Rilpivirine and cabotegravir trough concentrations in people with HIV on long-term treatment with long-acting injectable antiretrovirals.

OBJECTIVE: Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. METHODS: Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated. RESULTS: Sixty-seven PWH were identified. LAI treatment duration was 216 ±â€Š80 weeks (range 32-320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; P < 0.05). No differences were found in rilpivirine (160 ±â€Š118 versus 189 ±â€Š81 ng/mL; P = 0.430) and cabotegravir (1758 ±â€Š807 versus 1969 ±â€Š802 ng/mL; P = 0.416) trough concentrations in males (n = 55) versus females (n = 12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (n = 9) versus non-obese participants (1916 ±â€Š905 versus 1606 ±â€Š576 ng/mL; P = 0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load. CONCLUSIONS: At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included.

Anal HPV prevalence in individuals with and without other concomitant sexually transmitted infections.

The association between human papillomavirus (HPV) and other sexually transmitted infections (STIs) in anal lesions still remains unclear. Aim of the study was to evaluate the prevalence of simultaneous infection of HPV and Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis in individuals screened for HPV anal infection. A total of 507 anal samples were tested for both anal HPV and STIs: 16% resulted positive for one or more non-HPV STIs. Specifically, C. trachomatis, M. genitalium, and N. gonorrhoeae were detected in 8%, 5%, and 4% of cases, respectively. Two groups were considered, including a positive STI group and a negative STI group. The prevalence of HPV was similar in patients in both groups: high risk (HR)-HPV and low risk (LR)-HPV were 67% and 53% versus 62% (p = 0.361) and 54% (p = 0.864) of patients, respectively. However, HPV 16, 18, 35, 51, 59, and 69 were significantly more frequent in patients tested positive for other STIs versus HPV infection alone (p < 0.05). No significant differences between the two groups were observed in vaccination coverage, 28% versus 32% (p = 0.463), and HIV status, 86% versus 84% (p = 0.658). The study shows that the overall HPV status is not directly correlated to other STIs in the investigated population, except for certain HPV types, including HR-HPV 16, reinforcing the urge for a greater vaccination coverage.

High prevalence of high-risk HPV genotypes in individuals attending an infectious diseases clinic from 2018 to 2022 in Milan, Italy.

Human papillomavirus (HPV) is the most common sexually transmitted infection, linked to several types of lesions. HPV, specifically HPV 16, accounts for most of anal cancer cases. In this study, we evaluated the proportion of samples tested positive for HPV and characterized genotypes distribution in anal specimens collected from individuals at risk of anal HPV infection attending from 2018 to 2022 a large Infectious Diseases Department in Italy. The presence of HPV DNA was investigated through a commercial kit detecting 12 HR-HPV, 8 probable/possible HR-HPV, and 8 LR-HPV genotypes. Among 1514 samples, 84% (1266/1514) resulted positive for any type of HPV. The prevalence of high-risk HPV types remained high during all the years of the study period, from 2018 to 2022, ranging from 65% to 73%. Most of HR-HPV, LR-HPV and HPV 16 positive samples were collected from men >45 years. HPV 16 was also the most frequent type in men and women. We did not observe significant variations between years in detection of HR-HPV, instead of LR-HPV, that significantly decreased. In conclusion, the high prevalence of oncogenic HPV genotypes underlines the necessity of clear anal HPV screening guidelines and, along with frequent HR-HPV coinfections, reinforces the urge to intensify the anti-HPV vaccination campaign.

Early administration of nirmatrelvir/ritonavir leads to faster negative SARS-CoV-2 nasal swabs than monoclonal antibodies in COVID 19 patients at high-risk for severe disease.

