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1.
Front Immunol ; 13: 968991, 2022.
Article in English | MEDLINE | ID: covidwho-2022753

ABSTRACT

Background: SARS-CoV-2 induces a spectrum of clinical conditions ranging from asymptomatic infection to life threatening severe disease. Host microRNAs have been involved in the cytokine storm driven by SARS-CoV-2 infection and proposed as candidate biomarkers for COVID-19. Methods: To discover signatures of circulating miRNAs associated with COVID-19, disease severity and mortality, small RNA-sequencing was performed on serum samples collected from 89 COVID-19 patients (34 severe, 29 moderate, 26 mild) at hospital admission and from 45 healthy controls (HC). To search for possible sources of miRNAs, investigation of differentially expressed (DE) miRNAs in relevant human cell types in vitro. Results: COVID-19 patients showed upregulation of miRNAs associated with lung disease, vascular damage and inflammation and downregulation of miRNAs that inhibit pro-inflammatory cytokines and chemokines, angiogenesis, and stress response. Compared with mild/moderate disease, patients with severe COVID-19 had a miRNA signature indicating a profound impairment of innate and adaptive immune responses, inflammation, lung fibrosis and heart failure. A subset of the DE miRNAs predicted mortality. In particular, a combination of high serum miR-22-3p and miR-21-5p, which target antiviral response genes, and low miR-224-5p and miR-155-5p, targeting pro-inflammatory factors, discriminated severe from mild/moderate COVID-19 (AUROC 0.88, 95% CI 0.80-0.95, p<0.0001), while high leukocyte count and low levels of miR-1-3p, miR-23b-3p, miR-141-3p, miR-155-5p and miR-4433b-5p predicted mortality with high sensitivity and specificity (AUROC 0.95, 95% CI 0.89-1.00, p<0.0001). In vitro experiments showed that some of the DE miRNAs were modulated directly by SARS-CoV-2 infection in permissive lung epithelial cells. Conclusions: We discovered circulating miRNAs associated with COVID-19 severity and mortality. The identified DE miRNAs provided clues on COVID-19 pathogenesis, highlighting signatures of impaired interferon and antiviral responses, inflammation, organ damage and cardiovascular failure as associated with severe disease and death.


Subject(s)
COVID-19 , Circulating MicroRNA , MicroRNAs , Antiviral Agents , Humans , Inflammation , SARS-CoV-2 , Severity of Illness Index
3.
J Travel Med ; 29(2)2022 03 21.
Article in English | MEDLINE | ID: covidwho-1672228

ABSTRACT

BACKGROUND: Non-immune international travellers are at risk of acquiring hepatitis A. Although hepatitis A vaccination is recommended for unvaccinated travellers to high or intermediate hepatitis A virus endemicity, compliance with this recommendation is not universal.The main objective was to describe the demographic and travel characteristics of international travellers infected with hepatitis A during travel. METHODS: Available data on travellers with confirmed (positive molecular test) or probable (symptomatic individuals with a single positive IgM test) hepatitis A diagnosed during and after travel from January 2008 to December 2020 were obtained from the GeoSentinel Surveillance Network database. We analysed demographic and travel characteristics of infected travellers. RESULTS: Among 254 travellers with hepatitis A (185 confirmed and 69 probable), the median age was 28 years (interquartile range: 19-40), 150 (59%) were male, and among 54 travellers with information available, 53 (98%) were unvaccinated. The most common reasons for travel included tourism (n = 120; 47%) and visiting friends or relatives (VFR; n = 72; 28%). About two-thirds of VFR travellers with hepatitis A (n = 50; 69%) were younger than 20 years old. Hepatitis A was acquired most frequently in South-Central Asia (n = 63; 25%) and sub-Saharan Africa (n = 61; 24%), but 16 travellers (6%) acquired hepatitis A in regions with low endemicity including Western Europe (n = 7; 3%), the Caribbean (n = 6; 2%) and North America (n = 3; 1%). Median duration from illness onset to GeoSentinel site presentation was ~7 days (interquartile range : 4-14 days). Among 88 travellers with information available, 59% were hospitalized. CONCLUSIONS: Despite availability of highly effective vaccines, travellers still acquire hepatitis A, even when traveling to low-endemicity destinations. Providing pre-departure hepatitis A vaccine to susceptible travellers is crucial to reducing travel-associated hepatitis A and should be offered to all travellers as part of the pre-travel consultation, regardless of destination.


Subject(s)
Hepatitis A , Adult , Europe/epidemiology , Hepatitis A/epidemiology , Hepatitis A/prevention & control , Hepatitis A Vaccines , Humans , Male , Travel , Vaccination , Young Adult
6.
Medicina (Kaunas) ; 57(10)2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1444270

ABSTRACT

Background and Objectives: Studies have shown a lower prevalence of anti-SARS-CoV-2 antibodies in patients with inflammatory bowel disease (IBD), including amongst those receiving biological therapy. Aims were to determine the seroprevalence of anti-SARS-CoV-2 antibodies in IBD patients and to assess any association between seropositivity and IBD characteristics. Materials and Methods: Serum from adult IBD patients was prospectively collected between December 2020 and January 2021 and analyzed for anti-SARS-CoV-2 antibodies. Information about IBD characteristics and SARS-CoV-2 exposure risk factors was collected and analyzed. Serum from non-IBD healthcare workers formed the control group. Results: 311 IBD patients on biologics and 75 on mesalazine were enrolled. Ulcerative colitis (UC) extension (p < 0.001), Crohn's disease (CD) phenotype (p = 0.009) and use of concomitant corticosteroids (p < 0.001) were significantly different between the two IBD groups. Overall seroprevalence among IBD patients was 10.4%. The control group showed a prevalence of 13.0%, not significantly different to that of IBD patients (p = 0.145). Only a close contact with SARS-CoV-2 positive individuals and the use of non-FFP2 masks were independently associated with a higher likelihood of seropositivity amongst IBD patients. Conclusion: In IBD patients, the prevalence of anti-SARS-CoV-2 antibodies is not determined by their ongoing treatment. Disease-related characteristics are not associated with a greater risk of antibody seropositivity.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Antibodies, Viral , Humans , Inflammatory Bowel Diseases/epidemiology , Italy/epidemiology , Pandemics , SARS-CoV-2 , Seroepidemiologic Studies
7.
J Travel Med ; 28(8)2021 12 29.
Article in English | MEDLINE | ID: covidwho-1364814

ABSTRACT

BACKGROUND: In August 2020, in the context of COVID-19 pandemics, an autochthonous dengue outbreak was identified for the first time in Italy. METHODS: Following the reporting of the index case of autochthonous dengue, epidemiological investigation, vector control and substances of human origin safety measures were immediately activated, according to the national arbovirus surveillance plan. Dengue cases were followed-up with weekly visits and laboratory tests until recovery and clearance of viral RNA from blood. RESULTS: The primary dengue case was identified in a young woman, who developed fever after returning from Indonesia to northern Italy, on 27 July 2020. She spent the mandatory quarantine for COVID-19 at home with relatives, six of whom developed dengue within two weeks. Epidemiological investigation identified further five autochthonous dengue cases among people who lived or stayed near the residence of the primary case. The last case of the outbreak developed fever on 29 September 2020. Dengue cases had a mild febrile illness, except one with persistent asthenia and myalgia. DENV-1 RNA was detected in blood and/or urine in all autochthonous cases, up to 35 days after fever onset. All cases developed IgM and IgG antibodies which cross-reacted with West Nile virus (WNV) and other flaviviruses. Sequencing of the full viral genome from blood samples showed over 99% nucleotide identity with DENV-1 strains isolated in China in 2014-2015; phylogenetic analysis classified the virus within Genotype I. Entomological site inspection identified a high density of Aedes albopictus mosquitoes, which conceivably sustained local DENV-1 transmission. Aedes koreicus mosquitoes were also collected in the site. CONCLUSIONS: Areas in Europe with high density of Aedes mosquitoes should be considered at risk for dengue transmission. The presence of endemic flaviviruses, such as WNV, might pose problems in the laboratory diagnosis.


Subject(s)
Aedes , COVID-19 , Dengue Virus , Dengue , Animals , Dengue/epidemiology , Dengue Virus/genetics , Disease Outbreaks , Female , Humans , Italy/epidemiology , Mosquito Vectors , Phylogeny , SARS-CoV-2
8.
Clin Microbiol Infect ; 27(12): 1845-1850, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1330709

