Publications by authors named "Massimo Galli"

319 Publications

First report of Colletotrichum fioriniae and C. nymphaeae as Causal Agents of anthracnose on walnut in Italy.

Plant Dis 2021 Jul 14. Epub 2021 Jul 14.

Consiglio nazionale per la ricerca e la sperimentazione in agricoltura - Centro di Ricerca per la Patologia Vegetale (CRA-PAV), Via C. G. Bertero 22, Roma, Italy, 00156;

English walnut (Juglans regia L.) is species grown either for high quality wood or fruit production. In Italy walnut cultivation occupies an area of about 4600 ha (FAOSTAT, http://www.fao.org/faostat, 2020). In 2019-2020, walnut fruits (cv Lara) with anthracnose symptoms were collected from walnut orchards in Province of Venice (Northern Italy). Affected fruits showed necrotic and circular lesions with acervuli in the center causing the complete mummification of the fruit as described by Da Lio et al., 2018. Orange conidial masses appeared under wet conditions. The fungus was isolated from necrotic tissues and conidial masses were put on potato dextrose agar (PDA) medium. Plates were incubated at 25°C for 5 to 7 days. The colonies were white to pink on the upper side and pink with black spots on the reverse. Acervuli formed and produced conidial masses on PDA after 6 days. Culture and conidial morphology were in concordance with published descriptions of C. acutatum sensu lato (Damm et al., 2012). To confirm the identity, internal transcribed spacers (ITS), (glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT) and beta-tubulin (TUB2) genes were amplified and sequenced using the primer pairs ITS1/ITS4 (White at al. 1990), GDF1/GDR1 (Guerber et al., 2003), ACT512F/ACT783R and BT2Fd/BT4R primers (Da Lio et al., 2018). The isolates belonged to two different species of Colletotrichum acutatum complex: C. fioriniae (Marcelino & Gouli) and C. nymphaeae (Pass). Sequences of two representative isolates C. fioriniae CREADC-F2317 and C. nymphaeae CREADC-F2372 were deposited in GenBank with accession numbers MZ153170 and MZ191794 (ITS), MZ203522 and MZ224013 (GAPDH), MZ203521 and MZ224012 (ACT), and MZ203523 and MZ224014 (TUB2). For all the genes, isolates had a 100% similarity to multiple C. fioriniae and C. nymphaeae accessions, respectively. Maximum likelihood trees based on concatenated sequences of the four genes were constructed using MEGA 6.0 (Tamura et al., 2013). The phylogenetic analysis grouped the isolates in the C. fioriniae and nymphaeae clusters respectively. The two isolates CREADC-F2317 and CREADC-F2372 were used to confirm pathogenicity on walnut fruits. Fruits of cv Lara were surface disinfected by dipping in 3% NaOCl for 1 min, rinsed in sterile distilled water, and arranged in sterile humid chambers. Fruits were wounded with a sterile needle then inoculated with 20 μl of 106 conidia/ml suspensions of each isolate (one wound per fruit). Fruit treated with sterile distilled water served as a control. Inoculations were conducted on three fruits per replicate and three replicates per treatment arranged in a complete block randomized design. After 7 days incubation at 25 ± 1°C, all the inoculated fruits showed typical anthracnose symptoms and lesions with cream to salmon pink acervuli, whereas the controls remaied healthy. The species C. nymphaeae and C. fioriniae were reisolated from the rotted fruit. Pathogenicity tests were repeated twice with the same results. The morphology of the reisolated fungi was consistent with the inoculated one, fulfilling Koch's postulates. The species C. fioriniae and C. nymphaeae have been described affecting numerous species worldwide (Damm et al., 2012). C. fioriniae and C. nymphaeae have been previously reported to cause severe anthracnose on walnut, C. fioriniae in France (Da Lio et al., 2018) and Hungary (Varjas et al., 2019) and C. nymphaeae in France (Da Lio et al., 2018) and Brazil (Savian et al., 2019). To our knowledge, this is the first report of C. fioriniae and C. nymphaeae as causal agents of walnut anthracnose in Italy.
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http://dx.doi.org/10.1094/PDIS-05-21-1062-PDNDOI Listing
July 2021

Operative Torque Analysis to Evaluate Cutting Efficiency of Two Nickel-Titanium Rotary Instruments for Glide Path: An Comparison.

J Contemp Dent Pract 2021 Mar 1;22(3):215-218. Epub 2021 Mar 1.

Department of Oral and Maxillo-facial Sciences, Sapienza University of Rome, Rome, Italy.

Aim And Objective: The aim and objective of this study was to evaluate and compare the cutting efficacy of two different nickel titanium rotary instruments by a novel methodology: the operative torque (torque and time needed to progress toward the apex).

