Evaluation of Convalescent Plasma in the Management of Critically Ill COVID-19 Patients (with No Detectable Neutralizing Antibodies Nab) in Kashmir, India

Abstract

Background: For centuries, convalescent plasma (CP) has been recommended to treat a diverse set of viral diseases. Therefore, the present study was undertaken to evaluate the effectiveness of CP in critically ill COVID-19 patients. Methods and Materials: From 23 March 2021 to 29 December 2021, an open-label, prospective cohort, single-centre study was conducted at Chest Disease Hospital, Jammu and Kashmir, Srinagar. Patients with severe manifestation of coronavirus disease 2019 (COVID-19) under BST (best standard treatment) +CP were prospectively observed in order to evaluate effectiveness of CP therapy and historical control under BST were used as the control group Results: A total of 1667 patients were found positive for COVID-19. Of these, 873 (52.4%), 431 (28.8%), and 363 (21.8%) were moderately, severely, and critically ill, respectively. On 35th day post-infusion of CP, all-cause mortality was higher in the BST (best standard treatment) +CP group 12 (37.5%) compared to 127 (35%) in the BST group with an odds ratio (OR) of 1.4 and hazard ratio (HR) (95% CI: 1.08–1.79, p = 0.06). Similarly, 7 (21.9) patients in the BST+CP group and 121 (33.3) patients in the BST group showed the transition from critically ill to moderate disease with subhazard ratio (s-HR 1.37) (95% CI: 1.03–2.9). Conclusions: In the present study, we could not find any significant difference in the CP group and BST +CP in primary outcome of reducing all-cause mortality in critically ill patients with negligible Nabs levels. However, beneficial results were observed with use of CP in a limited number of secondary outcomes which includes days of hospitalization, negative conversion of SARS-CoV-2 on basis of RT-PCR on 7th day and 14th day, need for invasive mechanical ventilation on 14th day post-CP treatment, and resolution of shortness of breath.

The critical impacts of cytokine storms in respiratory disorders

“…Cytokines play vital role in progression, and outcome of the pulmonary diseases. After the disease's degenerative processes begin, clinical symptoms become more complicated and complex in manifestation [ 11 ]. Because of the simultaneous manifestation of hyper inflammation, hemostasis disruption, and reduced platelet counts, CS may result in a significant risk of spontaneous bleeding [ 1 ].…”

“…The criteria for recognition and diagnosis of CS constitute an important topic of discussion among researchers and the healthcare community. Various clinical, biochemical, and radiographic abnormalities are peculiar to CS patients and some of them are pathognomonic for diagnosis of CS [ 6 , 11 ] ( Table 2 , Table 3 ).…”

“…Other cellular determinant of cytokine storm recognized include significant neutrophilia which has been reported to cause cellular damage to the tissue architecture and causes necrosis of the tissues. Earlier studies conducted in Wuhan have reported significant elevation in neutrophil count in non-survivors compared to patients that survived, furthermore, a steady increase in mature and immature neutrophil levels was observed till the death of these patients [ 11 ]. Another study utilized a multi-omics approach and found that markers of neutrophil (Neutrophil Elastase and Myeloperoxidase) were significantly elevated in critically ill patients with cytokine storm compared to healthy counterparts [ 85 ].…”

“…The perplexing etiology of COVID-19 is marked by significantly enhanced cytokine production which results both in considerable mortality and grave disease progression [ 6 ] The increased case fatality of the recent SARS-CoV-2 pandemic is attributed to uncontrolled and dysregulated cytokine production which results from severe Acute Respiratory Distress Syndrome (ARDS) symptoms, which further causes significantly higher mortality rate in these patients [ 7 ]. Studies across the globe have reported that activation of immune cells by various viruses that infect the pulmonary system promotes secretion of a diverse set of cytokines which enhances endothelial-vascular permeability and allows blood cells and fluid to migrate into the alveoli henceforth causing dyspnea and respiratory failure [ [7] , [8] , [9] , [10] , [11] , [12] ]. In addition to SARS-CoV-2 viruses that induce CS include SARS-CoV-1, H1N1 influenza, H5N1 influenza, Ebola infections, and Influenza Band Parainfluenza virus, [ 13 ].…”

Clinical Characterization and Outcomes of Patients with Hypercreatinemia Affected by COVID-19

“…A pneumonic disease outbreak caused by a novel beta-coronavirus, named “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, China [ 1 , 2 , 3 ]. The disease caused by the virus is known as the Corona Virus Infectious Disease 2019 (COVID-19) and represents a source of concern for the treatment of patients with associated co-morbidities.…”