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Case Report: Use of Plasma Exchange Followed by Convalescent Plasma Therapy in a Critically Ill Patient with Severe Fever and Thrombocytopenia Syndrome-Associated Encephalopathy: Cytokine/Chemokine Concentrations, Viral Loads, and Antibody Responses.

ABSTRACT: We describe the case of a patient with severe fever with thrombocytopenia syndrome (SFTS) complicated by SFTS-associated encephalopathy who was successfully treated with 4-day plasma exchange followed by two-time convalescent plasma therapy. During plasma exchange, the plasma cytokines interferon-? and inducible protein-10 gradually decreased without change of plasma viral load. However, plasma viral load gradually decreased after convalescent plasma therapy. This case provides important insights for understanding the mechanisms of experimental therapy in severely affected SFTS patients.

SUBMITTER: Choi S

PROVIDER: S-EPMC6283494 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Case Report: Use of Plasma Exchange Followed by Convalescent Plasma Therapy in a Critically Ill Patient with Severe Fever and Thrombocytopenia Syndrome-Associated Encephalopathy: Cytokine/Chemokine Concentrations, Viral Loads, and Antibody Responses.

Choi Sungim S Kim Min-Chul MC Kwon Ji-Soo JS Kim Ji-Yeun JY Lee Keun Hwa KH Kim Sung-Han SH

The American journal of tropical medicine and hygiene 20180927 6

We describe the case of a patient with severe fever with thrombocytopenia syndrome (SFTS) complicated by SFTS-associated encephalopathy who was successfully treated with 4-day plasma exchange followed by two-time convalescent plasma therapy. During plasma exchange, the plasma cytokines interferon-α and inducible protein-10 gradually decreased without change of plasma viral load. However, plasma viral load gradually decreased after convalescent plasma therapy. This case provides important insight ...[more]

PMID: 30277197

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Project description:ImportanceCoronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments.ObjectiveTo determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Design, setting, and participantsCase series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion.ExposuresPatients received transfusion with convalescent plasma with a SARS-CoV-2-specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission.Main outcomes and measuresChanges of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion.ResultsAll 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion.Conclusions and relevanceIn this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.

Project description:BackgroundThe efficacy of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is primarily ascribed as a source of neutralizing anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, the composition of other immune components in CCP and their potential roles remain largely unexplored. This study aimed to describe the composition and concentrations of plasma cytokines and chemokines in eligible CCP donors.MethodsA cross-sectional study was conducted among 20 prepandemic healthy blood donors without SARS-CoV-2 infection and 140 eligible CCP donors with confirmed SARS-CoV-2 infection. Electrochemiluminescence detection-based multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n = 35 analytes). A SARS-CoV-2 microneutralization assay was also performed. Differences in the percentage of detection and distribution of cytokine and chemokine concentrations were examined by categorical groups using Fisher's exact and Wilcoxon rank-sum tests, respectively.ResultsAmong CCP donors (n = 140), the median time since molecular diagnosis of SARS-CoV-2 was 44 days (interquartile range = 38-50) and 9% (n = 12) were hospitalized due to COVID-19. Compared with healthy blood donor controls, CCP donors had significantly higher plasma levels of interferon (IFN)-γ, interleukin (IL)-10, IL-15, IL-21, and macrophage-inflammatory protein-1, but lower levels of IL-1RA, IL-8, IL-16, and vascular endothelial growth factor-A (P < .0014). The distributions of plasma levels of IL-8, IL-15, and IFN-inducible protein-10 were significantly higher among CCP donors with high (≥160) versus low (<40) anti-SARS-CoV-2 neutralizing antibody titers (P < .0014). The median levels of IL-6 were significantly higher among CCP donors who were hospitalized versus nonhospitalized (P < .0014).ConclusionsHeterogeneity in cytokine and chemokine composition of CCP suggests there is a different inflammatory state among the CCP donors compared with SARS-CoV-2 naive, healthy blood donors.

Project description:ImportanceThe evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.ObjectiveTo determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19.Design, setting, and participantsThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021.InterventionsThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916).Main outcomes and measuresThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events.ResultsAmong the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11 secondary outcomes. Serious adverse events were reported in 3.0% (32/1075) of participants in the convalescent plasma group and in 1.3% (12/905) of participants in the no convalescent plasma group.Conclusions and relevanceAmong critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days.Trial registrationClinicalTrials.gov Identifier: NCT02735707.

Dataset Information

Case Report: Use of Plasma Exchange Followed by Convalescent Plasma Therapy in a Critically Ill Patient with Severe Fever and Thrombocytopenia Syndrome-Associated Encephalopathy: Cytokine/Chemokine Concentrations, Viral Loads, and Antibody Responses.

Publications

Case Report: Use of Plasma Exchange Followed by Convalescent Plasma Therapy in a Critically Ill Patient with Severe Fever and Thrombocytopenia Syndrome-Associated Encephalopathy: Cytokine/Chemokine Concentrations, Viral Loads, and Antibody Responses.

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