Renal Transplantation in HIV-positive and HIV-negative People With Advanced Stages of Kidney Disease: Equity in Transplantation.

Background: People with HIV are at a greater risk of end-stage kidney disease than the general population. Considering the risk of death after end-stage kidney disease, access to renal transplantation in people with HIV is critically important. Methods: We included all adult patients on chronic dialysis in Ontario, Canada, between 1 April 2007 and 31 December 2020. We determined the probability of kidney transplantation with competing risk of death over time since the initiation of dialysis by calculating the adjusted subdistribution hazard ratios (sdHR; 95% confidence interval [CI]). We also compared long-term renal allograft and posttransplant mortality outcomes between HIV-negative and HIV-positive persons. Results: Of 40 686 people (median age, 68 years; interquartile range, 57-77; 38.4% women), 173 were HIV-positive and 40 513 were HIV-negative. The incidence of kidney transplantation in HIV-negative and HIV-positive patients was 40.5 (95% CI, 39.4-41.6)/1000 person-years and 35.0 (95% CI, 22.8-53.7)/1000 person-years, respectively (P = .51). Considering the competing risk of death, HIV-positive people had a significantly lower chance of receiving kidney transplants than HIV-negative people (sdHR, 0.46 [95% CI, .30-.70]). The long-term allograft failure risk was not significantly different between HIV-negative and HIV-positive people, considering the competing risk of posttransplant death (sdHR, 1.71 [95% CI, .46-6.35]). Conclusions: Although the incidence and crude probability of kidney transplantation were similar among HIV-negative and HIV-positive persons in this cohort, those with HIV had a significantly lower likelihood of kidney transplantation than those without HIV. Having HIV was not significantly associated with a poor long-term allograft outcome compared with patients without HIV.

Adjunctive glucocorticoid therapy for Pneumocystis jirovecii pneumonia in solid organ transplant recipients: A multicenter cohort, 2015-2020.

Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.

SARS-CoV-2 Infection, Hospitalization, and Mortality in Adults With and Without Cancer.

Importance: Patients with cancer are at increased risk of SARS-CoV-2-associated adverse outcomes. Objective: To determine the associations of tumor type with SARS-CoV-2 infection, hospitalization, intensive care unit (ICU) admission, and death. Design, Setting, and Participants: This retrospective, population-based cohort study included community-dwelling adults aged at least 18 years in Ontario, Canada, ICES-linked provincial health databases from January 1, 2020, to November 30, 2021. Data were analyzed from December 1, 2021, to November 1, 2022. Exposures: Cancer diagnosis. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection, and secondary outcomes included all-cause 14-day hospitalization, 21-day ICU admission, and 28-day death following SARS-CoV-2 infection. Cox proportional hazards models were used to obtain adjusted hazard ratios (aHRs) and 95% CIs. Results: Of 11 732 108 people in the ICES-linked health databases, 279 287 had cancer (57.2% female; mean [SD] age, 65.9 [16.1] years) and 11 452 821 people did not have cancer (45.7% female; mean [SD] age, 65.9 [16.0] years). Overall, 464 574 individuals (4.1%) developed SARS-CoV-2 infection. Individuals with hematologic malignant neoplasms (33 901 individuals) were at increased risk of SARS-CoV-2 infection (aHR, 1.19; 95% CI, 1.13-1.25), 14-day hospitalization (aHR, 1.75; 95% CI, 1.57-1.96), and 28-day mortality (aHR, 2.03; 95% CI, 1.74-2.38) compared with the overall population, while individuals with solid tumors (245 386 individuals) were at lower risk of SARS-CoV-2 infection (aHR, 0.93; 95% CI, 0.91-0.95) but increased risk of 14-day hospitalization (aHR, 1.11; 95% CI, 1.05-1.18) and 28-day mortality (aHR, 1.31; 95% CI, 1.19-1.44). The 28-day mortality rate was high in hospitalized patients with hematologic malignant neoplasms (163 of 321 hospitalized patients [50.7%]) or solid tumors (486 of 1060 hospitalized patients [45.8%]). However, the risk of 21-day ICU admission in patients with hematologic malignant neoplasms (aHR, 1.14; 95% CI, 0.93-1.40) or solid tumors (aHR, 0.93; 95% CI, 0.82-1.05) was not significantly different from that among individuals without cancer. The SARS-CoV-2 infection risk decreased stepwise with increasing numbers of COVID-19 vaccine doses received (1 dose: aHR, 0.63; 95% CI, 0.62-0.63; 2 doses: aHR, 0.16; 95% CI, 0.16-0.16; 3 doses: aHR, 0.05; 95% CI, 0.04-0.06). Conclusions and Relevance: These findings highlight the importance of prioritization strategies regarding ICU access to reduce the mortality risk in increased-risk populations, such as patients with cancer.

Immunogenicity and Safety of Booster SARS-CoV-2 mRNA Vaccine Dose in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are susceptible to severe outcomes of Coronavirus disease 2019 (COVID-19). Most guidelines recommend a fourth dose (ie, booster) of COVID-19 vaccine to reduce the infection risk, and observational studies are needed to determine the immunogenicity and safety of the booster dose in this population. The primary outcome was to determine the quantitative anti-receptor-binding domain (RBD) antibody titers after the fourth dose of the COVID-19 vaccine. The secondary outcomes included adverse effects and all-cause mortality. This single-group prospective cohort included allogeneic HSCT recipients age ≥18 years who received their fourth dose of COVID-19 mRNA vaccine between December 15, 2021, and August 2, 2022. We excluded patients with a history of COVID-19 diagnosis and those who received i.v. Ig within 21 days of antibody testing or rituximab within 6 months before study entry. We used regression models to determine the contributing factors significantly associated with post-fourth dose anti-RBD titer. Sixty-seven patients (median age, 59.5 years; IQR, 53.5 to 65.5 years; 33 males [61%]) received the fourth dose of vaccine, and 54 were included in the anti-RBD titer analysis. The median anti-RBD titers at 4 to 6 weeks after the third and fourth doses differed significantly (13,350 U/mL [IQR, 2618 to 34,740 U/mL] and 44,500 U/mL [IQR, 11,163 to 84,330 U/mL], respectively; P < .0001). In univariate analysis, the post-third dose anti-RBD titer (ß = .70; 95% CI, .54 to .87; P < .001) and treatment with mycophenolate compounds (ß = -1.05; 95% CI, -1.97 to -1.12; P = .03) significantly predicted the antibody response to the fourth dose. In multivariate analysis, the inverse association between treatment with mycophenolate compounds and the post-fourth dose anti-RBD antibody titer was not significant (ß = -.57; 95% CI, -1.32 to .19; P = .14), whereas the significant association between the anti-RBD titers following the third and fourth doses did not change considerably (ß = .66; 95% CI, .47 to .86; P < .001). The most frequent adverse event was vaccination site soreness (44%), followed by fatigue (16%), myalgia (4%), and headache (2%). No recipient experienced new or worsened preexisting graft-versus-host disease within 40 days of vaccination, and no patient died. Six patients (11%) developed breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection not associated with hospitalization or severe outcomes. The fourth dose of the COVID-19 vaccine appears to be highly immunogenic and safe in allogeneic HSCT recipients. Further studies are needed to determine the neutralizing antibody titers against SARS-CoV-2 subvariants and the effectiveness and immunogenicity of bivalent vaccines in allogeneic HSCT recipients.

The effect of late-onset CMV infection on the outcome of renal allograft considering initial graft function.

BACKGROUND: Delayed graft function (DGF) increases the renal allograft failure risk. Late-onset Cytomegalovirus (CMV) infection's effect on the association between DGF and allograft failure has not been determined. METHODS: In this retrospective cohort, we included all renal allograft recipients at London Health Sciences Centre from January 1, 2014 to December 30, 2017, and continued clinical follow-up until February 28, 2020. We determined whether late-onset CMV infection affects the association between DGF and allograft failure in stratified and Cox proportional hazard analyses. RESULTS: Of 384 patients (median age [interquartile range]: 55 [43.3-63]; 38.7% female), 57 recipients (14.8%) were diagnosed with DGF. Patients with DGF were at a greater risk of CMV infection than patients without DGF (22.8% vs. 11.3%, p = .017). Late-onset CMV infection (odds ratio [OR]: 4.7, 95% CI: 2.07-10.68) and rejection (OR: 9.59, 95% CI: 4.15-22.16) significantly increased the risk of allograft failure in recipients with DGF. Patients with DGF had a significantly greater risk of graft failure than those without DGF (17.5% vs. 6.1%, p = .007). In the adjusted Cox hazard model, CMV infection significantly increased the risk of allograft failure (aHR: 3.19, 95% CI: 1.49-6.84). CONCLUSION: Late-onset CMV infection considerably increased the risk of graft failure in patients with DGF. A hybrid preventive model including prophylaxis followed by CMV-specific cell-mediated immunity monitoring may decrease the risk of allograft failure in recipients with DGF.

