Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospital during COVID-19 pandemic in Italy

Aims Epidemiological evidence suggests that anti-inflammatory and immuno-modulatory properties of statins may reduce the risk of infections and infection-related complications. In this observational multi-centre study, we aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality. Methods and results Consecutive patients hospitalized for COVID-19 were considered and enrolled in four tertiary referral hospitals (Luigi Sacco Hospital, Milan;Policlinico Umberto I Hospital, Rome;Spedali Civili Hospital, Brescia;Humanitas Gavazzeni Hospital;Bergamo) From 23 February 2020 to 31 March 2020, in-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Among 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 [NEWS 4 (IQR: 2–6) vs. 3 (IQR: 2–5), P < 0.001]. Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with propensity score matching, statin therapy confirmed its association with a more severe disease (NEWS ≥ 5;61% vs. 48%, P = 0.025) but not with in-hospital mortality (26% vs. 28%, P = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR: 0.901;95% CI: 0.537–1.51;P = 0.692) and to be associated with a more severe disease (NEWS ≥ 5 OR: 1.7;95% CI: 1.067–2.71;P = 0.026). Conclusions Our results did not confirm the supposed favourable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.538 Figure 1

Epidemiology of SARS-CoV-2 infection in Italy using real-world data: methodology and cohort description of the second phase of web-based EPICOVID19 study. (preprint)

Digital technologies have been extensively employed in response to the SARS-CoV-2 pandemic worldwide. This study describes the methodology of the two-phase internet-based EPICOVID19 survey, and the characteristics of the adult volunteers respondents who lived in Italy during the first (April - May 2020) and the second wave (January - February 2021) of the epidemic. Validated scales and ad-hoc questionnaires were used to collect socio-demographic, medical and behavioural characteristics, as well as information on COVID-19. Among those who provided email addresses during phase I (105,355), 41,473 participated in phase II (mean age 50.7 years +/- 13.5 SD, 60.6% females). After a median follow-up of ten months, 52.8% had undergone naso-pharyngeal swab (NPS) testing and 13.2% had positive result. More than 40% had undergone serological test (ST) and 11.9% were positive. Out of the 2,073 participants with at least one positive ST, 72.8% had only negative results from NPS or never performed it. These results indicate that a large fraction of individuals remained undiagnosed, possibly contributing to the spread of the virus in the community. Participatory online surveys offer a unique opportunity to collect relevant data at individual level from large samples during confinement.

Phylogeography And Genomic Epidemiology of SARS-CoV-2 In Italy And Europe With Newly Characterized Italian Genomes (preprint)

The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including <80 Italian isolates, while most of the Italian strains were intermixed in the whole tree. Pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 developed most probably in other European countries entering Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, the reconstructed ancestral scenario suggests a central role of China and Italy in the widespread diffusion of the D614G variant in Europe in the early phase of the pandemic and more dispersed exchanges involving several European countries from the second half of March 2020.

Evolutionary Dynamics of SARS-CoV-2 in Space and Time During the First Phase of the Epidemic in Italy (preprint)

The aim of this study was the reconstruction of SARS-CoV-2 evolutionary dynamics in time and space in Italy and Europe between February and June 2020. The cluster analysis showed that pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 entered Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, the reconstructed ancestral scenario suggests a central role of China and Italy in the widespread diffusion of the D614G variant in Europe in the early phase of the pandemic and more dispersed exchanges involving several European countries from the second half of March 2020.

High Mortality Rate Among Latin American Immigrants With Covid-19 Hospitalised in Milan, Italy: Data From the Luigi Sacco Hospital Registry (preprint)

Background: To assess differences in the probability of COVID-19-related death between native Italians and immigrants hospitalised with COVID-19. Methods This was a retrospective study of prospectively collected data conducted at the ASST Fatebenefratelli-Sacco Hospital in Milan, Italy, between 21 February and 31 November 2020. Uni- and multivariable Cox proportional hazard models were used to assess the impact of the patients' origin on the probability of COVID-19-related death. Results The study population consisted of 1,179 COVID-19 patients: 921 Italians (78.1%) and 258 immigrants (21.9%) from Latin America (99, 38.4%), Asia (72, 27.9%), Africa (50, 19.4%) and central/eastern Europe (37, 14.3%). The Italians were older (p 

Impact estimation on COVID-19 infections following school reopening in September 2020 in Italy (preprint)

