Using machine learning to predict antibody response to SARS-CoV-2 vaccination in solid organ transplant recipients: the multicentre ORCHESTRA cohort.

OBJECTIVES: The study aim was to assess predictors of negative antibody response (AbR) in solid organ transplant (SOT) recipients after the first booster of SARS-CoV-2 vaccination. METHODS: Solid organ transplant recipients receiving SARS-CoV-2 vaccination were prospectively enrolled (March 2021-January 2022) at six hospitals in Italy and Spain. AbR was assessed at first dose (t0), second dose (t1), 3 ± 1 month (t2), and 1 month after third dose (t3). Negative AbR at t3 was defined as an anti-receptor binding domain titre <45 BAU/mL. Machine learning models were developed to predict the individual risk of negative (vs. positive) AbR using age, type of transplant, time between transplant and vaccination, immunosuppressive drugs, type of vaccine, and graft function as covariates, subsequently assessed using a validation cohort. RESULTS: Overall, 1615 SOT recipients (1072 [66.3%] males; mean age±standard deviation [SD], 57.85 ± 13.77) were enrolled, and 1211 received three vaccination doses. Negative AbR rate decreased from 93.66% (886/946) to 21.90% (202/923) from t0 to t3. Univariate analysis showed that older patients (mean age, 60.21 ± 11.51 vs. 58.11 ± 13.08), anti-metabolites (57.9% vs. 35.1%), steroids (52.9% vs. 38.5%), recent transplantation (<3 years) (17.8% vs. 2.3%), and kidney, heart, or lung compared with liver transplantation (25%, 31.8%, 30.4% vs. 5.5%) had a higher likelihood of negative AbR. Machine learning (ML) algorithms showing best prediction performance were logistic regression (precision-recall curve-PRAUC mean 0.37 [95%CI 0.36-0.39]) and k-Nearest Neighbours (PRAUC 0.36 [0.35-0.37]). DISCUSSION: Almost a quarter of SOT recipients showed negative AbR after first booster dosage. Unfortunately, clinical information cannot efficiently predict negative AbR even with ML algorithms.

Relationship Between Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines and Development of Breakthrough Infection in Solid Organ Transplant Recipients: The CONTRAST Cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients is associated with poorer antibody response (AbR) compared with non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) has yet to be assessed. METHODS: Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV-2 vaccination during a 1-year period (February 2021 - January 2022), end of follow-up April 2022. Patients were tested for AbR at multiple time points. The primary end-point was BI (laboratory-confirmed SARS-CoV-2 infection ≥14 days after the second dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization, and BI states were obtained for each type of graft and vaccination sequence using multistate survival analysis. Then, multivariable logistic regression was performed to analyze the risk of BI related to AbR levels. RESULTS: 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received 3 vaccine doses. The first 2 consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively. For the third dose, mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed the lowest probability of immunization (0.418) and the highest of BI (0.323); all mRNA-1273 vaccine sequences showed the highest probability of immunization (0.732) and the lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age, and shorter time from transplant. CONCLUSIONS: SOT patients with non-high-level AbR and shorter time from transplantation and heart recipients are at highest risk of BI.

Outcome of early treatment of SARS-CoV-2 infection in patients with haematological disorders.

Outcome of early treatment of COVID-19 with antivirals or anti-spike monoclonal antibodies (MABs) in patients with haematological malignancies (HM) is unknown. A retrospective study of HM patients treated for mild/moderate COVID-19 between March 2021 and July 2022 was performed. The main composite end-point was treatment failure (severe COVID-19 or COVID-19-related death). We included 328 consecutive patients who received MABs (n = 120, 37%; sotrovimab, n = 73) or antivirals (n = 208, 63%; nirmatrelvir/ritonavir, n = 116) over a median of two days after symptoms started; 111 (33.8%) had non-Hodgkin lymphoma (NHL); 89 (27%) were transplant/CAR-T (chimaeric antigen receptor T-cell therapy) recipients. Most infections (n = 309, 94%) occurred during the Omicron period. Failure developed in 31 patients (9.5%). Its independent predictors were older age, fewer vaccine doses, and treatment with MABs. Rate of failure was lower in the Omicron versus the pre-Omicron period (7.8% versus 36.8%, p < 0.001). During the Omicron period, predictors of failure were age, fewer vaccine doses and diagnosis of acute myeloid leukaemia/myelodysplastic syndrome (AML/MDS). Independent predictors of longer viral shedding were age, comorbidities, hospital admission at diagnosis, NHL/CLL, treatment with MABs. COVID-19-associated mortality was 3.4% (n = 11). The mortality in those who developed severe COVID-19 after early treatment was 26% in the Omicron period. Patients with HM had a significant risk of failure of early treatment, even during the Omicron period, with high mortality rate.