Breakthrough Invasive Fungal Infection After Coadministration of Venetoclax and Voriconazole.

Venetoclax requires a 75% dose reduction when coadministered with voriconazole. In a 10-year historical cohort of treatment with venetoclax, we did not observe a worse hematologic outcome in patients who received voriconazole prophylaxis versus those who did not. Subtherapeutic voriconazole levels and a triazole exposure history may contribute to breakthrough invasive fungal infection.

Association of Influenza Vaccination With SARS-CoV-2 Infection and Associated Hospitalization and Mortality Among Patients Aged 66 Years or Older.

Importance: Vaccine effectiveness studies have rarely implemented strategies to reduce the healthy vaccinee bias arising from differences in health care-seeking behavior between vaccinated and unvaccinated individuals. Although previous observational studies suggest that influenza vaccination is associated with a reduced risk of SARS-CoV-2-associated outcomes, the healthy vaccinee bias may have led to overestimating the vaccination effect. Objective: To estimate the association between influenza vaccination and SARS-CoV-2-associated outcomes. Design, Setting, and Participants: This cohort study was conducted over 2 consecutive influenza vaccination campaigns (2019-2020 and 2020-2021), owing to the substantial COVID-19 burden and the greater validity of influenza vaccination data in the studied age group. The study population included community-dwelling adults aged 66 years or older in Ontario, Canada. Exposure: Influenza vaccination for a given season. Main Outcomes and Measures: The outcomes of interest included SARS-CoV-2 infection, SARS-CoV-2-associated hospitalization, SARS-CoV-2-associated death, and a composite of SARS-CoV-2-associated hospitalization or death. Cox proportional hazards models were used to measure the association between influenza vaccination and SARS-CoV-2-associated outcomes, censoring individuals who moved into long-term care, received COVID-19 vaccines, or died before the observation period end date. Primary care periodic health examinations (PHEs) were explored as a negative tracer exposure (ie, no association expected with SARS-CoV-2 outcomes) and as an effect modifier of the association between influenza vaccination and SARS-CoV-2 outcomes. Results: Of 2 922 449 individuals aged 66 years or older (54.2% female) living in Ontario, 2 279 805 were included in the study. Among these, 1 234 647 (54.2%) were female and 1 045 158 (45.8%) were male; their mean (SD) age was 75.08 (7.21) years. Those who had received influenza vaccination exhibited a lower incidence of SARS-CoV-2 infection than unvaccinated individuals for the 2019-2020 cohort (adjusted hazards ratio [aHR], 0.78; 95% CI, 0.73-0.84) and the 2020-2021 cohort (aHR, 0.76; 95% CI, 0.74-0.78). This association was also observed for SARS-CoV-2-associated hospitalization or death (2019-2020: aHR, 0.83; 95% CI, 0.74-0.92; 2020-2021: aHR, 0.66; 95% CI, 0.63-0.70). Similarly, undergoing a PHE was also associated with a lower incidence of SARS-CoV-2 infection (aHR, 0.85; 95% CI, 0.78-0.91) and SARS-CoV-2-associated hospitalization or death (aHR, 0.80; 95% CI, 0.70-0.90), and modified the association between influenza vaccination and SARS-CoV-2 infection for vaccinated individuals who underwent PHE (aHR, 0.62; 95% CI, 0.52-0.74) and for vaccinated individuals who did not undergo PHE (aHR, 0.81; 95% CI, 0.76-0.87), and also SARS-CoV-2-associated hospitalization or death in vaccinated individuals who underwent PHE (aHR, 0.66; 95% CI, 0.49-0.88) and vaccinated individuals who did not undergo PHE (aHR, 0.85, 95% CI, 0.76-0.95). Conclusions and Relevance: The findings of this cohort study suggest that undergoing a PHE may at least partially modify the association between influenza vaccination and SARS-CoV-2-associated outcomes in individuals aged 66 years or older, providing evidence of the healthy vaccinee bias that may affect vaccine effectiveness studies.

