Breakthrough invasive fungal infections on isavuconazole prophylaxis in hematologic malignancy & hematopoietic stem cell transplant patients.

BACKGROUND: Isavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side-effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported. METHODS: In this single-center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs. RESULTS: We evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21-91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%). Nineteen patients (17.9%) developed bIFIs-nine proven [Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus, and six possible infections. Twelve patients were neutropenic for a median of 28 (8-253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 µg/mL) were comparable to industry-sponsored clinical trials. All-cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co-infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups. CONCLUSION: ISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side-effect and drug-interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs.

Early administration of SARS-CoV-2 monoclonal antibody reduces the risk of mortality in hematologic malignancy and hematopoietic cell transplant patients with COVID-19.

BACKGROUND: Data on severe acute respiratory distress syndrome coronavirus 2 monoclonal antibody (SARS-CoV-2-specific mAb) use in hematologic malignancy and hematopoietic cell transplantation (HM/HCT) patients are limited. Here, we describe our experience with the use of casirivimab-imdevimab or bamlanivimab for the treatment of coronavirus disease 2019 (COVID-19) in HM/HCT patients. METHODS: This was a retrospective chart review at the University of Miami Hospital and Sylvester Comprehensive Cancer Center for HM/HCT patients with COVID-19 who received casirivimab-imdevimab or bamlanivimab from November 21, 2020, to September 30, 2021. Outcomes measured were mortality, hospital admission, and infusion reaction to SARS-CoV-2-specific mAbs. RESULTS: We identified 59 HM/HCT patients with mild to moderate COVID-19 who received casirivimab-imdevimab or bamlanivimab. Median age was 57 years (interquartile range [IQR]: 45-65). Among the 59 patients, 25 (42%) received cellular therapy: 14 (24%) had undergone allogeneic HCT, nine (15%) autologous HCT, and two (3%) received chimeric antigen receptor T-cell therapy. The median time from COVID-19 symptom onset to SARS-CoV-2-specific mAb administration was 4 (IQR: 3-6) days. Forty-six (78%) patients received SARS-CoV-2-specific mAbs as outpatients and 13 (22%) patients received SARS-CoV-2-specific mAbs during hospitalization. Among patients who received SARS-CoV-2-specific mAbs as outpatients, only four (9%) visited the emergency department at days 10, 11, 15, and 35 after SARS-CoV-2-specific mAb administration. None of these four patients required hospital admission. Among the hospitalized patients, five (38%) were admitted to the hospital with neutropenic fever, four (31%) were already hospitalized for transplantation and cellular therapy, three (23%) were admitted for monitoring of COVID-19 symptoms, and one (8%) was admitted with acute kidney injury. Three hospitalized patients (23%) died at 14, 35, and 59 days after SARS-CoV-2-specific mAb administration; two of these three deaths were attributed to COVID-19 infection. One patient developed an immediate infusion reaction to bamlanivimab, and no infusion reactions were reported to casirivimab-imdevimab use. CONCLUSION: During the alpha and delta variant surges, early administration of bamlanivimab or casirivimab-imdevimab prevented hospitalization and death when given in the outpatient setting. Among patients who received mAbs at or after hospital admission, the risk of COVID-19 disease progression and death remains significant. Larger studies of the use of mAb therapy to treat COVID-19 in this population are needed.

Is the Omicron variant truly less virulent in solid organ transplant recipients?

Solid organ transplant (SOT) recipients are at high risk for severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Emerging variants of concern have disproportionately affected this population. Data on severity and outcomes with the Omicron variant in SOT recipients are limited. Thus we conducted this single-center, retrospective cohort study of SOT recipients diagnosed with SARS-CoV-2 infection from December 18, 2021 to January 18, 2022, when prevalence of the Omicron variant was more than 80%-95% in the community. Univariate and multivariate logistic regression analysis was performed to identify risk factors for hospital admission. We identified 166 SOT patients: 112 (67.5%) kidney, 22 (13.3%) liver, 10 (6.0%) lung, seven (4.2%) heart, and 15 (9.0%) combined transplants. SARS-CoV-2 vaccine series was completed in 59 (35.5%) recipients. Ninety-nine (59.6%) and 13 (7.8%) recipients received casirivimab/imdevimab and sotrovimab, respectively. Fifty-three (32%) recipients required hospital admission, of which 19 (35.8%) required intensive care unit level of care. Median follow-up was 50 (interquartile range, 25-59) days, with mortality reported in six (3.6%) patients. Risk factors identified for hospital admission were African American race (p < .001, odds ratio [OR] 4.00, 95% confidence interval [CI] 1.84-8.70), history of coronary artery disease (p = .031, OR 3.50, 95% CI 1.12-10.87), and maintenance immunosuppression with corticosteroids (p = .048, OR 2.00, 95% CI 1.01-4.00). In conclusion, contrary to that in the general population, we found a higher hospital admission rate in SOT recipients with omicron variant infection. Further studies to investigate the efficacy of newer treatments are necessary, even as outcomes continue to improve.

Impact of Antiretroviral Therapy on Kidney Disease in HIV Infected Individuals - A Qualitative Systematic Review.

Kidney disease is the fourth most common cause of non-AIDS-related mortality in people living with HIV. Combination antiretroviral therapy (cART) remains the cornerstone of treatment. However, little is known about the impact of cART on disease outcomes in patients with HIV-associated nephropathy (HIVAN) and HIV-immune complex kidney disease (HIVICK). This systematic review evaluates the impact of cART on progression to end-stage kidney disease (ESKD) and other outcomes in HIV-infected individuals. We conducted a literature search utilizing PubMed, and Cochrane database and 11 articles met inclusion criteria for analysis of which nine HIVAN studies showed decreased progression to ESKD or death for subjects when treated with cART versus those untreated. However, two studies showed no survival advantage with cART. Three HIVICK studies showed improvement in delaying ESKD in subjects on cART compared to untreated subjects. cART appeared to reduce the risk to ESKD or death in patients with both HIVAN and HIVICK.

Unusual presentation of Nocardia abscessus infection in an immunocompetent patient.

Introduction: Nocardia infections are being increasingly reported in both immunocompetent and immunocompromised patients. We describe a case of Nocardia abscessus infection with an atypical presentation in an immunocompetent patient. Case Presentation: A previously healthy 47-year-old gentleman presented with hiccups and paroxysmal spasms. Imaging revealed a pulmonary nodule, for which he underwent surgical resection. Pathologic evaluation demonstrated evidence of local inflammation, with growth of Nocardia abscessus on tissue cultures. Conclusion: Nocardia abscessus may have atypical presentations in immunocompetent patients. Further research is needed to understand the factors leading to Nocardia infections in immunocompetent patients.

Passive transfer of SARS-CoV-2 antibodies with platelet transfusions.

BACKGROUND: Although over 5000 platelet transfusions occur daily in the United States, the presence of SARS-CoV-2 antibodies in platelet units is not commonly evaluated for. The effects of platelet transfusions with SARS-CoV-2 antibodies remain largely unknown. We evaluated single-donor (apheresis) platelet units for SARS-CoV-2 antibodies and determined if platelet transfusions passively transferred antibodies to seronegative recipients. STUDY DESIGN AND METHODS: We conducted a retrospective analysis as part of a quality assurance initiative during February to March 2021 at a tertiary referral academic center in suburban New York. Platelet units and platelet recipients were evaluated for the presence of SARS-CoV-2 antibodies using the DiaSorin LIASON SARS-CoV-2 S1/S2 IgG assay. There were 47 platelet recipients eligible for study inclusion. The primary outcome was the presence of SARS-CoV-2 spike protein IgG antibodies in the recipient's blood after platelet transfusion. RESULTS: Twenty-three patients received platelets with SARS-CoV-2 spike protein IgG antibodies; 13 recipients had detection of SARS-COV-2 antibodies (56.5%), and 10 recipients did not. The median antibody titer in the platelet units given to the group with passive antibodies detected was significantly higher compared to the median antibody titer in the platelet units given to the group without antibodies detected (median [interquartile range]: 306 AU/ml [132, 400] vs. 96.1 AU/ml [30.6, 186], p = .027). CONCLUSIONS: Our study demonstrated a significant rate of passive transfer of SARS-CoV-2 spike protein IgG antibodies through platelet transfusions. Considering the volume of daily platelet transfusions, this is something all clinicians should be aware of.

COVID-19 in an Asymptomatic Renal Transplant Recipient Employed in the Health Care Setting: A Case Report.

During the ongoing pandemic, there have been varying presentations of coronavirus disease 2019 (COVID-19) infection, with the concern that patients who are immunosuppressed (due to underlying medical conditions and/or therapies) are at higher risk of severe disease. We report the case of an elderly renal transplant recipient working in a long-term health care facility who was being monitored by weekly surveillance testing and tested positive for COVID-19 by polymerase chain reaction (PCR) testing, despite having no clinical symptoms. He recovered with supportive care, despite being on multiple long-term immunosuppressant drugs and having multiple comorbidities. Additionally, it was found that he did not mount an antibody response, when he tested negative by serologic testing. Through this case, we wish to highlight the unique clinical scenario of asymptomatic patients who may have an underwhelming immune response to COVID-19, but may nevertheless be an important source of dissemination. We further discuss the probable mechanism of such asymptomatic presentations in immunosuppressed patients, while reinforcing the importance of self-isolation of COVID-19 patients (particularly in asymptomatic health care workers).

Hospital-Acquired Bloodstream Infections in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 Infection (Coronavirus Disease 2019): Association With Immunosuppressive Therapies.

BACKGROUND: Immunosuppressive therapies proposed for Coronavirus disease 2019 (COVID-19) management may predispose to secondary infections. We evaluated the association of immunosuppressive therapies with bloodstream-infections (BSIs) in hospitalized COVID-19 patients. METHODS: This was an institutional review board-approved retrospective, multicenter, cohort study of adults hospitalized with COVID-19 over a 5-month period. We obtained clinical, microbiologic and laboratory data from electronic medical records. Propensity-score-matching helped create balanced exposure groups. Demographic characteristics were compared across outcome groups (BSI/no BSI) using two-sample t-test and Chi-Square test for continuous and categorical variables respectively, while immunosuppressive therapy use was compared using McNemar's test. Conditional logistic regression helped assess the association between immunosuppressive therapies and BSIs. RESULTS: 13,007 patients were originally included, with propensity-score-matching producing a sample of 6,520 patients. 3.74% and 3.97% were diagnosed with clinically significant BSIs in the original and propensity-score-matched populations respectively. COVID-19 patients with BSIs had significantly longer hospitalizations, higher intensive care unit admission and mortality rates compared to those without BSIs. On univariable analysis, combinations of corticosteroids/anakinra [odds-ratio (OR) 2.00, 95% confidence intervals (C.I.) 1.05-3.80, P value.0342] and corticosteroids/tocilizumab [OR 2.13, 95% C.I. 1.16-3.94, P value .0155] were significantly associated with BSIs. On multivariable analysis (adjusting for confounders), combination corticosteroids/tocilizumab were significantly associated with any BSI [OR 1.97, 95% C.I. 1.04-3.73, P value.0386] and with bacterial BSIs [OR 2.13, 95% C.I. 1.12-4.05, p-value 0.0217]. CONCLUSIONS: Combination immunosuppressive therapies were significantly associated with BSI occurrence in COVID-19 patients; their use warrants increased BSI surveillance. Further studies are needed to establish their causative role.

A tale of caution: prolonged Bacillus clausii bacteraemia after probiotic use in an immunocompetent child.