Effect of a Fourth Dose of mRNA Vaccine and of Immunosuppression in Preventing SARS-CoV-2 Breakthrough Infections in Heart Transplant Patients.

Patients with heart transplantation (HT) have an increased risk of COVID-19 disease and the efficacy of vaccines on antibody induction is lower, even after three or four doses. The aim of our study was to assess the efficacy of four doses on infections and their interplay with immunosuppression. We included in this retrospective study all adult HT patients (12/21-11/22) without prior infection receiving a third or fourth dose of mRNA vaccine. The endpoints were infections and the combined incidence of ICU hospitalizations/death after the last dose (6-month survival rate). Among 268 patients, 62 had an infection, and 27.3% received four doses. Following multivariate analysis, three vs. four doses, mycophenolate (MMF) therapy, and HT < 5 years were associated with an increased risk of infection. MMF ≥ 2000 mg/day independently predicted infection, together with the other variables, and was associated with ICU hospitalization/death. Patients on MMF had lower levels of anti-RBD antibodies, and a positive antibody response after the third dose was associated with a lower probability of infection. In HT patients, a fourth dose of vaccine against SARS-CoV-2 reduces the risk of infection at six months. Mycophenolate, particularly at high doses, reduces the clinical effectiveness of the fourth dose and the antibody response to the vaccine.

Predictors of clinical evolution of SARS-CoV-2 infection in hematological patients: A systematic review and meta-analysis.

Main aim of this systematic review is to quantify the risk and identify predictors of clinical evolution of SARS-CoV-2 in hematological patients compared to different control populations. Two independent reviewers screened the literature assessing clinical outcomes of SARS-CoV-2 infection in adult patients with active hematological malignancies published up to June 2021. Primary outcome was COVID-19 related mortality, secondary outcomes were hospital and intensive-care admission, mechanical ventilation (MV), and thromboembolic events. Variables related to study setting, baseline patients' demographic, comorbidities, underlying hematological disease, ongoing chemotherapy, COVID-19 presentation, and treatments were extracted. A total of 67 studies including 10,061 hematological patients and 111,143 controls were included. Most of the studies were retrospective cohorts (51 studies, 76%) and only 19 (13%) provided data for a control group. A significant increased risk of clinical progression in the hematological population compared to the controls was found in terms of COVID-19 related mortality (OR, 2.12; 95% CI, 1.77-2.54), hospitalization (OR, 1.98; 95% CI, 1.15-3.43), intensive-care admission (OR, 1.77; 95% CI, 1.38-2.26), and MV (OR, 2.17; 95% CI, 1.71-2.75). The risk remained significantly higher in the subgroup analysis comparing hematological patients versus solid cancer. Meta-regression analysis of uncontrolled studies showed that older age, male sex, and hypertension were significantly related to worse clinical outcomes of COVID-19 in hematological population. Older age and hypertension were found to be associated also to thromboembolic events. In conclusion, hematological patients have a higher risk of COVID-19 clinical progression compared to both the general population and to patients with solid cancer.

Risk factors associated with bacteremia in COVID-19 patients admitted to intensive care unit: a retrospective multicenter cohort study.

