Interleukin-62/lymphocyte as a proposed predictive index for COVID-19 patients treated with monoclonal antibodies.

In a convenience sample of 93 patients treated with monoclonal antibodies (moAbs) against SARS-CoV-2, the interleukin-62/lymphocyte count ratio (IL-62/LC) was able to predict clinical worsening both in early stages of COVID-19 and in oxygen-requiring patients. Moreover, we analysed 18 most at-risk patients with asymptomatic or mild disease treated with both moAbs and antiviral treatment and found that only 2 had clinical progression, while patients with a similar risk were reported to have an unfavourable outcome in most cases from recent data. In only one of our 18 patients, clinical progression was attributable to COVID-19, and in the other cases, clinical progression was observed despite IL-62/LC being above the risk cut-off. In conclusion, IL-62/LC may be a valuable method to identify patients requiring more aggressive treatments both in earlier and later stages of the disease; however, most at-risk patients can be protected from clinical worsening by combining moAbs and antivirals, even if levels of the IL-62/LC biomarker are lower than the risk cut-off.

New advances in management and treatment of multidrug-resistant Klebsiella pneumoniae.

INTRODUCTION: The management of multidrug-resistant (MDR) Klebsiella pneumoniae (KP) represents a major challenge in the field of infectious diseases. It is associated with a high rate of nosocomial infections with a mortality rate that reaches approximately 50%, even when using an effective antimicrobial therapy. Therefore, combined actions addressing infection control and antibiotic stewardship are required to delay the emergence of resistance. Since new antimicrobial agents targeting MDR-GNB bacteria have been produced during the last years and are now available for physicians to treat MDR, it is fundamental to choose appropriate antimicrobial therapy for K. pneumoniae infection. AREAS COVERED: The PubMed database was searched to review the most significant recent literature on the topic, including data from articles coming from endemic areas and from the current European and American Guidelines. EXPERT OPINION: We explore the most effective strategies for prevention of MDR-KP spread and the currently available treatment options, focusing on comparing old strategies and new compounds. We reviewed data concerning newly developed drugs that could play an important role in the future; we also propose a treatment algorithm that could be useful for physicians in daily clinical practice.

The three facets of the SARS-CoV-2 pandemic during the first two waves in the northern, central, and southern Italy.

BACKGROUND: There is a scarcity of information in literature regarding the clinical differences and comorbidities of patients affected by Coronavirus disease 2019 (COVID-19), which could clarify the different prevalence of the outcomes (composite and only death) between several Italian regions. OBJECTIVE: This study aimed to assess the heterogeneity of clinical features of patients with COVID-19 upon hospital admission and disease outcomes in the northern, central, and southern Italian regions. METHODS: An observational cohort multicenter retrospective study including 1210 patients who were admitted for COVID-19 in Infectious diseases, Pulmonology, Endocrinology, Geriatrics and Internal Medicine Units in Italian cities stratified between north (263 patients); center (320 patients); and south (627 patients), during the first and second pandemic waves of SARS-CoV-2 (from February 1, 2020 to January 31, 2021). The data, obtained from clinical charts and collected in a single database, comprehended demographic characteristics, comorbidities, hospital and home pharmacological therapies, oxygen therapy, laboratory values, discharge, death and Intensive care Unit (ICU) transfer. Death or ICU transfer were defined as composite outcomes. RESULTS: Male patients were more frequent in the northern Italian region than in the central and southern regions. Diabetes mellitus, arterial hypertension, chronic pulmonary and chronic kidney diseases were the comorbidities more frequent in the southern region; cancer, heart failure, stroke and atrial fibrillation were more frequent in the central region. The prevalence of the composite outcome was recorded more frequently in the southern region. Multivariable analysis showed a direct association between the combined event and age, ischemic cardiac disease, and chronic kidney disease, in addition to the geographical area. CONCLUSIONS: Statistically significant heterogeneity was observed in patients with COVID-19 characteristics at admission and outcomes from northern to southern Italy. The higher frequency of ICU transfer and death in the southern region may depend on the wider hospital admission of frail patients for the availability of more beds since the burden of COVID-19 on the healthcare system was less intense in southern region. In any case, predictive analysis of clinical outcomes should consider that the geographical differences that may reflect clinical differences in patient characteristics, are also related to access to health-care facilities and care modalities. Overall, the present results caution against generalizability of prognostic scores in COVID-19 patients derived from hospital cohorts in different settings.

Lessons learned and implications of early therapies for coronavirus disease in a territorial service centre in the Calabria region: a retrospective study.