INTRODUCTION: Bacillus clausii as a probiotic supplement is increasingly used in both adult and paediatric patient populations. There is limited awareness about potential adverse effects. CASE PRESENTATION: We report a case of prolonged (111 days) B. clausii bacteraemia after brief probiotic use in a 17-month-old immunocompetent child, without a definite focus of infection and in the absence of predisposing risk factors or underlying co-morbidities. We identified seven probiotic use-associated cases of prolonged B. clausii bacteraemia (mean duration [range] 64 days [14-93 days] where data were available) in the literature, all with underlying co-morbidities. CONCLUSION: B. clausii probiotic preparations may cause prolonged bacteraemia, rendering patients with underlying co-morbidities as well as those with unrecognized risk factors vulnerable for significant infectious complications.

Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient - Case report and review of literature.

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.

Subacute Thyroiditis from COVID-19 Infection: A Case Report and Review of Literature.

INTRODUCTION: The novel severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) virus has led to the ongoing Coronavirus disease 2019 (COVID-19) disease pandemic. There are increasing reports of extrapulmonary clinical features of COVID-19, either as initial presentations or sequelae of disease. We report a patient diagnosed with subacute thyroiditis precipitated by COVID-19 infection, as well as review the literature of similar cases. CASE PRESENTATION: A 41-year-old female with no significant personal or family history of endocrinologic disorders presented with clinical features of thyroiditis that began after COVID-19 infection. Clinical, laboratory, and radiologic findings were indicative of subacute thyroiditis. Workup for potential triggers other than SARS-CoV-2 was negative. DISCUSSION/CONCLUSION: We compared the clinical and diagnostic findings of our patient with other well-documented cases of subacute thyroiditis presumed to be triggered by SARS-CoV-2 viral infection. We also reviewed the literature related to the potential mechanisms leading to thyroiditis. Clinicians must be aware of the possibility of thyroid dysfunction after COVID-19 infection. Early recognition and timely anti-inflammatory therapy help in successful management.

Coronavirus disease 2019 and extra-pulmonary tuberculosis co-infection - A case report and review of literature.

The Coronavirus disease 2019 (COVID-19) pandemic continues to cause significant global morbidity and mortality, leading to the need to study the course of the disease in different clinical circumstances and patient populations. While co-infection between COVID-19 and many pathogens has been reported, there has been limited published research regarding co-infection with Mycobacterium tuberculosis. We describe a case of co-infection involving COVID-19 and extra-pulmonary tuberculosis in a patient with cirrhosis, and review the current literature regarding COVID-19 and tuberculosis co-infection. In spite of several co-morbidities that have been shown to portend a poor prognosis in patients with COVID-19 infection, our patient fully recovered.

Cytomegalovirus Viremia in Renal Transplant Recipients After Influenza Vaccination.

Vaccination with the inactivated influenza vaccine is routinely recommended for all patients before and after transplant, with reduction in complications noted in transplant recipients. The vaccine is relatively well tolerated with few mild side effects. Cytomegalovirus (CMV) infection can reactivate in both solid organ transplant and hematopoietic stem cell transplant recipients, with some patients progressing to disease. There are multiple factors known to contribute to reactivation and subsequent CMV disease, however vaccination has not been reported as a specific risk factor. We report on two renal transplant recipients who were seen to develop CMV viremia and CMV disease after receiving the Influenza vaccine. We review the literature regarding viremia occurring after vaccination in HIV patients (a similar group of immunocompromised patients).

Coronavirus disease 2019 (Covid-19) presenting as purulent fulminant myopericarditis and cardiac tamponade: A case report and literature review.

The vast majority of patients in the ongoing coronavirus Disease 2019 (Covid-19) pandemic primarily present with severe respiratory illness. We report a Covid-19 patient who presented with findings of acute coronary syndrome and was found to have purulent fulminant myopericarditis and cardiac tamponade. We compare our case to the previously reported instances of Covid-19-associated myocarditis. Through review of the available literature, we also highlight the potential mechanisms of cardiac injury in Covid-19. We hope to increase awareness amongst clinicians about this unusual presentation of Covid-19.