Severe COVID-19 pneumonia in Piacenza, Italy — A cohort study of the first pandemic wave

International audienceBackground: Piacenza is the closest city to the first coronavirus disease 2019 (COVID-19) cluster in Italyand has the highest national COVID-19 death rates per population. The objective of this study is to presentcharacteristics and outcomes of patients admitted to medical departments of the Hospital of Piacenzaduring the first wave of the epidemic.Methods: A total of 218 patients with confirmed or suspect COVID-19 and severe pneumonia wereincluded from February 21st to May 15th, 2020. Routinely-collected clinical and laboratory data were ret-rospectively retrieved from electronic medical files. A Cox proportional-hazards model was fit to assessthe association of treatment and other variables with death.Results: Median age of patients was 68 years; 150 patients (69%) had comorbidities, mainly hypertension(107, 49%). Overall, 185 (85%) patients had acute respiratory distress syndrome (ARDS) on admission,including 103 (47%) with moderate or severe ARDS. Chest computed tomography scan showed bilateraldisease in 201 (98%) and extensive lung involvement in 79 (50%) patients. Most patients received antiviraltreatment (187, 86%) and corticosteroids (134, 61%). All patients received respiratory support and 64 (29%)were admitted to intensive care unit. As of June 30th, 100 patients (46%) died, 109 patients (50%) weredischarged, and 9 patients (4%) were still hospitalized. In multivariable Cox analysis, age above 65 years,having more than one comorbidity, severe ARDS, low platelet counts, and high LDH levels at admissionwere associated with mortality, while having diarrhea at admission was associated with survival. Theuse of antivirals or corticosteroids was not associated with surviva

Treatment for COVID-19—a cohort study from Northern Italy

International audienceMulticentre, retrospective cohort study with multivariable Cox proportional-hazards modelling and survival-time inverse-probability-weighting, evaluating the impact of different treatments on survival of proven COVID-19 patients admitted to two Hospitals in the province of Piacenza, Italy. Use of tocilizumab and of high doses of low molecular weight heparin, but not of antivirals (either alone or in combination), azithromycin, and any corticosteroid, was independently associated with lower mortality. Our results support further clinical evaluation of high doses of low molecular weight heparin and tocilizumab as COVID-19 therapeutics

Case Report: B Lymphocyte Disorders Under COVID-19 Inflammatory Pressure

Members of the COVID-Piacenza Group Daniela Aschieri, Mario Barbera, Carlo Cagnoni, Luigi Cavanna, Cosimo Franco, Chiara Gorrini, Andrea Magnacavallo, Massimo Nolli, Massimo Piepoli, Roberta Schiavo, Matteo Silva, Marco Stabile, Angela Rossi, Giovanni Vadacca. Affiliations for all members is: “Guglielmo da Saliceto” Piacenza Hospital, Via Taverna 49, 29121 Piacenza, ItalySevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects humans through the angiotensin converting enzyme-2 (ACE-2) receptor expressed on many cells, including lymphocytes. In Covid-19 patients IL-6 is overexpressed, and hyperactivated plasmacytoid lymphocytes are detected in peripheral blood film. We hypothesize that, due to the unpredictable interaction between the new virus and the B cell lineage of infected patients, a cascade of out of control events can ensue, capable of determining unexpected pathologic disorders involving such lineage. Here we report two cases of autoimmune hemolytic anemia (AIHA) and two cases of B-cell hematological malignancies developed or reactivated during acute SARS-CoV-2 infection. The temporal relationship of the events may suggest a potential causal relationship between SARS-CoV-2 infection and the hematopoietic disorders. We suggest that special attention should be paid to COVID-19 patients with underlining B cell lineage disorders.Peer reviewe

Evolution of blood-associated HIV-1 DNA levels after 48 weeks of switching to atazanavir/ritonavir+lamivudine dual therapy versus continuing triple therapy in the randomized AtLaS-M trial