Materials And Methods: Ten fresh extracted upper first premolars with two canals were instrumented with a KaVo (Biberach, Germany) and a KaVo 1:1 handpiece at 300 rpm with maximum torque set at 2 N. One canal was instrumented with ProGlider NiTi rotary instruments (Dentsply Sirona Endodontics, Ballaigues, Switzerland), with tip size of 16.02, and the other one with EgdeGlidePath rotary instrument (EdgeEndo, Albuquerque, New Mexico). Mean instrumentation time, mean torque values, and maximum torque values were evaluated for each instrument. The significance level was set at <0.05.

Results: EdgeGlidePath instruments reached the working length in significantly less time with a significantly smaller amount of torque when compared to ProGlider ( >0.05). No instruments exhibited flute deformation or underwent intracanal failure.

Conclusions: Operative torque is related to the capability to cut dentin and progress toward the apex: the smaller the torque values, the higher the cutting ability (and safety). Operative torque is also dependent on debris removal and irrigation techniques. Nevertheless, both operative torque and instrumentation time are clinically relevant parameters for evaluating instruments' performance (i.e., cutting ability).

Clinical Significance: Operative torque during endodontic instrumentation helps understanding the overall performance in terms of both cutting efficiency and safety.
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March 2021

Impact of switching to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG on cardiovascular risk and lipid profile in people living with HIV: a retrospective cohort study.

BMC Infect Dis 2021 Jun 22;21(1):595. Epub 2021 Jun 22.

Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.

Background: We aimed to assess the overall cardiovascular and metabolic effect of the switch to three different single tablet regimens (STRs) [tenofovir alafenamide/emtricitabine/rilpivirine (TAF/FTC/RPV), TAF/FTC/elvitegravir/cobi (TAF/FTC/EVG/cobi) and ABC/lamivudine/dolutegravir (ABC/3TC/DTG)] in a cohort of people living with HIV/AIDS (PLWH) under effective ART.

Methods: All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were retrospectively included in the analysis. Framingham risk score modification after 12 months from the switch such as lipid profile and body weight modification were assessed. The change from baseline to 12 months in mean cardiovascular risk and body weight in each of the STR's group were assessed by means of Wilcoxon signed-rank test whereas a mixed regression model was used to assess variation in lipid levels.

Results: Five-hundred and sixty PLWH were switched to an STR regimen of whom 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV and 199 (35.5%) to ABC/3TC/DTG. No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR's groups. No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG [200 (SD 38) mg/dl vs 201 (SD 35) mg/dl; p = 0.610] whereas a significant increment was observed in PLWH switched to TAF/FTC/EVG/cobi [192 (SD 34) mg/dl vs 208 (SD 40) mg/dl; p < 0.0001] and TAF/FTC/RPV [187 (SD 34) mg/dl vs 195 (SD 35) mg/dl; p = 0.027]. In addition, a significant variation in the mean body weight from baseline to 12 months was observed in PLWH switched to TAF/FTC/EVG/cobi [72.2 (SD 13.5) kilograms vs 74.6 (SD 14.3) kilograms; p < 0.0001] and TAF/FTC/RPV [73.4 (SD 11.6) kilograms vs 75.6 (SD 11.8) kilograms; p < 0.0001] whereas no difference was observed in those switched to ABC/3TC/DTG [71.5 (SD 12.8) kilograms vs 72.1 (SD 12.6) kilograms; p = 0.478].

Conclusion: No difference in the cardiovascular risk after 1 year from the switch to these STRs were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch.
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http://dx.doi.org/10.1186/s12879-021-06304-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220746PMC
June 2021

Vaccinations in patients with inflammatory bowel disease.

Dig Liver Dis 2021 Jun 8. Epub 2021 Jun 8.

Department of Biomedical and Clinical Sciences, L Sacco" University of Milan, Via Giovan Battista Grassi 74, Milan 20157, Italy.

Treatment of inflammatory bowel disease (IBD) frequently requires administration of immunosuppressive therapies, which increases susceptibility to a number of infectious pathogens. However, many infections can be prevented by correct and appropriate utilization of vaccinations. While several guidelines have been published on vaccination schedules in patients with IBD, vaccination rates remain suboptimal and even lower than those in the general population. This is due to many factors including poor awareness of the importance of vaccines by gastroenterologists and general practitioners as well as potential prejudices of patients regarding the safety and benefits of vaccines. With the aim of increasing awareness about the key role of immunization in the management of patients with IBD, the present review examines the existing literature relating to the main vaccinations and their application in these patients. We also summarize current evidence in order to provide clinicians with an easy source of reference for the principal recommendations for prevention of infectious diseases in patients with IBD. In addition, the recommendations about traveling for IBD patients are briefly explored. Lastly, since it is important for gastroenterologists to be aware of recommendations on vaccination, we recommend implementing educational programs to ensure compliance with current guidelines.
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http://dx.doi.org/10.1016/j.dld.2021.05.015DOI Listing
June 2021

Are Epidemiological Estimates Able to Describe the Ability of Health Systems to Cope with COVID-19 Epidemic?

