Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

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Background: SARS-CoV-2-infected subjects have been proven contagious in the symptomatic, pre-symptomatic and asymptomatic phase. The identification of these patients is crucial in order to prevent virus circulation. No reliable data on the sensitivity of nasopharyngeal swabs (NPS) are available because of the lack of a shared reference standard to identify SARS-CoV-2 infected patients. The aim of our study was to collect data on patients with a known diagnosis of COVID-19 who underwent serial testing to assess NPS sensitivity.Methods: The study was a multi-center, observational, retrospective clinical study with consecutive enrollment. We enrolled patients who met all of the following inclusion criteria: clinical recovery, documented SARS-CoV-2 infection (≥1 positive rRT-PCR result) and ≥1 positive NPS among the first two follow-up swabs. A positive NPS not preceded by a negative nasopharyngeal swab collected 24–48 h earlier was considered a true positive. A negative NPS followed by a positive NPS collected 24–48 h later was regarded as a false negative. The primary outcome was to define sensitivity of SARS-CoV-2 detection with NPS.Results: Three hundred and ninety three NPS were evaluated in 233 patients; the sensitivity was 77% (95% CI, 73 to 81%). Sensitivity of the first follow-up NPS (n = 233) was 79% (95% CI, 73 to 84%) with no significant variations over time. We found no statistically significant differences in the sensitivity of the first follow-up NPS according to time since symptom onset, age, sex, number of comorbidities, and onset symptoms.Conclusions: NPS utility in the diagnostic algorithm of COVID-19 should be reconsidered.

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Background Migrants and ethnic minorities have suffered a disproportionate impact of the COVID-19 pandemic compared to the general population from different perspectives. Our aim was to assess specifically their risk of infection in the 53 countries belonging to the World Health Organization European Region, during the first year of the pandemic. Methods We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD42021247326). We searched multiple databases for peer-reviewed literature, published on Medline, Embase, Scisearch, Biosis and Esbiobase in 2020 and preprints from PubMed up to 29/03/2021. We included cross-sectional, case-control, cohort, intervention, case-series, prevalence or ecological studies, reporting the risk of SARS-CoV-2 infection among migrants, refugees, and ethnic minorities. Results Among the 1905 records screened, 25 met our inclusion criteria and were included in the final analysis. We found that migrants and ethnic minorities during the first wave of the pandemic were at increased exposure and risk of infection and were disproportionately represented among COVID-19 cases. However, the impact of COVID-19 on minorities does not seem homogeneous, since some ethnic groups seem to be more at risk than others. Risk factors include high-risk occupations, overcrowded accommodations, geographic distribution, social deprivation, barriers to access to information concerning preventive measures (due to the language barrier or to their marginality), together with biological and genetic susceptibilities. Conclusions Although mixed methods studies will be required to fully understand the complex interplay between the various biological, social, and cultural factors underlying these findings, the impact of structural determinants of health is evident. Our findings corroborate the need to collect migration and ethnicity-disaggregated data and contribute to advocacy for inclusive policies and programmatic actions tailored to reach migrants and ethnic minorities.

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In HIV-positive patients (pts), CMV co-infection has been proposed as a key factor in sustaining immune activation, which in turn could play a role in determining immune senescence. We evaluated the prevalence and predictors of CMV co-infection in a cohort of HIV+ pts and assessed the impact of CMV co-infection on the risk of AIDS and non-AIDS events. We included pts in the ICONA study with<1 month follow-up and<1 CMVIgG (CMV) test available without active CMV disease. Pts' characteristics at time of the first CMV test (baseline) were compared in those tested positive (CMV+) and negative (CMV-) using X2/Wilcoxon tests. Factors associated with CMV+ were identified by logistic regression. A prospective analysis was also performed with endpoints AIDS/AIDS-related death and severe non-AIDS (SNA: cardio-cerebrovascular, neurologic disease, renal failure, non-AIDS tumours)/death due to SNA. Time to event was estimated by Kaplan-Meier curves and Cox regression (multivariable model included: age, gender, ethnicity, risk factor for HIV, HCVAb and HBsAg, AIDS and CD4 at baseline, initiation of ART prior to baseline). 6,053 pts were included; 83.7% were tested CMV+ a median of 17 (IQR 6–45) months after enrolment. As compared to CMV-, CMV+ were older (adjusted odds ratio (AOR) 1.03 per 1 year older [95% CI 1.02–1.04]), HIV infected by homosexual route (MSM) (AOR 1.39 [95% CI 1.06–1.82]), less frequently Caucasian (AOR 0.56 [95% CI 0.42–0.76]), with higher CD4 count at baseline (AOR per 1 cell higher 1.035 [95% CI 1.00–1.06] By 10 years from first CMV test, 402 (12.6% [95% CI 11.1–13.6]) CMV+ and 74 (10.1% [95% CI 7.7–12.5]) CMV- pts developed AIDS/AIDS-related death (log-rank p=0.43). After adjustment for potential confounders, CMV+was still not associated with the risk of AIDS/AIDS-related death (adjusted hazard ratio (AHR) 1.23 [95% CI 0.96–1.60]). By 10 years, 339 (10.6% [95% CI 9.4–11.9]) CMV+ and 41 (6.4% [95% CI 6.1–6.6]) CMV- pts experienced a non-AIDS event/non-AIDS death (log-rank p=0.0006): 151 cancers, 128 CVD, 33 neurological, 1 renal. The association was still significant after controlling for a number of potential confounders: AHR 1.77 [95% CI 1.25–2.51] p=0.001; Table). In our study population, CMV/HIV co-infection was associated with the risk of non-AIDS events/deaths independently of other prognostic factors, supporting a potential role of CMV infection in vascular/ degenerative organ disorders commonly associated with chronic immune activation and aging

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