Project description:High throughput sequencing is performed on mRNA isolated from whole blood of adult Covid-19 patients, bacterial coinfection with Covid-19 and healthy controls in a South Indian cohort. Samples were collected from individuals at the time of hospitalization or visit to clinic. The Covid-19 samples are categorized by severeity.
Project description:The recent outbreak of COVID-19 in the world is currently a big threat to global health and economy. Convalescent plasma has been confirmed effective against the novel corona virus in preliminary studies. In this paper, we first described the therapeutic schedule, antibody detection method, indications, contraindications of the convalescent plasmas and reported the effectiveness of convalescent plasma therapy by a retrospective cohort study.
Project description:BackgroundTransfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients.MethodsPlasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients.ResultsAnti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients.ConclusionOur results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.
Project description:The emergence of the COVID-19 pandemic has resulted in a very large number of infections and high number of mortality. There is no specific therapeutic options that are approved for clinical use. Administration of convalescent plasma as a possible therapy was used in the case of viral pneumonia including SARS and influenza. There have been multiple studies of COVID-19 patients utilizing convalescent plasma. These studies employed different dosage levels and different regiments, were observational and lacked control arms, and had variable outcomes. Two of these studies used plasma with anti-SARS-CoV-2 titers of >1:640 to >1:1000. A recent randomized controlled clinical trial showed no benefit of convalescent plasma in patients with severe diseases. However, the study was terminated early and thus further clinical trials are needed to show efficacy in patients with COVID-19 infection.
Project description:Background and objectivesIn the absence of a vaccine or specific drug treatment options for coronavirus disease (COVID-19), attention has been shifted in China to the possible therapeutic use of convalescent plasma. COVID-19 convalescent plasma (CCP) is currently under investigation. We summarized clinical studies and other research data available as of 5 May 2020 on CCP therapy according to the Clinical Treatment Guideline of COVID-19 Convalescent Plasma in China, as well as clinical experience at the First Affiliated Hospital of Zhejiang University, as part of a comprehensive anti-epidemic strategy.Materials and methodsAs of 5 May 2020, when the epidemic was well-controlled in China, healthcare databases and sources of English literature relating to convalescent plasma were searched and reviewed. Sources of clinical and methodological heterogeneity were identified.ResultsAs of 5 May 2020, up to 2000 samples of CCP had been collected across China and administered to 700 COVID-19 patients. From donors, 200-400 ml of plasma was collected at each donation, with antibody titres > 1:160. We identified three clinical studies for COVID-19 in China. Analyses showed a statistically significant improvement in clinical outcomes compared with untreated cases (P < 0.001). No adverse effects were reported.ConclusionFrom initial studies, convalescent plasma therapy appears effective and safe for COVID-19. However, there is clearly a need for well-designed RCTs (randomized controlled trials) or other formal studies to further evaluate the efficacy and any potential adverse effects of CCP.
Project description:In the absence of an effective vaccine or monoclonal therapeutic, transfer of convalescent plasma (CCP) was proposed early in the SARS-CoV-2 pandemic as an easily accessible therapy. However, despite the global excitement around this historically valuable therapeutic approach, results from CCP trials have been mixed and highly debated. Unlike other therapeutic interventions, CCP represents a heterogeneous drug. Each CCP unit is unique and collected from an individual recovered COVID-19 patient, making the interpretation of therapeutic benefit more complicated. While the prevailing view in the field would suggest that it is administration of neutralizing antibodies via CCP that centrally provides therapeutic benefit to newly infected COVID-19 patients, many hospitalized COVID-19 patients already possess neutralizing antibodies. Importantly, the therapeutic benefit of antibodies can extend far beyond their simple ability to bind and block infection, especially related to their ability to interact with the innate immune system. In our work we deeply profiled the SARS-CoV-2-specific Fc-response in CCP donors, along with the recipients prior to and after CCP transfer, revealing striking SARS-CoV-2 specific Fc-heterogeneity across CCP units and their recipients. However, CCP units possessed more functional antibodies than acute COVID-19 patients, that shaped the evolution of COVID-19 patient humoral profiles via distinct immunomodulatory effects that varied by pre-existing SARS-CoV-2 Spike (S)-specific IgG titers in the patients. Our analysis identified surprising influence of both S and Nucleocapsid (N) specific antibody functions not only in direct antiviral activity but also in anti-inflammatory effects. These findings offer insights for more comprehensive interpretation of correlates of immunity in ongoing large scale CCP trials and for the design of next generation therapeutic design.