Risk Manag Healthc Policy 2021 31;14:2221-2229. Epub 2021 May 31.

Department of Clinical Sciences and Community Health & DSRC, University of Milan, Milan, Italy.

Introduction: The coronavirus disease 2019 (COVID-19) epidemic is an infectious disease which was declared a pandemic and hit countries worldwide from the beginning of the year 2020. Despite the emergency vigilance plans, health systems in all countries experienced a different ratio of lethality, amount of admissions to intensive care units and quarantine management of positive patients. The aim of this study is to investigate whether some epidemiological estimates could have been useful in understanding the capacity of the Italian Regional Health Services to manage the COVID-19 epidemic.

Methods: We have compared data between two different Italian regions in the Northern part of Italy (Lombardy and Veneto) and the national data to determine whether different health strategies might be significant in explaining dissimilar patterns of the COVID-19 epidemic in Italy. Data have been extracted from a public database and were available only in an aggregated form.

Results: The regions in question displayed two different health policies to face the COVID-19 epidemic: while Veneto's health service was largely territorially oriented, Lombardy's strategy was more hospital-centered.

Discussion: The key to facing epidemics like this one consists in identifying solutions outside of hospitals. This however requires there be well-trained general practitioners and enough healthcare personnel working outside hospitals.
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http://dx.doi.org/10.2147/RMHP.S290801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180273PMC
May 2021

Hepatitis B Virus-Related Cryoglobulinemic Vasculitis: Review of the Literature and Long-Term Follow-Up Analysis of 18 Patients Treated with Nucleos(t)ide Analogues from the Italian Study Group of Cryoglobulinemia (GISC).

Viruses 2021 05 30;13(6). Epub 2021 May 30.

Rheumatology Clinic, Department of Medicine (DAME), ASUFC, University of Udine, 33100 Udine, Italy.

Hepatitis B virus (HBV) chronic infection causes progressive liver damage, although about 20% of patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV). Clinical manifestations range from mild to moderate (purpura, asthenia, arthralgia) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, non-Hodgkin lymphoma). A comprehensive review of therapeutic options for HBV-related CV is lacking. Nucleos(t)ide analogues (NA) suppress HBV replication in 90-100% of cases and induce clinical response in most patients with mild-to-moderate CV. Plasma exchange can be performed in patients with severe CV and should be considered in severe or life-threatening cases combined with high doses of corticosteroids and antiviral treatment. A cautious use of rituximab can be considered only in association with NA treatment in refractory cases. A review of the literature and an analysis of data collected by six centers of the Italian Group for the Study of Cryoglobulinemia on 18 HBV-CV nucleotide/nucleoside analogues (NAs)-treated patients were carried out.
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http://dx.doi.org/10.3390/v13061032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226459PMC
May 2021

Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection.

Nat Metab 2021 06 25;3(6):774-785. Epub 2021 May 25.

Infectious Diseases Unit, ASST Fatebenefratelli-Sacco, Milan, Italy.

Patients with coronavirus disease 2019 (COVID-19) are reported to have a greater prevalence of hyperglycaemia. Cytokine release as a consequence of severe acute respiratory syndrome coronavirus 2 infection may precipitate the onset of metabolic alterations by affecting glucose homeostasis. Here we describe abnormalities in glycometabolic control, insulin resistance and beta cell function in patients with COVID-19 without any pre-existing history or diagnosis of diabetes, and document glycaemic abnormalities in recovered patients 2 months after onset of disease. In a cohort of 551 patients hospitalized for COVID-19 in Italy, we found that 46% of patients were hyperglycaemic, whereas 27% were normoglycaemic. Using clinical assays and continuous glucose monitoring in a subset of patients, we detected altered glycometabolic control, with insulin resistance and an abnormal cytokine profile, even in normoglycaemic patients. Glycaemic abnormalities can be detected for at least 2 months in patients who recovered from COVID-19. Our data demonstrate that COVID-19 is associated with aberrant glycometabolic control, which can persist even after recovery, suggesting that further investigation of metabolic abnormalities in the context of long COVID is warranted.
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http://dx.doi.org/10.1038/s42255-021-00407-6DOI Listing
June 2021

Provisional recommendations for SARS-CoV-2 vaccination in patients with cryoglobulinaemic vasculitis.

Clin Exp Rheumatol 2021 Mar-Apr;39 Suppl 129(2):149-154. Epub 2021 Apr 30.

Department of Clinical and Biomedical Sciences "Luigi Sacco", University of Milano, III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milano, Italy.

People with cryoglobulinaemic vasculitis (CV) have an increased risk of infections, attributed to different causes: impairment of the immune system due to the disease itself, comorbidities, and immunosuppressive therapy. Therefore, these patients may be at high risk for a more severe course of COVID-19, including hospitalisation and death. Concerns about efficacy, immunogenicity and safety of vaccines, as well as doubts, not yet fully clarified in patients with systemic autoimmune diseases, represent other important factors for a low vaccination rate in people with (CV). Indeed, providing an expert position on the issues related to SARS-CoV-2 vaccination in patients suffering from CV is of critical relevance in order to help both patients and clinicians who are treating them in making the best choice in each case. A multidisciplinary task force of the Italian Group for the Study of Cryoglobulinaemia (GISC) was convened, and through a Delphi technique produced provisional recommendations regarding SARS-CoV-2 vaccination in cryoglobulinaemic patients.
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May 2021

How to Manage COVID-19 Vaccination in Immune-Mediated Inflammatory Diseases: An Expert Opinion by IMIDs Study Group.

Front Immunol 2021;12:656362. Epub 2021 Apr 15.

Gastroenterology Unit, ASST Fatebenefratelli-Sacco, Department of Biomedical and Clinical Sciences (DIBIC) L. Sacco, Università degli Studi di Milano, Milan, Italy.

Since March 2020, the outbreak of Sars-CoV-2 pandemic has changed medical practice and daily routine around the world. Huge efforts from pharmacological industries have led to the development of COVID-19 vaccines. In particular two mRNA vaccines, namely the BNT162b2 (Pfizer-BioNTech) and the mRNA-1273 (Moderna), and a viral-vectored vaccine, i.e. ChAdOx1 nCoV-19 (AstraZeneca), have recently been approved in Europe. Clinical trials on these vaccines have been published on the general population showing a high efficacy with minor adverse events. However, specific data about the efficacy and safety of these vaccines in patients with immune-mediated inflammatory diseases (IMIDs) are still lacking. Moreover, the limited availability of these vaccines requires prioritizing some vulnerable categories of patients compared to others. In this position paper, we propose the point of view about the management of COVID-19 vaccination from Italian experts on IMIDs and the identification of high-risk groups according to the different diseases and their chronic therapy.
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http://dx.doi.org/10.3389/fimmu.2021.656362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082137PMC
May 2021

Milestones to reach Hepatitis C Virus (HCV) elimination in Italy: From free-of-charge screening to regional roadmaps for an HCV-free nation.

Dig Liver Dis 2021 Apr 26. Epub 2021 Apr 26.

Department of Surgical, Oncological and Gastroenterological Sciences, Gastroenterology Unit, University of Padua, Padua, Italy. Italy Co-ordinating Committee of Associazione Italiana Studio Fegato (AISF), Italy.

Although Italy has been on track for Hepatitis C Virus (HCV) elimination since 2019, it fell off track due to the decrease in the number of treated patients. HCV elimination in Italy will be possible if immediate action is taken. A health policy was implemented beginning in 2021, consisting of screening among key populations and birth cohorts (1969-1989), estimated to have a high prevalence of undiagnosed individuals. The active screening requires regional governance that manages the processes' complexity integrating a well-organized network between territory assistance and hospital to achieve an effective HCV care cascade. This document aims to support the regional decision-making process by defining paths for screening and linkage-to-care. Implementing active screening strategies beyond a risk-based approach is required as a General Practitioners' task. Simplified paths must be drawn for the key populations screening. The infrastructure built for COVID-19 vaccination could be used also for HCV screening. According to a multidisciplinary care delivery, screening should be supplemented with rapid linkage-to-care and treatment of newly diagnosed patients. The realization of the proactive screening during the first two years is vital because it will define the tracks for the whole HCV cost-effective screening of 1948-1988 birth cohorts in Italy.
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http://dx.doi.org/10.1016/j.dld.2021.03.026DOI Listing
April 2021

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort.

Dig Liver Dis 2021 Apr 20. Epub 2021 Apr 20.

Center for Global Health, Istituto Superiore di Sanità, Rome, Italy. Electronic address:

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort.

Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used.

Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively.

Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.
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http://dx.doi.org/10.1016/j.dld.2021.03.020DOI Listing
April 2021

Anti-Tat immunity defines CD4 T-cell dynamics in people living with HIV on long-term cART.

EBioMedicine 2021 Apr 7;66:103306. Epub 2021 Apr 7.

National HIV/AIDS Research Center, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy. Electronic address:

Background: Low-level HIV viremia originating from virus reactivation in HIV reservoirs is often present in cART treated individuals and represents a persisting source of immune stimulation associated with sub-optimal recovery of CD4 T cells. The HIV-1 Tat protein is released in the extracellular milieu and activates immune cells and latent HIV, leading to virus production and release. However, the relation of anti-Tat immunity with residual viremia, persistent immune activation and CD4 T-cell dynamics has not yet been defined.

Methods: Volunteers enrolled in a 3-year longitudinal observational study were stratified by residual viremia, Tat serostatus and frequency of anti-Tat cellular immune responses. The impact of anti-Tat immunity on low-level viremia, persistent immune activation and CD4 T-cell recovery was investigated by test for partitions, longitudinal regression analysis for repeated measures and generalized estimating equations.

Findings: Anti-Tat immunity is significantly associated with higher nadir CD4 T-cell numbers, control of low-level viremia and long-lasting CD4 T-cell recovery, but not with decreased immune activation. In adjusted analysis, the extent of CD4 T-cell restoration reflects the interplay among Tat immunity, residual viremia and immunological determinants including CD8 T cells and B cells. Anti-Env immunity was not related to CD4 T-cell recovery.

Interpretation: Therapeutic approaches aiming at reinforcing anti-Tat immunity should be investigated to improve immune reconstitution in people living with HIV on long-term cART.

Trial Registration: ISS OBS T-002 ClinicalTrials.gov identifier: NCT01024556 FUNDING: Italian Ministry of Health, special project on the Development of a vaccine against HIV based on the Tat protein and Ricerca Corrente 2019/2020.
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http://dx.doi.org/10.1016/j.ebiom.2021.103306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105504PMC
April 2021

Prevalence and outcome of silent hypoxemia in COVID-19.

Minerva Anestesiol 2021 03;87(3):325-333

Department of Anesthesiology, Intensive Care and Emergency Medicine, Medical University of Göttingen, Göttingen, Germany.

Background: In the early stages of COVID-19 pneumonia, hypoxemia has been described in absence of dyspnea ("silent" or "happy" hypoxemia). Our aim was to report its prevalence and outcome in a series of hypoxemic patients upon Emergency Department admission.

Methods: In this retrospective observational cohort study we enrolled a study population consisting of 213 COVID-19 patients with PaO2/FiO2 ratio <300 mmHg at hospital admission. Two groups (silent and dyspneic hypoxemia) were defined. Symptoms, blood gas analysis, chest X-ray (CXR) severity, need for intensive care and outcome were recorded.

Results: Silent hypoxemic patients (68-31.9%) compared to the dyspneic hypoxemic patients (145-68.1%) showed greater frequency of extra respiratory symptoms (myalgia, diarrhea and nausea) and lower plasmatic LDH. PaO2/FiO2 ratio was 225±68 mmHg and 192±78 mmHg in silent and dyspneic hypoxemia respectively (P=0.002). Eighteen percent of the patients with PaO2/FiO2 from 50 to 150 mmHg presented silent hypoxemia. Silent and dyspneic hypoxemic patients had similar PaCO2 (34.2±6.8 mmHg vs. 33.5±5.7 mmHg, P=0.47) but different respiratory rates (24.6±5.9 bpm vs. 28.6±11.3 bpm respectively, P=0.002). Even when CXR was severely abnormal, 25% of the population was silent hypoxemic. Twenty-six point five percent and 38.6% of silent and dyspneic patients were admitted to the ICU respectively (P=0.082). Mortality rate was 17.6% and 29.7% (log-rank P=0.083) in silent and dyspneic patients.

Conclusions: Silent hypoxemia is remarkably present in COVID-19. The presence of dyspnea is associated with a more severe clinical condition.
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http://dx.doi.org/10.23736/S0375-9393.21.15245-9DOI Listing
March 2021

Non-human primate and human malaria: past, present and future.

J Travel Med 2021 Jul;28(5)

III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy.

Background: Studies of the malaria parasites infecting various non-human primates (NHPs) have increased our understanding of the origin, biology and pathogenesis of human Plasmodium parasites.This review considers the major discoveries concerning NHP malaria parasites, highlights their relationships with human malaria and considers the impact that this may have on attempts to eradicate the disease.

Results: The first description of NHP malaria parasites dates back to the early 20th century. Subsequently, experimental and fortuitous findings indicating that some NHP malaria parasites can be transmitted to humans have raised concerns about the possible impact of a zoonotic malaria reservoir on efforts to control human malaria.Advances in molecular techniques over the last 15 years have contributed greatly to our knowledge of the existence and geographical distribution of numerous Plasmodium species infecting NHPs, and extended our understanding of their close phylogenetic relationships with human malaria parasites. The clinical application of such techniques has also made it possible to document ongoing spillovers of NHP malaria parasites (Plasmodium knowlesi, P. cynomolgi, P. simium, P. brasilianum) in humans living in or near the forests of Asia and South America, thus confirming that zoonotic malaria can undermine efforts to eradicate human malaria.

Conclusions: Increasing molecular research supports the prophetic intuition of the pioneers of modern malariology who saw zoonotic malaria as a potential obstacle to the full success of malaria eradication programmes. It is, therefore, important to continue surveillance and research based on one-health approaches in order to improve our understanding of the complex interactions between NHPs, mosquito vectors and humans during a period of ongoing changes in the climate and the use of land, monitor the evolution of zoonotic malaria, identify the populations most at risk and implement appropriate preventive strategies.
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http://dx.doi.org/10.1093/jtm/taab036DOI Listing
July 2021

Human-to-Cat SARS-CoV-2 Transmission: Case Report and Full-Genome Sequencing from an Infected Pet and Its Owner in Northern Italy.

Pathogens 2021 Feb 23;10(2). Epub 2021 Feb 23.

Luigi Sacco Department of Biomedical and Clinical Sciences, Università Statale di Milano, 20157 Milan, Italy.

There have been previous reports of the human-to-cat transmission of SARS-CoV-2, but there are only a few molecular studies that have compared the whole genome of the virus in cats and their owners. We here describe a case of domestic SARS-CoV-2 transmission from a healthcare worker to his cat for which nasopharyngeal swabs of both the cat and its owner were used for full-genome analysis. The results indicate that quarantine measures should be extended to pets living in SARS-CoV-2-infected households.
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http://dx.doi.org/10.3390/pathogens10020252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926546PMC
February 2021

Time and Mode of Epidemic HCV-2 Subtypes Spreading in Europe: Phylodynamics in Italy and Albania.

Diagnostics (Basel) 2021 Feb 17;11(2). Epub 2021 Feb 17.

Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, 20157 Milan, Italy.

Hepatitis C virus (HCV) genotype 2 causes about 10% of global infections and has the most variable circulation profile in Europe. The history of "endemic" HCV-2 subtypes has been satisfactorily reconstructed, instead there is little information about the recent spread of the "epidemic" subtypes, including HCV-2c. To investigate the origin and dispersion pathways of HCV-2c, 245 newly characterized Italian and Albanian HCV-2 NS5B sequences were aligned with 247 publicly available sequences and included in phylogeographic and phylodynamic analyses using the Bayesian framework. Our findings show that HCV-2c was the most prevalent subtype in Italy and Albania. The phylogeographic analysis suggested an African origin of HCV-2c before it reached Italy about in the 1940s. Phylodynamic analysis revealed an exponential increase in the effective number of infections and Re in Italy between the 1940s and 1960s, and in Albania between the 1990s and the early 2000s. It seems very likely that HCV-2c reached Italy from Africa at the time of the second Italian colonization but did not reach Albania until the period of dramatic migration to Italy in the 1990s. This study contributes to reconstructing the history of the spread of epidemic HCV-2 subtypes to Europe.
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http://dx.doi.org/10.3390/diagnostics11020327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922790PMC
February 2021

Association Between Smoking and SARS-CoV-2 Infection: Cross-sectional Study of the EPICOVID19 Internet-Based Survey.

JMIR Public Health Surveill 2021 04 28;7(4):e27091. Epub 2021 Apr 28.

see Acknowledgments, Segrate (MI), Italy.

Background: Several studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn.

Objective: We investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders.

Methods: The nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics.

Results: Out of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19-like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked.

Conclusions: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association.

Trial Registration: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.
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http://dx.doi.org/10.2196/27091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081027PMC
April 2021

Prevalence of SARS-CoV-2 in an area of unrestricted viral circulation: Mass seroepidemiological screening in Castiglione d'Adda, Italy.

PLoS One 2021 24;16(2):e0246513. Epub 2021 Feb 24.

Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, Milano, Italy.

Castiglione D'Adda is one of the municipalities more precociously and severely affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic in Lombardy. With our study we aimed to understand the diffusion of the infection by mass serological screening. We searched for SARS-CoV-2 IgGs in the entire population on a voluntary basis using lateral flow immunochromatographic tests (RICT) on capillary blood (rapid tests). We then performed chemioluminescent serological assays (CLIA) and naso-pharyngeal swabs (NPS) in a randomized representative sample and in each subject with a positive rapid test. Factors associated with RICT IgG positivity were assessed by uni- and multivariate logistic regression models. Out of the 4143 participants, 918 (22·2%) showed RICT IgG positivity. In multivariable analysis, IgG positivity increases with age, with a significant non-linear effect (p = 0·0404). We found 22 positive NPSs out of the 1330 performed. Albeit relevant, the IgG prevalence is lower than expected and suggests that a large part of the population remains susceptible to the infection. The observed differences in prevalence might reflect a different infection susceptibility by age group. A limited persistence of active infections could be found after several weeks after the epidemic peak in the area.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246513PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904134PMC
March 2021

Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.

Cell 2021 03 28;184(5):1171-1187.e20. Epub 2021 Jan 28.

MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK.

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.
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http://dx.doi.org/10.1016/j.cell.2021.01.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843029PMC
March 2021

Age-Related Changes in Clinical Presentation of Covid-19: the EPICOVID19 Web-Based Survey.

Eur J Intern Med 2021 04 29;86:41-47. Epub 2021 Jan 29.

Geriatrics Unit, Department of Medicine, Biomedical Campus of Rome, via Alvaro del Portillo, 21, 00128 Rome, Italy.

Background: The influence of aging and multimorbidity on Covid-19 clinical presentation is still unclear.

Objectives: We investigated whether the association between symptoms (or cluster of symptoms) and positive SARS-CoV-2 nasopharyngeal swab (NPS) was different according to patients' age and presence of multimorbidity.

Methods: The study included 6680 participants in the EPICOVID19 web-based survey, who reported information about symptoms from February to June 2020 and who underwent at least one NPS. Symptom clusters were identified through hierarchical cluster analysis. The associations between symptoms (and clusters of symptoms) and positive NPS were investigated through multivariable binary logistic regression in the sample stratified by age (<65 vs ≥65 years) and number of chronic diseases (0 vs 1 vs ≥2).

Results: The direct association between taste/smell disorders and positive NPS was weaker in older and multimorbid patients than in their younger and healthier counterparts. Having reported no symptoms reduced the chance of positive NPS by 86% in younger (95%CI: 0.11-0.18), and by 46% in older participants (95%CI: 0.37-0.79). Of the four symptom clusters identified (asymptomatic, generic, flu-like, and combined generic and flu-like symptoms), those associated with a higher probability of SARS-CoV-2 infection were the flu-like for older people, and the combined generic and flu-like for the younger ones.

Conclusions: Older age and pre-existing chronic diseases may influence the clinical presentation of Covid-19. Symptoms at disease onset tend to aggregate differently by age. New diagnostic algorithms considering age and chronic conditions may ease Covid-19 diagnosis and optimize health resources allocation.

Trial Registration: NCT04471701 (ClinicalTrials.gov).
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http://dx.doi.org/10.1016/j.ejim.2021.01.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846211PMC
April 2021

Dynamics of the seroprevalence of SARS-CoV-2 antibodies among healthcare workers at a COVID-19 referral hospital in Milan, Italy.

Occup Environ Med 2021 Feb 4. Epub 2021 Feb 4.

Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milano, Italy.

Objectives: Healthcare workers (HCWs) are at high risk of developing SARS-CoV-2 infection. The aim of this single-centre prospective study was to evaluate the trend of SARS-CoV-2 seroprevalence in HCWs working at the primary referral centre for infectious diseases and bioemergencies (eg, COVID-19) in Northern Italy and investigate the factors associated with seroconversion.

Methods: Six hundred and seventy-nine HCW volunteers were tested for anti-SARS-CoV-2 antibodies three times between 4 March and 27 May 2020 and completed a questionnaire covering COVID-19 exposure, symptoms and personal protective equipment (PPE) training and confidence at each time.

Results: SARS-CoV-2 seroprevalence rose from 3/679 to 26/608 (adjusted prevalence: 0.5%, 95% CI 0.1 to 1.7% and 5.4%, 95% CI 3.6 to 7.9, respectively) between the first two time points and then stabilised, in line with the curve of the COVID-19 epidemic in Milan. From the first time point, 61.6% of the HCWs had received training in the use of PPE and 17 (61.5%) of those who proved to be seropositive reported symptoms compatible with SARS-CoV-2 infection. Contacts with ill relatives or friends and self-reported symptoms were independently associated with an increased likelihood of seroconversion (p<0.0001 for both), whereas there was no significant association with professional exposure.

