Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. However, the role of the gut microbiota in regulating these responses has not been thoroughly investigated. In order to identify mechanisms underpinning microbiota interactions with host immune and metabolic systems that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalized COVID-19 patients and compared those with the most severe outcome (i.e. death, n = 41) to those with severe non-fatal disease (n = 89), or mild/moderate disease (n = 42), that recovered. A distinct subset of 8 cytokines (e.g. TSLP) and 140 metabolites (e.g. quinolinate) in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the fecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts, such as Enterococcus . In contrast, less severe clinical outcomes are associated with clusters of anti-inflammatory microbes such as Bifidobacterium or Ruminococcus , short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents.

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Aims We prospectively assessed and compared the accuracy of cardiovascular risk scores in people living with HIV (PLWH) and individuals from the general population. Methods and results The Systematic Coronary Risk Evaluation Score 2 (SCORE2), the Pooled Cohort Equations (PCE), and the HIV-specific Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) score were calculated in participants free from atherosclerotic cardiovascular disease (ASCVD) between 2003 and 2009. In total, 6373 [mean age, 40.6 years (SD, 9.9)] PLWH from the Swiss HIV Cohort Study (SHCS) and 5403 [52.8 years (SD, 10.7)] individuals from the CoLaus|PsyCoLaus study were eligible for analysis. We tested discrimination and calibration, and the value of adding HIV-specific factors to scores using the net reclassification improvement (NRI). During mean follow-ups of 13.5 (SD, 4.1) in SHCS and 9.9 (SD, 2.3) years in CoLaus|PsyCoLaus study, 533 (8.4%) and 374 (6.9%) people developed an incident ASCVD, respectively. This translated into age-adjusted incidence rates of 12.9 and 7.5 per 1000 person-year, respectively. In SHCS, SCORE2, PCE, and D:A:D presented comparable discriminative capacities [area under the receiver operating characteristic curve of 0.745 (95% confidence interval, CI, 0.723–0.767), 0.757 (95% CI, 0.736–0.777), and 0.763 (95% CI, 0.743–0.783)]. Adding HIV-specific variables (CD4 nadir and abacavir exposure) to SCORE2 and PCE resulted in an NRI of −0.1% (95% CI, −1.24 to 1, P = 0.83) and of 2.7% (95% CI, 0.3–5.1, P = 0.03), respectively. Conclusions PLWH present a two-fold higher rate of incident ASCVD compared to individuals from the general population. SCORE2 and PCE, which are clinically easier to use (reduced set of variables without adding HIV-specific factors), are valid to predict ASCVD in PLWH.

The diagnosis of cystic echinococcosis (CE) is based on imaging, while serology is a complementary test of particular use when imaging is inconclusive. Serology has several limitations. Among them, false‐positive results are often obtained in subjects with alveolar echinococcosis (AE), rendering difficult the differential diagnosis. We set up an immune assay based on IL‐4‐specific production after stimulating whole blood with an antigen B (AgB)‐enriched fraction from E granulosus that associates with CE and CE cysts in active stage. We aimed to evaluate potential cross‐reactivity of this test using samples from patients with AE. Twelve patients with AE were recruited; IL‐4 levels ranged from 0 to 0.07 pg/mL. Based on the previously identified cut‐off of 0.39 pg/mL using samples from patients with CE, none of samples from AE patients scored positive. In contrast, almost 80% of samples from AE patients scored positive in serology tests based on different E granulosus‐derived antigenic preparations. Our preliminary data show that this experimental whole‐blood assay has no cross‐reactivity in our cohort of patients with AE, in turn indicating a high specificity of the assay for CE diagnosis. This result supports further work towards the development of improved diagnostic tests for CE.

Background: COVID-19 superinfection by Aspergillus (COVID-19-associated aspergillosis, CAPA) is increasingly observed due to increased awareness and use of corticosteroids. The aim of this study is to compare clinical and imaging features between COVID-19 patients with and without associated pulmonary aspergillosis. Material and Methods: In this case–control study, hospitalized patients between March 2020 and March 2021 were evaluated. Two observers independently compared 105 chest CTs of 52 COVID-19 patients without pulmonary aspergillosis to 40 chest CTs of 13 CAPA patients. The following features were evaluated: lung involvement, predominant main pattern (ground glass opacity, crazy paving, consolidation) and additional lung and chest findings. Chronological changes in the abnormal extent upon CT and chronological changes in the main patterns were compared with mixed models. Patient-wise comparisons of additional features and demographic and clinical data were performed using Student’s t-test, Chi-squared test, Fisher’s exact tests and Wilcoxon rank-sum tests. Results: Compared to COVID-19 patients without pulmonary aspergillosis, CAPA patients were older (mean age (±SD): 70.3 (±7.8) versus 63.5 (±9.5) years (p = 0.01). The time-dependent evolution rates for consolidation (p = 0.02) and ground glass (p = 0.006) differed. In early COVID-19 disease, consolidation was associated with CAPA, whereas ground glass was less common. Chronological changes in the abnormal extent upon CT did not differ (p = 0.29). Regardless of the time point, bronchial wall thickening was observed more frequently in CAPA patients (p = 0.03). Conclusions: CAPA patients showed a tendency for consolidation in early COVID-19 disease. Bronchial wall thickening and higher patient age were associated with CAPA. The overall lung involvement was similar between both groups.