The intestinal microbiota predicts COVID-19 severity and fatality regardless of hospital feeding method.

SARS-CoV-2-positive patients exhibit gut and oral microbiome dysbiosis, which is associated with various aspects of COVID-19 disease (1-4). Here, we aim to identify gut and oral microbiome markers that predict COVID-19 severity in hospitalized patients, specifically severely ill patients compared to moderately ill ones. Moreover, we investigate whether hospital feeding (solid versus enteral), an important cofounder, influences the microbial composition of hospitalized COVID-19 patients. We used random forest classification machine learning models with interpretable secondary analyses. The gut, but not the oral microbiota, was a robust predictor of both COVID-19-related fatality and severity of hospitalized patients, with a higher predictive value than most clinical variables. In addition, perturbations of the gut microbiota due to enteral feeding did not associate with species that were predictive of COVID-19 severity. IMPORTANCE SARS-CoV-2 infection leads to wide-ranging, systemic symptoms with sometimes unpredictable morbidity and mortality. It is increasingly clear that the human microbiome plays an important role in how individuals respond to viral infections. Our study adds to important literature about the associations of gut microbiota and severe COVID-19 illness during the early phase of the pandemic before the availability of vaccines. Increased understanding of the interplay between microbiota and SARS-CoV-2 may lead to innovations in diagnostics, therapies, and clinical predictions.

SARS-CoV-2 Serosurveys: How Antigen, Isotype and Threshold Choices Affect the Outcome.

BACKGROUND: Evaluating the performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays and clearly articulating the utility of selected antigens, isotypes, and thresholds is crucial to understanding the prevalence of infection within selected communities. METHODS: This cross-sectional study, implemented in 2020, screened PCRconfirmed coronavirus disease 2019 patients (n 86), banked prepandemic and negative samples (n 96), healthcare workers and family members (n 552), and university employees (n 327) for antiSARS-CoV-2 receptor-binding domain, trimeric spike protein, and nucleocapsid protein immunoglobulin (Ig)G and IgA antibodies with a laboratory-developed enzyme-linked immunosorbent assay and tested how antigen, isotype and threshold choices affected the seroprevalence outcomes. The following threshold methods were evaluated: (i) mean 3 standard deviations of the negative controls; (ii) 100 specificity for each antigen-isotype combination; and (iii) the maximal Youden index. RESULTS: We found vastly different seroprevalence estimates depending on selected antigens and isotypes and the applied threshold method, ranging from 0.0 to 85.4. Subsequently, we maximized specificity and reported a seroprevalence, based on more than one antigen, ranging from 9.3 to 25.9. CONCLUSIONS: This study revealed the importance of evaluating serosurvey tools for antigen-, isotype-, and threshold-specific sensitivity and specificity, to interpret qualitative serosurvey outcomes reliably and consistently across studies.

Fever of Unknown Origin: Could It Be a Pheochromocytoma? A Case Report and Review of the Literature.

Pheochromocytomas are rare tumors that arise from the adrenal medulla, with an incidence of less than 1 per 100,000 person-years. These tumors are characterized by excess catecholamine secretion and classically present with the triad of headaches, palpitations, and sweating episodes. However, the clinical presentation can be quite variable. Herein, we present a patient who presented with persistent fevers. An adrenal mass was incidentally discovered during the extensive investigation for the fever of unknown origin. Consequently, blood and urine tests were done and found to be consistent with a pheochromocytoma. The resection of this pheochromocytoma resulted in resolution of fevers. It is hypothesized that fevers in patients with pheochromocytomas occur due to the excess catecholamine or possibly due to interleukins. This clinical presentation serves as a learning point that adrenal incidentalomas in the setting of fever of unknown origin should not be ignored. It also reminds clinicians that pheochromocytomas which present with fevers may have tumor necrosis and many such patients are at risk for multisystem crises.

Anal high-risk human papillomavirus infection and high-grade anal intraepithelial neoplasia detected in women and heterosexual men infected with human immunodeficiency virus.

BACKGROUND: Although anal high-risk human papillomavirus (HR-HPV) infection and anal cytological abnormalities are highly prevalent among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM), there are insufficient data on these abnormalities among HIV-infected heterosexual men (HSM) and women. In this study, we evaluated the prevalence of anal HR-HPV, cytological abnormalities, and performance of these screening tests in detecting high-grade anal intraepithelial neoplasia (AIN2+) among our cohort of HIV-infected MSM and non-MSM (HSM and women). METHODS: A single-center, retrospective cohort study was conducted with HIV-infected individuals who underwent anal cancer screening with anal cytology and HR-HPV testing from January 2011 to January 31, 2013. RESULTS: Screening of 221 HIV-infected individuals for both HR-HPV and anal cytology showed the presence of HR-HPV in 54% (abnormal anal cytology 48%) of MSM, 28% (abnormal anal cytology 28%) of HSM, and 27% (abnormal anal cytology 34%) of women. Among 117 (53%) individuals with abnormal results (HR-HPV-positive and/or cytology was atypical squamous cells of undetermined significance or above), 67 underwent high resolution anoscopy. Of these 67 individuals, 22 individuals had AIN2+ (17 MSM, four women, and one HSM). HR-HPV correlated better with AIN2+ than with anal cytology on biopsy in both MSM (r=0.29 versus r=0.10; P=0.05 versus P=0.49) and non-MSM (r=0.36 versus r=-0.34; P=0.08 versus P=0.09). CONCLUSION: Given the presence of AIN2+ in screened HIV-infected HSM and women, routine anal cancer screening in all HIV-infected individuals should be considered. HR-HPV merits further evaluation for anal cancer screening among non-MSM.

Invasive Aspergillus infections in hospitalized patients with chronic lung disease.

BACKGROUND: Although invasive pulmonary aspergillosis (IPA) is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients. METHODS: The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis. RESULTS: Baseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61%) and asthma (18%), and immunocompromised patients primarily had malignancies (27%) and bone marrow transplants (14%). A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03). The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14); 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75). CONCLUSION: Nontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the more traditional immunocompromised population.

A retrospective evaluation of completion rates, total cost, and adverse effects for treatment of latent tuberculosis infection in a public health clinic in central massachusetts.

Completion rates, total cost, and adverse effects were compared for patients in central Massachusetts treated for latent tuberculosis infection with 9 months of isoniazid or 4 months of rifampin. Although the adverse effects were similar between the 2 groups, 4 months of rifampin was associated with significantly better completion rates and less hepatotoxicity yet higher total cost.

Paecilomyces lilacinus olecranon bursitis in an immunocompromised host: case report and review.

Paecilomyces lilacinus is a little-known mold that causes rare cases of invasive infections in humans regardless of their immune status. We present a unique case in an immunocompromised host with olecranon bursitis because of multidrug-resistant P. lilacinus treated with systemic ketoconazole therapy and surgical debridement. Recognition of this fungus is difficult initially because of its appearance, which can be confused with that of other fungi. Once this organism has been identified, it is recommended that antifungal susceptibility testing be obtained to guide appropriate therapy. Combination of therapeutic modalities requires case-by-case assessment. Surgical debridement and removal of prosthesis may be indicated. Although P. lilacinus can be a laboratory contaminant, in our case, causation was established as the organism grew in repeated cultures, sufficient to confirm a fungal origin for his bursitis.