ABSTRACT

OBJECTIVES: To assess the antibody response to BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers (HCW), comparing individuals with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and SARS-CoV-2-naive individuals. METHODS: HCW were tested at T0 (day of first dose), T1 (day of second dose) and T2 (2-3 weeks after second dose) for IgG anti-nucleocapsid protein, IgM anti-spike protein and IgG anti-receptor binding domain (IgG-RBD-S). The antibody response was compared between four main groups: group A, individuals with previous infection and positive antibodies at baseline; group B, individuals with the same history but negative antibodies; group C, individuals with no infection history but positive antibodies; group D, naive individuals. Repeated measures analysis was used to compare results over time-points. RESULTS: A total of 1935 HCW were included. Median IgG-RBD-S titre was significantly higher for group A (232 individuals) than for group B (56 individuals) both at T1 (A: 22 763 AU/mL, interquartile range (IQR) 14 222-37 204 AU/mL; B: 1373 AU/mL, IQR 783-3078 AU/mL, p 0.0003) and T2 (A: 30 765 AU/mL, IQR 19 841-42 813 AU/mL; B: 13 171 AU/mL, IQR 2324-22 688 AU/mL, p 0.0038) and for group D (1563 individuals; 796 AU/mL, IQR 379-1510 AU/mL at T1; 15 494 AU/mL, IQR 9122-23 916 AU/mL at T2, p < 0.0001 for both time-points). T1 values of group A were also significantly higher than T2 values of group D (p < 0.0001). Presence of symptoms, younger age and being female were associated with stronger antibody response. HCW infected in March showed a significantly stronger response (T1: 35 324 AU/mL, IQR 22 003-44 531 AU/mL; T2: 37 648 AU/mL, IQR 27 088-50 451 AU/mL) than those infected in November (T1: 18 499 AU/mL, IQR 11 492-27 283 AU/mL; T2: 23 210 AU/mL, IQR 18 074-36 086 AU/mL, p < 0.0001 for both time-points. CONCLUSIONS: Individuals with past SARS-CoV-2 infection had a strong antibody response after one single vaccine shot. A single dose might be sufficient for this group, regardless of the time elapsed since infection; however, the clinical correlation with antibody response needs to be studied.


Subject(s)
Antibodies, Viral/blood , Antibody Formation , COVID-19 , COVID-19/prevention & control , Health Personnel , Humans , Immunoglobulin G/blood , Prospective Studies , RNA, Messenger
9.
Viruses ; 13(3)2021 03 05.
Article in English | MEDLINE | ID: covidwho-1167750

ABSTRACT

Although antibody levels progressively decrease following SARS-CoV-2 infection, the immune memory persists for months. Thus, individuals who naturally contracted SARS-CoV-2 are expected to develop a more rapid and sustained response to COVID-19 vaccines than naïve individuals. In this study, we analyzed the dynamics of the antibody response to the BNT162b2 mRNA COVID-19 vaccine in six healthcare workers who contracted SARS-CoV-2 in March 2020, in comparison to nine control subjects without a previous infection. The vaccine was well tolerated by both groups, with no significant difference in the frequency of vaccine-associated side effects, with the exception of local pain, which was more common in previously infected subjects. Overall, the titers of neutralizing antibodies were markedly higher in response to the vaccine than after natural infection. In all subjects with pre-existing immunity, a rapid increase in anti-spike receptor-binding domain (RBD) IgG antibodies and neutralizing antibody titers was observed one week after the first dose, which seemed to act as a booster. Notably, in previously infected individuals, neutralizing antibody titers 7 days after the first vaccine dose were not significantly different from those observed in naïve subjects 7 days after the second vaccine dose. These results suggest that, in previously infected people, a single dose of the vaccine might be sufficient to induce an effective response.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , RNA, Messenger/immunology , RNA, Viral/immunology , SARS-CoV-2/immunology , Adult , Antibody Formation , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/genetics , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , RNA, Messenger/administration & dosage , RNA, Messenger/genetics , RNA, Viral/administration & dosage , RNA, Viral/genetics , SARS-CoV-2/genetics
11.
Vaccines (Basel) ; 9(1)2021 Jan 11.
Article in English | MEDLINE | ID: covidwho-1022025

ABSTRACT

A workflow for rapid SARS-CoV-2 epitope discovery on peptide microarrays is herein reported. The process started with a proteome-wide screening of immunoreactivity based on the use of a high-density microarray followed by a refinement and validation phase on a restricted panel of probes using microarrays with tailored peptide immobilization through a click-based strategy. Progressively larger, independent cohorts of Covid-19 positive sera were tested in the refinement processes, leading to the identification of immunodominant regions on SARS-CoV-2 spike (S), nucleocapsid (N) protein and Orf1ab polyprotein. A summary study testing 50 serum samples highlighted an epitope of the N protein (region 155-71) providing good diagnostic performance in discriminating Covid-19 positive vs. healthy individuals. Using this epitope, 92% sensitivity and 100% specificity were reached for IgG detection in Covid-19 samples, and no cross-reactivity with common cold coronaviruses was detected. Likewise, IgM immunoreactivity in samples collected within the first month after symptoms onset showed discrimination ability. Overall, epitope 155-171 from N protein represents a promising candidate for further development and rapid implementation in serological tests.

12.
Euro Surveill ; 25(36)2020 09.
Article in English | MEDLINE | ID: covidwho-976158

ABSTRACT

In August 2020, during the coronavirus disease (COVID-19) pandemic, five locally acquired cases of dengue virus type 1 were detected in a family cluster in Vicenza Province, North-East Italy where Aedes albopictus mosquitoes are endemic. The primary case was an importation from West Sumatra, Indonesia. This is the first outbreak of autochthonous dengue reported in Italy. During the COVID-19 pandemic, screening of febrile travelers from endemic countries is crucial in areas where competent vectors are present.


Subject(s)
Dengue Virus/isolation & purification , Dengue/diagnosis , Travel , Adult , Child, Preschool , Dengue/epidemiology , Dengue/immunology , Dengue/virology , Dengue Virus/genetics , Disease Outbreaks , Disease Transmission, Infectious , Female , Fever/etiology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Indonesia , Italy/epidemiology , Male , Middle Aged , RNA, Viral/blood , Reverse Transcriptase Polymerase Chain Reaction
13.
Clin Microbiol Infect ; 27(1): 131.e1-131.e3, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-845648

ABSTRACT

OBJECTIVES: In Italy the burden of patients with coronavirus disease 2019 (COVID-19) gradually decreased from March to the end of May. In this work we aimed to evaluate a possible association between the severity of clinical manifestations and viral load over time during the epidemiological transition from high-to low-transmission settings. METHODS: We reviewed the cases of COVID-19 diagnosed at the emergency room of our hospital, retrieving the proportion of patients admitted to the intensive care unit. A raw estimation of the viral load was done evaluating the Ct (cycle threshold) trend obtained from our diagnostic reverse transcriptase real-time PCR test. RESULTS: The proportion of patients requiring intensive care significantly decreased from 6.7% (19/281) in March to 1.1% (1/86) in April, and to none in May (Fisher's test p 0.0067). As for viral load, we observed a trend of Ct increasing from a median value of 24 (IQR 19-29) to 34 (IQR 29-37) between March and May, with a statistically significant difference between March and April (pairwise Wilcoxon test with stepdown Bonferroni adjustment for multiple testing, p 0.0003). CONCLUSIONS: We observed a reduction over time in the proportion of patients with COVID-19 requiring intensive care, along with decreasing median values of viral load. As the epidemiological context changes from high-to low-transmission settings, people are presumably exposed to a lower viral load which has been previously associated with less severe clinical manifestations.


Subject(s)
COVID-19/epidemiology , COVID-19/physiopathology , Pandemics , SARS-CoV-2/genetics , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/transmission , COVID-19 Testing , Emergency Service, Hospital , Female , Hospitals , Humans , Intensive Care Units , Italy/epidemiology , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/pathogenicity , Severity of Illness Index , Viral Load
14.
Diagnostics (Basel) ; 10(9)2020 Sep 03.
Article in English | MEDLINE | ID: covidwho-742756

ABSTRACT

BACKGROUND: We assessed the sensitivity, specificity and positive and negative predictive value (PPV and NPV) of molecular and serological tests for the diagnosis of SARS-CoV-2 infection. METHODS: A total of 346 patients were enrolled in the emergency room. We evaluated three Reverse Transcriptase-real time PCRs (RT-PCRs) including six different gene targets, five serologic rapid diagnostic tests (RDT) and one ELISA. The final classification of infected/non-infected patients was performed using Latent Class Analysis combined with clinical re-assessment of incongruous cases. RESULTS: Out of these, 24.6% of patients were classified as infected. The molecular test RQ-SARS-nCoV-2 showed the highest performance with 91.8% sensitivity, 100% specificity, 100.0% PPV and 97.4% NPV respectively. Considering the single gene targets, S and RdRp of RQ-SARS-nCoV-2 had the highest sensitivity (94.1%). The in-house RdRp presented the lowest sensitivity (62.4%). The specificity ranged from 99.2% for in-house RdRp and N2 to 95.0% for E. The PPV ranged from 97.1% of N2 to 85.4% of E and the NPV from 98.1% of S to 89.0% of in-house RdRp. All serological tests had < 50% sensitivity and low PPV and NPV. VivaDiag IgM (RDT) had 98.5% specificity, with 84.0% PPV, but 24.7% sensitivity. CONCLUSION: Molecular tests for SARS-CoV-2 infection showed excellent specificity, but significant differences in sensitivity. Serological tests have limited utility in a clinical context.

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