Safety and Immunogenicity After a Three-Dose SARS-CoV-2 Vaccine Schedule in Allogeneic Stem Cell Transplant Recipients.

In allogeneic stem cell transplant (Allo-SCT) recipients, the cell-mediated and humoral immunogenicity of the 3-dose SARS-CoV-2 vaccination schedule has not been investigated in prospective studies. In a prospective cohort, we recruited 122 Allo-SCT recipients since August 2021, when Ontario began offering a 3-dose vaccine schedule for Allo-SCT recipients. We determined humoral and cell-mediated immunity and adverse effects of the 3-dose SARS-COV-2 vaccination schedule in Allo-SCT recipients. In immunogenicity analysis (n = 95), the median (interquartile range [IQR]) antibody titer against the receptor-binding domain (RBD) of the spike (S) protein after the third dose (10,358.0 U/mL [IQR = 673.9-31,753.0]) was significantly higher than that after the first (10.2 U/mL [IQR = 0.6-37.0]) and the second doses (125.6 U/mL [IQR = 2.8-1251.0]) (P < .0001). The haploidentical donor status was an independent risk factor (adjusted odds ratio = 7.67, 95% confidence interval [CI], 1.86-31.60) for suboptimal antibody response (anti-RBD < 100 U/mL). S-specific CD4+ and CD8+ T-cell responses were measured in a subset of Allo-SCT recipients (n = 20) by flow cytometry. Most developed antigen-specific CD4+ (55%-80%) and CD8+ T-cells (80%) after 2 doses of vaccine. Frequencies of CD4+ polyfunctional (P = .020) and IL-2 monofunctional (P = .013) T-cells significantly increased after the third dose. Twenty-three episodes (23/301 doses [7.6%]) of new-onset or worsening pre-existing graft-versus-host disease (GVHD) occurred, including 4 episodes after the third dose. We observed 4 relapses (3.27%). Seven patients developed SARS-CoV-2 infection despite vaccination, although none required hospitalization. In conclusion, the 3-dose SARS-CoV-2 vaccine schedule provided immunity associated with a low risk of GVHD and other adverse effects. This prospective cohort showed that the third dose of SARS-CoV-2 vaccine in allogeneic stem cell transplant recipients promoted better humoral and cellar immune responses than after the initial series without increasing the risk of GVHD or severe adverse effects.

Concurrent Infection with SARS-CoV-2 and Pneumocystis jirovecii in Immunocompromised and Immunocompetent Individuals.

Coronavirus disease 2019 (COVID-19) may occur with concurrent infections caused by bacterial and fungal microorganisms. This systematic review evaluated studies reporting concomitant COVID-19 and Pneumocystis jirovecii pneumonia (PJP). We found 39 patients (74% male, median age: 56.8 (range: 11-83) years), including 66% immunosuppressed individuals (23% HIV-infected and 41% on long-term corticosteroid therapy). Patients were characteristically severely ill (mechanical ventilation: 70%), associated with 41% mortality. The median lymphocyte count was 527 cells/mm3 (range: 110-2200), and the median CD4+ T cell count was 206 cells/mm3 (range: 8-1021). We identified three patterns of concurrent COVID-19 and P. jirovecii infection. The first pattern (airway colonization with a low burden of P. jirovecii) does not seem to modify the COVID-19 course of illness. However, P. jirovecii superinfection, typically occurring weeks after COVID-19 diagnosis as a biphasic illness, and P. jirovecii coinfection characteristically results in progressive multilobar pneumonia, which is associated with poor outcomes. To support this categorization, we reported three patients with concurrent PJP and COVID-19 identified in our institution, presenting these clinical scenarios. The diagnosis of PJP requires a high index of suspicion, since clinical and radiological characteristics overlap with COVID-19. Observational studies are necessary to determine the PJP burden in patients with COVID-19 requiring hospitalization.

First reported case of Robinsoniella peoriensis pyometra and bloodstream infection: A case report and review of the literature.

