Response to COVID-Vaccination and Infection in Islet Transplant Recipients

Background: Since response to COVID-vaccine among transplant recipients remains diminished comparing to general population, we decided to assess effect of COVID-specifically among islet transplant patients. Methods: Response to COVID-infection and vaccine was assessed in a cohort of 20 islet transplant recipients: N=13 after islet transplant alone (ITx) , N=7 with islet after kidney (IAK) or pancreas after islet transplantation (PAI) . The median age was 48 years (25-62) . Maintenance immunosuppression included tacrolimus and an antimetabolite in addition to 5mg of Prednisone in IAK and PAI recipients. Nine patients received booster. Results: Seven patients (38%) chose not to be vaccinated and 4 (57%) of them remained COVID-free with no SARS-CV-2 Spike total antibody (Spike ab) present in their blood. The other three patients (43%) developed only mild symptoms of infection with a high level of Spike ab (>2,500 U/ml) afterwards. In contrast, all remaining 13 patients (62%) , who were vaccinated while on immunosuppression for a median of 7 years (0.5-16) , remained COVID-free (p=0.11, Fischer) . The level of Spike ab in response to vaccine varied: undetected- (N=4) , in range 1-100U/ml (N=6) , around 400U/ml (N=2) , and above 2,500U/ml (N=1) . Presence of 5mg of Prednisone did not affect the outcomes. Booster was administered in patients and increased the level of Spike ab above 100U/ml in all of them, in 7 (78%) to over 2,500 U/ml. One patient responded neither to vaccine nor to booster. There were no SAEs related to the vaccination or booster. Islet graft function remained stable in all but one patient after initial vaccination or COVID-19. Conclusion: Nearly half of unvaccinated islet transplant recipients developed Covid-19, however, all of them presented only with mild symptoms. In contrast, none of vaccinated transplant patients developed COVID-infection with 69% rate of seroconversion. Booster increased level of the Spike ab in those patients who responded to the original vaccination.

The Impact of COVID-19 on Kidney Transplant Recipients in Pre-Vaccination and Delta Strain Era: A Systematic Review and Meta-Analysis.

Herein, we performed a meta-analysis of published clinical outcomes of corona virus disease 2019 (COVID-19) in hospitalized kidney transplant recipients. A systematic database search was conducted between December 1, 2019 and April 20, 2020. We analyzed 48 studies comprising 3137 kidney transplant recipients with COVID-19. Fever (77%), cough (65%), dyspnea (48%), and gastrointestinal symptoms (28%) were predominant on hospital admission. The most common comorbidities were hypertension (83%), diabetes mellitus (34%), and cardiac disease (23%). The pooled prevalence of acute respiratory distress syndrome and acute kidney injury were 58% and 48%, respectively. Invasive ventilation and dialysis were required in 24% and 22% patients, respectively. In-hospital mortality rate was as high as 21%, and increased to over 50% for patients in intensive care unit (ICU) or requiring invasive ventilation. Risk of mortality in patients with acute respiratory distress syndrome (ARDS), on mechanical ventilation, and ICU admission was increased: OR = 19.59, OR = 3.80, and OR = 13.39, respectively. Mortality risk in the elderly was OR = 3.90; however, no such association was observed in terms of time since transplantation and gender. Fever, cough, dyspnea, and gastrointestinal symptoms were common on admission for COVID-19 in kidney transplant patients. Mortality was as high as 20% and increased to over 50% in patients in ICU and required invasive ventilation.

A Comparison of the Clinical, Viral, Pathologic, and Immunologic Features of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus 2019 (COVID-19) Diseases.

CONTEXT.­: The purpose of this review was to compare 3 coronavirus diseases, including severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 caused by SARS-CoV, MERS-CoV, and SARS-CoV-2 viruses, respectively. OBJECTIVE.­: To cover the following topics: clinical considerations, viral characteristics, pathology, immune response, pathogenesis, and the prognosis associated with each coronavirus disease in humans. DATA SOURCES.­: Clinically, flu-like symptoms are usual at the time of presentation for all 3 diseases, but these vary from asymptomatic to severe multisystem involvement. The pathology associated with symptomatic severe acute respiratory syndrome and COVID-19 has been well described, the most prominent of which is diffuse alveolar damage. The immune response to each of these viruses is highly complex and includes both humoral and cellular components that can have a significant impact on prognosis. In severe cases of COVID-19, a dysregulated innate host immune system can initiate a hyperinflammatory syndrome dominated by endothelial dysfunction that can lead to a hypercoagulable state with microthrombi, resulting in a systemic microvascular and macrovascular disease. CONCLUSIONS.­: The severe acute respiratory syndrome and Middle East respiratory syndrome epidemics have been limited, involving approximately 8000 and 2500 individuals, respectively. In contrast, COVID-19 has resulted in a worldwide pandemic with more than 177 million cases and 3.9 million deaths as of June 15, 2021, and fatality rates ranging from less than 0.1% to approximately 10% depending upon the country. Ending on a positive note, the development of a number of vaccines, at least 6 of which now are in clinical use, should mitigate and eventually control the devastating COVID-19 pandemic.

COVID-19 in hospitalized liver transplant recipients: An early systematic review and meta-analysis.

Adverse clinical outcomes related to SARS-CoV-2 infection among liver transplant (LTx) recipients remain undefined. We performed a meta-analysis to determine the pooled prevalence of outcomes among hospitalized LTx recipients with COVID-19. A database search of literature published between December 1, 2019, and November 20, 2020, was performed per PRISMA guidelines. Twelve studies comprising 517 hospitalized LTx recipients with COVID-19 were analyzed. Common presenting symptoms were fever (71%), cough (62%), dyspnea (48%), and diarrhea (28%). Approximately 77% (95% CI, 61%-93%) of LTx recipients had a history of liver cirrhosis. The most prevalent comorbidities were hypertension (55%), diabetes (45%), and cardiac disease (21%). In-hospital mortality was 20% (95% CI, 13%-28%) and rose to 41% (95% CI, 19%-63%) (P < 0.00) with ICU admission. Additional subgroup analysis demonstrated a higher mortality risk in the elderly (>60-65 years) (OR 4.26; 95% CI, 2.14-8.49). There was no correlation in respect to sex or time since transplant. In summary, LTx recipients with COVID-19 had a high prevalence of dyspnea and gastrointestinal symptoms. In-hospital mortality was comparable to non-transplant populations with similar comorbidities but appeared to be less than what is reported elsewhere for cirrhotic patients (26%-40%). Importantly, the observed high case fatality in the elderly could be due to age-associated comorbidities.