Giada Rossini

@unibo.it

AZIENDA OSPEDALIERO UNIVERSITARIA DI BOLOGNA

RESEARCH INTERESTS

Virology

81

Scopus Publications

Scopus Publications

  • Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients
    Adrian Gervais, Francesca Rovida, Maria Antonietta Avanzini, Stefania Croce, Astrid Marchal, Shih-Ching Lin, Alessandro Ferrari, Christian W. Thorball, Orianne Constant, Tom Le Voyer,et al.

    Rockefeller University Press
    Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0–24.0, P value <10–15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1–186.4, P value <10–15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.

  • Antiviral Activity of Cannabidiolic Acid and Its Methyl Ester against SARS-CoV-2
    Martina Tamburello, Stefano Salamone, Lisa Anceschi, Paolo Governa, Virginia Brighenti, Alice Morellini, Giada Rossini, Fabrizio Manetti, Giorgio Gallinella, Federica Pollastro,et al.

    American Chemical Society (ACS)
    In the present study, the antiviral activity of cannabinoids isolated from Cannabis sativa L. was assessed in vitro against a panel of SARS-CoV-2 variants, indicating cannabidiolic acid (CBDA) was the most active. To overcome the instability issue of CBDA, its methyl ester was synthesized and tested for the first time for its antiviral activity. CBDA methyl ester showed a neutralizing effect on all the SARS-CoV-2 variants tested with greater activity than the parent compound. Its stability in vitro was confirmed by ultra-high-performance liquid chromatography (UHPLC) analysis coupled with high-resolution mass spectrometry (HRMS). In addition, the capacity of both CBDA and its derivative to interact with the virus spike protein was assessed in silico. These results showed that CBDA methyl ester can be considered as a lead compound to be further developed as a new effective drug against COVID-19 infection.

  • Case report of Usutu virus infection in an immunocompromised patient in Italy, 2022
    Paolo Gaibani, Nicole Barp, Marco Massari, Emanuele Alberto Negri, Giada Rossini, Caterina Vocale, Chiara Trenti, Altea Gallerani, Samuele Cantergiani, Federico Romani,et al.

    Springer Science and Business Media LLC

  • Dengue and falciparum malaria co-infection in travelers returning from Burkina Faso: Report of two cases in Northeastern Italy
    Antonio Mastroianni, Caterina Vocale, Vittorio Sambri, Tiziana Lazzarotto, Paolo Gaibani, Giada Rossini, and Stefania Varani

    Medknow
    Rationale: Malaria and dengue are the most prevalent vector-borne diseases in tropical countries. Plasmodium parasite and dengue virus (DENV) concurrent infection is possible and often under-recognized in geographical areas where these infections are both endemic. Patients concern and diagnosis: We describe the first two cases of Plasmodium falciparum and DENV-3 co-infection in travelers returning to northeastern Italy from Burkina Faso during 2013-2014. Interventions: Malaria infection in both patients was treated with mefloquine. Due to the persistence of symptoms despite of the antimalaria treatment, dengue was also investigated; the treatment of dengue was symptomatic. Outcomes: The patients were discharged in good general condition. Lessons: The need for surveillance of potential malaria and dengue co-infection in travelers returning to Europe from endemic areas is highlighted, as infection with Plasmodium does not exclude arboviral co-infection.

  • Vector Competence of Northern European Culex pipiens Biotype pipiens and Culex torrentium to West Nile Virus and Sindbis Virus
    Stephanie Jansen, Anna Heitmann, Ruut Uusitalo, Essi M. Korhonen, Renke Lühken, Konstantin Kliemke, Unchana Lange, Michelle Helms, Lauri Kirjalainen, Roope Nykänen,et al.

    MDPI AG
    The West Nile Virus (WNV) and Sindbis virus (SINV) are avian-hosted mosquito-borne zoonotic viruses that co-circulate in some geographical areas and share vector species such as Culex pipiens and Culex torrentium. These are widespread in Europe, including northern parts and Finland, where SINV is endemic, but WNV is currently not. As WNV is spreading northwards in Europe, we wanted to assess the experimental vector competence of Finnish Culex pipiens and Culex torrentium mosquitoes to WNV and SINV in different temperature profiles. Both mosquito species were found susceptible to both viruses and got infected via infectious blood meal at a mean temperature of 18 °C. WNV-positive saliva was detected at a mean temperature of 24 °C, whereas SINV-positive saliva was detected already at a mean temperature of 18 °C. Cx. torrentium was found to be a more efficient vector for WNV and SINV over Cx. pipiens. Overall, the results were in line with the previous studies performed with more southern vector populations. The current climate does not seem optimal for WNV circulation in Finland, but temporary summertime transmission could occur in the future if all other essential factors are in place. More field data would be needed for monitoring and understanding the northward spreading of WNV in Europe.

