and immunological benefits of convalescent plasma therapy in severe COVID-19: insights from a single center open label randomised control trial

Clinical and immunological benefits of convalescent plasma therapy in severe COVID-19: insights from a single center open label randomised control trial

Evidence favouring the efficacy of convalescent plasma for COVID-19 therapy

Convalescent Plasma Use in the United States was inversely correlated with COVID-19 Mortality: Did Plasma Hesitancy cost lives?

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