PURPOSE: This multicenter observational study was done to evaluate risk factors related to the development of BSI in patients admitted to ICU for COVID-19. METHODS: All patients with COVID-19 admitted in two COVID-19 dedicated ICUs in two different hospital between 02-2020 and 02-2021 were recruited. RESULT: 537 patients were included of whom 265 (49.3%) experienced at least one BSI. Patients who developed bacteremia had a higher SOFA score [10 (8-12) vs 9 (7-10), p < 0.001], had been intubated more frequently [95.8% vs 75%, p < 0.001] and for a median longer time [16 days (9-25) vs 8 days (5-14), p < 0.001]. Patients with BSI had a median longer ICU stay [18 days (12-31.5) vs 9 days (5-15), p < 0.001] and higher mortality [54% vs 42.3%, p < 0.001] than those who did not develop it. Development of BSI resulted in a higher SOFA score [aHR 1.08 (95% CI 1.03-1.12)] and a higher Charlson score [csAHR 1.15 (95% CI 1.05-1.25)]. CONCLUSION: A high SOFA score and a high Charlson score resulted associated with BSI's development. Conversely, immunosuppressive therapy like steroids and tocilizumab, has no role in increasing the risk of bacteremia.

Association of Patients' Epidemiological Characteristics and Comorbidities with Severity and Related Mortality Risk of SARS-CoV-2 Infection: Results of an Umbrella Systematic Review and Meta-Analysis.

The objective of this study was to assess the association between patients' epidemiological characteristics and comorbidities with SARS-CoV-2 infection severity and related mortality risk. An umbrella systematic review, including a meta-analysis examining the association between patients' underlying conditions and severity (defined as need for hospitalization) and mortality of COVID-19, was performed. Studies were included if they reported pooled risk estimates of at least three underlying determinants for hospitalization, critical disease (ICU admission, mechanical ventilation), and hospital mortality in patients diagnosed with SARS-CoV-2 infection. Evidence was summarized as pooled odds ratios (pOR) for disease outcomes with 95% confidence intervals (95% CI). Sixteen systematic reviews investigating the possible associations of comorbidities with severity or death from COVID-19 disease were included. Hospitalization was associated with age > 60 years (pOR 3.50; 95% CI 2.97-4.36), smoking habit (pOR 3.50; 95% CI 2.97-4.36), and chronic pulmonary disease (pOR 2.94; 95% CI 2.14-4.04). Chronic pulmonary disease (pOR 2.82; 95% CI 1.92-4.14), cerebrovascular disease (pOR 2.74; 95% CI 1.59-4.74), and cardiovascular disease (pOR 2.44; 95% CI 1.97-3.01) were likely to be associated with increased risk of critical COVID-19. The highest risk of mortality was associated with cardiovascular disease (pOR 3.59; 95% CI 2.83-4.56), cerebrovascular disease (pOR 3.11; 95% CI 2.35-4.11), and chronic renal disease (pOR 3.02; 95% CI 2.61-3.49). In conclusion, this umbrella systematic review provides a comprehensive summary of meta-analyses examining the impact of patients' characteristics on COVID-19 outcomes. Elderly patients and those cardiovascular, cerebrovascular, and chronic renal disease should be prioritized for pre-exposure and post-exposure prophylaxis and early treatment.

Rapid diagnostic tests in the management of pneumonia.

INTRODUCTION: Pneumonia is one of the main causes of mortality associated with infectious diseases worldwide. Several challenges have been identified in the management of patients with pneumonia, ranging from accurate and cost-effective microbiological investigations, prompt and adequate therapeutic management, and optimal treatment duration. AREAS COVERED: In this review, an updated summary on the current management of pneumonia patients is provided and the epidemiological issues of infectious respiratory diseases, which in the current pandemic situation are of particular concern, are addressed. The clinical and microbiological approaches to pneumonia diagnosis are reviewed, including discussion about the new molecular assays pointing out both their strengths and limitations. Finally, the current recommendations about antibiotic treatment are examined and discussed depending on the epidemiological contexts, including those with high prevalence of multidrug-resistant bacteria. EXPERT OPINION: We claim that rapid diagnostic tests, if well-positioned in the diagnostic workflow and reserved for the subset of patients who could most benefit from these technologies, may represent an interesting and feasible tool to optimize timing of targeted treatments especially in terms of early de-escalation or discontinuation of antibiotic therapy.

Harmonization and standardization of data for a pan-European cohort on SARS- CoV-2 pandemic.

The European project ORCHESTRA intends to create a new pan-European cohort to rapidly advance the knowledge of the effects and treatment of COVID-19. Establishing processes that facilitate the merging of heterogeneous clusters of retrospective data was an essential challenge. In addition, data from new ORCHESTRA prospective studies have to be compatible with earlier collected information to be efficiently combined. In this article, we describe how we utilized and contributed to existing standard terminologies to create consistent semantic representation of over 2500 COVID-19-related variables taken from three ORCHESTRA studies. The goal is to enable the semantic interoperability of data within the existing project studies and to create a common basis of standardized elements available for the design of new COVID-19 studies. We also identified 743 variables that were commonly used in two of the three prospective ORCHESTRA studies and can therefore be directly combined for analysis purposes. Additionally, we actively contributed to global interoperability by submitting new concept requests to the terminology Standards Development Organizations.

Evaluation of the Kinetics of Antibody Response to COVID-19 Vaccine in Solid Organ Transplant Recipients: The Prospective Multicenter ORCHESTRA Cohort.

Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients' characteristics.

Predictive model for bacterial co-infection in patients hospitalized for COVID-19: a multicenter observational cohort study.

OBJECTIVE: The aim of our study was to build a predictive model able to stratify the risk of bacterial co-infection at hospitalization in patients with COVID-19. METHODS: Multicenter observational study of adult patients hospitalized from February to December 2020 with confirmed COVID-19 diagnosis. Endpoint was microbiologically documented bacterial co-infection diagnosed within 72 h from hospitalization. The cohort was randomly split into derivation and validation cohort. To investigate risk factors for co-infection univariable and multivariable logistic regression analyses were performed. Predictive risk score was obtained assigning a point value corresponding to ß-coefficients to the variables in the multivariable model. ROC analysis in the validation cohort was used to estimate prediction accuracy. RESULTS: Overall, 1733 patients were analyzed: 61.4% males, median age 69 years (IQR 57-80), median Charlson 3 (IQR 2-6). Co-infection was diagnosed in 110 (6.3%) patients. Empirical antibiotics were started in 64.2 and 59.5% of patients with and without co-infection (p = 0.35). At multivariable analysis in the derivation cohort: WBC ≥ 7.7/mm3, PCT ≥ 0.2 ng/mL, and Charlson index ≥ 5 were risk factors for bacterial co-infection. A point was assigned to each variable obtaining a predictive score ranging from 0 to 5. In the validation cohort, ROC analysis showed AUC of 0.83 (95%CI 0.75-0.90). The optimal cut-point was ≥2 with sensitivity 70.0%, specificity 75.9%, positive predictive value 16.0% and negative predictive value 97.5%. According to individual risk score, patients were classified at low (point 0), intermediate (point 1), and high risk (point ≥ 2). CURB-65 ≥ 2 was further proposed to identify patients at intermediate risk who would benefit from early antibiotic coverage. CONCLUSIONS: Our score may be useful in stratifying bacterial co-infection risk in COVID-19 hospitalized patients, optimizing diagnostic testing and antibiotic use.

Clinical outcome in solid organ transplant recipients affected by COVID-19 compared to general population: a systematic review and meta-analysis.

BACKGROUND: A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in solid organ transplant (SOT) recipients is an issue still under debate, due to conflicting evidence that has emerged from different observational studies. OBJECTIVES: We performed a systematic review with a meta-analysis to assess the clinical outcome in SOT recipients with COVID-19 compared with the general population. DATA SOURCES: PubMed-MEDLINE and Scopus were independently searched until 13 October 2021. STUDY ELIGIBILITY CRITERIA: Prospective or retrospective observational studies comparing clinical outcome in SOT recipients versus general populations affected by COVID-19 were included. The primary endpoint was 30-day mortality. PARTICIPANTS: Participants were patients with confirmed COVID-19. INTERVENTIONS: Interventions reviewed were SOTs. METHODS: The quality of the included studies was independently assessed with the Risk of Bias in Non-randomized Studies of Interventions tool for observational studies. The meta-analysis was performed by pooling ORs retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity. RESULTS: A total of 3501 articles were screened, and 31 observational studies (N = 590 375; 5759 SOT recipients vs. 584 616 general population) were included in the meta-analyses. No difference in 30-day mortality rate was found in the primary analysis, including studies providing adjustment for confounders (N = 17; 3752 SOT recipients vs. 159 745 general population; OR: 1.13; 95% CI, 0.94-1.35; I2 = 33.9%). No evidence of publication bias was reported. A higher risk of intensive care unit admission (OR: 1.56; 95% CI, 1.03-2.63) and occurrence of acute kidney injury (OR: 2.50; 95% CI, 1.81-3.45) was found in SOT recipients. CONCLUSIONS: No increased risk in mortality was found in SOT recipients affected by COVID-19 compared with the general population when adjusted for demographic and clinical features and COVID-19 severity.

Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study.

OBJECTIVES: To analyse the impact of cefiderocol use on outcome in patients admitted to the ICU for severe COVID-19 and further diagnosed with carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. METHODS: Retrospective multicentre observational study was performed at four Italian hospitals, from January 2020 to April 2021. Adult patients admitted to ICU for severe COVID-19 and further diagnosed with CR-Ab infections were enrolled. Patients treated with cefiderocol, as compassionate use, for at least 72 h were compared with those receiving alternative regimens. Primary endpoint was all-cause 28 day mortality. The impact of cefiderocol on mortality was evaluated by multivariable Cox regression model. RESULTS: In total, 107 patients were enrolled (76% male, median age 65 years). The median time from ICU admission to CR-Ab infection diagnosis was 14 (IQR 8-20) days, and the main types of CR-Ab infections were bloodstream infection (58%) and lower respiratory tract infection (41%). Cefiderocol was administered to 42 patients within a median of 2 (IQR 1-4) days after CR-Ab infection diagnosis and as monotherapy in all cases. The remaining patients received colistin, mostly (82%) administered as combination therapy. All-cause 28 day mortality rate was 57%, without differences between groups (cefiderocol 55% versus colistin 58% P = 0.70). In multivariable analysis, the independent risk factor for mortality was SOFA score (HR 1.24, 95% CI 1.15-1.38, P < 0.001). Cefiderocol was associated with a non-significant lower mortality risk (HR 0.64, 95% CI 0.38-1.08, P = 0.10). CONCLUSIONS: Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.

SARS-CoV-2 vaccination in solid-organ transplant recipients: What the clinician needs to know.

In response to the COVID-19 pandemic, SARS-CoV-2 vaccines have been developed at an unparalleled speed, with 14 SARS-CoV-2 vaccines currently authorized. Solid-organ transplant (SOT) recipients are at risk for developing a higher rate of COVID-19-related complications and therefore they are at priority for immunization against SARS-CoV-2. Preliminary data suggest that although SARS-CoV-2 vaccines are safe in SOT recipients (with similar rate of adverse events than in the general population), the antibody responses are decreased in this population. Risk factors for poor vaccine immunogenicity include older age, shorter time from transplantation, use of mycophenolate and belatacept, and worse allograft function. SOT recipients should continue to be advised to maintain hand hygiene, use of facemasks, and social distancing after SARS-CoV-2 vaccine. Vaccination of household contacts should be also prioritized. Although highly encouraged for research purposes, systematic assessment in clinical practice of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, since correlation between immunological findings and clinical protection from severe COVID-19, and cutoffs for protection are currently unknown in SOT recipients. Alternative immunization schemes, including a booster dose, higher doses, and modulation of immunosuppression during vaccination, need to be assessed in the context of well-designed clinical trials.

Carbapenem-resistant bacteria in an intensive care unit during the coronavirus disease 2019 (COVID-19) pandemic: A multicenter before-and-after cross-sectional study.

