COVID-19 in Solid Organ Transplant Recipient: Exploring Cumulative Incidence, Seroprevalence and Risk Factors for Disease Severity

Background: Solid organ transplant (SOT) recipients may be at increased risk for severe disease and mortality from COVID-19 because of immunosuppression and prolonged end-stage organ disease. As a transplant center serving a diverse patient population, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in our cohort of SOT recipients. Methods: We prospectively included in this observational study SOT recipients with a functioning kidney (n = 201), pancreas ± kidney (n = 66) or islet transplant (n = 24), attending outpatient regular follow-up at the San Raffaele Hospital from February 2020 to April 2021. Antibodies to SARS-CoV-2 were tested in all patients by a luciferase immunoprecipitation system assay. Results: Of the 291 SOT recipients, 30 (10.3%) tested positive for SARS-CoV-2 during the study period and prevalence was not different among different transplants. The SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR. As for the WHO COVID-19 severity classification, 19 (63.3%) SOT recipients were mild, nine (30%) were moderate, and two were critical and died yielding a crude mortality rate in our patient population of 6.7%. Kidney transplant (OR 12.9 (1.1–150) p = 0.041) was associated with an increased risk for moderate/critical disease, while statin therapy (OR 0.116 (0.015–0.926) p = 0.042) and pancreas/islet transplant (OR 0.077 (0.007–0.906) p = 0.041) were protective. Conclusions: The incidence of SARS-CoV-2 infection in SOT recipients may be higher than previously described. Due to the relative high crude mortality, symptomatic SOT recipients must be considered at high risk in case of SARS-CoV-2 infection.

The Tumor Microenvironment of Cutaneous Squamous Cell Carcinoma in Immunosuppressed Patients

Nonmelanoma skin cancer is the most common malignancy and immunosuppression is a key risk factor. Despite the promising data demonstrating the efficacy of immune checkpoint inhibition in the treatment of cutaneous squamous cell carcinoma (cSCC), most immunosuppressed patients are not included in immunotherapy trials due to the risk for toxicity and the lack of data regarding cSCC immune landscape in immunosuppressed patients. To characterize the specific alterations accounting for a diminished antitumor immune response in immunosuppressed patients, we used multispectral imaging on cSCC pathology specimens from immunosuppressed patients with age and stage matched immunocompetent controls. We show that densities of CD68+ cells are diminished in immunosuppressed patients. Moreover, using an organ transplant recipient cohort from two cancer centers, we found significantly lower effector T-cells densities as compared with controls. Overall, density of CD68+ and CD8+LAG3+ cells were predictors of disease-specific and disease-free survival. These findings provide insight into the patterns of immune infiltrating cells in patients with different types of immunosuppression; leading us to conjecture that different immune based therapeutic approaches may be needed to treat immunosuppressed cSCC patients.

Robust and Persistent B- and T-Cell Responses after COVID-19 in Immunocompetent and Solid Organ Transplant Recipient Patients

The development and persistence of SARS-CoV-2-specific immune response in immunocompetent (IC) and immunocompromised patients is crucial for long-term protection. Immune response to SARS-CoV-2 infection was analysed in 57 IC and 15 solid organ transplanted (TX) patients. Antibody responses were determined by ELISA and neutralization assay. T-cell response was determined by stimulation with peptide pools of the Spike, Envelope, Membrane, and Nucleocapsid proteins with a 20-h Activation Induced Marker (AIM) and 7-day lymphoproliferative assays. Antibody response was detected at similar levels in IC and TX patients. Anti-Spike IgG, IgA and neutralizing antibodies persisted for at least one year, while anti-Nucleocapsid IgG declined earlier. Patients with pneumonia developed higher antibody levels than patients with mild symptoms. Similarly, both rapid and proliferative T-cell responses were detected within the first two months after infection at comparable levels in IC and TX patients, and were higher in patients with pneumonia. T-cell response persisted for at least one year in both IC and TX patients. Spike, Membrane, and Nucleocapsid proteins elicited the major CD4+ and CD8+ T-cell responses, whereas the T-cell response to Envelope protein was negligible. After SARS-CoV-2 infection, antibody and T-cell responses develop rapidly and persist over time in both immunocompetent and transplanted patients.

Optimal Anticoagulant Dosing in Patients with COVID-19, a Retrospective Review

Background Hospitalized patients with coronavirus disease 2019 (COVID-19) infection have higher rates of venous thromboembolism (VTE).Higher mortality rates have been reported in severe cases of COVID-19 including those who have elevated D-dimer levels and have thromboembolic phenomena. Objective The objective of this retrospective and observational study was to ascertain which type and dosages of anticoagulation provide a mortality benefit and decrease the risk of developing VTE. Methods We evaluated the risk factors for VTEs in patients with a confirmed polymerase chain reaction test positive for COVID-19 who were admitted to our facility from April 1 to July 1, 2020. In addition, we performed a logistic regression to examine the relationship between mortality and intensive care unit (ICU) admission, specific risk factors outlined in the study, D-dimer, ferritin, prothrombin time (PT) and international normalized ratio (INR). Patients with a history of VTE, those already on anticoagulation (AC) prior to hospitalization, and patients on comfort care were excluded from study. Results There were originally 331 patients in the data set. Of those, 111 patients were excluded based on exclusion criteria and 4 additional patients were removed as they were the only individual patients in their specific AC covariant group. The analysis was performed on the remaining 216 patients. We divided the AC medications administered to the patients into five separate covariates: 1. enoxaparin 40 mg subcutaneous (sq) daily, 2. enoxaparin 40 mg sq every 12 hours (q12h), 3. heparin 5000 mg sq q12h, 4. heparin 5000 mg sq every 8 hours (q8h), 5. Patients taking multiple AC or deep venous thrombosis (DVT) prophylaxis medications. 6. No AC and examined them via logistic regression for mortality at 28 days and 60 days (Table 1). Patients in enoxaparin 40 mg daily group had statistically significant lower 28 day mortality. There was no statistically significant relationship between the use of enoxaparin 40 mg q12h and 28 day mortality rate. Patients in both heparin groups did not have significantly lower 28 day mortality rates. Patients in groups 5 & 6 had significantly higher 28 day mortality rates (Table 1). It is important to note that 33 patients underwent a pulmonary computed tomography angiography due to concern for pulmonary embolism and 38 patients underwent an ultrasound of their lower extremities to rule out the development of DVT. For patients with additional risk factors defined as chronic kidney disease, chronic obstructive pulmonary disease, organ transplant recipient, obesity (BMI > 30), cardiac disease (heart failure, coronary artery disease or cardiomyopathy), sickle cell disease, diabetes mellitus and smoking history, the odds of death at 28 days increased by a factor of 1.71, at 60 days by a factor of 1.63 and being admitted to the ICU by a factor of 1.41. Patients with 3-5 risk factors are 2.48 times more likely to be admitted to the ICU than patients with 0-2 risk factors. Patients with 4 or 5 risk factors are 3.56 times more likely to be admitted to the ICU than patients with 0-3 risk factors (Table 2). Predictably, patients that were admitted to the ICU had a significantly increased rate of mortality compared to those who were not (Table 3). Per our analysis, there was no relationship between PT or INR and mortality. At 28 days and 2 months, the D-dimer > 4000 was indicative of a higher odds of death versus patients with a D-dimer < 4000. An increased ferritin was also indicative of a higher mortality rate (Table 4). Conclusion Patients receiving enoxaparin 40 mg daily benefited more than any other AC regimen with respect to the development of VTE at both 28 days and 2 months. Increasing the dosing to twice daily did not decrease mortality. Additionally, patients receiving heparin did not have a decreased mortality. It is important to note that there was no standard protocol used to determine which patients received daily or twice daily dosing. The type and dose of AC was determined based on the clinical judgment of intensivists in each case. It is also possible that patients with severe COVID-19 infection were more likely to be given twice daily dosing which could account for the lack of mortality benefit with more frequent dosing. We did not report bleeding rates in AC groups in our study and this can be a possible reason for no mortality benefit among higher dose AC groups. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

A Streamlined Approach to the Solid Organ Transplant Recipient with an Infection

Addressing these three simple questions can assist any physician in making the best-informed decision about diagnostic tests and treatments in regard to a solid organ transplant recipient with an infection. This article serves as a preliminary guide to finding the simplest approach to what is typically a complicated patient and the course of the disease.

Rapidly Growing Mycobacterium tuberculosis in the Form of Empyema Necessitans: A Case Report

We present a case of rapidly growing disseminated Mycobacterium tuberculosis (MTB) that presented as an empyema necessitans (EN) in a 65-year-old woman with a single right lung transplant admitted for progressive dyspnea. While hospitalized, she had daily fevers and was found to have a right-sided chest wall abscess and pleural effusion. Acid-fast bacilli cultures from the abscess and pleural fluid grew MTB within 4 and 6 days, respectively. Blood cultures later grew MTB as well. Upon initiation of rifampin, isoniazid, pyrazinamide, and ethambutol, she developed hemorrhagic pancreatitis and distributive shock secondary to antituberculosis medications and disseminated MTB. Noteworthy features of this case include the rapid rate of MTB culture growth in less than a week, the development of a likely donor-derived MTB EN, and the clinical challenges of MTB screening and MTB infection management in a solid organ transplant recipient.