PURPOSE: Besides the well-established efficacy in preventing severe COVID-19, the impact of early treatments, namely antivirals and monoclonal antibodies (mAbs), on the time length to negativization of SARS-CoV-2 nasal swabs is still unclear. The aim of this study was to compare the efficacy of different early treatments in reducing the SARS-CoV-2 viral shedding, identifying a single drug that might potentially lead to a more rapid negativization of SARS-CoV-2 nasal swab. METHODS: This was a single-centre, retrospective, observational study conducted at Ospedale Luigi Sacco in Milan. Data of high-risk COVID-19 patients who received early treatments between 23 December 2021 and March 2023 were extracted. The comparison across treatments was conducted using the Kruskall-Wallis test for continuous variables. Dunn's test with Bonferroni adjustment was performed for post-hoc comparisons of days to negativization. Secondly, a negative binomial regression adjusted for age, sex, number of comorbidities, immunosuppression, and SARS-CoV-2 vaccination status was implemented. RESULTS: Data from 428 patients receiving early treatments were collected. The majority were treated with Nirmatrelvir/Ritonavir and were affected by SARS-CoV-2 Omicron infection with BA.2 sublineage. The median length time to SARS-CoV-2 nasal swab negativization was 9 days [IQR 7-13 days]. We found that Nirmatrelvir/Ritonavir determined a significant decrease of the length time to SARS-CoV-2 nasal swab negativization compared to mAbs (p = 0.003), but not compared to Remdesivir (p = 0.147) and Molnupiravir (p = 0.156). CONCLUSION: Our findings highlight the importance of promptly treating high-risk COVID-19 patients with Nirmatrelvir/Ritonavir, as it also contributes to achieving a faster time to negative SARS-CoV-2 nasal swabs.

First imported case of Candida auris infection in Milan, Italy: genomic characterisation.

PURPOSE: Candida auris, an emerging multidrug-resistant yeast, has been reported worldwide. In Italy, the first case was reported in 2019. We describe the first case of C. auris, imported from Greece, in Milan, using whole genome sequencing to characterise mutations associated with antifungal resistance. CASE PRESENTATION: On October 2022 an 80-year-old Italian man was hospitalised in Greece. In the absence of clinical improvement, the patient was transferred to our hospital, in Italy, where blood culture resulted positive for C. auris. Despite therapy, the patient died of septic shock. In a phylogenetic analysis the genome was assigned to Clade I with strains from Kenya, United Arab Emirates and India. D1/D2 region resulted identical to a Greek strain, as for many other strains from different World regions, highlighting the diffusion of this strain. CONCLUSION: Importation of C. auris from abroad has been previously described. We report the first case of C. auris imported into Italy from Greece, according to phylogenetic analysis. This case reinforces the need for monitoring critically ill hospitalised patients also for fungi and addresses the need for the standardisation of susceptibility testing and strategies for diagnosis and therapy.

Major Bleeding Events in Hospitalized COVID-19 Patients: A Retrospective Observational Study.

Thromboprophylaxis/anticoagulation treatment is often required in hospitalized COVID-19 patients. We aimed to estimate the prevalence of major bleeding events in hospitalized COVID-19 patients. This was a retrospective observational study including all COVID-19 hospitalized patients ≥18 years of age at one reference center in northern Italy. The crude prevalence (between February 2020-2022) of major bleeding events was estimated as the number of major bleeding episodes divided by patients at risk. Uni- and multivariable Cox models were built to assess factors potentially associated with major bleeding events. Twenty-nine (0.98%) out of 2,945 COVID-19 patients experienced a major bleeding event [prevalence of 0.55% (95%CI 0.37-0.79)], of which five were fatal. Patients who experienced a major bleeding event were older [78 years (72-84 IQR) vs. 67 years (55-78 IQR), p-value < 0.001] and more frequently exposed to anti-aggregating therapy (44.8% vs. 20.0%, p-value 0.002) when compared to those who did not. In the multivariable Cox model, age [per 1 year more AHR 1.05 (CI95% 1.02-1.09)] was independently associated with an increased risk of major bleeding events. A strict monitoring of older hospitalized COVID-19 patients is warranted due to the risk of major bleeding events.

The Defenders of the Alveolus Succumb in COVID-19 Pneumonia to SARS-CoV-2 and Necroptosis, Pyroptosis, and PANoptosis.

Alveolar type II (ATII) pneumocytes as defenders of the alveolus are critical to repairing lung injury. We investigated the ATII reparative response in coronavirus disease 2019 (COVID-19) pneumonia, because the initial proliferation of ATII cells in this reparative process should provide large numbers of target cells to amplify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus production and cytopathological effects to compromise lung repair. We show that both infected and uninfected ATII cells succumb to tumor necrosis factor-α (TNF)-induced necroptosis, Bruton tyrosine kinase (BTK)-induced pyroptosis, and a new PANoptotic hybrid form of inflammatory cell death mediated by a PANoptosomal latticework that generates distinctive COVID-19 pathologies in contiguous ATII cells. Identifying TNF and BTK as the initiators of programmed cell death and SARS-CoV-2 cytopathic effects provides a rationale for early antiviral treatment combined with inhibitors of TNF and BTK to preserve ATII cell populations, reduce programmed cell death and associated hyperinflammation, and restore functioning alveoli in COVID-19 pneumonia.

Long-term outcome of dolutegravir-containing regimens according to sex: data from the ICONA study.

OBJECTIVES: To compare the long-term risk of treatment failure of dolutegravir-based ART in men and women in a real-life setting. PATIENTS AND METHODS: Persons living with HIV (PLWH) from the ICONA cohort were included if they had started dolutegravir in a two- or three-drug regimen as ART-naive or as virologically controlled ART-experienced. The primary endpoint was time to treatment failure (virological/clinical failure or dolutegravir discontinuation). Secondary endpoints were: time to dolutegravir discontinuation due to toxicity and to neuropsychiatric adverse events; and time to virological failure. Cox regression analyses focused on differences in outcomes by sex. RESULTS: A total of 2304 PLWH (15% women) initiated dolutegravir-based therapy from ART-naive, and 1916 (19.8% women) while experienced. After a median follow-up of 2.2 (IQR: 0.9-3.9) years in ART-naive and 2.4 (IQR: 1.1-4.3) years in experienced, the 4-year cumulative probability of treatment failure was 33% (95% CI 30.5-35.1) and 20% (95% CI 17.8-22.3), respectively. In the multivariable analyses, in ART-naive the risk of treatment failure was higher for women, but not different after excluding women discontinuing dolutegravir for pregnancy concerns. We also observed a higher risk of discontinuation for toxicity in women (ART-naives: Adjusted Hazard Ratio (AHR): 1.56%; 95% CI: 1.03-2.37; ART-experienced: AHR: 1.53%; 95% CI: 1.01-2.32), although the absolute 4-year probability was low: 7.7% (95% CI 6.5-9.2) in ART-naive and 8.3% (95% CI 6.9-9.9) in experienced. CONCLUSIONS: In our cohort of PLWH treated with dolutegravir-based regimens and followed up for up to 4 years, we observed a low risk of treatment failure and no evidence for a difference by sex, after excluding discontinuation due to pregnancy concerns. However, we observed a higher risk of dolutegravir discontinuation for toxicity in women.

Concomitant diagnosis of sexually transmitted infections and human monkeypox in patients attending a sexual health clinic in Milan, Italy.

In 2022, many monkeypox (MPX) outbreaks have been documented in countries where MPX was not endemic. It spread all around the world, especially in European Union and United States. While MPX is classically considered to be transmitted through close contact with lesions, the hypothesis of sexual transmission has been proposed. This study considered a total of 49 patients suspected for MPX that were also tested for other sexually transmitted infections (STIs), including Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis. The data from coinfected patients suggested that MPXV and STIs might share the same route of inoculum, corroborating the hypothesis of possible sexual transmission for the emerging poxvirus. And like any other STI, MPX should be considered without stigmatization.

Efficacy and tolerability of dolutegravir/lamivudine versus dolutegravir/rilpivirine in switching from a three-drug regimen based on nonnucleoside reverse transcriptase inhibitors: A retrospective cohort study.

