A strong cocktail against SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the trimeric spike protein that decorates the virus and binds the ACE2 receptor. Antibodies against the spike that neutralize viral infection have potential as therapeutics. Tortorici et al. describe two very potent antibodies, S2E12 and S2M11. Electron microscopy structures characterized the binding and showed that S2E12 traps the spike in a conformation that cannot bind ACE2. Both antibodies protected hamsters against SARS-CoV-2 challenge and may be useful in antibody cocktails to combat the virus and prevent the development of resistance. Science , this issue p. 950

Objective: To conduct a long‐term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV).Methods: Fifty‐nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non‐RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non‐RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months.Results: Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated.Conclusion: RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.

To investigate the prevalence, metabolic features and risk factors of a particular pattern of fat redistribution (FR), characterized by a progressive enlargement of breast and abdominal girth associated with a wasting of the lower limbs, observed in HIV-infected women treated with combined antiretroviral (ARV) therapy. Cross-sectional study. Outpatients attending the Institute of Infectious Diseases, University of Milan, Milan, Italy. HIV-infected women treated with two or more ARV drugs, observed between December 1997 and February 1998. FR was confirmed by means of a physical examination and dual-energy X-ray absorptiometry (DEXA). The metabolic and endocrinological measurements in patients with FR were compared with those in FR-free women. FR was observed in 32 out of 306 women (10.5%). DEXA revealed more trunk fat (P<0.01) and less leg fat (P<0.001) in the patients with FR than in the matched controls. There were no significant differences in laboratory test results between the two groups. All of the FR patients were taking lamivudine-containing regimens; 20 of them were also taking a protease inhibitor (PI). The association of FR with lamivudine-including regimens was statistically significant (P=0.017). Among the patients taking lamivudine, the risk associated with treatments including PI was 1.8 (95% CI 0.8-3.8, P=0.12). A total duration of ARV therapy of more than 1000 days was associated with a greater risk of developing FR (OR 10.8; 95% CI 1.4-80.5; P=0.0207). Stepwise logistic regression analyses indicated that prolonged ARV therapy and a viral load of more than 10000 copies per ml at the beginning of the last ARV regimen were the only variables that significantly and independently correlated with the risk of FR. The observed body modifications are caused by a redistribution of body fat without fat loss that is apparently not associated with hyperlipidemia, altered glucose metabolism or other endocrinological disorders. The development of FR in patients receiving only reverse transcriptase (RT) inhibitors suggests the presence of a PI-independent mechanism that deserves further investigation.

Objectives: We investigated the significance of microbial translocation measured on average 3 years after HIV seroconversion in driving disease progression in HIV⁺ untreated patients with high CD4⁺ cell count. Design: We included ICONA patients with documented last HIV-negative and first HIV-positive test, at least one plasma sample stored while antiretroviral therapy (ART)-naive and CD4⁺ cell count greater than 200 cells/μl. Methods: Microbial translocation [lipopolysaccharide (LPS), sCD14 and EndoCAb] and immune activation (IL-6 and TNF-α) were measured. Correlation between immune activation, microbial translocation, CD4⁺ and plasma HIV-RNA was evaluated by linear regression and nonparametric Spearman's rho. The independent predictive value of these markers on time to progression to the combined endpoint of AIDS, death, CD4⁺ cell count less than 200 cells/μl or start of antiretroviral therapy (ART) was assessed using survival analysis. Results: We analysed 1488 biomarker measures from 379 patients. A median of 3.1 years after the estimated seroconversion date [interquartile range (IQR) 1.6–5.4], median (IQR) markers values were LPS, 110 pg/ml (IQR 75–215), sCD14, 3.3 μg/ml (2.2–4.8), IL-6, 1.1 pg/ml (0.6–1.9) and TNF-α, 2.4 pg/ml (1.8–3.4). Two hundred and sixty progression events were recorded over a median of 1.6 years from the first sample (2% AIDS, 84% ART initiation, 12% CD4⁺ cell count less than 200 cells/μl and 2% death). LPS was the only biomarker associated with this primary composite outcome independently of age, HIV-RNA and CD4⁺ (relative hazard = 1.40 per log_e higher, 95% confidence interval 1.18–1.66, P < 0.001). Conclusion: Circulating LPS in the first years of chronic HIV infection is a strong predictor of disease progression independent of CD4⁺ cell count and HIV viraemia and may be considered a candidate biomarker for HIV monitoring and evaluation in clinical trials.

Research from JAMA Internal Medicine — Incidence and Characteristics of Non-Hodgkin Lymphomas in a Multicenter Case File of Patients With Hepatitis C Virus–Related Symptomatic Mixed Cryoglobulinemias