Deciphering Factors Linked With Reduced Severe Acute Respiratory Syndrome Coronavirus 2 Susceptibility in the Swiss HIV Cohort Study.

BACKGROUND: Factors influencing susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain to be resolved. Using data from the Swiss HIV Cohort Study on 6270 people with human immunodeficiency virus (HIV) and serologic assessment for SARS-CoV-2 and circulating human coronavirus (HCoV) antibodies, we investigated the association of HIV-related and general parameters with SARS-CoV-2 infection. METHODS: We analyzed SARS-CoV-2 polymerase chain reaction test results, COVID-19-related hospitalizations, and deaths reported to the Swiss HIV Cohort Study between 1 January 2020 and 31 December 2021. Antibodies to SARS-CoV-2 and HCoVs were determined in prepandemic (2019) and pandemic (2020) biobanked plasma samples and compared with findings in HIV-negative individuals. We applied logistic regression, conditional logistic regression, and bayesian multivariate regression to identify determinants of SARS-CoV-2 infection and antibody responses to SARS-CoV-2 in people with HIV. RESULTS: No HIV-1-related factors were associated with SARS-CoV-2 acquisition. High prepandemic HCoV antibodies were associated with a lower risk of subsequent SARS-CoV-2 infection and with higher SARS-CoV-2 antibody responses on infection. We observed a robust protective effect of smoking on SARS-CoV-2 infection risk (adjusted odds ratio, 0.46 [95% confidence interval, .38-.56]; P < .001), which occurred even in previous smokers and was highest for heavy smokers. CONCLUSIONS: Our findings of 2 independent protective factors, smoking and HCoV antibodies, both affecting the respiratory environment, underscore the importance of the local immune milieu in regulating susceptibility to SARS-CoV-2.

Imaging of macrophages in soft-tissue infection in rats: relationship between ultrasmall superparamagnetic iron oxide dose and MR signal characteristics.

PURPOSE: To describe dose-dependent signal intensity (SI) characteristics of experimentally induced soft-tissue abscesses on 1.5-T T1- and T2*-weighted magnetic resonance (MR) images obtained 24 hours after administration of ultrasmall superparamagnetic iron oxide (USPIO) and to describe the relationship between SI and amount of USPIO uptake and macrophage iron content. MATERIALS AND METHODS: Local institutional review committee on animal care approved the experiments, which were performed according to the guidelines of the National Institutes of Health and the committee on animal research at our institution. Unilateral calf muscle abscesses were induced in 21 rats with an injection of a Staphylococcus aureus suspension. The rats were divided into three groups of seven animals each: low USPIO dose (50 micromol of iron per kilogram of body weight), high USPIO dose (150 micromol Fe/kg), and control (saline solution). All rats were imaged before and 24 hours after USPIO administration at 1.5 T (transverse T1-weighted spin-echo, T2*-weighted fast gradient-echo, and short inversion time inversion-recovery sequences). Images were analyzed quantitatively and qualitatively with regard to SI and signal pattern. Temporal variation of calculated contrast-to-noise ratios was analyzed with the Wilcoxon signed rank test. MR findings were correlated with histopathologic findings, including those of electron microscopy. RESULTS: Twenty-four hours after USPIO administration in the high-dose group, susceptibility effects were present in abscess periphery on postcontrast T2*-weighted images (P=.04), and SI enhancement was noted on postcontrast T1-weighted images within both abscess wall and abscess center (P=.04 for both). In the low-dose group, SI enhancement was noted in entire abscess on T1-weighted postcontrast images (P=.03). Neither significant SI loss (P=.09) nor susceptibility effects were detected in periphery or center of any abscess on postcontrast T2*-weighted images. There was no obvious difference in total amount of macrophages among the groups, but there was a clear difference with regard to individual iron content of iron-positive macrophages between the USPIO dose groups. CONCLUSION: At 1.5 T, SI characteristics of abscesses on T1- and T2*-weighted images obtained 24 hours after USPIO injection strongly depend on administered dose of the contrast agent. At low doses, T1 effects were stronger than T2* effects.

Influence of ceftriaxone treatment on FDG uptake--an in vivo [18F]-fluorodeoxyglucose imaging study in soft tissue infections in rats.

Our aim was to determine the influence of antibiotic treatment using ceftriaxone on [18F]-fluorodeoxyglucose (FDG) uptake in experimental soft tissue infections. PET scans were performed in two groups (treated n=4; non-treated n=4) at days 3, 5, and 6 after inoculation of the infection. Additional autoradiography was performed in four animals at day 7 and in three animals at day 11. The difference of FDG uptake on day 5 (after three days of antibiotic treatment) between both groups proved to be significant (df=6; T=2.52; p=0.045). FDG uptake determined at the other days did not reveal significant difference between the two groups. It seems to be possible that the effect of antibiotic treatment on FDG uptake is less evident than reported for therapy monitoring of cancer treatment. The change of FDG uptake over time in treated and untreated infections is complex and further in vivo experiments have to be initiated to investigate the potential value of clinical FDG PET in therapy monitoring of infection.

(18)F-FDG and (18)F-FET uptake in experimental soft tissue infection.

The aim of this study was to compare the uptake of (18)F-fluoroethyl- L-tyrosine ((18)F-FET) with that of (18)F-fluorodeoxyglucose ((18)F-FDG) in activated inflammatory white blood cells. Unilateral thigh muscle abscesses were induced in 11 rats by intramuscular inoculation of 0.1 ml of a bacterial suspension ( S. aureus, 1.2 x 10(9) CFU/ml). Four animals were intraperitoneally injected with 130-180 MBq (18)F-FDG, four with 140-170 MBq (18)F-FET and three with a mixture of 140-170 MBq (18)F-FET and 1.8 MBq (14)C-deoxyglucose. Autoradiography (10 microm slice thickness) of the abscess and the contralateral muscle was performed and detailed spatial correlation of autoradiography and histopathology (haematoxylin-eosin staining) was obtained. Regions of interest were placed on the abscess wall and the grey values (digitised image intensities) measured were converted to kBq/cc per kBq injected activity per gram (SUV). Areas with increased (18)F-FDG uptake corresponded to cellular inflammatory infiltrates mainly consisting of granulocytes. The SUV was calculated to be 4.08+/-0.65 (mean+/-SD). The uptake of (18)F-FET in activated white blood cells was not increased: the SUV of the abscess wall, at 0.74+/-0.14, was even below that of contralateral muscle. The low uptake of (18)F-FET in non-neoplastic inflammatory cells promises a higher specificity for the detection of tumour cells than is achieved with (18)F-FDG, since the immunological host response will not be labelled and inflammation can be excluded.