Genomic Characterization of Carbapenem-Resistant Acinetobacter baumannii (CRAB) in Mechanically Ventilated COVID-19 Patients and Impact of Infection Control Measures on Reducing CRAB Circulation during the Second Wave of the SARS-CoV-2 Pandemic in Milan, Italy.

COVID-19 has significantly affected hospital infection prevention and control (IPC) practices, especially in intensive care units (ICUs). This frequently caused dissemination of multidrug-resistant organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB). Here, we report the management of a CRAB outbreak in a large ICU COVID-19 hub Hospital in Italy, together with retrospective genotypic analysis by whole-genome sequencing (WGS). Bacterial strains obtained from severe COVID-19 mechanically ventilated patients diagnosed with CRAB infection or colonization between October 2020 and May 2021 were analyzed by WGS to assess antimicrobial resistance and virulence genes, along with mobile genetic elements. Phylogenetic analysis in combination with epidemiological data was used to identify putative transmission chains. CRAB infections and colonization were diagnosed in 14/40 (35%) and 26/40 (65%) cases, respectively, with isolation within 48 h from admission in 7 cases (17.5%). All CRAB strains belonged to Pasteur sequence type 2 (ST2) and 5 different Oxford STs and presented blaOXA-23 gene-carrying Tn2006 transposons. Phylogenetic analysis revealed the existence of four transmission chains inside and among ICUs, circulating mainly between November and January 2021. A tailored IPC strategy was composed of a 5-point bundle, including ICU modules' temporary conversion to CRAB-ICUs and dynamic reopening, with limited impact on ICU admission rate. After its implementation, no CRAB transmission chains were detected. Our study underlies the potentiality of integrating classical epidemiological studies with genomic investigation to identify transmission routes during outbreaks, which could represent a valuable tool to ensure IPC strategies and prevent the spread of MDROs. IMPORTANCE Infection prevention and control (IPC) practices are of paramount importance for preventing the spread of multidrug-resistant organisms (MDROs) in hospitals, especially in the intensive care unit (ICU). Whole-genome sequencing (WGS) is seen as a promising tool for IPC, but its employment is currently still limited. COVID-19 pandemics have posed dramatic challenges in IPC practices, causing worldwide several outbreaks of MDROs, including carbapenem-resistant Acinetobacter baumannii (CRAB). We present the management of a CRAB outbreak in a large ICU COVID-19 hub hospital in Italy using a tailored IPC strategy that allowed us to contain CRAB transmission while preventing ICU closure during a critical pandemic period. The analysis of clinical and epidemiological data coupled with retrospective genotypic analysis by WGS identified different putative transmission chains and confirmed the effectiveness of the IPC strategy implemented. This could be a promising approach for future IPC strategies.

Anti-Sars-CoV-2 vaccination campaign in children aged 5-11 years: the experience of a mass vaccination center in the city of Milan.

BACKGROUND AND AIM: After the approval of the anti-Sars-CoV-2 vaccines for the pediatric population, it is necessary to encourage the immunization of children aged 5-11 years, as this can reduce intergenerational transmission. Therefore, this goal has become a priority for the COVID 19 vaccination campaign in Italy. In the city of Milan, the mass vaccination center (MVC) Fiera Milano City, previously settled for general population, became the main site to host pediatric vaccinations. The center was consequently remodeled to ensure a suitable space for children. This paper provides an overview on the organization strategy implemented by Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. The modular structure and the wide surface available in the center allowed the administration of hundreds of vaccines per day, especially in the first opening phase. METHODS: All the data for the entire period of activity of Fiera MCV, from December 16th 2021 to February 20th 2022, were analyzed using descriptive statistics. RESULTS: During the entire period of activity, from 16 December 2021 to 20 February 2022, 23% of the population in the province of Milan aged 5-11 years has been reached and vaccinated with at least one shot of vaccine in this center. CONCLUSIONS: Despite an enthusiastic response in the first weeks of the campaign, a progressive reduction in vaccination adherence was observed, maybe due to the absence of restrictive measures for unvaccinated children in Italy.

Italy's rollout of COVID-19 vaccinations: The crucial contribution of the first experimental mass vaccination site in Lombardy.

BACKGROUND: In occurrence of the coronavirusdisease 19 (COVID-19) pandemic, carrying out an efficient large-scale vaccination campaign is vital in order to control the virus. Especially in high prevalence areas of COVID - 19, it is crucial to implement an effective vaccination strategy. In Italy, programming an efficient COVID-19 mass vaccination campaign has been the main target of the Ministry of Health. AIMS: This paper gives a comprehensive overview of how the mass vaccination campaign is performed in Milan, one of the cities that has been mostly affected by the COVID-19 pandemic in Italy. We analyze the vaccination strategy implemented by Fondazione Ca' Granda - Ospedale Maggiore Policlinico located in Milan. Furthermore, we compare the organization of this campaign in regards of those carried out across EU and UK. MATERIALS AND METHODS: The data derive from an analysis of the different vaccination plans implemented across EU and UK from the 27/12/2020 to the 15/06/2020. In addition, we discuss the data collected from the internal data server of IRCCS Fondazione Ca' Granda - Ospedale Maggiore Policlinico from the 15/02/2021 to the 15/06/2021.The collected data are examined by means of descriptive statistics. RESULTS: From the analysis of the internal data server, we observe that the modular organization of Fiera Milano City guarantees up to 5000 vaccinations/day. Moreover, the precise flow organization of users and a series of strategies adopted to avoid identification errors or vaccine type administration errors are crucial to reach the aforementioned target. CONCLUSIONS: The institution of mass vaccination centers thanks to the optimization of all the involved processes and the meticulous organization of these structures, allows to avoid crowds and guarantees the administration of elevated amounts of vaccines. All these elements assure a rapid vaccination coverage of the population in Lombardy, with a meaningful increase in daily administration doses.

Pressure on the Health-Care System and Intensive Care Utilization During the COVID-19 Outbreak in the Lombardy Region of Italy: A Retrospective Observational Study in 43,538 Hospitalized Patients.

During the spring of 2020, the coronavirus disease 2019 (COVID-19) epidemic caused an unprecedented demand for intensive-care resources in the Lombardy region of Italy. Using data on 43,538 hospitalized patients admitted between February 21 and July 12, 2020, we evaluated variations in intensive care unit (ICU) admissions and mortality over the course of 3 periods: the early phase of the pandemic (February 21-March 13), the period of highest pressure on the health-care system (March 14-April 25, when numbers of COVID-19 patients exceeded prepandemic ICU bed capacity), and the declining phase (April 26-July 12). Compared with the early phase, patients aged 70 years or more were less often admitted to an ICU during the period of highest pressure on the health-care system (odds ratio (OR) = 0.47, 95% confidence interval (CI): 0.41, 0.54), with longer ICU delays (incidence rate ratio = 1.82, 95% CI: 1.52, 2.18) and lower chances of dying in the ICU (OR = 0.47, 95% CI: 0.34, 0.64). Patients under 56 years of age had more limited changes in the probability of (OR = 0.65, 95% CI: 0.56, 0.76) and delay to (incidence rate ratio = 1.16, 95% CI: 0.95, 1.42) ICU admission and increased mortality (OR = 1.43, 95% CI: 1.00, 2.07). In the declining phase, all quantities decreased for all age groups. These patterns may suggest that limited health-care resources during the peak phase of the epidemic in Lombardy forced a shift in ICU admission criteria to prioritize patients with higher chances of survival.

The early phase of the COVID-19 epidemic in Lombardy, Italy.

BACKGROUND: In the night of February 20, 2020, the first epidemic of the novel coronavirus disease (COVID-19) outside Asia was uncovered by the identification of its first patient in Lombardy region, Italy. In the following weeks, Lombardy experienced a sudden increase in the number of ascertained infections and strict measures were imposed to contain the epidemic spread. METHODS: We analyzed official records of cases occurred in Lombardy to characterize the epidemiology of SARS-CoV-2 during the early phase of the outbreak. A line list of laboratory-confirmed cases was set up and later retrospectively consolidated, using standardized interviews to ascertained cases and their close contacts. We provide estimates of the serial interval, of the basic reproduction number, and of the temporal variation of the net reproduction number of SARS-CoV-2. RESULTS: Epidemiological investigations detected over 500 cases (median age: 69, IQR: 57-78) before the first COVID-19 diagnosed patient (February 20, 2020), and suggested that SARS-CoV-2 was already circulating in at least 222 out of 1506 (14.7%) municipalities with sustained transmission across all the Lombardy provinces. We estimated the mean serial interval to be 6.6 days (95% CrI, 0.7-19). Our estimates of the basic reproduction number range from 2.6 in Pavia (95% CI, 2.1-3.2) to 3.3 in Milan (95% CI, 2.9-3.8). A decreasing trend in the net reproduction number was observed following the detection of the first case. CONCLUSIONS: At the time of first case notification, COVID-19 was already widespread in the entire Lombardy region. This may explain the large number of critical cases experienced by this region in a very short timeframe. The slight decrease of the reproduction number observed in the early days after February 20, 2020 might be due to increased population awareness and early interventions implemented before the regional lockdown imposed on March 8, 2020.

