Key PointsQuestionWhat is the effect of convalescent plasma therapy added to standard treatment, compared with standard treatment alone, on clinical outcomes in patients with severe or life-threatening coronavirus disease 2019 (COVID-19)?FindingIn this randomized clinical trial that included 103 patients and was terminated early, the hazard ratio for time to clinical improvement within 28 days in the convalescent plasma group vs the standard treatment group was 1.40 and was not statistically significant.MeaningAmong patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment did not significantly improve the time to clinical improvement within 28 days, although the trial was terminated early and may have been underpowered to detect a clinically important difference.

Background: Because treatment options for coronavirus disease 2019 (COVID-19) are very limited, the use of convalescent plasma has bee explored. Case presentation and treatment: A male centenarian with cough and dyspnea for 2 months was diagnosed with COVID-19. Without effective treatments and with the increased risks of antiviral therapy for the elderly, this patient was given convalescent plasma. The viral load, complete blood count, inflammatory indicators, vital signs, and clinical symptoms were observed before and after COVID-19 convalescent plasma transfusion. Results: After convalescent plasma transfusion, significant improvement was observed on laboratory indicators and clinical symptoms of the patient. Concurrently, SARS-CoV-2 viral load decreased sharply after the first transfusion (from 2.55 × 104 to 1.39 × 103 copies/mL) and became undetectable after the second transfusion. Conclusions: With the substantial increase of COVID-19 in recent months,treatment for elderly patients has become restricted in some countries. The successful treatment of this 100-year-old patient using convalescent plasma suggests that we should consider adding convalescent plasma in th management of the elderly.

Background: This study measured the serum levels of complement component (C)3a and C5a and the placental expressions of C3a receptor (R) and C5aR to determine a potential correlation with circulating angiotensin II type 1 (AT1) receptor agonistic autoantibody (AT1-AA) in severe pre-eclampsia. Methods: A total of 118 women were recruited and divided into 2 groups: the control group (normotensive preterm pregnancies, n = 66) and severe pre-eclampsia group (n = 52). Levels of C3a, C5a and AT1-AA in serum were measured by enzyme-linked immunosorbent assay and C3aR and C5aR in placenta by Western blotting. Results: Levels of C3a, C5a and AT1-AA in serum from the severe pre-eclampsia group were significantly higher than in controls (p < 0.05). Placental expression of C3aR and C5aR in the pre-eclampsia group was lower than that in controls (p < 0.05). There were significant positive correlations between levels of C3a, C5a and AT1-AA in serum from the pre-eclampsia group (p < 0.05). In contrast, there was no correlation between C3aR and C5aR in the placenta and AT1-AA in serum in the pre-eclampsia group (p > 0.05). Conclusion: Increased C3a, C5a and AT1-AA in the serum provide indirect evidence that AT1-AA-mediated activation contributes to activate complement, which is a key mechanism underlying the pathogenesis of severe pre-eclampsia.

Background Transfusion-related immunomodulation (TRIM) can be caused by exosomes, in which case, microRNAs (miRNAs) are one critical factor impacting exosome behavior. This study aims to investigate and analyze the expression profiles of exosomal miRNA in red blood cell (RBC) suspensions during storage and to identify potential TRIM-related miRNAs as well as their potential functions. Methods A total of 25 packs of RBC suspensions were randomly collected. Exosome were extracted by ultracentrifugation and then identified and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and western blot (WB). Exosomal miRNA profiles were acquired using gene chips in five packs on week 1 and week 5. The expression data were compared from the two time points identifying accumulated miRNAs with statistical significance and their predicted targeting genes were analyzed. Based on the gene chip results, quantitative reverse transcription-polymerase chain reactions (qRT-PCR) were performed to verify miRNA accumulation in the rest 20 packs sampling on week 1, 3 and 5. Results Gene chip analysis revealed that most exosomal miRNAs were enriched as the storage period progressed. Compared to samples from week 1, week 5 samples exhibited a total of 539 differential miRNA expressions, among which, 159 were statistically significant (P < 0.05) and 148 (93.08%) were accumulated. In the bioinformatics functional analysis, significant immunoregulatory annotations related to the thyroid hormone, mitogen-activated protein kinase (MAPK), focal adhesion and RAS signaling pathways were identified. The top 17 differential expression miRNAs were validated by qRT-PCR. The results confirmed that all the 17 miRNAs were accumulated with increasing storage time. In particular, miRNA-1246 and miRNA-150-3p were the most enriched strands by more than 150-folds in the 5-week storage period. Conclusions As storage progressed, numerous exosomal miRNAs accumulated in the RBC suspensions, which are informatically connected to multiple immuno-signaling pathways. MiRNA-1246 and miRNA-150-3p may be essential mediators impacting the immunoregulation functions of exosomes in RBC suspensions, considering their significant accumulating scales. Further research should therefore focus on the relationship between these miRNAs and TRIM.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is one of the most serious adverse events following transfusion, and there is no specific treatment in clinical practice. However, regulatory T cells (Tregs) have been suggested to play a potential role in the treatment of TRALI. This study investigated whether interleukin (IL)-2 or IL-2/anti-IL-2 complexes (IL-2c), which are mediators of Treg expansion, can modulate the severity of antibody-mediated TRALI in vivo. STUDY DESIGN AND METHODS:This study utilized a mouse model of the "two-hit" mechanism: BALB/c mice were primed with lipopolysaccharide (LPS) as the first hit, and then TRALI was induced by injecting major histocompatibility complex Class I antibodies. Mice injected with LPS only or LPS combined with isotype control antibodies served as controls. For the Tregdepleted groups, mice were infused with anti-mouse IL-2Rα first and then subjected to the same treatments as the TRALI group. Regarding IL-2-and IL-2c-treated mice, recombinant murine IL-2 or IL-2c was intraperitoneally administered to mice for 5 consecutive days before induction of the TRALI model. Samples were collected 2 hours after TRALI induction. RESULTS: Prophylactic administration of IL-2 or IL-2cto mice prevented the onset of edema, pulmonary protein levels, and proinflammatory factors that inhibited polymorphonuclear neutrophil aggregation in the lungs. Furthermore, the percentage of CD4 + CD25 + FoxP3 + Tregs was expanded in vivo using IL-2 and IL-2c compared to TRALI mice, as was confirmed through analysis of the spleen, blood, and lung. CONCLUSION:This study validates that the protective mechanisms against TRALI involve CD4 + CD25 + FoxP3 + Tregs, which can be expanded in vivo by IL-2 and IL-2c. This results in increased IL-10 levels and decreased IL-17A, thereby prophylactically preventing antibodymediated murine TRALI. ABBREVIATIONS: BALF = bronchoalveolar lavage fluid; HNA = human neutrophil antigen; IL = interleukin; IL-2c = IL-2/anti-IL-2 complexes; LPS = lipopolysaccharide; MPO = myeloperoxidase; MHC = major histocompatibility complex; Th17 = T helper 17; TRALI = transfusion-related acute lung injury; Tregs = regulatory T cells; W/D = wet-to-dry. From the