Real-life comparisons of dolutegravir/rilpivirine (DTG/RPV) and DTG/lamivudine (3TC) regimens in people living with human immunodeficiency virus (PLWHIV) who switched from a standard three-drug regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTIs) are missing. This study aimed to compare DTG/3TC and DTG/RPV in virologically suppressed patients (HIV-RNA < 50 copies/mL) coming from any NNRTI-based regimen in terms of discontinuation due to virologic failure (VF) discontinuation rates due to all causes, and adverse events. As a secondary outcome, we evaluated the difference in creatinine, total cholesterol, CD4, and triglycerides from baseline to weeks 48 after the switch. Of the 415 PLWHs included in the study, 278 (66.9%) switched to DTG/3TC, and 137 (33.1%) switched to DTG/RPV. Overall, 48 PLWHs (11.6%) discontinued the treatment:38 with DTG/3TC and 10 with DTG/RPV with similar discontinuation rates: 5.01 × 100 py (95% confidence interval [CI] 3.64-6.94) and 4.66 × 100 py (95% CI 2.51-8.67), respectively. The most common reason for discontinuation was toxicity (26 patients, 22/278 [7.9%] in the DTG/3TC group and 4/137 [2.9%] in the DTG/RPV group), mainly neurologic toxicity (never above grade 2). We found no differences in discontinuation rates due to treatment adverse events. Two study participants experienced virological failure in the DTG/3TC arm. We observed no significant difference in CD4 cell counts, lipid parameters, or renal function between the two groups at 48 weeks. This study demonstrated that, in clinical practice, a two-drug regimen with DTG/3TC or DTG/RPV is characterized by a low discontinuation rate and VF in virologically suppressed PLWHs switched from an NNRTI-based three antiretroviral drugs regimen.

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.

Neglected Tropical Diseases in Italy: introducing IN-NTD, the Italian network for NTDs.

The World Health Organization (WHO) defines neglected tropical diseases (NTDs) as a diverse group of primarily infectious diseases, which disproportionately affect poor and marginalized populations worldwide. In this context, NTDs are responsible for important morbidity and mortality and justify a global response. Moreover, NTDs are relatively neglected by research and development as well as by funding, if compared with the magnitude of the public health problem they represent. This happens even though, unlike other infectious diseases, they can be prevented, controlled and eliminated by targeted public health interventions. NTDs are mainly prevalent in communities from low-income countries in tropical and sub-tropical areas but are also present in upper­middle-income countries, including several in Europe. Here, we provide an update on the most relevant parasitic endemic or imported NTDs in Italy and illustrate the rationale for the establishment of the Italian network on NTDs, an alliance of scientific societies, institutes, foundations, universities and non-profit organizations united to fight NTDs.

Evaluation of residual humoral immune response against SARS-CoV-2 by a surrogate virus neutralization test (sVNT) 9 months after BNT162b2 primary vaccination.

The humoral response to SARS-CoV-2 vaccination has shown to be temporary, although may be more prolonged in vaccinated individuals with a history of natural infection. We aimed to study the residual humoral response and the correlation between anti-Receptor Binding Domain (RBD) IgG levels and antibody neutralizing capacity in a population of health care workers (HCWs) after 9 months from COVID-19 vaccination. In this cross-sectional study, plasma samples were screened for anti-RBD IgG using a quantitative method. The neutralizing capacity for each sample was estimated by means of a surrogate virus neutralizing test (sVNT) and results expressed as the percentage of inhibition (%IH) of the interaction between RBD and the angiotensin-converting enzyme. Samples of 274 HCWs (227 SARS-CoV-2 naïve and 47 SARS-CoV-2 experienced) were tested. The median level of anti-RBD IgG was significantly higher in SARS-CoV-2 experienced than in naïve HCWs: 2673.2 AU/mL versus 610.9 AU/mL, respectively (p <0.001). Samples of SARS-CoV-2 experienced subjects also showed higher neutralizing capacity as compared to naïve subjects: median %IH = 81.20% versus 38.55%, respectively; p <0.001. A quantitative correlation between anti-RBD Ab and inhibition activity levels was observed (Spearman's rho = 0.89, p <0.001): the optimal cut-off correlating with high neutralization was estimated to be 1236.1 AU/mL (sensitivity 96.8%, specificity 91.9%; AUC 0.979). Anti-SARS-CoV-2 hybrid immunity elicited by a combination of vaccination and infection confers higher anti-RBD IgG levels and higher neutralizing capacity than vaccination alone, likely providing better protection against COVID-19.

On-chip magnetophoretic capture in a model of malaria-infected red blood cells.

The search for new rapid diagnostic tests for malaria is a priority for developing an efficient strategy to fight this endemic disease, which affects more than 3 billion people worldwide. In this study, we characterize systematically an easy-to-operate lab-on-chip, designed for the magnetophoretic capture of malaria-infected red blood cells (RBCs). The method relies on the positive magnetic susceptibility of infected RBCs with respect to blood plasma. A matrix of nickel posts fabricated in a silicon chip placed face down is aimed at attracting infected cells, while healthy cells sediment on a glass slide under the action of gravity. Using a model of infected RBCs, that is, erythrocytes with methemoglobin, we obtained a capture efficiency of about 70% after 10 min in static conditions. By proper agitation, the capture efficiency reached 85% after just 5 min. Sample preparation requires only a 1:10 volume dilution of whole blood, previously treated with heparin, in a phosphate-buffered solution. Nonspecific attraction of untreated RBCs was not observed in the same time interval.

Mortality among Italians and immigrants with COVID-19 hospitalised in Milan, Italy: data from the Luigi Sacco Hospital registry.

BACKGROUND: To compare differences in the probability of COVID-19-related death between native Italians and immigrants hospitalised with COVID-19. METHODS: This retrospective study of prospectively collected data was conducted at the ASST Fatebenefratelli-Sacco Hospital in Milan, Italy, between 21 February and 31 November 2020. Uni- and multivariable Cox proportional hazard models were used to assess the impact of the patients' origin on the probability of COVID-19-related death. RESULTS: The study population consisted of 1,179 COVID-19 patients: 921 Italians (78.1%) and 258 immigrants (21.9%) who came from Latin America (99, 38%), Asia (72, 28%), Africa (50, 19%) and central/eastern Europe (37, 14%). The Italians were significantly older than the immigrants (median age 70 years, interquartile range (IQR) 58-79 vs 51 years, IQR 41-60; p < 0.001), and more frequently had one or more co-morbidities (79.1% vs 53.9%; p < 0.001). Mortality was significantly greater among the Italians than the immigrants as a whole (26.6% vs 12.8%; p < 0.001), and significantly greater among the immigrants from Latin America than among those from Asia, Africa or central/eastern Europe (21% vs 8%, 6% and 8%; p = 0.016). Univariable analysis showed that the risk of COVID-19-related death was lower among the immigrants (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.30-0.63; p < 0.0001], but the risk of Latin American immigrants did not significantly differ from that of the Italians (HR 0.74, 95% CI 0.47-1.15; p = 0.183). However, after adjusting for potential confounders, multivariable analysis showed that there was no difference in the risk of death between the immigrants and the Italians (adjusted HR [aHR] 1.04, 95% CI 0.70-1.55; p = 0.831), but being of Latin American origin was independently associated with an increased risk of death (aHR 1.95, 95% CI 1.17-3.23; p = 0.010). CONCLUSIONS: Mortality was lower among the immigrants hospitalised with COVID-19 than among their Italian counterparts, but this difference disappeared after adjusting for confounders. However, the increased risk of death among immigrants of Latin American origin suggests that COVID-19 information and prevention initiatives need to be strengthened in this sub-population.

Isolation of viable monkeypox virus from anal and urethral swabs, Italy, May to July 2022.

Anal and urethral samples from confirmed cases of monkeypox were screened for monkeypox virus (MPXV) by real-time PCR. Isolation of the virus was subsequently attempted in cell culture. Actively-replicating virus was demonstrated in 13 of 18 and 11 of 15 PCR-positive anal and urethral swabs, respectively, collected within 7 days from symptoms onset. Two asymptomatic secondary cases had detectable MPXV genetic material in urethral secretion and for one, MPXV was successfully isolated, supporting a potential MPXV sexual transmission hypothesis.

Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study.

