Background: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Because the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed. Objective: Our aim was to develop a model able to predict the risk of fatal outcome in patients with COVID-19 that could be used easily at the time of patients' arrival at the hospital. Methods: We constructed a prospective cohort with 611 adult patients in whom COVID-19 was diagnosed between March 10 and April 12, 2020, in a tertiary hospital in Madrid, Spain. The analysis included 501 patients who had been discharged or had died by April 20, 2020. The capacity of several biomarkers, measured at the beginning of hospitalization, to predict mortality was assessed individually. Those biomarkers that independently contributed to improve mortality prediction were included in a multivariable risk model. Results: High IL-6 level, C-reactive protein level, lactate dehydrogenase (LDH) level, ferritin level, D-dimer level, neutrophil count, and neutrophil-to-lymphocyte ratio were all predictive of mortality (area under the curve >0.70), as were low albumin level, lymphocyte count, monocyte count, and ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2). A multivariable mortality risk model including the SpO 2 /FiO 2 ratio, neutrophil-to-lymphocyte ratio, LDH level, IL-6 level, and age was developed and showed high accuracy for the prediction of fatal outcome (area under the curve 0.94). The optimal cutoff reliably classified patients (including patients with no initial respiratory distress) as survivors and nonsurvivors with 0.88 sensitivity and 0.89 specificity. Conclusion: This mortality risk model allows early risk stratification of hospitalized patients with COVID-19 before the appearance of obvious signs of clinical deterioration, and it can be used as a tool to guide clinical decision making. (J Allergy Clin Immunol 2020;146:799-807.)

The evaluation of CD4CD25CD62LCD45RO aTreg cells may be useful as pretransplantation predictive biomarker of AR in kidney transplant patients. Definitive confirmation of our results awaits tests in validation groups.

Objective Patients with coronavirus disease 2019 (COVID‐19) present coagulation abnormalities and thromboembolic events that resemble antiphospholipid syndrome (APS). This work has aimed to study the prevalence of APS‐related antigens, antibodies, and immune complexes in patients with COVID‐19 and their association with clinical events. Methods A prospective study was conducted on 474 adults with severe acute respiratory syndrome coronavirus 2 infection hospitalized in two Spanish university hospitals. Patients were evaluated for classic and extra‐criteria antiphospholipid antibodies (aPLs), immunoglobulin G (IgG)/immunoglobulin M (IgM) anticardiolipin, IgG/IgM/immunoglobulin A (IgA) anti‐β2‐glicoprotein‐I (aβ2GPI), IgG/IgM antiphosphatidylserine/prothrombin (aPS/PT), the immune complex of IgA aβ2GPI (IgA‐aβ2GPI), bounded to β2‐glicoprotein‐1 (β2GPI) and β2GPI levels soon after COVID‐19 diagnosis and were followed‐up until medical discharge or death. Results Prevalence of aPLs in patients with COVID‐19 was as follows: classic aPLs, 5.8%; aPS/PT, 4.6%; IgA‐aβ2GPI, 15%; and any aPL, 21%. When patients were compared with individuals of a control group of a similar age, the only significant difference found was the higher prevalence of IgA‐aβ2GPI (odds ratio: 2.31; 95% confidence interval: 1.16‐4.09). No significant differences were observed in survival, thrombosis, or ventilatory failure in aPL‐positive versus aPL‐negative patients. β2GPI median levels were much lower in patients with COVID‐19 (15.9 mg/l) than in blood donors (168.8 mg/l; P < 0.001). Only 3.5% of patients with COVID‐19 had normal levels of β2GPI (>85 mg/l). Low levels of β2GPI were significantly associated with ventilatory failure (P = 0.026). Conclusion β2GPI levels were much lower in patients with COVID‐19 than in healthy people. Low β2GPI‐levels were associated with ventilatory failure. No differences were observed in the COVID‐19 evolution between aPL‐positive and aPL‐negative patients. Functional β2GPI deficiency could trigger a clinical process similar to that seen in APS but in the absence of aPLs.

Pretransplantation sensitization against MICA and HLA are independent events. Preformed anti-MICA antibodies independently increase risk for kidney rejection and enhance the deleterious effect of PRA+ status early after transplantation.

We examined intraepithelial lymphocytes (IELs)

Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2‐specific T cell–mediated immunity (SARS‐CoV‐2‐CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS‐CoV‐2‐CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)‐γ FluoroSpot assay after a median of 103 days from COVID‐19 diagnosis. Serum SARS‐CoV‐2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post‐transplant SARS‐CoV‐2‐CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN‐γ‐producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike‐specific and nucleoprotein‐specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein‐specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike‐specific IFN‐γ‐producing SFUs and time from diagnosis (Spearman's rho: −0.418; p value = .024). Two recipients (6.5%) failed to mount either T cell–mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable—but declining over time—SARS‐CoV‐2‐CMI after a median of 3 months from COVID‐19, with no meaningful differences with immunocompetent patients.

Preformed anti-MICA antibodies may occasionally be cytotoxic by fixing and activating complement. This way they might contribute to worse early kidney graft function.

Rejection is one of the most important drawbacks for graft and patient survival in intestinal and multivisceral transplantation. However, there is no consensus on the diagnostic criteria for humoral rejection, and the literature about the role of donor-specific antibodies (DSA) on allograft outcome and the risk factors that contribute to their development is scant with contradictory results. The present study analyzes the role of DSA exclusively in a pediatric cohort of 43 transplants. Among our patients, 11.6% showed preformed DSA, but they did not correlate with more rejection or less allograft survival. Having previous transplants was the main sensitization factor with an odds ratio (OR) = 44.85 (P = 0.001). In total, 16.3% of recipients developed de novo donor-specific antibodies (dnDSA), mostly directed against human leukocyte antigen (HLA) class II, polyspecific and complement fixing. Additionally, the presence of dnDSA had a deleterious effect on graft rejection (hazard ratio [HR] = 11.00; P = 0.01) and survival (HR = 66.52; P < 0.001) in an observational period of 5 years after transplantation. The inclusion of the liver emerged as the main protective factor against dnDSA development with an OR = 0.07 (P = 0.007). The analysis of HLA compatibility at the serological and epitope level with the computational tools HLAMatchmaker and PIRCHE revealed no association between HLA mismatching and dnDSA. In conclusion, this study performed in pediatric recipients shows the deleterious effect of dnDSA on intestinal transplantation supported by the complement-fixing activity observed. Additionally, the liver inclusion in the allografts showed to be a protective factor against dnDSA generation.