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy.

Importance: In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective: To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants: Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results: Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2 was greater than 50% in 89% of patients. The median Pao2/Fio2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, -10% [95% CI, -14% to 6%]; P = .006), and median Pao2/Fio2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, -8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao2/Fio2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, -27 [95% CI, -42 to -12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age ≥64 years) had higher mortality than younger patients (n = 795; age ≤63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001). Conclusions and Relevance: In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

Nasopharyngeal Testing among Healthcare Workers (HCWs) of a Large University Hospital in Milan, Italy during Two Epidemic Waves of COVID-19.

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 < 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.

SARS-CoV-2 anti-spike antibody titres after vaccination with BNT162b2 in naïve and previously infected individuals.

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.

Seroprevalence of and Risk Factors Associated With SARS-CoV-2 Infection in Health Care Workers During the Early COVID-19 Pandemic in Italy.

Importance: Identifying health care settings and professionals at increased risk of SARS-CoV-2 infection is crucial to defining appropriate strategies, resource allocation, and protocols to protect health care workers (HCWs) and patients. Moreover, such information is crucial to decrease the risk that HCWs and health care facilities become amplifiers for SARS-CoV-2 transmission in the community. Objective: To assess the association of different health care professional categories and operational units, including in-hospital wards, outpatient facilities, and territorial care departments, with seroprevalence and odds of SARS-CoV-2 infection. Design, Setting, and Participants: This cross-sectional study was conducted using IgG serological tests collected from April 1 through May 26, 2020, in the Lombardy region in Italy. Voluntary serological screening was offered to all clinical and nonclinical staff providing any health care services or support to health care services in the region. Data were analyzed from June 2020 through April 2021. Exposures: Employment in the health care sector. Main Outcomes and Measures: Seroprevalence of positive IgG antibody tests for SARS-CoV-2 was collected, and odds ratios of experiencing infection were calculated. Results: A total of 140 782 professionals employed in the health sector were invited to participate in IgG serological screening, among whom 82 961 individuals (59.0% response rate) were tested for SARS-CoV-2 antibodies, with median (interquartile range [IQR]; range) age, 50 (40-56; 19-83) years and 59 839 (72.1%) women. Among these individuals, 10 115 HCWs (12.2%; 95% CI, 12.0%-12.4%) had positive results (median [IQR; range] age, 50 [39-55; 20-80] years; 7298 [72.2%] women). Statistically significantly higher odds of infection were found among health assistants (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33-1.65) and nurses (aOR, 1.28; 95% CI, 1.17-1.41) compared with administrative staff and among workers employed in internal medicine (aOR, 2.24; 95% CI, 1.87-2.68), palliative care (aOR, 1.84; 95% CI, 1.38-2.44), rehabilitation (aOR, 1.59; 95% CI, 1.33-1.91), and emergency departments (aOR, 1.56; 95% CI, 1.29-1.89) compared with those working as telephone operators. Statistically significantly lower odds of infection were found among individuals working in forensic medicine (aOR, 0.40; 95% CI, 0.19-0.88), histology and anatomical pathology (aOR, 0.71; 95% CI, 0.52-0.97), and medical device sterilization (aOR, 0.54; 95% CI, 0.35-0.84) compared with those working as telephone operators. The odds of infection for physicians and laboratory personnel were not statistically significantly different from those found among administrative staff. The odds of infection for workers employed in intensive care units and infectious disease wards were not statistically significantly different from those of telephone operators. Conclusions and Relevance: These findings suggest that professionals partially accustomed to managing infectious diseases had higher odds of SARS-CoV-2 infection. The findings further suggest that adequate organization of clinical wards and personnel, appropriate personal protective equipment supply, and training of all workers directly and repeatedly exposed to patients with clinical or subclinical COVID-19 should be prioritized to decrease the risk of infection in health care settings.

Age-specific SARS-CoV-2 infection fatality ratio and associated risk factors, Italy, February to April 2020.

We analysed 5,484 close contacts of coronavirus disease (COVID-19) cases in Italy, all tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection fatality ratio was 0.43% (95% confidence interval (CI): 0.21-0.79) for individuals younger than 70 years and 10.5% (95% CI: 8.0-13.6) for older individuals. Risk of death after infection was 62% lower (95% CI: 31-80) in clusters identified after 16 March 2020 and 1.8-fold higher for males (95% CI: 1.03-3.16).