  • CFTR Inhibitors Display In Vitro Antiviral Activity against SARS-CoV-2
    Anna Lagni, Virginia Lotti, Erica Diani, Giada Rossini, Ercole Concia, Claudio Sorio, and Davide Gibellini

    MDPI AG
    Several reports have indicated that SARS-CoV-2 infection displays unexpected mild clinical manifestations in people with cystic fibrosis (pwCF), suggesting that CFTR expression and function may be involved in the SARS-CoV-2 life cycle. To evaluate the possible association of CFTR activity with SARS-CoV-2 replication, we tested the antiviral activity of two well-known CFTR inhibitors (IOWH-032 and PPQ-102) in wild type (WT)-CFTR bronchial cells. SARS-CoV-2 replication was inhibited by IOWH-032 treatment, with an IC50 of 4.52 μM, and by PPQ-102, with an IC50 of 15.92 μM. We confirmed this antiviral effect on primary cells (MucilAirTM wt-CFTR) using 10 μM IOWH-032. According to our results, CFTR inhibition can effectively tackle SARS-CoV-2 infection, suggesting that CFTR expression and function might play an important role in SARS-CoV-2 replication, revealing new perspectives on the mechanisms governing SARS-CoV-2 infection in both normal and CF individuals, as well as leading to potential novel treatments.

  • Monkeypox Outbreak 2022: Clinical and Virological Features of 30 Patients at the Sexually Transmitted Diseases Centre of Sant’ Orsola Hospital, Bologna, Northeastern Italy
    Valeria Gaspari, Giada Rossini, Silvia Robuffo, Luca Rapparini, Alessandra Scagliarini, Alessandra Mistral De Pascali, Bianca Maria Piraccini, and Tiziana Lazzarotto

    American Society for Microbiology
    Monkeypox infection is a zoonosis first described in humans in 1970 in Congo. While previously manifesting in small, confined outbreaks, the disease is rapidly spreading globally.

  • Virological and histological evaluation of intestinal samples in COVID-19 patients
    Dajana Cuicchi, Liliana Gabrielli, Maria Lucia Tardio, Giada Rossini, Antonietta D’Errico, Pierluigi Viale, Tiziana Lazzarotto, and Gilberto Poggioli

    Baishideng Publishing Group Inc.
    BACKGROUND Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen responsible for pandemic coronavirus disease 2019 (COVID-19). It is a highly contagious virus which primarily affects the respiratory tract, nevertheless, the lungs are not the only target organs of the virus. The intestinal tract could represent an additional tropism site for SARS-CoV-2. Several observations have collectively suggested that enteric infections can occur in COVID-19 patients. However, the detection of viral RNA in gastrointestinal (GI) tissue samples has not been adequately investigated and results are conflicting. AIM To detect the presence of SARS-CoV-2 RNA in intestinal mucosa samples and to evaluate histological features. METHODS The COVID-19 patients hospitalized at an Italian tertiary hospital from April 2020 to March 2021 were evaluated for enrollment in an observational, monocentric trial. The study population was composed of two groups of adult patients. In the first group (biopsy group, 30 patients), patients were eligible for inclusion if they had mild to moderate disease and if they agreed to have a rectal biopsy; in the second group (surgical specimen group, 6 patients), patients were eligible for inclusion if they underwent intestinal resection during index hospitalization. Fifty-nine intestinal mucosal samples were analyzed. RESULTS Viral RNA was not detectable in any of the rectal biopsies performed (0/53). Histological examination showed no enterocyte damage, but slight edema of the lamina propria with mild inflammatory lymphoplasmacytic infiltration. There was no difference in inflammatory infiltrates in patients with and without GI symptoms. SARS-CoV-2 RNA was detected in fecal samples in 6 cases out of 14 cases examined (42.9%). In the surgical specimen group, all patients underwent emergency intestinal resection. Viral RNA was detected in 2 surgical specimens of the 6 examined, both of which were from patients with active neoplastic disease. Histological examination also pointed out abundant macrophages, granulocytes and plasma cells infiltrating the muscular layer and adipose tissue, and focal vasculitis. CONCLUSION Mild-moderate COVID-19 may not be associated with rectal infection by the virus. More comprehensive autopsies or surgical specimens are needed to provide histological evidence of intestinal infection.

