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Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March–April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4 years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2 days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2 days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55 days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented.

Objectives: Viral blips (VB) have been reported in people with HIV (PWH) after COVID-19 vaccination. Materials and Methods: We performed a retrospective cohort study among virally suppressed PWH vaccinated against COVID-19 with mRNA-1273, comparing the occurrence of VB in the 12 months after the first vaccine shot with those recorded in the 12 months before. The association between several clinical and immunologic variables and VB have been evaluated through logistic regression. Results: Overall, 48 individuals were included in our analysis. No difference was recorded between VB incidence in the 12 months before and after vaccination [11/48 (23%) vs 15/48 (31.3%), p=0.42]. No significant association was detected between selected variables and VB occurrence after vaccination. In a post hoc analysis including also 8 PWH excluded for not reaching the definition of viral suppression, we observed 15 increases of HIV RNA out of 56 PWH (26.8%) before vaccination and 23 increases of HIV RNA out of 56 PWH after vaccination (41.1%). This difference in incidence remained not significant (p=0.10) but a strong association between increases of HIV RNA occurrence before and after vaccination [p=0.02, OR 4.3 (95% CI 1-22-15.17)] was found. Conclusion: Among virally suppressed PWH, COVID-19 vaccination with mRNA-1273 is not associated with increased occurrence of VB.

The pandemic caused by SARS-COV-2 has increased Semi-Intensive Care Unit (SICU) admission, causing an increase in healthcare-associated infection (HAI). Mostly HAI reveals the same risk factors, but fewer studies have analyzed the possibility of multiple coinfections in these patients. The study aimed was to identify patterns of co-presence of different species describing at the same time the association between such patterns and patient demographics and, finally, comparing the patterns between the two cohorts of COVID-19 patients admitted at Policlinico during the first wave and the second one).All the patients admitted to SICUs during two COVID-19 waves, from March to June 2020 months and from October to December 2020, were screened following the local infection control surveillance program; whoever manifested fever has undergone on microbiological culture to detect bacterial species. Statistical analysis was performed to observe the existence of microbiological patterns through DBSCAN method.246 patients were investigated and 83 patients were considered in our study because they presented infection symptoms with a mean age of 67 years and 33.7% of female patients. During the first and second waves were found respectively 10 and 8 bacterial clusters with no difference regarding the most frequent species.The results show the importance of an analysis which considers the risk factors for the possibility of co- and superinfection (such as age and gender) to structure a good prognostic tool to predict which patients will encounter severe coinfections during hospitalization.

to evaluate immunogenicity and effectiveness of BNT162b2 COVID-19 vaccine in a cohort of healthcare workers (HCWs).cohort study.in a hospital in Milan (Lombardy Region, Northern Italy) HCWs without ("negative cohort") and with ("positive cohort") history of SARS-CoV-2 infection or elevated serum antibody before the vaccination campaign (27.12.2020) were included. Data collection and follow-up covered the period 27.12.2020-13.05.2022.1. serum anti-spike-1 (anti-S1) antibody levels after vaccination; 2. vaccine effectiveness (VE) against SARS-CoV-2 infections (either symptomatic or not) in the negative cohort. Data on infections were extracted from multiple sources (laboratory, accident reports, questionnaires). Vaccination was treated as a time-dependent variable. Using unvaccinated person-time as reference, hazard ratios (HR) of infections and 95% confidence intervals (95%CI) were calculated with a Cox regression model adjusted for gender, age, and occupation. VE was calculated as (1 - HR)×100.5,596 HCWs were included, 4,771 in the negative and 825 in the positive cohort. In both cohorts, serum anti-S1 antibodies were high one months after the second dose, halved after six months, and returned to high levels after the third dose. In the negative cohort, 1,401 SARS-CoV-2 infections were identified. VE was 70% (95%CI 54-80; 46 infected) in the first four months after the second dose and later declined to 16% (95%CI 0-43; 97 infected). After the third dose, VE increased to 57% (95%CI 35-71; 61 infected) in the first month but rapidly declined over time, particularly after three months (24% in the fourth month and 1% afterwards). The number of infections avoided by vaccination was estimated to be 643 (95%CI 236-1,237).in spite of rapidly declining effectiveness, vaccination helped to avoid several hundred infections in the considered hospital.

Great expectations are placed in vaccines against COVID-19 to control the pandemic. We reviewed the antibody titres in a cohort of healthcare workers (HCWs) vaccinated with BNT162b2 to assess the influence of a previous infection on them. We stratified the results according to the individual history of nasopharyngeal swab (NPS) and symptoms. Among 3475 HCWs the highest titres were recorded among those infected more than 6 months before vaccination, independently of symptoms, followed by those infected less than 6 months before vaccination, especially in those with symptoms, and by uninfected HCWs. Vaccination with BNT162b2 can boost immunity acquired through infection, particularly in those infected more than 6 months before vaccination.

Background: since October 2020, a second SARS-CoV-2 epidemic wave has hit Italy. We investigate the frequency of positive nasopharyngeal swabs among HCWs during the two waves and the association with occupation and demographic characteristics. Methods: this is a retrospective, observational study conducted in a large university hospital in Milan, Northern Italy. We defined two epidemic waves: 1st (February 2020–July 2020) and 2nd (August 2020–January 2021). Occupational and demographic characteristics of HCWs who underwent nasopharyngeal swabs for SARS-CoV-2 were collected. Results: in the 1st wave, 242 positive subjects (7.2%) were found among 3378 HCWs, whereas in the 2nd wave, the positive subjects were 545 out of 4465 (12.2%). In both epidemic waves positive NPSs were more frequent among HCWs with health-related tasks and lower among students (p &lt, 0.001). However, in the 2nd wave, workers engaged in non-health-related tasks had a peak of 20.7% positivity. Among 160 positive HCWs in the 1st wave who were tested again in the 2nd wave, the rate of reinfection based on SARS-CoV2 RNA cycle quantification value was 0.6%. Conclusions: during the 2nd epidemic wave, we confirmed a significant impact of COVID-19 among HCWs. The rise of infection rate among HCWs seems to reflect the increasing spread of SARS-CoV-2 among the overall population.

Background: The containment measures adopted during COVID-19 pandemic have influenced the epidemiology of other respiratory viruses.Aim: We analyzed the modification of the incidence and etiology of lower respiratory tract infections (LRTIs) in young children during COVID-19 pandemic.Methods: Case series of all children under 2 years old hospitalized at a tertiary care Hospital in the Center of Milan, Italy diagnosed with LRTIs in three consecutive winter seasons (from the 1st of November to the last day of February in 2018/2019, 2019/2020 and 2020/2021). We compared the number of hospitalizations and viral detections in the 2020/2021 with the average of 2018/2019 and 2019/2020 (pre-COVID-19) using the Poisson distribution.Results: we enrolled 178 patients (66 from 2018/2019, 96 from 2019/2020, 16 from 2020/2021) 94 males (53%) and 84 females (47%), with a median (IQR) age of 5 (2–13) months. The number of hospitalizations during the 2020/2021 season was 80% lower than the average of the pre-COVID-19 seasons (16 vs. 81, p<0.001). Overall, 171 (96%) patient's nasopharyngeal aspirate (NPA) detected at least one virus (110, 64%, single-detection, 61, 36%, co-detections). In 2020/2021 we observed the disappearance of Respiratory Syncytial virus (0 vs. 54, p < 0.001), Influenza virus (0 vs. 6.5, p = 0.002), Metapneumovirus (0 vs. 8, p < 0.001), Parainfluenza viruses (0 vs. 3.5, p = 0.03) and a significant reduction of Adenovirus (2 vs. 7, p = 0.03), Bocavirus (2 vs. 7.5, p = 0.02) and Enterovirus (1 vs. 5, p = 0.04). No significant difference was found for Rhinoviruses (14 cases vs. 17, p = 0.2), other Coronaviruses (0 vs. 2, p = 0.1), and Cytomegalovirus (1 vs. 1, p = 0.7).Conclusions: We observed a striking reduction in hospitalizations due to LRTIs and a modification of the etiology, with enveloped viruses mainly affected.

Background: Vaccines against COVID-19 are a powerful tool to control the current SARS-CoV-2 pandemic. A thorough description of their immunogenicity among people living with HIV (PLWHIV) is necessary. We aimed to assess the immunogenicity of the mRNA-1273 vaccine among PLWHIV. Methods: In this prospective cohort, adult PLWHIV outpatients were enrolled during the Italian vaccination campaign. Enrolment was allowed irrespective of ongoing combination antiretroviral therapy (ART), plasma HIV viral load and CD4+ T cell count. A two-dose regimen of mRNA-1273, with administrations performed 28 days apart, was employed. The primary outcomes were anti-spike (anti-S) antibody titres and neutralising antibody activity, assessed 28 days after completing the vaccination schedule, compared with individuals not affected by HIV (referred as healthy-donors, HDs). Findings: CD4+ T cell count groups and anti-nucleocapside (anti-N) positive serology were the only variables associated with anti-spike (anti-S) antibody titres (expressed as U/mL) and neutralising antibody activity. Anti-S antibodies were higher in COVID-19-experienced PLWHIV (median 12500 U/mL IQR [5704-12500]) than in COVID-19-naive PLWHIV (median 2437 U/mL IQR [1485-4526]) but did not differ from those observed in COVID-19-experienced HDs (median 1077 U/mL IQR [702-7551]). Neutralising antibody activity in sera was higher in COVID-19-experienced PLWHIV (median 10888 IQR [2478-14416]) compared to COVID-19-naive PLWHIV (median 1192 IQR [742-2421]) but was comparable to those observed in COVID-19-experienced HDs (median 20959 U/mL IQR [10060-31857]). When stratified according to CD4+ T cell count ( 500 cells/μL), anti-S antibody titres (median 2173 U/mL [IQR 897-4109], 5763 IU/mL [IQR 4801-12500], 2449 U/mL [IQR 1524-5704]) were not lower to those observed among HDs (median 1425 U/mL [IQR 599-6131]). In addition, neutralising antibody activity, stratified according to the CD4+ T cell count (median 1314 [IQR 606-2477], 3329 IU/mL [IQR 1905-10508], 1227 U/mL [IQR 761-3032]), was similar to those displayed by HDs (median 2112 U/mL [IQR 719-8889]). Interpretation: Inoculation with mRNA-1273 vaccine given 4 weeks apart produced adequate immune responses in PLWHIV, who are well controlled on ART, irrespective of CD4+ T cell count and equivalent to individuals without HIV infection, supporting vaccination in PLWHIV. Funding: This study was partially supported by Italian Ministry of Health Ricerca Corrente 2021 and Grant Ricerca Finalizzata GR 2018-12365699, by Intesa San Paolo COVID-19 emergency 2020 funds, and by Fondazione Cariplo (INNATE-CoV). Declaration of Interest: All other authors declare no competing interests. Ethical Approval: The study protocol (286_2021) was approved by the INMI “Lazzaro Spallanzani” Ethics Committee (Roma, Italy)

ObjectivesTo assess the seroprevalence of anti-SARS-CoV-2 IgG among health careworkers (HCWs) in our university hospital and verify the risk of acquiring the infection according to work area.DesignCross-sectional study.SettingMonocentric, Italian, third-level university hospital.ParticipantsAll the employees of the hospital on a voluntary base, for a total of 4055 participants among 4572 HCWs (88.7%).Primary and secondary outcome measuresNumber of anti-SARS-CoV-2 positive serology according to working area. Association of anti-SARS-CoV-2 positive serology to selected variables (age, gender, country of origin, body mass index, smoking, symptoms and contact with confirmed cases).ResultsFrom 27 April 2020 to 12 June 2020, 4055 HCWs were tested and 309 (7.6%) had a serological positive test. No relevant difference was found between men and women (8.3% vs 7.3%, p=0.3), whereas a higher prevalence was observed among foreign-born workers (27/186, 14.5%, pConclusionsSARS-CoV-2 infection occurred undetected in a large fraction of HCWs and it was not associated with working in COVID-19 frontline areas. Beyond the hospital setting, exposure within the community represents an additional source of infection for HCWs.

Widespread use of direct-acting antiviral (DAA) agents to treat patients with hepatitis C virus (HCV) infection has reduced the need for monitoring of HCV RNA levels, because viral kinetics do not predict sustained virologic response (SVR) to these drugs. However, the performance of cheaper tests such as the assay to quantify HCV core antigen (HCV Ag) has not been determined. We investigated the accuracy of the HCV Ag test in predicting which patients receiving DAAs will achieve SVRs at week 12 (SVR12).We performed a prospective study of 58 patients infected with HCV genotypes 1-5 (45% with HCV genotype 1, 72% with cirrhosis) receiving DAA therapy from the Liver Center at the Università degli Studi of Milan in Italy from January to March 2015. We collected blood samples and measured levels of HCV Ag and HCV RNA at baseline, after 2 and 4 weeks of treatment, the end of treatment, and 12 weeks after treatment ended. We compared the ability of these assays to predict which patients would have SVR12.The median baseline level of HCV RNA was 5.79 log10 IU/mL (range, 3.51-7.31 log10 IU/mL) and of HCV Ag was 3226.87 fmol/L (range, 17.30-54,927.00 fmol/L). HCV Ag became undetectable in 71% of patients at week 2, 84% at week 4, and 93% at the end of treatment. HCV RNA became undetectable in 10% of patients at week 2, 43% at week 4, and 100% at the end of treatment (P.0001). Concordance between the tests in identifying patients who would achieve SVR12 was 40% at week 2, 55% at week 4, and 95% at the end of treatment. Fifty-three of 58 patients (91%) achieved an SVR12; the test for HCV Ag identified 97% of these patients. The tests for HCV Ag and HCV RNA predicted which patients would have SVR12 with positive predictive values of 90% vs 83%, respectively, at week 2 and 89% vs 92%, respectively, at week 4.Tests that measure HCV Ag monitor efficacy of DAA therapy for HCV infection as well as assays that measure HCV RNA and can be recommended for clinical practice. However, measurement of HCV RNA after treatment can rule out relapse in HCV Ag-positive patients.

Human adenoviruses (HAdVs) cause a wide spectrum of clinical syndromes, depending on species and types, from mild respiratory infections to deadly pneumonia: in particular, severe infections occur in immunocompromised patients. In this report, we describe the case of a 36 years-old woman admitted to our intensive care unit (ICU) with severe respiratory distress syndrome caused by adenovirus pneumonia, that required invasive respiratory support (mechanical ventilation and extracorporeal membrane oxygenation). Molecular assays detected the virus in respiratory and plasma specimen and sequencing procedure identified HAdV type 4. Patient improved after cidofovir administration. Leukopenia and subsequent bacterial infection occurred, but the patient recovered completely and was discharged from the hospital after 54days.

Background Acute gastroenteritis is a common cause of morbidity and mortality in humans worldwide. The rapid and specific identification of infectious agents is crucial for correct patient management. However, diagnosis of acute gastroenteritis is usually performed with diagnostic panels that include only a few pathogens. In the present bicentric study, the diagnostic value of FilmArray™ GI panels was assessed in unformed stool samples of patients with acute gastroenteritis and in a series of samples collected from pediatric patients with heamorragic diarrhea. The clinical performance of the FilmArray™ gastrointestinal (GI) panel was assessed in 168 stool samples collected from patients with either acute gastroenteritis or hemorragic diarrhea. Samples showing discordant results between FilmArray and routine methods were further analyzed with an additional assay. Results Overall, the FilmArray™ GI panel detected at least one potential pathogen in 92/168 (54.8%) specimens. In 66/92 (71.8%) samples, only one pathogen was detected, while in 26/92 (28.2%) multiple pathogens were detected. The most frequent pathogens were rotavirus 13.9% (22/168), Campylobacter 10.7% (18/168), Clostridium difficile 9.5% (16/168), and norovirus 8.9% (15/168). Clostridium difficile was identified only in patients with acute gastroenteritis (p

• Clinical utility of measuring CMV-specific CD8 + T cell response as a prognostic tool is evaluated.

A seroprevalence study for anti West Nile virus was carried out among 864 healthy blood donors living in the metropolitan area of Milan by using a commercially available ELISA method. In addition, the performance of a novel ELISA assay for WNV antibodies was assessed. The sero-prevalence rate of WNV antibodies was 0.57% thus showing that WNV is likely circulating also in this up to now unknown area. The overall sensitivity and specificity of the novel ELISA were 99.9% and 45.4%, respectively, well comparable with that of the chosen reference immunoenzimatic method.