BackgroundSince its outbreak, CoViD-19 (formally known as 2019-nCoV) has been triggering many questions among public authorities, social organisms and school officials, as to when students should be allowed to return to school. Such a decision is critical and must take into account, other than its beneficial effects, also those associated with an increased exposition of the students to the virus, which, as a result, might spread at a faster rate. To date, in Italy, a few studies have rigorously investigated the correlation between school reopening and number of people tested positive to CoViD-19. Therefore, this paper aims to provide an assessment of such an impact as well as to illustrate the methodology followed. MethodsOfficial daily data on the cumulative number of people tested positive to CoViD-19 - in conjunction with external information accounting for the different points in time schools reopened in the various Italian regions - have been employed to build a stochastic model of the type Seasonal Autoregressive Moving Average embodying external information. ResultsThere was a statistically significant increase in the number of positive cases in all the Italian regions related to schools reopening. Such an increase occurred, in average, about 18.9 days after the schools have been reopened. Schools reopening have been significantly contributed to the diffusion of the pandemic, with an overall estimated impact of about 228,724 positive cases. ConclusionsThe results suggest the need for strict control of all in-school activities. This could be done by using, to a variable extent, all the non-pharmaceutical interventions available, such as limited access to school spaces, no overlapping practices between different sports in the same space, universal masking, bubble-size classroom. However, in many cases, such measures might not be a viable option, at least in the short run, nor be reasonably applicable. Therefore, whenever the established safety criteria could not be met, school buildings should remain closed. Key MessagesO_LIDue to CoViD-19 pandemic, physical school attendance is at the center of an intense political and social debates; C_LIO_LIschools reopening decision should be based on reliable and well maintained data-sets; C_LIO_LIin the lack of quality data, it is advisable to use a portion of them, to reduce uncertainty. C_LI

Circulating SARS-CoV-2 Variants in Italy, October 2020-March 2021 (preprint)

A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.

Circulating SARS-CoV-2 Variants in Italy, October 2020-March 2021 (preprint)

A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.

Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network (preprint)

The COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as "human identical sequences (HIS)". HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2 RNA directly binds to the targeted loci in human genome and further interacts with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.

The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity (preprint)

SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and in vitro replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of 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.

Missed opportunities of flu vaccination in Italian target categories: insights from the online EPICOVID 19 survey (preprint)

We aimed to assess the reported rate of flu vaccination in the season 2019/2020 in respondents to the Italian nationwide online EPICOVID 19 survey. A national convenience sample of volunteers aged 18 or older was assessed between 13th April and 2nd June 2020. Flu vaccine rates were calculated for all classes of age. The association between the independent variables and the flu vaccine was assessed by applying a multivariable binary logistic regression model. Of the 198,822 respondents 41,818 (21.0%) reported to have received a flu vaccination shot during the last influenza season. In particular, 15,009 (53.4%) subjects aged 65 years or older received a flu vaccination shot. Being 65 years aged or older (aOR 3.06, 95%CI 2.92-3.20) and having a high education level (aOR 1.34. 95%CI 1.28-1.41) were independently associated to flu vaccination. Heart and lung diseases were the morbidities associated with the higher odds of being vaccinated [aOR 1.97 (95%CI 1.86-2.09) and aOR 1.92 (95%CI 1.84-2.01), respectively]. Nursing home residents aged [≥] 65 years showed a lower odds of being vaccinated [aOR 0.39 (95%CI 0.28-0.54)]. Our data claims for an urgent public heath effort to fill the gap of missed vaccination opportunities reported in the past flu seasons.

EPICOVID19: Psychometric assessment and validation of a short diagnostic scale for a rapid Covid-19 screening based on reported symptoms (preprint)

BackgroundConfirmed COVID-19 cases have been registered in more than two hundred countries and regions and of July 28 over 16 million cases of COVID-19, including 650805 deaths, have been reported to WHO. The number of cases changes quickly and varies depending upon which source you use to track, so in the current epidemiological context, the early recognition is critical for the rapid identification of suspected cases (with SARS-CoV-2 infection-like symptoms and signs) to be immediately subjected to quarantine measures. Although surveys are widely used for identifying COVID-19 cases, outcomes and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection in the population so far. MethodsOur study is the phase II of the EPICOVID19 Italian national survey, launched in April 2020 including a national convenience sample of 201121 adults, who voluntarily filled the EPICOVID19 questionnaire. The phase II questionnaire was mailed to all subjects who underwent tests for COVID-19 by nasopharyngeal swab (NPS) and who accepted to be involved in the second phase of the study, focused on the results reported for NPS and/or serological IgG/IgM tests. We evaluated the capability of the self-reported symptoms collected through the EPICOVID19 questionnaire to discriminate the COVID-19 among symptomatic subjects, in order to identify possible cases to undergo instrumental measurements and clinical examinations. We defined a method for the identification of a total score and validated it with reference to the serological and molecular clinical diagnosis, using four standard steps: identification of critical factors, confirmation of presence of latent variable, development of optimal scoring algorithm and validation of the scoring algorithm. Findings2703 subjects [66% response rate] completed the Phase II questionnaire. Of 2703 individuals, 694 (25.7%) were NPS(+) and of these 84 (12.1% of the 694 NPS(+)) were asymptomatic. In the individuals who performed serological testing, of the 472 who did IgG(+) and 421 who did IgM(+), 22.9% and 11.6% tested positive, respectively. Among IgG(+) 1 of 108 subjects was asymptomatic (0.9%) while 5/49 subjects among IgM(+) were asymptomatic (10.2%). Compared with NPS(-), among NPS(+) subjects there was a higher rate for Fever (421 [60.7%] vs 391[19.5%]; p<0.0001), Loss of Taste and/or Smell (365 [52.6%] vs 239 [11.9%]; p<0.0001) and Cough (352 [50.7%] vs 580 [28.9%]; p<0.0001). Also for other symptoms the frequencies were significantly higher in NPS(+) subjects than in NPS(-) ones (p<0.001). Among groups with serological tests, the symptoms with higher percentages in the subjects IgG(+) were Fever (65 [60.2%] vs 43[11.8%]; p<0.0001) and Pain in muscles, bones, joints (73 [67.6%] vs 71 [19.5%]; p<0.0001). For the COVID-19 self-reported symptoms items, exploratory (proportion variance explained [89.9%]) and confirmatory factor analysis results (SMSR 0.072; RMSEA 0.052) highlights the presence of one latent variable (factor) underlying the symptoms. We define the one-factor solution as EPICOVID19 diagnostic scale and optimal score for each items was identified: Respiratory problems (1.03), Chest pain (1.07), Loss of Taste and/or Smell (0.97) and Tachycardia (palpitations) (1.05) were the most important symptoms. The cut-off score was 2.56 (Sensitivity 76.56%; Specificity 68.24%) in NPS(+) and 2.59 (Se 80.37; Sp 80.17) in IgG(+) subjects. InterpretationWe developed a short diagnostic scale to detect subjects with symptoms potentially associated with COVID-19 among a wide population. Early recognition screening and rapid diagnosis are essential to prevent transmission and provide supportive care in a timely manner and our score supports the potential for identifying individuals who need to seek immediate clinical evaluation. Although these results are referred to the Italian pandemic period, this short diagnostic scale could be optimised and tested as a screening tool in other similar pandemic contexts.

Molecular Tracing of SARS-CoV-2 in Italy in the First Three Months of the Epidemic (preprint)

The aim of this study is the characterization and genomic tracing by phylogenetic analyses of 59 new SARS-CoV-2 Italian isolates obtained from patients attending clinical centres in North and Central Italy until the end of April 2020. All but one of the newly characterized genomes belonged to the lineage B.1, the most frequently identified in European countries, including Italy. Only a single sequence was found to belong to lineage B. A mean of 6 nucleotide substitutions per viral genome was observed, without significant differences between synonymous and non-synonymous mutations, indicating genetic drift as a major source for virus evolution. tMRCA estimation confirmed the probable origin of the epidemic between the end of January and the beginning of February with a rapid increase in the number of infections between the end of February and mid-March. Since early February, an effective reproduction number (Re) greater than 1 was estimated, which then increased reaching the peak of 2.3 in early March, confirming the circulation of the virus before the first COVID-19 cases were documented. Continuous use of state-of-the-art methods for molecular surveillance is warranted to trace virus circulation and evolution and inform effective prevention and containment of future SARS-CoV-2 outbreaks.

Molecular tracing of SARS-CoV-2 in Italy in the first three months of the epidemic (preprint)

The aim of this study is the characterization and genomic tracing by phylogenetic analyses of 59 new SARS-CoV-2 Italian isolates obtained from patients attending clinical centres in North and Central Italy until the end of April 2020. All but one of the newly characterized genomes belonged to the lineage B.1, the most frequently identified in European countries, including Italy. Only a single sequence was found to belong to lineage B. A mean of 6 nucleotide substitutions per viral genome was observed, without significant differences between synonymous and non-synonymous mutations, indicating genetic drift as a major source for virus evolution. tMRCA estimation confirmed the probable origin of the epidemic between the end of January and the beginning of February with a rapid increase in the number of infections between the end of February and mid-March. Since early February, an effective reproduction number (Re) greater than 1 was estimated, which then increased reaching the peak of 2.3 in early March, confirming the circulation of the virus before the first COVID-19 cases were documented. Continuous use of state-of-the-art methods for molecular surveillance is warranted to trace virus circulation and evolution and inform effective prevention and containment of future SARS-CoV-2 outbreaks.

Seroprevalence of SARS-CoV-2 IgG significantly varies with age: results from a mass population screening (SARS-2-SCREEN-CdA). (preprint)

ObjectivesCastiglione DAdda 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 seroprevalence screening. MethodsWe searched for SARS-CoV-2 IgGs in the entire voluntary population using lateral flow immune-cromatographic tests on capillary blood (rapid tests). We then performed chemioluminescent serological assays (CLIA) and naso-pharyngeal swabs in a randomized representative sample of 562 subjects and in every subject with a positive rapid test. ResultsBased on CLIA serologies on the representative random sample (509 subjects), we estimated a 23% IgG seroprevalence. We also found a strong correlation between age and prevalence, with the elderly showing the highest probability of a positive serological test. ConclusionsIn an area of unrestricted viral circulation less than one-fourth of the population tested positive for SARS-CoV-2 IgG. Seroprevalence increased with increasing age, possibly suggesting differences in susceptibility to the infection.

Are health indicators able to describe the ability to cope of Health Systems with COVID-19 epidemic? (preprint)

The Coronavirus Disease 19 epidemic is an infectious disease which was declared as a pandemic and hit all the Countries, all over the world, from the beginning of the year 2020. Despite the emergency vigilance plans, in all the Countries, Health Systems experienced a different ratio of lethality, admissions to intensive care units and managing quarantine of positive patients. The aim of this study is to investigate if some health indicators might have been useful to understand the capacity of Italian National Health Service to manage the COVID 19 epidemic. We will compare data in two different Italian regions in the Northern part of Italy (Lombardy and Veneto) with the national data to understand if different health strategies might be significant to explain different patterns of COVID 19 epidemic in Italy. The two regions have two different health policies to face CoViD-2019 epidemic. To face epidemic like this one the answer should be outside hospitals but this means to have general practitioners well-trained and enough healthcare personnel working outside hospitals.

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study. (preprint)

Background The potential benefit of a combination therapy with lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) on COVID-19 has been speculated. We explored the effect of the timing of LPV/r + HCQ initiation on the outcome of patients with COVID-19. Methods A retrospective cohort study was conducted on patients with COVID-19 who started treatment with LPV/r plus HCQ between February 21 and March 20, 2020, at Luigi Sacco Hospital in Milan, Italy. Over time cumulative incidence of clinical improvement was compared between patients who started treatment less than 5 days from the onset of symptoms [early treatment group (ET)] and those who initiated it later [delayed treatment group (DT)]. The association of LPV/r plus HCQ initiation timing on 30-day mortality was also assessed by univariate and multivariate logistic models. Results The study included 172 patients, prevalently males (72%) in their sixties, with a moderate (53.4%) or severe (34.9%) disease. Fourty-three (25%) patients were included in the ET group and and 129 (75%) in the DT group. Severity of disease did not significantly differ between the two groups. Conclusion Timing of LPV/r + HCQ initiation seems to have no impact on COVID-19 clinical course in terms of improvement and 30-day mortality. These findings rise doubts on the clincial efficacy of this regimen.

Pulmonary Post-Mortem Findings in a Large Series of COVID-19 Cases from Northern Italy (preprint)

Importance: The analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness.Objective: To determine the histological patterns in lung tissue of patients with severe COVID-19.Design and Participants: Lungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed.Results: The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstitium. Electron microscopy revealed viral particles within cytoplasmic vacuoles of pneumocytes.Conclusions and Relevance: The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.Funding Statement: No FundingDeclaration of Interests: No Conflict of InterestEthics Approval Statement: Tissue samples were taken as part of routine autopsies

Dynamics of the SARS-CoV-2 epidemic in the earliest-affected areas in Italy: 1 Mass screening for SARS-CoV-2 serological positivity (SARS-2-SCREEN). (preprint)

Background Several municipalities in the Lombardy Region have been affected by the SARS-CoV-2 infection since the earliest stages of the epidemic. To date, 89442 confirmed cases have been diagnosed in Lombardy, and mortality in several municipalities has already surpassed that of the past decade. Currently, the true extent of the SARS-CoV-2 infection remains unknown as several affected subjects may have been asymptomatic or have presented mild disease, thus not resulting in the identified COVID-19 cases. Methods This cross-sectional study aims to define the spread of infection within the population by determining the seroprevalence of IgG antibodies directed against SARS-CoV-2 by rapid immunochromatographic testing and subsequent confirmation by serology on venous blood by liquid phase immunochemical testing, also allowing to compare the two methods. Testing will be performed on adults and minors residing, domiciled or working in several municipalities of the Lombardy Region, involved in the initial stages of the epidemic. The study will include rapid finger-prick testing and venous sampling for antibodies against SARS-CoV-2, and nasopharyngeal swabbing (NPS). Concurrent notification of test results will occur via the regional healthcare information system (SISS). Discussion This study was developed with the desire to understand the seroprevalence of SARS-CoV-2 infection and the epidemiological transmission characteristics of this virus. Understanding the spread and severity of the disease could help in the implementation of effective infection surveillance containment and countermeasures facilitating the identification of cases that have been exposed to the virus and the traceability of contacts. This study has been approved by the Ethics Committee of the University of Milan (35/2020).