Clinical Presentation, Treatment, and Mortality Rate in Liver Transplant Recipients With Coronavirus Disease 2019: A Systematic Review and Quantitative Analysis.

Liver transplant recipients may be at increased risk for adverse outcomes with coronavirus disease 2019 (COVID-19) infection because of chronic immunosuppression and associated comorbidities. There is a paucity of literature describing clinical presentation, treatments, and outcomes in liver transplant recipients with COVID-19. A systematic search was performed for articles published up to June 15, 2020, revealing 223 liver transplant recipients with COVID-19 in 15 studies. Patients most commonly presented with fever (66.7%), dyspnea (34.0%), and diarrhea (28.4%). Of these, 77.7% required hospitalization, 24% had mild disease, 40% had moderate disease, and 36% had severe disease. Immunosuppression was modified in 32.8% of recipients. The case fatality rate was 19.3%. Dyspnea on presentation, diabetes mellitus, and age 60 years or older were significantly associated with increased mortality (P ≤ .01) with a trend to higher mortality rate observed in those with hypertension and those receiving corticosteroids at the time of COVID-19 diagnosis. The median time from symptoms to death was 11.5 days (2-45 days). In conclusion, liver transplant recipients with severe acute respiratory syndrome coronavirus 2 are overrepresented with regard to severe disease and hospitalizations. Older liver transplant patients with diabetes mellitus or hypertension, who are on maintenance corticosteroids, with a diagnosis of COVID-19 and describing breathlessness should be aggressively monitored for signs of deterioration because of the risk for mortality

COVID-MATCH65-A prospectively derived clinical decision rule for severe acute respiratory syndrome coronavirus 2

OBJECTIVES: We report on the key clinical predictors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and present a clinical decision rule that can risk stratify patients for COVID-19. DESIGN, PARTICIPANTS AND SETTING: A prospective cohort of patients assessed for COVID-19 at a screening clinic in Melbourne, Australia. The primary outcome was a positive COVID-19 test from nasopharyngeal swab. A backwards stepwise logistic regression was used to derive a model of clinical variables predictive of a positive COVID-19 test. Internal validation of the final model was performed using bootstrapped samples and the model scoring derived from the coefficients, with modelling performed for increasing prevalence. RESULTS: Of 4226 patients with suspected COVID-19 who were assessed, 2976 patients underwent SARS-CoV-2 testing (n = 108 SARS-CoV-2 positive) and were used to determine factors associated with a positive COVID-19 test. The 7 features associated with a positive COVID-19 test on multivariable analysis were: COVID-19 patient exposure or international travel, Myalgia/malaise, Anosmia or ageusia, Temperature, Coryza/sore throat, Hypoxia-oxygen saturation < 97%, 65 years or older-summarized in the mnemonic COVID-MATCH65. Internal validation showed an AUC of 0.836. A cut-off of ≥ 1.5 points was associated with a 92.6% sensitivity and 99.5% negative predictive value (NPV) for COVID-19. CONCLUSIONS: From the largest prospective outpatient cohort of suspected COVID-19 we define the clinical factors predictive of a positive SARS-CoV-2 test. The subsequent clinical decision rule, COVID-MATCH65, has a high sensitivity and NPV for SARS-CoV-2 and can be employed in the pandemic, adjusted for disease prevalence, to aid COVID-19 risk-assessment and vital testing resource allocation

CD8 + T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity

To better understand primary and recall T cell responses during coronavirus disease 2019 (COVID-19), it is important to examine unmanipulated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells. By using peptide-human leukocyte antigen (HLA) tetramers for direct ex vivo analysis, we characterized CD8+ T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8+ T cells directed toward subdominant epitopes (B7/N257, A2/S269, and A24/S1,208) CD8+ T cells specific for the immunodominant B7/N105 epitope were detected at high frequencies in pre-pandemic samples and at increased frequencies during acute COVID-19 and convalescence. SARS-CoV-2-specific CD8+ T cells in pre-pandemic samples from children, adults, and elderly individuals predominantly displayed a naive phenotype, indicating a lack of previous cross-reactive exposures. T cell receptor (TCR) analyses revealed diverse TCRαβ repertoires and promiscuous αβ-TCR pairing within B7/N105+CD8+ T cells. Our study demonstrates high naive precursor frequency and TCRαβ diversity within immunodominant B7/N105-specific CD8+ T cells and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses

Mycoplasma and Ureaplasma Infections in Transplantation: A Big Impact Despite the Lack of a Cell Wall

In the general population, Mycoplasma spp. and Ureaplasma spp. are considered as pathogens with low virulence. Asymptomatic urogenital colonization with genital mycoplasmas is common. M. pneumoniae infections most frequently present as tracheobronchitis. In immunosuppressed individuals, a broad spectrum of invasive diseases has been attributed to these pathogens. After kidney transplantation and hematopoietic stem cell transplantation, Mycoplasma spp. and Ureaplasma spp. have been detected as causative pathogens in urogenital infections. Surgical site infections following solid organ transplantation are rarely caused by Mycoplasma spp. and Ureaplasma spp.. Recently, an association between hyperammonemia syndrome and genital mycoplasmas has been described after lung, kidney, and hematopoietic stem cell transplantation. Hyperammonemia syndrome, characterized by a combination of progressive elevations in plasma ammonium levels and worsening neurological symptoms, is a rare but potentially fatal disorder. Routine cultural approaches are poorly sensitive, and nucleic acid amplification tests should be applied for diagnosis. Commonly used broad-spectrum antibiotics are frequently not active against these cell wall-lacking bacteria. Mycoplasma spp. or Ureaplasma spp. should be considered as etiologic agents if routine diagnostics do not identify relevant pathogens or if response to empiric antibiotic therapy is insufficient