BACKGROUND: Monoclonal antibodies (mAbs) and antivirals have been approved for early therapy of coronavirus disease (COVID-19), however, in the real-life setting, there are difficulties to prescribe these therapies within few days from symptom onset as recommended, and effectiveness of combined use of these drugs have been hypothesised in most-at-risk patients (such as those immunocompromised) but data supporting this strategy are limited. METHODS: We describe the real-life experience of SARS-CoV-2 antivirals and/or monoclonal antibodies (mAbs) and focus on the hospitalisation rate due to the progression of COVID-19. Clinical results obtained through our risk-stratification algorithm and benefits achieved through a strategic proximity territorial centre are provided. We also report a case series with an in-depth evaluation of SARS-CoV-2 genome in relationship with treatment strategy and clinical evolution of patients. RESULTS: Two hundred eighty-eight patients were analysed; 94/288 (32.6%) patients were treated with mAb monotherapy, 171/288 (59.4%) patients were treated with antivirals, and 23/288 (8%) patients received both mAbs and one antiviral drug. Haematological malignancies were more frequent in patients treated with combination therapy than in the other groups (p = 0.0003). There was a substantial increase in the number of treated patients since the opening of the centre dedicated to early therapies for COVID-19. The provided disease-management and treatment appeared to be effective since 98.6% patients recovered without hospital admission. Moreover, combination therapy with mAbs and antivirals seemed successful because all patients admitted to the hospital for COVID-19 did not receive such therapies, while none of the most-at-risk patients treated with combination therapy were hospitalized or reported adverse events. CONCLUSIONS: A low rate of COVID-19 progression requiring hospital admission was observed in patients included in this study. The dedicated COVID-19 proximity territorial service appeared to strengthen the regional sanitary system, avoiding the overwhelming of other services. Importantly, our results also support early combination therapy: it is possible that this strategy reduces the emergence of escape mutants of SARS-CoV-2, thereby increasing efficacy of early treatment, especially in immunocompromised individuals.

Cytokine Profile of Invasive Pulmonary Aspergillosis in Severe COVID-19 and Possible Therapeutic Targets.

During the SARS-CoV-2 pandemic, a higher incidence of invasive pulmonary aspergillosis was observed in patients affected by Coronavirus disease 2019 (COVID-19), leading to the delineation of a new entity named COVID-19 associated pulmonary aspergillosis (CAPA). A predisposition to invasive infection caused by Aspergillus spp. in SARS-CoV-2 infected patients can be ascribed either to the direct viral-mediated damage of the respiratory epithelium, as already observed in influenza H1N1 virus infections, or to the dysregulated immunity associated with COVID-19. This narrative review focuses on the impact of immune impairment, particularly due to cytokine dysregulation caused by Aspergillus spp. superinfection in COVID-19 for a more in-depth understanding of the molecular pathways implicated in CAPA. As immune competence has proven to be essential in protecting against CAPA onset, a role already threatened by SARS-CoV-2 infection itself, preventive strategies should focus on reducing factors that could further target the host immune system. We also aimed to focus on well-known and less-known risk factors for IPA in COVID-19 patients, related to the main causes of immune suppression, both virus-mediated and iatrogenic, including treatments currently indicated for COVID-19. Lastly, possible preventive strategies aimed at reducing morbidity and mortality due to CAPA could be implemented.

Is the Pendulum of Antimicrobial Drug Resistance Swinging Back after COVID-19?

The COVID-19 pandemic may have had an effect on antimicrobial resistance. We compared the prevalence of ESKAPE multidrug-resistant (MDR) bacterial infections in COVID-19 affected/unaffected patients admitted to intensive care units (ICU) or infectious disease units at the "Mater Domini" University Hospital of Catanzaro between 1 March 2020 and 31 July 2021. Moreover, an analysis of MDR rates in ICU comparing the pre-pandemic period with the pandemic period was performed, and the possible consequence on in-hospital mortality was explored. One hundred and eighty-four ESKAPE isolates were analyzed from 362 SARS-CoV-2 positive and 199 negative patients. In total, 116 out of 171 Gram-negative isolates were classified as MDR, and a higher frequency was observed in COVID-19 compared with non-COVID-19 patients (74.2% vs. 60.3%; p = 0.052). A higher rate of MDR ESKAPE bacteria was observed in COVID-19 patients admitted to the ICU compared with COVID-19 unaffected patients admitted to the same ward in 2019 (88% vs. 80.4%; p = 0.186). Acinetobacter baumannii was the main pathogen in COVID-19 patients (58.7%), where it was the most frequent cause of bloodstream infection with the highest mortality rate (68.7%). Increase in MDR appeared to be associated with COVID-19 but only in the ICU setting. Acinetobacter baumannii was associated with the risk of death, indicating the importance of implementing infection control measures urgently.