We report on a 47-year-old woman with jejunal adenocarcinoma and concurrent endometrial cancer, admitted with sepsis. Uterine fluid and blood cultures were positive for Robinsoniella peoriensis. This is the first case report of Robinsoniella peoriensis in Canada. We encourage clinicians to publish their experience treating gynecologic infections caused by Robinsoniella peoriensis. Failure to recognize this pathogen as causative for pyometra, may result in insufficient antimicrobial treatment, and death.

Incidence and Outcomes Associated With Clostridioides difficile Infection in Solid Organ Transplant Recipients.

Importance: Little is known about the incidence and outcomes of Clostridioides difficile infection (CDI) in solid organ transplant (SOT) recipients. Objective: To estimate the CDI incidence and outcomes in SOT recipients. Design, Setting, and Participants: A population-based cohort study was conducted using administrative health care data for all Ontario, Canada, residents who received organ allografts from April 1, 2003, to December 31, 2017; March 31, 2020, was the end of the study period. Main Outcomes and Measures: The primary outcome was hospital admission with CDI diagnosis. The secondary outcomes included all-cause death, intensive care unit admission, acute kidney injury requiring dialysis, and fulminant CDI comprising any of the following: toxic megacolon, ileus, perforation, or colectomy. The association between short- vs long-term mortality (ie, death occurring within or after 90 days post-CDI) and the following variables was evaluated: age, sex, Deyo-Charlson Comorbidity Index, SOT type, early- vs late-onset CDI, fulminant CDI, intensive care unit admission, and acute kidney injury requiring acute dialysis. Results: Overall, 10 724 SOT recipients (6901 [64.4%] men; median age, 54 [IQR, 44-62] years) were eligible. Kidney transplant was the most common SOT type (6453 [60.2%]). The median follow-up time was 5.0 (IQR, 2.3-8.8) years, resulting in 61 987 person-years of follow-up. A total of 726 patients (6.8%) were hospitalized with CDI. The 1-year CDI incidence significantly increased in annual cohorts (ie, from 23.1; 95% CI, 12.8-41.8 per 1000 person-years in 2004 to 46.7; 95% CI, 35.0-62.3 per 1000 person-years in 2017; P = .001). Clostridioides difficile was associated with a 16.8% rate (n = 122) of 90-day mortality. In patients who underwent kidney transplant, CDI was typically late-onset (median interval, 2.2; IQR, 0.4-6.0 years) compared with recipients of other organs. Acute kidney injury requiring dialysis was significantly associated with short-term (adjusted odds ratio [aOR], 1.86; 95% CI, 1.07-3.26) and long-term (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.29-2.78) mortality, and late-onset CDI was also significantly associated with a greater risk of short-term (aOR, 4.26; 95% CI, 2.51-7.22) and long-term (aHR, 2.49; 95% CI, 1.78-3.49) mortality. Conclusions and Relevance: In this study, increasing CDI trends in annual cohorts of SOT recipients were observed. Posttransplant CDI was associated with mortality, and late-onset CDI was associated with a greater risk of death than early-onset CDI. These findings suggest that preventive strategies should not be limited to the initial months following transplantation. Comprehensive therapeutic approaches targeting acute kidney injury risk factors in SOT recipients may reduce short- and long-term post-CDI mortality.

Evaluating the safety and effectiveness of a nurse-led outpatient virtual IV vancomycin monitoring clinic: a retrospective cohort study.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) with vancomycin is a common treatment modality for certain Gram-positive infections. Data regarding the safety of various models of delivery are limited. OBJECTIVES: To review outcomes of a nurse-led OPAT vancomycin monitoring service. METHODS: This was a retrospective cohort study of consecutive patients referred to a nurse-led OPAT vancomycin clinic from December 2015 to March 2018. Patients were administered IV vancomycin in the home with active laboratory monitoring of vancomycin trough levels, renal function and complete blood count using an integrated electronic database linked with community laboratories (virtual vancomycin clinic, VVC). Monitoring was coordinated by nurses with physician approval of recommended dosing changes. Data were extracted from the electronic medical record. Demographics; clinical indication; microbial aetiology; culture source; antimicrobial regimen(s); serum creatinine and vancomycin trough values; initiation, discharge and completion dates; hospitalizations; adverse events; and outcomes were all evaluated. RESULTS: Two hundred and seventy-five patients underwent a total of 301 courses of OPAT with vancomycin; 285 courses were completed. The rate of treatment discontinuation due to adverse effects was 33/301 (11.0%), with 15/33 (45.5%) being due to renal adverse effects (15/301 [5.0%] of episodes). Two of 15 (18.2%) patients developed stage 2 acute kidney injury (AKI), and no patients had stage 3 AKI or required haemodialysis. Nine of 301 (3.0%) required readmission for treatment failure. Nursing costs associated with monitoring were $63.93 CAD/patient ($48.43 USD). CONCLUSIONS: A nurse-led VVC was a safe, effective and inexpensive modality for administering outpatient vancomycin.

Gastrointestinal Histoplasmosis Mimicking Crohn's Disease.

Disseminated histoplasmosis is a life-threatening disease usually seen in immunocompromised patients living in endemic areas. We present an apparently immunocompetent patient with gastrointestinal histoplasmosis who was initially diagnosed with biopsy-proven Crohn's disease. Following discontinuation of anti-inflammatory drugs and institution of antifungal therapy, his gastrointestinal illness completely improved. Specific fungal staining should be routinely included in histopathologic assessment of tissue specimens diagnosed as Crohn's disease.

Prospective Clinical, Virologic, and Immunologic Assessment of COVID-19 in Transplant Recipients.

BACKGROUND: Several studies have described the clinical features of COVID-19 in solid-organ transplant recipients. However, many have been retrospective or limited to more severe cases (hospitalized) and have not routinely included serial virological sampling (especially in outpatients) and immunologic assessment. METHODS: Transplant patients diagnosed with COVID-19 based on a respiratory sample PCR were prospectively followed up to 90 d. Patients provided consent for convalescent serum samples and serial nasopharyngeal swabs for SARS-CoV-2 antibody (antinucleoprotein and anti-RBD) and viral load, respectively. RESULTS: In the 161 SOT recipients diagnosed with COVID-19, the spectrum of disease ranged from asymptomatic infection (4.3%) to hospitalization (60.6%), supplemental oxygen requirement (43.1%), mechanical ventilation (22.7%), and death (15.6%). Increasing age (OR, 1.031; 95% CI, 1.001-1.062; P = 0.046) and ≥2 comorbid conditions (OR, 3.690; 95% CI, 1.418-9.615; P = 0.007) were associated with the need for supplemental oxygen. Allograft rejection was uncommon (3.7%) despite immunosuppression modification. Antibody response at ≥14 d postsymptoms onset was present in 90% (anti-RBD) and 76.7% (anti-NP) with waning of anti-NP titers and stability of anti-RBD over time. Median duration of nasopharyngeal positivity was 10.0 d (IQR, 5.5-18.0) and shedding beyond 30 d was observed in 6.7% of patients. The development of antibody did not have an impact on viral shedding. CONCLUSIONS: This study demonstrates the spectrum of COVID-19 illness in transplant patients. Risk factors for severe disease are identified. The majority form antibody by 2 wk with differential stability over time. Prolonged viral shedding was observed in a minority of patients. Reduction of immunosuppression was a safe strategy.

Six-month risk of Pneumocystis pneumonia following acute cellular rejection: A case-control study in solid organ transplant recipients.

BACKGROUND: Solid organ transplant (SOT) recipients are at risk of Pneumocystis pneumonia (PCP). PCP is associated with significant morbidity and mortality. The effect of acute T cell-mediated rejection (TCMR) on post-transplant PCP has not been determined yet. METHODS: In this case-control study, we estimated the risk of PCP following acute TCMR during a lookback period of 180 days. We also determined the effects of contributing factors such as CMV infection. RESULTS: We compared 15 SOT (8 kidney, 4 heart, 2 liver, and 1 kidney-pancreas) recipients with PCP with 60 matched recipients who did not develop PCP (control group) during the study period (December 2013 to February 2016). PCP occurred after a complete course of prophylaxis (ie, late-onset PCP) in 60% of patients. Patients with PCP frequently required intensive care unit (ICU) admission (73.3%). Post-transplant PCP was associated with considerable allograft loss (53.4%) and mortality (26.7%). In the 6-month lookback period, acute TCMR (OR: 13.1, 95% CI: 3.2, 53.2), and CMV infection (OR: 15.1,95% CI: 4.0, 53.2.1) were significantly associated with post-transplant PCP. CONCLUSIONS: Post-transplant PCP is associated with substantial risk of ICU admission, allograft failure, and mortality. Anti-Pneumocystis prophylaxis for at least 6 months following acute TCMR may reduce the risk.

Late-onset allograft rejection, cytomegalovirus infection, and renal allograft loss: Is anti-CMV prophylaxis required following late-onset allograft rejection?

Renal transplant recipients remain at risk of delayed-onset cytomegalovirus (CMV) infection occurring beyond a complete course of prophylaxis. In this retrospective cohort, all 278 patients who received renal allografts from deceased donors from 2014 to 2016 were followed until September 1, 2019. We determined the effect of early-vs late-onset acute rejection (EAR vs LAR [ie, occurring beyond 12 months after transplantation]) on CMV infection and subsequently long-term allograft outcome. Median (IQR) duration of follow-up was 1186.0 (904.7-1531.2) days. Seventy patients including 49 patients with EAR and 21 with LAR received augmented immunosuppression. In the same interval, 40 patients developed CMV infection (36 patients beyond 90 days after transplantation [90%]). In logistic regression analysis, D+/R- CMV serostatus (OR: 5.5, 95% CI: 2.5-12.2) and LAR (OR: 7.9, 95% CI: 2.8-22.2) significantly increased the risk of CMV infection. In Cox proportional hazard model, delayed-onset CMV infection (HR: 2.51, 95% CI: 1.08-5.86) and LAR (HR: 5.46, 95% CI: 2.26-13.14) significantly increased the risk of allograft loss. Patients with LAR are at risk of late-onset CMV infection. Post-LAR, targeted prophylaxis may reduce the risk of CMV infection and subsequently allograft loss. Further studies are required to demonstrate the effect of targeted prophylaxis following LAR.

Long-lasting cluster of nosocomial pneumonia with a single Pneumocystis jirovecii genotype involving different organ allograft recipients.

Pneumocystis pneumonia (PCP) outbreaks may occur in solid organ transplant (SOT) patients. Transmissibility of Pneumocystis jirovecii among SOT and non-SOT patients has not been investigated. Ten SOT (ie, 4 heart, 4 kidney, 2 liver allograft recipients) and 11 non-SOT (ie, 7 HIV-infected, 3 hematologic malignancies, and 1 stem cell transplant) patients with PCP were admitted to London Health Sciences Center (LHSC) from October 2014 to August 2016. We investigated the course of illness and outcome of PCP in SOT and non-SOT patients. Post-transplant PCP was frequently an acute-onset disease (90% vs. 18.2%, p = .01) requiring ICU admission (70% vs. 20%, p = .03) and hemodialysis (60% vs. 0, p = .003). Mortality was more frequent in SOT patients (40% vs. 18.1%, p = .36). Multilocus sequence typing (MLST) demonstrated circulation of a single genotype of P. jirovecii among SOT patients. However, 8 different genotypes were detected from non-SOT patients. Reinstitution of prophylaxis successfully controlled post-transplant cluster until end of observation period in October 2019. No transmission was detected from non-SOT patients to SOT recipients. Detection of a single P. jirovecii genotype from all SOT recipients highlights the likelihood of nosocomial transmission. No source control method is recommended by current guidelines. Improvement of preventive strategies is required.

The effect of human leukocyte antigen A1 and B35-Cw4 on sustained BK polyomavirus DNAemia after renal transplantation.

Human leukocyte antigen (HLA) class I presentation pathway plays a central role in natural killer (NK) cell and cytotoxic T-cell activities against BK polyomavirus (BKPyV) DNAemia. We determined the risk of sustained BKPyV DNAemia in 175 consecutive renal transplant recipients considering the simultaneous effect of donor/recipient HLA class I antigens and pre- or post-transplant variables. Median (IQR) age was 53 (44-64) years, and 37% of patients were female. 40 patients (22.9%) developed sustained BKPyV DNAemia [median (IQR) viral load: 9740 (4350-17 125) copies/ml]. In the Cox proportional hazard analysis, HLA-A1 (HR: 3.06, 95% CI: 1.51-6.17) and HLA-B35-Cw4 (HR: 4.63, 95% CI: 2.12-10.14) significantly increased the risk of sustained BKPyV DNAemia, while 2 HLA-C mismatches provided a marginally protective effect (HR: 0.32, 95% CI: 0.10-0.98). HLA-Cw4 is a ligand for NK cell inhibitory receptor, and HLA-B35 is in strong linkage disequilibrium with the HLA-Cw4 allele. The association between HLA-B35-Cw4 expression and sustained BKPyV DNAemia supports the important role of cytotoxic T cells and NK cells that would normally control BKPyV activation through engagement with immunoglobulin-like killer receptors (KIRs). Further studies are required to investigate the effect of HLA-C alleles along with NK cell activity against BKPyV DNAemia.