Conclusion: The seroprevalence of SARS-CoV-2 among the HCWs at our COVID-19 referral hospital was low at the time of the peak of the epidemic. The seroconversions were mainly attributable to extrahospital contacts, probably because the hospital readily adopted effective infection control measures. The relatively high number of asymptomatic seropositive HCWs highlights the need to promptly identify and isolate potentially infectious HCWs.
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http://dx.doi.org/10.1136/oemed-2020-107060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868130PMC
February 2021

SARS-CoV-2 seroprevalence trends in healthy blood donors during the COVID-19 outbreak in Milan.

Blood Transfus 2021 05 3;19(3):181-189. Epub 2021 Feb 3.

Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: The Milan metropolitan area in Northern Italy was among the most severely hit by the SARS-CoV-2 outbreak. The aim of this study was to examine the seroprevalence trends of SARS-CoV-2 in healthy asymptomatic adults, and the risk factors and laboratory correlates of positive tests.

Materials And Methods: We conducted a cross-sectional study in a random sample of blood donors, who were asymptomatic at the time of evaluation, at the beginning of the first phase (February 24 to April 8 2020; n=789). Presence of IgM/IgG antibodies against the SARS-CoV-2-Nucleocapsid protein was assessed by a lateral flow immunoassay.

Results: The test had a 100/98.3 sensitivity/specificity (n=32/120 positive/negative controls, respectively), and the IgG test was validated in a subset by an independent ELISA against the Spike protein (n=34, p<0.001). At the start of the outbreak, the overall adjusted seroprevalence of SARS-CoV-2 was 2.7% (95% CI: 0.3-6%; p<0.0001 vs 120 historical controls). During the study period, characterised by a gradual implementation of social distancing measures, there was a progressive increase in the adjusted seroprevalence to 5.2% (95% CI: 2.4-9.0; 4.5%, 95% CI: 0.9-9.2% according to a Bayesian estimate) due to a rise in IgG reactivity to 5% (95% CI: 2.8-8.2; p=0.004 for trend), but there was no increase in IgM (p=not significant). At multivariate logistic regression analysis, IgG reactivity was more frequent in younger individuals (p=0.043), while IgM reactivity was more frequent in individuals aged >45 years (p=0.002).

Discussion: SARS-CoV-2 infection was already circulating in Milan at the start of the outbreak. The pattern of IgM/IgG reactivity was influenced by age: IgM was more frequently detected in participants aged >45 years. By the end of April, 2.4-9.0% of healthy adults had evidence of seroconversion.
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http://dx.doi.org/10.2450/2021.0324-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092034PMC
May 2021

Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population.

Dig Liver Dis 2021 03 26;53(3):263-270. Epub 2020 Dec 26.

Gastroenterology Unit, ASST Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences "L.Sacco" University of Milan, Italy.

Background: It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19.

Objectives: This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders.

Methods: This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed.

Results: 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28-0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03-0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02-1.17).

Conclusion: IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.
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http://dx.doi.org/10.1016/j.dld.2020.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762705PMC
March 2021

Detecting HCV infection by means of mass population SARS-CoV-2 screening: A pilot experience in Northern Italy.

J Hepatol 2021 08 13;75(2):484-486. Epub 2021 Jan 13.

Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy; Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, Università degli Studi di Milano, Italy.

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http://dx.doi.org/10.1016/j.jhep.2020.12.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804391PMC
August 2021

Unveiling the basis of antiretroviral therapy-induced osteopenia: the effects of Dolutegravir, Darunavir and Atazanavir on osteogenesis.

AIDS 2021 02;35(2):213-218

Infectious Diseases Unit, Department of Biomedical and Clinical Sciences 'Luigi Sacco', Università degli Studi di Milano, Milan, Italy.

Objectives: Osteopenia is frequent in HIV-infected patients treated with antiretroviral therapy (ART) and has been linked to increased osteoclastogenesis. Little is known about the effects of ART on osteogenesis.

Design: We investigated the effect on human mesenchymal stem cells (hMSC) and osteoblasts of Darunavir and Dolutegravir, the most highly used as anchor drugs within a three-drug regimen, and Atazanavir, which was widely utilized in the past.

Results: We found that Atazanavir and Dolutegravir delay the osteogenic differentiation of hMSC, impair the activity of osteoblasts and inhibit their conversion into osteocytes, whereas Darunavir exerts no effect.

Conclusion: Atazanavir and Dolutegravir impair osteogenesis. It is essential to diagnose impaired osteogenesis early and to devise effective therapeutic interventions to preserve bone health in ART-treated HIV patients, putting it in the context of a correct antiretroviral combination.
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http://dx.doi.org/10.1097/QAD.0000000000002732DOI Listing
February 2021
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