BACKGROUND: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. METHODS: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. RESULTS: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P = .002), neutropenia (P < .001), or an INCREMENT score ≥8 (P = .01); with lower respiratory tract infection (LRTI) (P = .04); and with CAZ-AVI dose adjustment for renal function (P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P = .006). All associations remained significant after propensity score adjustment. CONCLUSIONS: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.

COVID-19-Associated Pulmonary Aspergillosis, March-August 2020.

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.

Performance of the COVID19SEROSpeed IgM/IgG Rapid Test, an Immunochromatographic Assay for the Diagnosis of SARS-CoV-2 Infection: a Multicenter European Study.

This study assessed the diagnostic performance of the new COVID19SEROSpeed IgM/IgG rapid test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders). The clinical sensitivity was evaluated on 710 sera from 564 patients whose SARS-CoV-2 infection was confirmed by quantitative reverse transcription-PCR (qRT-PCR) and whose antibody response was compared to that measured by five other commercial tests. The kinetics of the antibody response were also analyzed in seven symptomatic patients. The specificity of the test (BioS) on prepandemic specimens was 98.1% (95% confidence interval [CI], 96.2% to 99.4%). When tested on the 710 pandemic specimens, BioS showed an overall clinical sensitivity of 86.0% (95% CI, 0.83 to 0.89), with good concordance with the Euroimmun assay (overall concordance of 0.91; Cohen's kappa coefficient of 0.62). Due in part to simultaneous detection of IgM and IgG for both S1 and N proteins, BioS exhibited the highest positive percent agreement at ≥11 days post-symptom onset (PSO). In conclusion, the BioS IgM/IgG rapid test was highly specific and demonstrated a higher positive percentage of agreement than all the enzyme-linked immunosorbent assay/chemiluminescence immunoassay (ELISA/CLIA) commercial tests considered in this study. Moreover, by detecting the presence of antibodies prior to 11 days PSO in 78.2% of the patients, the BioS test increased the efficiency of the diagnosis of SARS-CoV-2 infection in the early stages of the disease.

Unexpectedly High Frequency of Enterococcal Bloodstream Infections in Coronavirus Disease 2019 Patients Admitted to an Italian ICU: An Observational Study.

OBJECTIVES: We aimed to assess the frequency of ICU-acquired bloodstream infections in coronavirus disease 2019 patients. DESIGN: Retrospective observational study. SETTING: The emergency expansion of an ICU from eight general beds to 30 coronavirus disease 2019 beds. PARTICIPANTS: Patients with coronavirus disease 2019 admitted to the ICU of Luigi Sacco Hospital (Milan, Italy) for greater than or equal to 48 hours between February 21, 2020, and April 30, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The frequency of bloodstream infections per 1,000 days of ICU stay was calculated in 89 coronavirus disease 2019 patients, and the cumulative probability of bloodstream infection was estimated using death and ICU discharge as competing events. Sixty patients (67.4%) experienced at least one of the 93 recorded episodes of bloodstream infection, a frequency of 87 per 1,000 days of ICU stay (95% CI, 67-112).The patients who experienced a bloodstream infection had a higher Sequential Organ Failure Assessment score upon ICU admission (9.5; interquartile range, 8-12 vs 8, interquartile range, 5-10; p = 0.042), a longer median ICU stay (15 d; interquartile range, 11-23 vs 8, interquartile range, 5-12; p < 0.001), and more frequently required invasive mechanical ventilation (98.3% vs 82.8%; p = 0.013) than those who did not. The median time from ICU admission to the first bloodstream infection episode was 10 days. Gram-positive bacteria accounted for 74 episodes (79.6%), with Enterococcus species being the most prevalent (53 episodes, 55.8%). Thirty-two isolates (27.3%) showed multidrug resistance. CONCLUSIONS: Coronavirus disease 2019 seemed to increase the frequency of bloodstream infections (particularly Enterococcus-related bloodstream infection) after ICU admission. This may have been due to enteric involvement in patients with severe coronavirus disease 2019 and/or limitations in controlling the patient-to-patient transmission of infectious agents in extremely challenging circumstances.