  • Tracking the progressive spread of the SARS-CoV-2 Omicron variant in Italy, December 2021 to January 2022
    Paola Stefanelli, Filippo Trentini, Daniele Petrone, Alessia Mammone, Luigina Ambrosio, Mattia Manica, Giorgio Guzzetta, Valeria d'Andrea, Valentina Marziano, Agnese Zardini,et al.

    European Centre for Disease Control and Prevention (ECDC)
    Background The SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021. Aim To comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level. Methods We analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility. Results Omicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9–80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7–3.3 days. As of 17 January 2022, Delta variant represented < 6% of cases. During the Omicron expansion in December 2021, the estimated mean net reproduction numbers respectively rose from 1.15 to a maximum of 1.83 for symptomatic cases and from 1.14 to 1.36 for hospitalised cases, while remaining relatively stable, between 0.93 and 1.21, for cases needing intensive care. Despite a reduction in relative proportion, Delta infections increased in absolute terms throughout December contributing to an increase in hospitalisations. A significant reproduction numbers’ decline was found after mid-January, with average estimates dropping below 1 between 10 and 16 January 2022. Conclusion Estimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at population level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection.

  • CFTR Modulation Reduces SARS-CoV-2 Infection in Human Bronchial Epithelial Cells
    Virginia Lotti, Flavia Merigo, Anna Lagni, Andrea Di Clemente, Marco Ligozzi, Paolo Bernardi, Giada Rossini, Ercole Concia, Roberto Plebani, Mario Romano,et al.

    MDPI AG
    People with cystic fibrosis should be considered at increased risk of developing severe symptoms of COVID-19. Strikingly, a broad array of evidence shows reduced spread of SARS-CoV-2 in these subjects, suggesting a potential role for CFTR in the regulation of SARS-CoV-2 infection/replication. Here, we analyzed SARS-CoV-2 replication in wild-type and CFTR-modified human bronchial epithelial cell lines and primary cells to investigate SARS-CoV-2 infection in people with cystic fibrosis. Both immortalized and primary human bronchial epithelial cells expressing wt or F508del-CFTR along with CRISPR/Cas9 CFTR-ablated clones were infected with SARS-CoV-2 and samples were harvested before and from 24 to 72 h post-infection. CFTR function was also inhibited in wt-CFTR cells with the CFTR-specific inhibitor IOWH-032 and partially restored in F508del-CFTR cells with a combination of CFTR modulators (VX-661+VX-445). Viral load was evaluated by real-time RT-PCR in both supernatant and cell extracts, and ACE-2 expression was analyzed by both western blotting and flow cytometry. SARS-CoV-2 replication was reduced in CFTR-modified bronchial cells compared with wild-type cell lines. No major difference in ACE-2 expression was detected before infection between wild-type and CFTR-modified cells, while a higher expression in wild-type compared to CFTR-modified cells was detectable at 72 h post-infection. Furthermore, inhibition of CFTR channel function elicited significant inhibition of viral replication in cells with wt-CFTR, and correction of CFTR function in F508del-CFTR cells increased the release of SARS-CoV-2 viral particles. Our study provides evidence that CFTR expression/function is involved in the regulation of SARS-CoV-2 replication, thus providing novel insights into the role of CFTR in SARS-CoV-2 infection and the development of therapeutic strategies for COVID-19.

  • Vector competence of the invasive mosquito species Aedes koreicus for arboviruses and interference with a novel insect specific virus
    Stephanie Jansen, Dániel Cadar, Renke Lühken, Wolf Peter Pfitzner, Hanna Jöst, Sandra Oerther, Michelle Helms, Branka Zibrat, Konstantin Kliemke, Norbert Becker,et al.

    MDPI AG
    The global spread of invasive mosquito species increases arbovirus infections. In addition to the invasive species Aedes albopictus and Aedes japonicus, Aedes koreicus has spread within Central Europe. Extensive information on its vector competence is missing. Ae. koreicus from Germany were investigated for their vector competence for chikungunya virus (CHIKV), Zika virus (ZIKV) and West Nile virus (WNV). Experiments were performed under different climate conditions (27 ± 5 °C; 24 ± 5 °C) for fourteen days. Ae. koreicus had the potential to transmit CHIKV and ZIKV but not WNV. Transmission was exclusively observed at the higher temperature, and transmission efficiency was rather low, at 4.6% (CHIKV) or 4.7% (ZIKV). Using a whole virome analysis, a novel mosquito-associated virus, designated Wiesbaden virus (WBDV), was identified in Ae. koreicus. Linking the WBDV infection status of single specimens to their transmission capability for the arboviruses revealed no influence on ZIKV transmission. In contrast, a coinfection of WBDV and CHIKV likely has a boost effect on CHIKV transmission. Due to its current distribution, the risk of arbovirus transmission by Ae. koreicus in Europe is rather low but might gain importance, especially in regions with higher temperatures. The impact of WBDV on arbovirus transmission should be analyzed in more detail.

  • Respiratory bacterial co-infections in intensive care unit-hospitalized COVID-19 patients: Conventional culture vs BioFire FilmArray pneumonia Plus panel
    Claudio Foschi, Anna Zignoli, Paolo Gaibani, Caterina Vocale, Giada Rossini, Silvia Lafratta, Andrea Liberatore, Gabriele Turello, Tiziana Lazzarotto, and Simone Ambretti

    Elsevier BV
    The prevalence and microbiology of concomitant respiratory bacterial infections in patients with SARS-CoV-2 infection are not yet fully understood. In this retrospective study, we assessed respiratory bacterial co-infections in lower respiratory tract samples taken from intensive care unit-hospitalized COVID-19 patients, by comparing the conventional culture approach to an innovative molecular diagnostic technology. A total of 230 lower respiratory tract samples (i.e., bronchial aspirates or bronchoalveolar lavages) were taken from 178 critically ill COVID-19 patients. Each sample was processed by a semi-quantitative culture and by a multiplex PCR panel (FilmArray Pneumonia Plus panel), allowing rapid detection of a wide range of clinically relevant pathogens and a limited number of antimicrobial resistance markers. More than 30% of samples showed a positive bacterial culture, with Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus the most detected pathogens. FilmArray showed an overall sensitivity and specificity of 89.6% and 98.3%, respectively, with a negative predictive value of 99.7%. The molecular test significantly reduced the turn-around-time (TAT) and increased the rates of microbial detection. Most cases missed by culture were characterized by low bacterial loads (104–105 copies/mL). FilmArray missed a list of pathogens not included in the molecular panel, especially Stenotrophomonas maltophilia (8 cases). FilmArray can be useful to detect bacterial pathogens in lower respiratory tract specimens of COVID-19 patients, with a significant decrease of TAT. The test is particularly useful to rule out bacterial co-infections and avoid the inappropriate prescription of antibiotics.

  • COVID-19 in patients with HIV-1 infection: a single-centre experience in northern Italy
    Leonardo Calza, Isabella Bon, Marina Tadolini, Marco Borderi, Vincenzo Colangeli, Lorenzo Badia, Gabriella Verucchi, Giada Rossini, Caterina Vocale, Paolo Gaibani,et al.

    Springer Science and Business Media LLC
    Since the end of February 2020, the Coronavirus Disease 2019 (COVID-19) outbreak rapidly spread throughout Italy and other European countries, but limited information has been available about its characteristics in HIV-infected patients. We have described a case series of patients with HIV infection and COVID-19 diagnosed at the S.Orsola Hospital (Bologna, Italy) during March and April, 2020. We reported a case series of 26 HIV-infected patients with COVID-19. Nineteen subjects were men, the median age was 54 years, 73% of patients had one or more comorbidities. Only 5 patients with interstitial pneumonia were hospitalized, but there were no admissions to intensive care unit and no deaths. In our experience, COVID-19 associated with HIV infection had a clinical presentation comparable to the general population and was frequently associated with chronic comorbidities.

  • Recent Advances in the Evaluation of Serological Assays for the Diagnosis of SARS-CoV-2 Infection and COVID-19
    A. Chiereghin, R. M. Zagari, S. Galli, A. Moroni, L. Gabrielli, S. Venturoli, I. Bon, G. Rossini, I. Saracino, M. Pavoni,et al.


    Introduction: Few data on the diagnostic performance of serological tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are currently available. We evaluated sensitivity and specificity of five different widely used commercial serological assays for the detection of SARS-CoV-2–specific IgG, IgM, and IgA antibodies using reverse transcriptase-PCR assay in nasopharyngeal swab as reference standard test. Methods: A total of 337 plasma samples collected in the period April–June 2020 from SARS-CoV-2 RT-PCR positive (n = 207) and negative (n = 130) subjects were investigated by one point-of-care lateral flow immunochromatographic assay (LFIA IgG and IgM, Technogenetics) and four fully automated assays: two chemiluminescence immunoassays (CLIA-iFlash IgG and IgM, Shenzhen YHLO Biotech and CLIA-LIAISON® XL IgG, DiaSorin), one electrochemiluminescence immunoassay (ECLIA-Elecsys® total predominant IgG, Roche), and one enzyme-linked immunosorbent assay (ELISA IgA, Euroimmune). Results: The overall sensitivity of all IgG serological assays was >80% and the specificity was >97%. The sensitivity of IgG assays was lower within 2 weeks from the onset of symptoms ranging from 70.8 to 80%. The LFIA and CLIA-iFlash IgM showed an overall low sensitivity of 47.6 and 54.6%, while the specificity was 98.5 and 96.2%, respectively. The ELISA IgA yielded a sensitivity of 84.3% and specificity of 81.7%. However, the ELISA IgA result was indeterminate in 11.7% of cases. Conclusions: IgG serological assays seem to be a reliable tool for the retrospective diagnosis of SARS-CoV-2 infection. IgM assays seem to have a low sensitivity and IgA assay is limited by a substantial rate of indeterminate results.

  • Serodiagnosis of visceral leishmaniasis in northeastern italy: Evaluation of seven serological tests
    Margherita Ortalli, Daniele Lorrai, Paolo Gaibani, Giada Rossini, Caterina Vocale, Maria Carla Re, and Stefania Varani

    MDPI AG
    This study compares the performance of seven assays, including two ELISA (Leishmania ELISA IgG + IgM, Vircell Microbiologists; Leishmania infantum IgG ELISA, NovaTec), three rK39-based immunochromatographic tests (rK39-ICTs) (Leishmania Dipstick Rapydtest, Apacor; On Site Leishmania IgG/IgM Combo Rapid Test, CTK Biotech; LEISHMANIA Strip quick Test, Cypress Diagnostic), one indirect immunofluorescent antibody test (IFAT) (Leishmania-Spot IF, BioMérieux), and one western blot (WB) (Leishmania WESTERN BLOT IgG, LDBio Diagnostics) for serodiagnosis of visceral leishmaniasis (VL). Serum samples from 27 VL patients living in northeastern Italy were analyzed, as well as the serum samples from 50 individuals in whom VL diagnosis was excluded. The WB and the IFAT had 96% sensitivity, followed by the ELISA (63% and 74%, respectively). The rK39-ICT exhibited the worst performance among the serological tests, with sensitivities ranging from 52% to 70%. By combining selected ELISA/ICT, the sensitivity of VL detection reached 89%. IFAT and WB outperformed ELISA and rK39-ICT by possessing optimal sensitivity, but their high cost and complexity of execution would not allow their employment as screening tests. In conclusion, the combination of easy-to-perform tests, such as ICT and ELISA, could improve sensitivity in the serodiagnosis of Mediterranean VL.

  • Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study)
    Michele Bartoletti, Maddalena Giannella, Luigia Scudeller, Sara Tedeschi, Matteo Rinaldi, Linda Bussini, Giacomo Fornaro, Renato Pascale, Livia Pancaldi, Zeno Pasquini,et al.

    Elsevier BV
    Abstract Objectives We aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19). Methods We performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from February 22 to April 3 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: SpO2<93% with 100% FiO2, respiratory rate (RR)>30bpm, or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, β-coefficients were used to develop a risk score. Trial Registration NCT04316949. Results We analyzed 1113 patients (644 derivation, 469 validation cohort). Mean (±standard deviation)age was 65.7(±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in derivation and validation cohort, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years [OR 2.74 (95%CI 1.66-4.50)], obesity [OR 4.62 (95%CI 2.78-7.70)], body temperature ≥38°C [OR 1.73 (95%CI 1.30-2.29)], RR ≥22bpm [OR 3.75 (95%CI 2.01-7.01)], lymphocytes ≤900/mm3 [OR 2.69 (95%CI 1.60-4.51)], creatinine ≥1 mg/dl [OR 2.38 (95%CI 1.59-3.56)], C-reactive protein ≥10mg/dl [OR 5.91 (95%CI 4.88-7.17)], and lactate dehydrogenase ≥350IU/L[OR 2.39 (95%CI 1.11-5.11)]. Assigning points to each variable an individual risk score (PREDI-CO score) was obtained. Area under receiver-operator curve (AUROC) was 0.89 (0.86-0.92). At score of >3, sensitivity, specificity, positive and negative predictive values were 71.6%(65-79%), 89.1% (86-92%), 74%(67-80%), and 89%(85-91%), respectively;. PREDI-CO score showed similar prognostic ability in the validation cohort: AUROC 0.85 (0.81-0.88). At score of >3, sensitivity, specificity, positive and negative predictive values were 80% (73-85%), 76 (70-81%), 69%(60-74%) and 85% (80-89%), respectively. Conclusion PREDI-CO score can be useful to allocate resources and prioritize treatments during COVID-19 pandemic.

  • Subcortical Myoclonus in Coronavirus Disease 2019: Comprehensive Evaluation of a Patient
    Lorenzo Muccioli, Francesca Rondelli, Lorenzo Ferri, Giada Rossini, Pietro Cortelli, and Maria Guarino

    Wiley
    A 58-year-old hypertensive man with a 1-week history of fever and cough presented to the emergency department with dyspnea. A nasopharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The patient was admitted to the intensive care unit after 1 week and placed on invasive mechanical ventilation as a result of respiratory distress. He was treated with hydroxychloroquine, tocilizumab, and remdesivir. Respiratory status quickly improved, thus he was extubated after 5 days, and oxygen therapy was progressively weaned off. Two days after discharge from the intensive care unit, he became markedly agitated. His mental status normalized in 48 hours; however, at this point he developed multifocal myoclonus elicited by action and tactile stimuli, predominant in the right proximal inferior limb muscles, preventing his ability to stand (Video SS1). Cognitive deficits were not observed. Electrolytes and renal and liver function tests were unremarkable. Cerebrospinal fluid (CSF) analysis, performed 8 days after myoclonus onset, demonstrated 5 leukocytes/μL, elevated protein levels (75 mg/dL) and CSF/serum albumin ratio (13.1), and negative SARS-CoV-2 reverse-transcription polymerase chain reaction. Cytokine analyses revealed interleukin-6 at 11.6 pg/mL in CSF (29.3 pg/mL in serum, reference < 5.9) and interleukin-8 at 38 pg/ mL in CSF (11 pg/mL in serum, reference < 70). A serologic panel of autoantibodies against neuronal intracellular and cell surface antigens was negative. Brain magnetic resonance imaging showed cerebral small-vessel disease of moderate severity. Electroencephalogram (EEG) was unremarkable. Polymyography confirmed the presence of multifocal positive myoclonus with a burst duration of 140 to 220 milliseconds. Back-averaging analysis did not show EEG timelocked discharges (Fig. 1). The patient was treated with clonazepam and levetiracetam, resulting in marked amelioration of the myoclonus within 5 days.

  • Encephalopathy in COVID-19 Presenting With Acute Aphasia Mimicking Stroke
    Umberto Pensato, Lorenzo Muccioli, Elena Pasini, Maria Tappatà, Lorenzo Ferri, Lilia Volpi, Laura Licchetta, Stella Battaglia, Giada Rossini, Isabella Bon,et al.

    Frontiers Media SA
    Introduction: Neurological manifestations are emerging as relatively frequent complications of corona virus disease 2019 (COVID-19), including stroke and encephalopathy. Clinical characteristics of the latter are heterogeneous and not yet fully elucidated, while the pathogenesis appears related to neuroinflammation in a subset of patients. Case: A middle-aged man presented with acute language disturbance at the emergency department. Examination revealed expressive aphasia, mild ideomotor slowing, and severe hypocapnic hypoxemia. Multimodal CT assessment and electroencephalogram (EEG) did not reveal any abnormalities. COVID-19 was diagnosed based on chest CT findings and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR (RT-PCR) on nasopharyngeal swab. The following day, neurological symptoms progressed to agitated delirium and respiratory status worsened, requiring admission to the ICU and mechanical ventilation. Brain MRI and cerebrospinal fluid (CSF) studies were unremarkable. RT-PCR for SARS-CoV-2 on CSF was negative. He received supportive treatment and intravenous low-dose steroids. His neurological and respiratory status resolved completely within 2 weeks. Conclusions: We report a patient with reversible COVID-19-related encephalopathy presenting as acute aphasia, mimicking stroke or status epilepticus, eventually evolving into delirium. Although large-vessel stroke is frequently encountered in COVID-19, our case suggests that focal neurological deficits may occur as the earliest feature of encephalopathy. Neurological status reversibility and the absence of abnormalities on brain MRI are consistent with a functional rather than a structural neuronal network impairment.

  • There is a role in detection of SARS-CoV-2 in conjunctiva and tears: A comprehensive review


  • Genetic and Functional Characterization of Toll-Like Receptor Responses in Immunocompetent Patients With CMV Mononucleosis
    Giada Frascaroli, Giada Rossini, Virginia Maltoni, Michele Bartoletti, Patrizia Ortolani, Sara Gredmark-Russ, Francesco Gelsomino, Alessandra Moroni, Silvia Silenzi, Gastone Castellani,et al.

    Frontiers Media SA
    Background: Human cytomegalovirus (CMV) modulates both innate and adaptive immune responses. However, limited data are available on the role of receptors of innate immunity, such as toll-like receptors (TLRs) in contributing to antiviral responses and inflammation. Objectives: The aim of this translational study was to characterize TLR responses in immunocompetent patients with primary and symptomatic CMV infection. Study Design: The study population consisted of 40 patients suffering from CMV mononucleosis and 124 blood donors included as controls. We evaluated the association between TLR2, 3, 4, 7 and 9 gene single nucleotide polymorphism (SNP) and susceptibility to symptomatic CMV infection in immunocompetent adults. Additionally, functional TLR-mediated cytokine responses in supernatants of short-term cultures of whole blood from patients with CMV mononucleosis and blood donors were evaluated. Results: TLR2 and TLR7/8 responses were altered in CMV infected patients as compared to healthy donors and were associated with the release of higher levels of the pro-inflammatory cytokines IL-6 and TNF-α, but not of the anti-inflammatory mediator IL-10. The analysis on the TLR SNPs indicated no difference between patients with CMV infection and the control group. Conclusions: No variation in the TLR2,3,4,7 and 9 genes was associated to the development of symptomatic CMV infection in immunocompetent adults. Nevertheless, TLR-mediated responses in CMV-infected patients appeared to be skewed toward a pro-inflammatory profile, which may contribute to the development of inflammatory symptoms during the CMV mononucleotic syndrome.

  • Kidney Biopsy Findings in a Critically Ill COVID-19 Patient With Dialysis-Dependent Acute Kidney Injury: A Case Against “SARS-CoV-2 Nephropathy”
    Giovanni Maria Rossi, Marco Delsante, Francesco Paolo Pilato, Letizia Gnetti, Liliana Gabrielli, Giada Rossini, Maria Carla Re, Giovanna Cenacchi, Paola Affanni, Maria Eugenia Colucci,et al.

    Elsevier BV
    Giovanni Maria Rossi, Marco Delsante, Francesco Paolo Pilato, Letizia Gnetti, Liliana Gabrielli, Giada Rossini, Maria Carla Re, Giovanna Cenacchi, Paola Affanni, Maria Eugenia Colucci, Edoardo Picetti, Sandra Rossi, Elisabetta Parenti, Caterina Maccari, Paolo Greco, Francesca Di Mario, Umberto Maggiore, Giuseppe Regolisti and Enrico Fiaccadori Renal Unit, University Hospital of Parma, Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy; Pathological Anatomy and Histology, University Hospital of Parma, Parma, Italy; Clinical Microbiology, University Hospital Sant’Orsola of Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University “Alma Mater” of Bologna, Bologna, Italy; Pathological Anatomy, Sector of Diagnostic and Subcellular Pathology, University Hospital Sant’Orsola of Bologna, Bologna, Italy; Hygiene and Public Health Laboratory, Department of Medicine and Surgery, University of Parma, Parma, Italy; and U.O 1st Anesthesia and Resuscitation, University Hospital of Parma, Parma, Italy


  • Detection of specific antibodies against toscana virus among blood donors in northeastern Italy and correlation with sand fly abundance in 2014
    Silvia Morini, Mattia Calzolari, Giada Rossini, Nadia Pascarelli, Andrea Porcellini, Vanda Randi, Maria Carla Re, Alessandro Albieri, Paolo Bonilauri, Romeo Bellini,et al.

