Histoplasmosis is a global disease endemic to regions of all six inhabited continents. The areas of highest endemicity lie within the Mississippi and Ohio River Valleys of North America and parts of Central and South America. As a result of climate change and anthropogenic land utilization, the conditions suitable for Histoplasma capsulatum are changing, leading to a corresponding change in epidemiology. The clinical manifestations of histoplasmosis are protean, variably resembling other common conditions such as community-acquired pneumonia, tuberculosis, sarcoidosis, Crohn's disease, or malignancy. Making a successful diagnosis is contingent on a thorough understanding of epidemiology, common clinical presentations, and best testing practices for histoplasmosis. While most subclinical or self-limited diseases do not require treatment in immunocompetent patients, all immunocompromised patients and those with progressive disseminated disease or chronic pulmonary disease should be treated. Liposomal amphotericin B is the preferred agent for severe or disseminated disease, while itraconazole is adequate for milder cases and “step-down” therapy following response to amphotericin B. In this review, we discuss the current evidence-based approaches to the epidemiology, diagnosis, and management of histoplasmosis.

The SARS-CoV-2 pandemic continues to place a substantial burden on healthcare systems. Outpatient therapies for mild-to-moderate disease have reduced hospitalizations and deaths in clinical trials, but the real-world effectiveness of monoclonal antibodies and oral antiviral agents in solid organ transplant recipients (SOTR) with coronavirus disease-2019 (COVID-19) is largely uncharacterized. We conducted a single-center, retrospective review of 122 SOTR diagnosed with COVID-19 in the outpatient setting during the Omicron surge to address this knowledge gap. The mean age was 54 years, 57% were males, and 67% were kidney transplant recipients. The mean time from transplant to COVID-19 diagnosis was 75 months. Forty-nine (40%) received molnupiravir, 24 (20%) received sotrovimab, and 1 (0.8%) received nirmatrelvir/ritonavir. No outpatient therapy was administered in 48 (39%). All 122 SOTR had >30 days follow-up. Rates of hospitalization within 30 days of initiating therapy for molnupiravir, nirmatrelvir/ritonavir, and sotrovimab were 16% (8/49), 0% (0/1), and 8% (2/24), respectively, compared to 27% (13/48) in patients without outpatient therapy. There were no deaths in those who received any therapy versus 3 (6%) deaths in patients without outpatient therapy (p = .002). Overall, our experience suggests a role for monoclonal antibodies and oral antiviral agents in reducing COVID-19-related morbidity and mortality in SOTR.

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020–June 19, 2020) and late 2020 (June 20, 2020–December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46–0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.

The COVID-19 pandemic has disproportionately impacted immunosuppressed patients, including solid organ transplant recipients (SOTR). COVID-19-associated mortality among SOTR was estimated at 20.5% in the early phase of the pandemic(1). SARS-CoV-2 vaccination may help reduce the morbidity and mortality of COVID-19 among SOTR. Under emergency use authorization, the US Food Drug Administration approved two SARS-CoV-2 messenger RNA vaccines [BNT162b2 (Pfizer), mRNA-1273 (Moderna)] and an adenovirus vector-based vaccine [Ad26.COV2.S (Johnson and Johnson)].

Background: This document provides evidence-based clinical practice guidelines on the diagnostic utility of nucleic acid–based testing of respiratory samples for viral pathogens other than influenza in adults with suspected community-acquired pneumonia (CAP). Methods: A multidisciplinary panel developed a Population–Intervention–Comparison–Outcome question, conducted a pragmatic systematic review, and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. Results: The panel evaluated the literature to develop recommendations regarding whether routine diagnostics should include nucleic acid–based testing of respiratory samples for viral pathogens other than influenza in suspected CAP. The evidence addressing this topic was generally adjudicated to be of very low quality because of risk of bias and imprecision. Furthermore, there was little direct evidence supporting a role for routine nucleic acid–based testing of respiratory samples in improving critical outcomes such as overall survival or antibiotic use patterns. However, on the basis of direct and indirect evidence, recommendations were made for both outpatient and hospitalized patients with suspected CAP. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was not addressed in the literature at the time of the evidence review. Conclusions: The panel formulated and provided their rationale for recommendations on nucleic acid–based diagnostics for viral pathogens other than influenza for patients with suspected CAP.

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality.