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1.
Expert Rev Vaccines ; : 1-8, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1778823

ABSTRACT

BACKGROUND: Consolidated information on the effectiveness of COVID-19 booster vaccination in Europe are scarce. RESEARCH DESIGN AND METHODS: We assessed the effectiveness of a booster dose of an mRNA vaccine against any SARS-CoV-2 infection (symptomatic or asymptomatic) and severe COVID-19 (hospitalization or death) after over two months from administration among priority target groups (n = 18,524,568) during predominant circulation of the Delta variant in Italy (July-December 2021). RESULTS: Vaccine effectiveness (VE) against SARS-CoV-2 infection and, to a lesser extent, against severe COVID-19, among people ≥60 years and other high-risk groups (i.e. healthcare workers, residents in long-term-care facilities, and persons with comorbidities or immunocompromised), peaked in the time-interval 3-13 weeks (VE against infection = 67.2%, 95% confidence interval (CI): 62.5-71.3; VE against severe disease = 89.5%, 95% CI: 86.1-92.0) and then declined, waning 26 weeks after full primary vaccination (VE against infection = 12.2%, 95% CI: -4.7-26.4; VE against severe disease = 65.3%, 95% CI: 50.3-75.8). After 3-10 weeks from the administration of a booster dose, VE against infection and severe disease increased to 76.1% (95% CI: 70.4-80.7) and 93.0% (95% CI: 90.2-95.0), respectively. CONCLUSIONS: These results support the ongoing vaccination campaign in Italy, where the administration of a booster dose four months after completion of primary vaccination is recommended.

2.
J Community Health ; 2022 Mar 25.
Article in English | MEDLINE | ID: covidwho-1756842

ABSTRACT

This study describes a SARS-CoV-2 outbreak caused by the Delta (B.1.617.2) variant in a nursing home in Central Italy during October-November 2021. Trained interviewers collected data from residents, staff, and administration officers with an agreed informed consent procedure. Thirty-two (44.5%) out of 72 residents (median age 89 years) and six (26.1%) of 23 healthcare workers were found to be infected with SARS-CoV-2. Infections occurred more often among residents with a higher index of independence in daily living activities, suggesting an increased risk for those with more interactions. Twenty-five infected residents (78.1%) received the booster dose of mRNA anti-COVID-19 vaccine > 7 days before SARS-CoV-2 onset. Half of the infected residents had mild symptoms, and only three required hospitalisation, one of whom died from COVID-19 complications. The study underlines the effectiveness of a booster dose in providing a high protection against severe disease and hospitalisation even among vulnerable individuals infected with the Delta variant of concern.

3.
Annali dell'Istituto Superiore di Sanita ; 58(1):1-5, 2022.
Article in English | ProQuest Central | ID: covidwho-1738008

ABSTRACT

Introduction. Multiple variants of SARS-CoV-2, since the end of 2020 have emerged in many geographical areas and are currently under surveillance worldwide highlighting the continuing need for genomic monitoring to detect variants previously not yet identified. Methods. In this study, we used whole-genome sequencing (WGS) and phylogenetic analysis to investigate A.27 lineage SARS-CoV-2 from Sardinia, Italy. Results. The Italian A.27 lineage genomes from Sardinia appeared related in a clade with genomes from France. Among the key mutations identified in the spike protein, the N501Y and the L452R deserve attention as considered likely vaccine escape mutations. Additional mutations were also here reported. Conclusion. A combination of features could explain our data such as SARS-CoV-2 genetic variability, viral dynamics, the human genetic diversity of Sardinian populations, the island context probably subjected to different selective pressures. Molecular and genomic investigation is essential to promptly identify variants with specific mutations with potential impact on public health and vaccine formulation.

4.
Viruses ; 14(3)2022 02 25.
Article in English | MEDLINE | ID: covidwho-1737036

ABSTRACT

We performed next-generation sequencing (NGS), phylogenetic analysis, gene flows, and N- and O-glycosylation prediction on SARS-CoV-2 genomes collected from lab-confirmed cases from different Italian regions. To this end, a total of 111 SARS-CoV-2 genomes collected in Italy between 29 January and 27 March 2020 were investigated. The majority of the genomes belonged to lineage B.1, with some descendant lineages. The gene flow analysis showed that the spread occurred mainly from the north to the center and to the south of Italy, as confirmed by epidemiological data. The mean evolutionary rate estimated here was 8.731 × 10-4 (95% highest posterior density, HPD intervals 5.809 × 10-4 to 1.19 × 10-3), in line with values reported by other authors. The dated phylogeny suggested that SARS-CoV-2 lineage B.1 probably entered Italy between the end of January and early February 2020. Continuous molecular surveillance is needed to trace virus circulation and evolution.


Subject(s)
COVID-19 , Genome, Viral , COVID-19/epidemiology , Genomics , Humans , Phylogeny , SARS-CoV-2/genetics
5.
Clin Infect Dis ; 2022 Jan 21.
Article in English | MEDLINE | ID: covidwho-1722269

ABSTRACT

We identified the first case in Italy of SARS-CoV-2 B.1.1.529 variant by whole genome sequencing in an Italian subject travelling from Mozambique. Specific mutation profiles deserve further investigations to clarify potential effects on vaccination efficacy. This case highlights the crucial role of rapid and continuous surveillance of SARS-CoV-2 variant circulation.

6.
Vaccine ; 40(15): 2324-2330, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1703831

ABSTRACT

The COVID-19 pandemic has changed routine care practice for older persons, especially in those with frailty living in long term care (LTC) facilities. Due to the high mortality rates of Nursing home (NH) residents during the first wave of the COVID-19 pandemic, priority for COVID-19 vaccinations was given to this vulnerable population. However, the safety and efficacy of such vaccines in older frail elders remains questionable due to the fact that initial randomized clinical trials (RCTs) for such vaccines did not include this population. This type of discrimination in patient participation in RCTs continues and has been recognized in the literature. Nevertheless, in the context of a worldwide emergency, COVID-19 vaccination in older persons living in LTC facilities may provide a solid basis to protect against negative outcomes, such as COVID-19 infection and death. In this report, we present the protocol of the GeroCovid Vax study, an Italian study that began in February 2021 which is aimed at investigating the safety and efficacy of the anti-SARS-CoV-2 vaccinations in older persons living in LTCs. This protocol specially aims to continuously and closely monitor events related to- and following- the anti-SARS-CoV-2 vaccination in elderly living in LTC facilities. In this report, we will provide information related to the study protocol and describe baseline characteristics of the sample.


Subject(s)
COVID-19 , Frailty , Aged , Aged, 80 and over , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Long-Term Care , SARS-CoV-2
7.
Euro Surveill ; 27(5)2022 02.
Article in English | MEDLINE | ID: covidwho-1700766

ABSTRACT

BackgroundSeveral SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains.AimWe aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility.MethodsWe conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains.ResultsThe Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55-1.57 times the level of historical lineages (95% CrI: 1.45-1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03-1.23) with complete immune evasion to 1.39 (95% CrI: 1.26-1.56) for complete cross-protection.ConclusionWe assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Italy/epidemiology , Models, Theoretical
8.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327217

ABSTRACT

The SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021. Data from three genomic surveys conducted in Italy between December 2021 and January 2022 suggest that Omicron became dominant in less than one month (prevalence on January 3: 78.6%-83.8%) with a doubling time of 2.7-3.1 days. The mean net reproduction number rose from about 1.15 in absence of Omicron to a peak of 1.83 for symptomatic cases and 1.33 for hospitalized cases, while it remained stable for critical cases.

9.
Children (Basel) ; 9(2)2022 Feb 12.
Article in English | MEDLINE | ID: covidwho-1686623

ABSTRACT

Data on the effective burden of the SARS-CoV-2 pandemic in the pediatric population are limited. We aimed at assessing the prevalence of SARS-CoV-2 IgG antibodies in children at three subsequent time-points. The study was conducted between January 2021 and July 2021 among children referring to the Research Institute for Maternal and Child Health "Burlo Garofolo" in Trieste, a referral regional hospital in Friuli Venezia Giulia, Italy. A multivariate analysis was conducted to assess factors independently associated with seroconversion. A total of 594 children were included. Anti-SARS-CoV-2 trimeric Spike protein IgG antibodies were found in 32 (15.4%) children tested in April-May and in 20 (11.8%) in June-July 2021, compared with 24 (11.1%) of those tested in January-February 2021 (p = 0.37, Armitage exact test for trend over time p = 0.76). A subgroup analysis and a multivariate logistic regression analysis were performed considering sociodemographic, clinical, and historical variables. Three categories of children showed statistically significant increased odds of positive anti-SARS-CoV-2 IgG antibodies: children previously positive to a nasopharyngeal swab (AdjOR 15.41, 95%CI 3.44-69.04, p < 0.001), cohabitant with a person with an history of a previous positive nasopharyngeal swab (AdjOR 9.95, 95%CI 5.35-18.52, p < 0.001), and children with a foreign citizenship (AdjOR 2.4, 95%CI 1.05-5.70, p = 0.002). The study suggests that seroprevalence studies may be of limited help in estimating the prevalence of the COVID-19 pandemic in children. Further studies are needed to identify other markers of previous SARS-CoV-2 infection in children, such as CD4+ T cells or memory B-cells.

10.
Ann Ist Super Sanita ; 57(4): 265-271, 2021.
Article in English | MEDLINE | ID: covidwho-1614145

ABSTRACT

INTRODUCTION: To evaluate the decline of antibodies induced by SARS-CoV-2 infection, the individuals resident in 5 municipalities of the Autonomous Province of Trento, Northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) in May 2020, were tested four months later. METHODS: Anti-SARS-CoV-2 NC antibodies were detected using the Abbott SARS-CoV-2 IgG assay. Samples that gave a negative result were re-tested using the Liaison SARS-CoV-2 IgG assay to assess anti-spike (S) S1/S2 antibodies. The fifty-percent tissue culture infective dose (TCID50) neutralizing assay was performed on a subgroup of formerly positive sera. Statistical analysis was performed by STATA version 16.1 (STATA Corp., College Station, Texas, USA). RESULTS: Overall, 480 out of 1159 participants became seronegative for anti-NC IgG antibodies. Age above 70 years and cough were associated with persistent anti-NC IgG levels. Most anti-NC IgG negative sera were positive for anti-S IgG (77.9%). The neutralization assay showed high concordance with anti-S antibodies positivity. CONCLUSION: In conclusion, a decline of anti-NC IgG values was recorded four months after the first evaluation. A high proportion of anti-NC seronegative individuals were positive for anti-spike IgG antibodies, which appear to persist longer and to better correlate with neutralization activity.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Aged , Antibodies, Viral , COVID-19 Serological Testing , Humans , SARS-CoV-2
11.
Nat Commun ; 12(1): 7272, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1574987

ABSTRACT

COVID-19 vaccination is allowing a progressive release of restrictions worldwide. Using a mathematical model, we assess the impact of vaccination in Italy since December 27, 2020 and evaluate prospects for societal reopening after emergence of the Delta variant. We estimate that by June 30, 2021, COVID-19 vaccination allowed the resumption of about half of pre-pandemic social contacts. In absence of vaccination, the same number of cases is obtained by resuming only about one third of pre-pandemic contacts, with about 12,100 (95% CI: 6,600-21,000) extra deaths (+27%; 95% CI: 15-47%). Vaccination offset the effect of the Delta variant in summer 2021. The future epidemic trend is surrounded by substantial uncertainty. Should a pediatric vaccine (for ages 5 and older) be licensed and a coverage >90% be achieved in all age classes, a return to pre-pandemic society could be envisioned. Increasing vaccination coverage will allow further reopening even in absence of a pediatric vaccine.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Vaccination , Adolescent , Child , Child, Preschool , Humans , Italy , Models, Theoretical , Pandemics , SARS-CoV-2 , Vaccination Coverage
12.
J Photochem Photobiol ; 8: 100082, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1568867

ABSTRACT

Difficulty in controlling SARS-CoV-2 transmission made the ability to inactivate viruses in aerosols and fomites to be an important and attractive risk reduction measure. Evidence that light frequencies have the ability to inhibit microorganisms has already been reported by many studies which, however, focused on ultraviolet (UV) wavelengths, which are known to induce potential injury in humans. In the present study, the effect on suspensions of SARS-CoV-2 of a Light Emitting Diode (LED) device capable of radiating frequencies in the non-hazardous visible light spectrum (VIS) was investigated. In order to evaluate the efficiency of viral inactivation, plaque assay and western blot of viral proteins were performed. The observed results showed a significant reduction in infectious particles that had been exposed to the LED irradiation of visible light. Furthermore, the analysis of the intracellular expression of viral proteins confirmed the inactivating effect of this irradiation technology. This in vitro study revealed for the first time the inactivation of SARS-CoV-2 through LED irradiation with multiple wavelengths of the visible spectrum. However additional and more in-depth studies can aim to demonstrate the data obtained during these experiments in different matrices, in mutable environmental conditions and on other respiratory viruses such as the influenza virus. The type of LED technology can decisively contribute on reducing virus transmission through the continuous sanitation of common environments without risks for humans and animals.

13.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295429

ABSTRACT

Vaccination campaigns against COVID-19 are allowing the progressive release of physical distancing restrictions in many countries. However, the global spread of the highly transmissible Delta variant has likely suppressed the residual chances of SARS-CoV-2 elimination through herd immunity alone. Here we assess the impact of the vaccination program in Italy since its start on December 27, 2020 and evaluate possible prospects for reopening the society while at the same time keeping COVID-19 under control. To this aim, we propose a mathematical modeling framework where levels of social activity are adjusted to match the time-series of the net reproduction number as estimated from surveillance data. We compared the estimated level of social contacts, number of deaths, and transmission potential with those of a counterfactual scenario where the same epidemic trajectory is obtained in absence of vaccination. We then evaluate the prospective impact of different scenarios of vaccination coverage and different social activity levels on SARS-CoV-2 reproduction number. We estimate that by June 30, 2021, the COVID-19 vaccination program allowed the resumption of about half the social contacts that were recorded in pre-pandemic times;in absence of vaccination, only about one third could have been resumed to obtain the same number of cases, with the added cost of about 12,100 (95%CI: 6,600-21,000) extra deaths (+27%;95%CI: 15-47%) between December 27, 2020 and June 30, 2021. We show that the negative effect of the Delta variant diffusion in July was entirely offset by vaccination in the month of July and August 2021. Finally, we estimate that a complete return to the pre-pandemic life could be safely attained only if >90%, including children from 5 years on, will be vaccinated using mRNA vaccines developed in 2020. In any case, increasing the vaccination coverage will allow further margins for societal reopening even in absence of a pediatric vaccine. These results may support the definition of vaccination targets for countries that have already achieved a broad population coverage.

14.
Pathog Glob Health ; : 1-3, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1541473

ABSTRACT

We investigated the impact of social distancing measures, used to contain or mitigate SARS-CoV-2 spread, on the transmission of invasive meningococcal disease (IMD) in Italy. To this end, the temporal correlation between the implementation of lockdown measures in 2020 and IMD incidence was evaluated. A dramatic decline of IMD incidence was observed, suggesting that the measures applied to contain SARS-CoV-2 in Italy affected other infectious diseases transmitted through direct contact and droplets, at least in the early phase of the COVID-19 pandemic.

15.
Biomedicines ; 9(11)2021 Nov 19.
Article in English | MEDLINE | ID: covidwho-1523868

ABSTRACT

Polyphenols have been widely studied for their antiviral effect against respiratory virus infections. Among these, resveratrol (RV) has been demonstrated to inhibit influenza virus replication and more recently, it has been tested together with pterostilbene against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present work, we evaluated the antiviral activity of polydatin, an RV precursor, and a mixture of polyphenols and other micronutrients, named A5+, against influenza virus and SARS-CoV-2 infections. To this end, we infected Vero E6 cells and analyzed the replication of both respiratory viruses in terms of viral proteins synthesis and viral titration. We demonstrated that A5+ showed a higher efficacy in inhibiting both influenza virus and SARS-CoV-2 infections compared to polydatin treatment alone. Indeed, post infection treatment significantly decreased viral proteins expression and viral release, probably by interfering with any step of virus replicative cycle. Intriguingly, A5+ treatment strongly reduced IL-6 cytokine production in influenza virus-infected cells, suggesting its potential anti-inflammatory properties during the infection. Overall, these results demonstrate the synergic and innovative antiviral efficacy of A5+ mixture, although further studies are needed to clarify the mechanisms underlying its inhibitory effect.

16.
Diagn Microbiol Infect Dis ; 102(1): 115586, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1505932

ABSTRACT

We determined the kinetics of anti-SARS-CoV-2 antibody response in fifteen hospitalized COVID-19 patients. Patients were divided into mild/moderate (mild, n = 1; moderate, n = 4) or severe (n = 10) and virus-specific anti-Nucleocapsid IgM, anti-Spike IgG and anti-Spike IgA were measured in serial serum samples collected 0 to 15 days after hospital admission. Surrogate neutralization assays were performed by testing inhibition of ACE-2 binding to Spike. In 3 patients (2 severe and 1 moderate case), serum antibodies and T-cell memory were monitored 6 months after baseline. Although IgM response tended to appear first, patients affected by less severe disease were more prone to an early IgG/IgA response. Neutralization of Spike binding to ACE2 correlated with anti-Spike IgG and IgA. IgG and IgA antibody response persisted at the 6 months follow-up. A recall T-cell response to the Spike antigen was observed in 2 out of 3 patients, not related to disease severity.