OBJECTIVE: To assess the incidence of colonization and infection with carbapenemase-producing Enterobacteriaceae (CPE) and carbapenem-resistant Acinetobacter baumannii (CR-Ab) in the ICUs of our city hospitals before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a multicenter, before-and-after, cross-sectional study to compare the rates of colonization and infection with CPE and/or CR-Ab in 2 study periods, period 1 (January-April 2019) and period 2 (January-April 2020). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of weekly colonization and infection rates for each period were compared for the 2 study periods using Poisson regression. Weekly trends in the incidence of colonization or infection for each study period were summarized using local weighted (Loess) regression. RESULTS: We detected no significant change in either IRR and weekly trend in CPE colonization and infection during the 2 study periods. A shift from KPC to other CPE mechanisms (OXA-48 and VIM) was observed during period 2. Compared to period 1, during period 2 the IRR of colonization and infection with CR-Ab increased 7.5- and 5.5-fold, respectively. Genome sequencing showed that all CR-Ab strains belonged to the CC92/IC2 clonal lineage. Clinical strains clustered closely into a single monophyletic group in 1 of the 3 centers, whereas they segregated in 2 different clusters in the other 2 centers, which strongly indicates horizontal transmission. CONCLUSIONS: Our findings indicate the need to conduct infection control activities targeted against the spread of antimicrobial resistance between and within hospitals during the COVID-19 pandemic, and if necessary, remodulating them according to the new organizational structures imposed by the pandemic.

The Gut Microbiota of Critically Ill Patients With COVID-19.

The SARS-CoV-2-associated COVID-19 pandemic has shaken the global healthcare system. Although the best-known symptoms are dry cough and pneumonia, viral RNA has been detected in the stool and about half of COVID-19 patients exhibit gastrointestinal upset. In this scenario, special attention is being paid to the possible role of the gut microbiota (GM). Fecal samples from 69 COVID-19 patients from three different hospitals of Bologna (Italy) were analyzed by 16S rRNA gene-based sequencing. The GM profile was compared with the publicly available one of healthy age- and gender-matched Italians, as well as with that of other critically ill non-COVID-19 patients. The GM of COVID-19 patients appeared severely dysbiotic, with reduced diversity, loss of health-associated microorganisms and enrichment of potential pathogens, particularly Enterococcus. This genus was far overrepresented in patients developing bloodstream infections (BSI) and admitted to the intensive care unit, while almost absent in other critically ill non-COVID-19 patients. Interestingly, the percentage of patients with BSI due to Enterococcus spp. was significantly higher during the COVID-19 pandemic than in the previous 3 years. Monitoring the GM of critically ill COVID-19 patients could help clinical management, by predicting the onset of medical complications such as difficult-to-treat secondary infections.

Effective Containment of a COVID-19 Subregional Outbreak in Italy Through Strict Quarantine and Rearrangement of Local Health Care Services.

BACKGROUND: Since the beginning of the pandemic, the epidemiology of coronavirus disease 2019 (COVID-19) in Italy has been characterized by the occurrence of subnational outbreaks. The World Health Organization recommended building the capacity to rapidly control COVID-19 clusters of cases in order to avoid the spread of the disease. This study describes a subregional outbreak of COVID-19 that occurred in the Emilia Romagna region, Italy, and the intervention undertaken to successfully control it. METHODS: Cases of COVID-19 were defined by a positive reverse transcriptase polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on nasopharyngeal swab. The outbreak involved the residential area of a small town, with ~10 500 inhabitants in an area of 9 km2. After the recognition of the outbreak, local health care authorities implemented strict quarantine and a rearrangement of health care services, consisting of closure of general practitioner outpatient clinics, telephone contact with all residents, activation of health care units to visit at-home patients with symptoms consistent with COVID-19, and a dedicated Infectious Diseases ambulatory unit at the nearest hospital. RESULTS: The outbreak lasted from February 24 to April 6, 2020, involving at least 170 people with a cumulative incidence of 160 cases/10 000 inhabitants; overall, 448 inhabitants of the municipality underwent at least 1 nasopharyngeal swab to detect SARS-CoV-2 (positivity rate, 38%). Ninety-three people presented symptoms before March 11 (pre-intervention period), and 77 presented symptoms during the postintervention period (March 11-April 6). CONCLUSIONS: It was possible to control this COVID-19 outbreak by prompt recognition and implementation of a targeted local intervention.