    MDPI AG
    Toscana virus (TOSV) is a Phlebovirus transmitted by phlebotomine sand flies and is an important etiological agent of summer meningitis in the Mediterranean basin. Since TOSV infection is often asymptomatic, we evaluated the seroprevalence in blood donors (BDs) in the Bologna and Ferrara provinces (Northeastern Italy)—the areas with the highest and lowest numbers of TOSV neuroinvasive cases in the region, respectively. A total of 1208 serum samples from BDs were collected in April–June 2014 and evaluated for the presence of specific TOSV-IgG by ELISA. The IgG-reactive samples were confirmed by indirect immunofluorescence assay (IIF) and by microneutralization test (MN). Serum samples were defined as positive for anti-TOSV IgG when reactive by ELISA and by at least one second-level test; TOSV seroprevalence was 6.8% in the Bologna province, while no circulation of TOSV was detected in the Ferrara province. Sand fly abundance in 2014 was also estimated by a geographic information system using a generalized linear model applied to a series of explanatory variables. TOSV seroprevalence rate was strongly associated with the sand fly abundance index in each municipality, pointing out the strong association between sand fly abundance and human exposure to TOSV.

  • Culex torrentium: A potent vector for the transmission of west nile virus in central Europe
    Stephanie Jansen, Anna Heitmann, Renke Lühken, Mayke Leggewie, Michelle Helms, Marlis Badusche, Giada Rossini, Jonas Schmidt-Chanasit, and Egbert Tannich

    MDPI AG
    The continuous circulation of West Nile virus (WNV) in Central, South and East Europe and its recent detection in several dead birds and two horses in Germany highlights the need for information on WNV vector competence of mosquitoes from Central Europe. Therefore, three common Culex species (Culex pipiens biotype pipiens, Culex pipiens biotype molestus and Culex torrentium) from Germany were orally infected with WNV and kept at 18 °C, 21 °C, 24 °C or 27 °C for 14 or 21 days post infection (dpi). Thereafter viable WNV was present in the saliva in all tested taxa, but only at incubation temperatures of 24 °C or 27 °C and predominantly at the extended incubation period of 21 dpi. Highest transmission efficiency rates of 17 % (24 °C) and 24% (27 °C) were found for Cx. torrentium. Culex p. pipiens and Cx. p. molestus showed low transmission efficiencies with a maximum of only 3%. Consequently, temperatures above 21 °C support transmission of WNV, which matches the predominant distribution of human WNV cases around the Mediterranean Sea and in South-East Europe. Culex torrentium has been identified as a potent vector for WNV in Central and Northern Europe, which highlights the need for surveillance of mosquito-borne viruses north of the Alps.

  • Two cases of relapsed HIV-associated visceral leishmaniasis successfully treated with combination therapy
    Antonio Mastroianni, Paolo Gaibani, Giada Rossini, Caterina Vocale, Maria Carla Re, Gianfranco Ravaglia, Vittorio Sambri, and Stefania Varani

    Springer Science and Business Media LLC
    BackgroundThe management of visceral leishmaniasis (VL) in HIV-infected patients is often complex with patients experiencing higher mortality rates, more toxic side effects and a higher possibility of treatment failure and relapse than HIV-negative individuals with VL.Case presentationWe report on successful salvage therapy in two HIV-infected patients suffering with disseminated cutaneous and visceral leishmaniasis, recalcitrant to therapy with liposomal amphotericin B. After the employment of combination anti-leishmanial treatment, parasite genomes were not detectable up to the last follow up visit, 57 and 78 weeks after treatment onset, respectively. CD4+ lymphocyte counts fluctuated over time, but were generally higher than counts detected at treatment onset, which likely contributed to protection against VL relapse.ConclusionsResults achieved with the anti-leishmanial combination treatment were promising, but are based on only two patients. Future investigation is necessary to confirm the efficacy of this salvage therapy in sustaining the immunological response and control of VL.