Subject(s)
Antibodies, Viral/blood , COVID-19/etiology , Immunoglobulin A/blood , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/immunology , Female , Hospitalization , Humans , Immunoglobulin M/blood , Immunologic Memory , Male , Middle Aged , Neutralization Tests , Patient Acuity , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , T-Lymphocytes/immunology
17.
Clin Infect Dis ; 73(9): e3019-e3026, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501050

ABSTRACT

BACKGROUND: Recent findings indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the cerebrospinal fluid (CSF) correlates of SARS-CoV-2 encephalitis. METHODS: Patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC), and healthy controls (HC) underwent an extended panel of CSF neuronal (neurofilament light chain [NfL], T-tau), glial (glial fibrillary acidic protein [GFAP], soluble triggering receptor expressed on myeloid cells 2 [sTREM2], chitinase-3-like protein 1 [YKL-40]) and inflammatory biomarkers (interleukin [IL]-1ß, IL-6, Il-8, tumor necrosis factor [TNF] α, CXCL-13, and ß2-microglobulin). RESULTS: Thirteen COV-Enc, 21 ENC, and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- α, and ß2-microglobulin and glial markers (GFAP, sTREM2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-tau were abnormal only in severe cases. CONCLUSIONS: SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2-related encephalitis.


Subject(s)
COVID-19 , Encephalitis , Cytokine Release Syndrome , Glial Fibrillary Acidic Protein , Humans , SARS-CoV-2
18.
Infect Genet Evol ; 96: 105108, 2021 12.
Article in English | MEDLINE | ID: covidwho-1458605

ABSTRACT

A high-quality dataset of 3289 complete SARS-CoV-2 genomes collected in Europe and European Economic Area (EAA) in the early phase of the first wave of the pandemic was analyzed. Among all single nucleotide mutations, 41 had a frequency ≥ 1%, and the phylogenetic analysis showed at least 6 clusters with a specific mutational profile. These clusters were differentially distributed in the EU/EEA, showing a statistically significant association with the geographic origin. The analysis highlighted that the mutations C14408T and C14805T played an important role in clusters selection and further virus spread. Moreover, the molecular analysis suggests that the SARS-CoV-2 strain responsible for the first Italian confirmed COVID-19 case was already circulating outside the country.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Mutation , Phylogeny , SARS-CoV-2/genetics , Europe/epidemiology , Genome, Viral , Humans , Italy/epidemiology , Mutation Rate
19.
Diagn Microbiol Infect Dis ; 105(1): 115539, 2021 Sep 12.
Article in English | MEDLINE | ID: covidwho-1401414

ABSTRACT

We determined the kinetics of anti-SARS-CoV-2 antibody response in fifteen hospitalized COVID-19 patients. Patients were divided into mild/moderate (mild, n = 1; moderate, n = 4) or severe (n = 10) and virus-specific anti-Nucleocapsid IgM, anti-Spike IgG and anti-Spike IgA were measured in serial serum samples collected 0 to 15 days after hospital admission. Surrogate neutralization assays were performed by testing inhibition of ACE-2 binding to Spike. In 3 patients (2 severe and 1 moderate case), serum antibodies and T-cell memory were monitored 6 months after baseline. Although IgM response tended to appear first, patients affected by less severe disease were more prone to an early IgG/IgA response. Neutralization of Spike binding to ACE2 correlated with anti-Spike IgG and IgA. IgG and IgA antibody response persisted at the 6 months follow-up. A recall T-cell response to the Spike antigen was observed in 2 out of 3 patients, not related to disease severity.

20.
PLoS Pathog ; 17(9): e1009878, 2021 09.
Article in English | MEDLINE | ID: covidwho-1394563

ABSTRACT

SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.


Subject(s)
COVID-19/immunology , Dendritic Cells/classification , Interferon Type I/metabolism , SARS-CoV-2/immunology , Adult , Aged, 80 and over , Asymptomatic Infections , Cell Line, Tumor , Dendritic Cells/immunology , Dendritic Cells/virology , Epithelial Cells/cytology , Female , Hospitalization , Humans , Interferon Type I/immunology , Lung/cytology , Male , Middle Aged , Neuropilin-1/metabolism , Phenotype , Severity of Illness Index , Toll-Like Receptor 7/metabolism
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