Incidence and outcomes of invasive fungal infection among solid organ transplant recipients: A population-based cohort study.

BACKGROUND: Invasive fungal infection (IFI) in solid organ transplant (SOT) recipients is associated with significant morbidity and mortality. The long-term probability of post-transplant IFI is poorly understood. METHODS: We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada, to determine the incidence rate; 1-, 5-, and 10-year cumulative probabilities of IFI; and post-IFI all-cause mortality in SOT recipients from 2002 to 2016. We also determined post-IFI, death-censored renal allograft failure. RESULTS: We included 9326 SOT recipients (median follow-up: 5.35 years). Overall, the incidence of IFI was 8.3 per 1000 person-years. The 1-year cumulative probability of IFI was 7.4% for lung, 5.4% for heart, 1.8% for liver, 1.2% for kidney-pancreas, and 1.1% for kidney-only allograft recipients. Lung transplant recipients had the highest incidence rate and 10-year probability of IFI: 43.0 per 1000 person-years and 26.4%, respectively. The 1-year all-cause mortality rate after IFI was 34.3%. IFI significantly increased the risk of mortality in SOT recipients over the entire follow-up period (hazard ratio: 6.50, 95% CI: 5.69-7.42). The 1-year probability of death-censored renal allograft failure after IFI was 9.8%. CONCLUSION: Long-term cumulative probability of IFI varies widely among SOT recipients. Lung transplantation was associated with the highest incidence of IFI with considerable 1-year all-cause mortality.

Corneal biomechanical properties after SMILE versus FLEX, LASIK, LASEK, or PRK: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to compare the postoperative corneal biomechanical properties between small incision lenticule extraction (SMILE) and other corneal refractive surgeries. METHODS: A systematic review and meta-analysis were conducted. Articles from January 2005, to April 2019, were identified searching PubMed, EMBASE, Web of Science, and International Clinical Trials Registry Platform. Studies that compared SMILE with other corneal refractive surgeries on adult myopia patients and evaluated corneal biomechanics were included. Multiple effect sizes in each study were combined. Random-effects model was conducted in the meta-analysis. RESULTS: Twenty-two studies were included: 5 randomized controlled trials (RCTs), 9 prospective and 6 retrospective cohort studies, and 2 cross-sectional studies. Using the combined effect of corneal hysteresis (CH) and corneal resistance factor (CRF), which were obtained from ocular response analyzer (ORA), the pooled Hedges' g of SMILE versus femtosecond laser-assisted in situ keratomileusis (FS-LASIK) was 0.41 (95% CI, 0.00 to 0.81; p = 0.049; I2 = 78%), versus LASIK was 1.31 (95% CI, 0.54 to 2.08; p < 0.001; I2 = 77%), versus femtosecond lenticule extraction (FLEX) was - 0.01 (95% CI, - 0.31 to 0.30; p = 0.972; I2 = 20%), and versus the group of photorefractive keratectomy (PRK) and laser-assisted sub-epithelial keratectomy (LASEK) was - 0.26 (95% CI, - 0.67 to 0.16; p = 0.230; I2 = 54%). The summary score of Corvis ST (CST) after SMILE was comparable to FS-LASIK/LASIK with the pooled Hedges' g = - 0.05 (95% CI, - 0.24 to 0.14; p = 0.612, I2 = 55%). CONCLUSIONS: In terms of preserving corneal biomechanical strength after surgeries, SMILE was superior to either FS-LASIK or LASIK, while comparable to FLEX or PRK/LASEK group based on the results from ORA. More studies are needed to apply CST on evaluating corneal biomechanics after refractive surgeries.