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Although COVID-19 affects older people more severely, health policies during the first wave of the pandemic often prioritized younger individuals. We investigated whether age had influenced the access to a diagnostic test for SARS-CoV-2 infection and whether clinical complexity and healthcare resources availability could have impacted such differences. This work included 126,741 Italian participants in the EPICOVID19 web-based survey, who reported having had contacts with known/suspected COVID-19 cases (epidemiological criterion) and/or COVID-19-like signs/symptoms (clinical criterion) from February to June 2020. Data on sociodemographic, medical history and access to SARS-CoV-2 nasopharyngeal swab (NPS) were collected. Logistic regressions estimated the probability of accessing NPS as a function of age and the possible modifying effect of chronic diseases' number and residential areas in such association. A total of 6136 (4.8%) participants had undergone an NPS. Older participants had lower NPS frequencies than the younger ones when reporting epidemiological (14.9% vs. 8.8%) or both epidemiological and clinical criteria (17.5% vs. 13.7%). After adjustment for potential confounders, including epidemiological and clinical criteria, the chance of NPS access decreased by 29% (OR=0.71, 95%CI:0.63-0.79) in older vs. younger individuals. Such disparity was accentuated in areas with greater healthcare resources. In conclusion, in the first wave of the pandemic, age may have affected the access to COVID-19 diagnostic testing, disadvantaging older people.

The northern Italian region of Lombardy has been severely affected by the COVID-19 pandemic since its arrival in Europe. However, there are only a few published studies of the possible influence of social and cultural factors on its prevalence in the general population. This cross-sectional study of the San Siro social-housing neighbourhood of Milan, which was carried about between 23 December 2020 and 19 February 2021, found that the prevalence of anti-SARS-CoV-2 nucleocapsid antibodies in the population as a whole was 12.4% (253/2044 inhabitants), but there was a more than two-fold difference between non-Italians and Italians (23.3% vs. 9.1%). Multivariable analyses showed that being more than 50 years old, living in crowded accommodation, being a non-Italian, and having a low educational level were associated with higher odds of a positive SARS-CoV-2 test, whereas a higher level of education, retirement, and being a former or current cigarette smoker were inversely associated with SARS-CoV-2 infection. Our findings are in line with previous observations indicating that a lower socio-economic status may be a risk factor for COVID-19 and show that non-Italians are disproportionately affected by SARS-CoV-2 infection. This suggests that public health policies should focus more on disadvantaged populations.

Crusted scabies is an infrequent disease caused by Sarcoptes scabiei that usually affects patients with underlying medical conditions leading to immunosuppression. Here, we present the case of an 81 years old man, diagnosed with crusted scabies who came to our attention after multiple misdiagnosis and incorrect and potentially detrimental treatment with steroids. He was admitted to our inpatients ward and treated with oral ivermectin plus local permethrin. The hospitalization was complicated by a secondary bacterial skin infection caused by methicillin-sensitive Staphylococcus aureus. Crusted scabies is commonly misdiagnosed in elderly and immunosuppressed people due to its unusual occurrence and atypical clinical presentation. It should be considered in the differential diagnosis of skin lesions associated with pruritus in patients with underling medical conditions leading to immunosuppression. A prompt diagnosis and treatment are warranted due to the potential secondary infections and subsequent related morbidity and mortality.

BACKGROUND Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. 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 general population. OBJECTIVE We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score. METHODS Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests. RESULTS Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; PPPPP CONCLUSIONS We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics.

Introduction: Castiglione D’Adda is one of the municipalities more precociously and severely affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic in Lombardy. With our study we aimed to understand the diffusion of the infection by mass serological screening. Methods: We searched for SARS-CoV-2 IgGs in the population on a voluntary basis using lateral flow immunochromatographic tests (RICT) on capillary blood (rapid tests). We then performed chemioluminescent serological assays (CLIA) and naso-pharyngeal swabs (NPS) in a randomized representative sample and in each subject with a positive rapid test. Factors associated with RICT IgG positivity were assessed by uni- and multivariable logistic regression models. Results: Out of the 4143 participants, 918 (22·2%) showed an RICT IgG positivity. In multivariable analysis, IgG positivity increases with age, with a significant non-linear effect (p=0·0404). We found 22 positive NPSs out of the 1330 performed. Conclusions: Albeit relevant, the IgG prevalence is lower than expected and suggests that a large part of the population remains susceptible to the infection. The observed differences in prevalence might reflect a different infection susceptibility by age group. A limited persistence of active infections (positive NPSs) could be found after several weeks after the epidemic peak in the area. Funding Statement: CISOM (Corpo Italiano di Soccorso dell'Ordine di Malta), FC Internazionale Milano, SFD s.p.a , Emporio Armani Olimpia Milano through donations to the Dipartimento di Scienze Biomediche e Cliniche (DIBIC) of the University of Milan and to Banca Mediolanum through donation to ASST FatebenefratelliSacco, Milano. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by University of Milan’s Ethical Committee.

SummaryBackgroundConfirmed 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%]; pThe 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.

BACKGROUND Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce. OBJECTIVE The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population. METHODS EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19–like infection in the nontested population. RESULTS A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection. CONCLUSIONS Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection. CLINICALTRIAL ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701

ObjectivesCastiglione D’Adda is one of the municipalities more precociously and severely affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic in Lombardy. With our study we aimed to understand the diffusion of the infection by mass 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.

As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy.The aim of this retrospective intent-to-treat analysis of the hospitalized patients who started off-label treatment with LPV/ritonavir (LPV/r)+HCQ between 21 February and 20 March 2020 was to compare the rate of clinical improvement between those who started the treatment within five days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). The association between the timing of treatment and the probability of 30-day mortality was also assessed using uni- and multivariable logistic models.The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray’s test P = 0.213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment because of severe gastrointestinal disorders attributable to LPV/r.The timing of the start of LPV/r+HCQ treatment does not seem to affect the clinical course of hospitalised patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.

BackgroundSeveral 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.MethodsThis 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).DiscussionThis 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).

Dengue Fever (DF), transmitted by Aedes mosquitoes, is the most common arthropod-borne infection, it is almost ubiquitous in tropical and subtropical areas with an estimate of 360 million infections per year. A competent vector (A. albopictus) is present in most of Southern Europe and is endemic in Italy. We conducted a 16-year retrospective study of probable/confirmed dengue fever observed at the Department of Infectious Diseases of Luigi Sacco Hospital in Milan, Italy. Overall 122 patients were included in the study, 106 with probable and 16 with proven diagnosis of dengue fever. Most patients (91%) were Italian, with a median age of 35 years (IQR 29-46 years) and similar gender distribution, travelling for tourism (80%). Asia (mainly South East Asia and Indian Subcontinent) was the most frequent travel destination (55%), followed by Central America and the Caribbeans (22%). August-September was the peak season of presentation (42.6%). The majority of our diagnoses were based on serology alone. The most common signs and symptoms were fever (99,2%), maculopapular rash (50,8%), headache (50,8%), arthralgias (50,8%) and myalgias (46,7%). Leukopenia (77%), thrombocytopenia (81%) and altered LDH, AST and ALT (respectively 60,6%, 54,1% and 45,9%) were the most common laboratory test's abnormalities. No cases of severe DF were recorded. Our epidemiological and clinical findings are largely in accordance with most recent studies about imported DF in Europe. Although very similar in presentation to other arthropod-borne illnesses, some clinical features may help in differentiating DF from other causes of fever in the returning traveler.

Graphical abstract, SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94% in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63%) and discontinued by 13, of whom eight (22.8%) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3%) patients from IDW were discharged, two were still hospitalized and one died (5.9%), whereas in ICU 6 (33.3%) were discharged, 8 (44.4%) patients died, three (16.7%) were still mechanically ventilated and one (5.6%) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8% and 22.8% of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.

Background Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce. Objective The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population. Methods EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19–like infection in the nontested population. Results A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection. Conclusions Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection. Trial Registration ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701

Background Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. 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 general population. Objective We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score. Methods Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests. Results Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; P Conclusions We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics.