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Dysregulated plasma lipid mediator profiles in critically ill COVID-19 patients.

ABSTRACT: Coronavirus disease (COVID)-19, as a result of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has been the direct cause of over 2.2 million deaths worldwide. A timely coordinated host-immune response represents the leading driver for restraining SARS-CoV-2 infection. Indeed, several studies have described dysregulated immunity as the crucial determinant for critical illness and the failure of viral control. Improved understanding and management of COVID-19 could greatly reduce the mortality and morbidity caused by SARS-CoV-2. One aspect of the immune response that has to date been understudied is whether lipid mediator production is dysregulated in critically ill patients. In the present study, plasma from COVID-19 patients with either severe disease and those that were critically ill was collected and lipid mediator profiles were determined using liquid chromatography tandem mass spectrometry. Results from these studies indicated that plasma concentrations of both pro-inflammatory and pro-resolving lipid mediator were reduced in critically ill patients when compared with those with severe disease. Furthermore, plasma concentrations of a select group of mediators that included the specialized pro-resolving mediators (SPM) Resolvin (Rv) D1 and RvE4 were diagnostic of disease severity. Interestingly, peripheral blood SPM concentrations were also linked with outcome in critically ill patients, where we observed reduced overall concentrations of these mediators in those patients that did not survive. Together the present findings establish a link between plasma lipid mediators and disease severity in patients with COVID-19 and indicate that plasma SPM concentrations may be linked with survival in these patients.

SUBMITTER: Palmas F

PROVIDER: S-EPMC8389414 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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Dysregulated plasma lipid mediator profiles in critically ill COVID-19 patients.

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