Objectives: The AtLaS-M randomized trial showed that in patients with HIV-1 RNA <50 copies/mL on atazanavir/ ritonavir + two NRTIs, switching to a dual therapy with atazanavir/ritonavir+lamivudine had superior efficacy as compared with continuing the previous triple therapy. This substudy was designed to evaluate at 48 weeks the impact of the dual therapy versus the three-drug atazanavir/ritonavir-based therapy on the HIV-1 cellular reservoir as reflected by the quantification of blood-associated HIV-1 DNA levels. Methods: In a representative subset of 201 of 266 randomized patients (104 in the dual-therapy arm and 97 in the triple-therapy arm) total HIV-1 DNA levels in whole blood at baseline and after 48 weeks and factors associated with the HIV-1 DNA levels were evaluated. Results: The mean baseline HIV-1 DNA levels (2.47 log10copies/106leucocytes) were comparable between arms. A significant mean decrease between baseline and week 48 was observed: -0.069 log10copies/106leucocytes in the dual-therapy arm (P=0.046) and -0.078 in the triple-therapy arm (P=0.011); the mean difference between arms was -0.009 (P=0.842). Nadir CD4 count was inversely correlated with baseline HIV-1 DNA (P=0.009); longer duration of ART and lower nadir CD4 correlated with a less prominent HIV-1 DNA decrease (both P<0.005). Higher baseline HIV-1 DNA was associated with residual viraemia at week 48 (P=0.031). Conclusions: When compared with continuing three-drug therapy, atazanavir/ritonavir+lamivudine dual therapy resulted in a similar decline in HIV-1 DNA levels in patients with sustained virological suppression. These data support the safety of this simplified treatment strategy in terms of its effect on the cellular HIV-1 reservoir

Systemic inflammation markers after simplification to atazanavir/ritonavir plus lamivudine in virologically suppressed HIV-1-infected patients: ATLAS-M substudy

Background Biomarkers of systemic inflammation predict non-AIDS events and overall mortality in virologically suppressed HIV-1-infected patients. Objectives To determine whether switching to a dual antiretroviral maintenance therapy was associated with modification of biomarkers of systemic inflammation as compared with continuation of successful standard triple therapy. Methods In this substudy of the randomized ATLAS-M trial, we compared in virologically suppressed patients the impact at 1 year of simplification to a dual therapy with atazanavir/ritonavir plus lamivudine versus maintaining atazanavir/ritonavir plus two NRTI triple therapy on markers of systemic inflammation. Plasma levels of interleukin-6, C-reactive protein (CRP), soluble CD14 (sCD14) and D-dimer were quantified by ELISA at baseline and at 48 weeks. Results A subset of 139 of 266 randomized patients with available samples was analysed: 69 in the triple therapy arm and 70 in the dual therapy arm. The baseline biomarker levels were comparable between randomization arms. No significant differences in changes from baseline to week 48 were observed between arms (dual therapy versus triple therapy): IL-6, −0.030 versus −0.016 log10 pg/L; CRP, +0.022 versus +0.027 log10 pg/mL; sCD14, −0.016 versus +0.019 log10 pg/mL; and D-dimer, −0.031 versus +0.004 log10 pg/mL. A history of cancer was associated with higher baseline levels of IL-6 (P = 0.002) and CRP (P = 0.049). No relationship was observed between baseline biomarker level and persistent residual viraemia, HIV-1 DNA load, plasma lipids and other potential explanatory variables. Conclusions Simplification with atazanavir/ritonavir plus lamivudine does not affect plasma markers of systemic inflammation in virologically suppressed patients. The association between these findings and clinical outcomes requires further evaluatio

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-na\uefve patients from 2006 to 2016. Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/\u3bcL [interquartile range (IQR) 169\u2013521 cells/\u3bcL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1\u20135.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P&nbsp;=&nbsp;0.003): TDR to NRTIs from 9.9 to 2.9% (P&nbsp;=&nbsp;0.003) and TDR to NNRTIs from 5.1 to 3.7% (P&nbsp;=&nbsp;0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P&nbsp;&lt;&nbsp;0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P&nbsp;&lt;&nbsp;0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P&nbsp;=&nbsp;0.04) but not in non-B subtypes (from 6.1 to 5.8%; P&nbsp;=&nbsp;0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93\u20134.39; P&nbsp;&lt;&nbsp;0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75\u20130.99; P&nbsp;=&nbsp;0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40\u20130.91; P&nbsp;=&nbsp;0.01), and earlier calendar year (per 1&nbsp;year more recent: AOR 0.95; 95% CI 0.91\u20130.99; P&nbsp;=&nbsp;0.02). Conclusions: The prevalence of HIV-1 TDR has declined during the last 10&nbsp;years in Italy

Impact of the M184V resistance mutation on virological efficacy and durability of lamivudine-based dual antiretroviral regimens as maintenance therapy in individuals with suppressed HIV-1 RNA: A cohort study

Background. Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection. Methods. We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis. Results. Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (P = .016). Conclusions. Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips