Fifty years after the first identification of Toscana virus in Italy: Genomic characterization of viral isolates within lineage A and aminoacidic markers of evolution.

Toscana Virus (TosV) was firstly isolated from phlebotomine in our Institute about fifty years ago. Later, in 1984-1985, TosV infection, although asymptomatic in most cases, was shown to cause disease in humans, mainly fever and meningitis. By means of genetic analysis of part of M segment, we describe 3 new viral isolates obtained directly from cerebrospinal fluid or sera samples of patients diagnosed with TosV infection in July 2020 in Tuscany region. Phylogenesis was used to propose the clustering of TosV lineage A strains in 3 main groups, whereas deep mutational analysis based on 12 amino acid positions, allowed the identification of 9 putative strains. We discuss deep mutational analysis as a method to identify molecular signature of host adaptation and/or pathogenesis.

Chronic antibiotic suppressive therapy with dalbavancin: a case series.

Dalbavancin is a relatively new long-acting anti-Gram positive antimicrobial approved for the treatment of acute bacterial skin and skin structures infections. An increasing number of observational studies and case series were published on its off-label uses. Great interest is emerging about complicated cases where antibiotic treatment cannot be discontinued, and a chronic suppressive therapy is needed. We described a case series of 6 patients treated or ongoing on treatment with dalbavancin as chronic suppressive therapy (CAST) administered with the following regimen: dalbavancin 1500 mg on day 1 and 8 and then every 4 weeks. CAST median duration was 27 weeks. Five out of 6 patients reached a good clinical control of the infection (one of them completely resolved) while in one case we observed a recurrence of the infection. No adverse events were detected. Larger studies are needed to better clarify dalbavancin off-label uses and the most appropriate dose regimen.

Role of Cefiderocol in Multidrug-Resistant Gram-Negative Central Nervous System Infections: Real Life Experience and State-of-the-Art.

Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is no consensus on the dosing scheme of cefiderocol to penetrate the blood-brain barrier. We present a case series and a literature review of CNS infections caused by MDR pathogens that were treated with cefiderocol: some of these patients were treated with different dose schemes of cefiderocol and underwent therapeutic drug monitoring both on plasma and cerebrospinal fluid (CSF). The CSF penetration rates and the clinical outcomes were evaluated.

Tixagevimab/Cilgavimab: Still a Valid Prophylaxis against COVID-19 New Variants?

BACKGROUND: this study aims to evaluate the efficacy of tixagevimab/cilgavimab (Evusheld™) against various SARS-CoV-2 variants, including newer Omicron sublineages, in an immunocompromised cohort and in vitro. STUDY DESIGN: Conducted in Italy, this research involves immunocompromised patients who received Evusheld. It evaluates serum neutralization activity against different SARS-CoV-2 strains (20A.EU1, BA.5, BQ.1, XBB.1.5, XBB.1.16, and EG.5) before (T0), after 14 (T1), and after 30 (T2) days from the tixagevimab/cilgavimab injection. Furthermore, the in vitro activity of Evusheld against SARS-CoV-2 VOCs was evaluated. RESULTS: The cohort was composed of 72 immunocompromised patients. The serum neutralizing activity of tixagevimab/cilgavimab-treated patients was notably lower against newer variants such as BQ.1, XBB.1.5, XBB.1.16, and EG.5. Then, the in vitro study detailed specific EC50 values to quantify the activity of tixagevimab/cilgavimab against various SARS-CoV-2 VOCs. Newer variants like BQ.1 and XBB.1.5 exhibited notably lower neutralization, underscoring the challenges in effectively countering the evolving virus. Interestingly, tixagevimab/cilgavimab maintained reduced but still valid activity against EG.5 with an EC50 of 189 ng/mL and Cmax/EC90 of 110.7. CONCLUSIONS: Tixagevimab/cilgavimab efficacy wanes against novel subvariants. This underscores the critical need for ongoing adaptation and vigilance in prophylactic strategies to effectively counter the dynamic and unpredictable nature of the COVID-19 pandemic.

In-label, off-label prescription, efficacy and tolerability of dalbavancin: report from a National Registry.

PURPOSE: Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration. METHODS: We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments. RESULTS: During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%). CONCLUSION: In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections.

Impaired neutralizing antibody efficacy of tixagevimab-cilgavimab 150+150 mg as pre-exposure prophylaxis against Omicron BA.5. A real-world experience in booster vaccinated immunocompromised patients.

BACKGROUND: Tixagevimab-cilgavimab has been approved as primary pre-exposure prophylaxis in immunocompromised patients as support or replacement for vaccination, even though the Omicron variant of concern (VOC) was spreading at the time. OBJECTIVES: The aim of our study was to evaluate the post-injection neutralising activity (NT90-Abs titre) against the Omicron BA.5 variant in fully vaccinated immunocompromised patients. STUDY DESIGN: NT90-Abs titres against BA.5 and 20A.EU1 as well as anti-spike and anti-receptor-binding domain IgG were evaluated 0, 14, and 30 d after tixagevimab-cilgavimab administration. The primary end point was NT90-Abs titres ≥ 80 against BA.5 in ≥ 25% of patients, and the secondary end point was NT90-Abs titres ≥ 1280 against 20A.EU1 in >50% of patients on day 14. RESULTS: At baseline, 35.2%, 37.02%, and 32.5% of booster vaccinated patients exhibited undetectable levels of anti-S and anti-RBD IgG antibodies such as NT90-Abs titres against A20.EU1. Moreover, 35 patients (61.5%) had undetectable NT90-Abs titres against BA.5. On day 14, IgG anti-S and anti-RBD levels were 3880 BAU/mL and 776.6 AU/mL, respectively. Only 12.5% of patients met a NT90-Abs titres ≥ 80 against BA.5, whereas the median NT90-Abs titre against 20A.EU1 was 1280. NT90-Abs titres against BA.5 were 64-fold lower than those against A20.EU1. Four patients (7.5%) had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the 3 months after treatment, all with a time gap between the booster vaccination and injection. CONCLUSIONS: To date, tixagevimab-cilgavimab cannot be considered a substitute for vaccination but may be a useful supporting therapy if the recommended dose for pre-exposure prophylaxis is doubled.

Acute gastroenteritis due to Vibrio cholerae biovar albensis infection: A case report.

Vibrio cholerae represents diverse species and includes pathogenic and non-pathogenic variants. Particularly serogroups O1 and O139 are related to cholera epidemics, while non-O1/O139 serogroups (NOVC) in general are non-pathogenic or asymptomatic colonizers in humans, but also can cause different diseases. Vibrio albensis, a non-O1/non-O-139 serogroup, is rarely implicated in human infections. Only a few cases of human pathology related to this species are described in the literature. We present the menagement of V. albensis gastroenteritis in a a 47-year-old woman and discuss clinical presentation, diagnosis and treatement.

Mortality in KPC-producing Klebsiella pneumoniae bloodstream infections: a changing landscape.

OBJECTIVES: To assess the impact of carbapenem resistance on mortality in Klebsiella pneumoniae bloodstream infection (BSI) in the era of novel ß-lactam/ß-lactamase inhibitor combinations. MATERIAL AND METHODS: Retrospective study of patients with K. pneumoniae BSI between January and August 2020 in 16 centres (CARBANEW study within the MULTI-SITA project). RESULTS: Overall, 426 patients were included: 107/426 (25%) had carbapenem-resistant K. pneumoniae (CR-Kp) BSI and 319/426 (75%) had carbapenem-susceptible K. pneumoniae (CS-Kp) BSI. Crude cumulative 30 day mortality was 33.8% and 20.7% in patients with, respectively, CR-Kp BSI and CS-Kp BSI (P = 0.027). Carbapenemase production or carbapenemase-encoding genes were detected in 84/98 tested CR-Kp isolates (85.7%), mainly KPC (78/84; 92.9%). Ceftazidime/avibactam was the most frequently used appropriate therapy for CR-Kp BSI (80/107; 74.7%). In multivariable analyses, variables showing an unfavourable association with mortality after correction for multiple testing were age-adjusted Charlson comorbidity index (HR 1.20; 95% CI 1.10-1.31, P < 0.001) and Pitt score (HR 1.33; 95% CI 1.15-1.55, P < 0.001), but not carbapenem resistance (HR 1.28, 95% CI 0.74-2.22, P = 0.410). In a propensity score-matched analysis, there was no difference in mortality between patients appropriately treated with ceftazidime/avibactam for CR-Kp BSI and patients appropriately treated with other agents (mainly meropenem monotherapy or piperacillin/tazobactam monotherapy) for CS-Kp BSI (HR 1.07; 95% CI 0.50-2.29, P = 0.866). CONCLUSIONS: Our results suggest that the increased mortality in CR-Kp BSI compared with CS-Kp BSI is not (or no longer) dependent on the type of therapy in areas where ceftazidime/avibactam-susceptible KPC-producing isolates are the most prevalent type of CR-Kp.

Adherence to 2015 ESC Guidelines for the Treatment of Infective Endocarditis: A Retrospective Multicentre Study (LEIOT Study).

BACKGROUND: Infective endocarditis (IE) is still a severe disease with elevated morbidity and mortality. Nevertheless, the last European guidelines (GL) date back to 2015, and a recent survey described a diffuse suboptimal adherence to their recommendations. Here, we described a real-life scenario about adherence to IE treatment GL. METHODS: This was a retrospective, multicentric, case-control study. All the cases of IE admitted to our wards from 2016 to 2020 were enrolled. Patients were divided into two groups, according to the non-adherence (group A, cases) or adherence (group B, controls) to 2015 ESC guidelines. Only targeted treatments were considered. Groups were compared for demographic, clinical, microbiological, and laboratory data and outcome. As a post hoc analysis, we analysed the characteristics of deviations from the guidelines and how these deviations affected mortality. RESULTS: A total of 246 patients were enrolled, with 128 (52%) in group A and 118 (48%) in group B. Groups were homogeneous except for aetiologies: staphylococcal and blood-culture-negative IE were more frequent in group A, while streptococcal and enterococcal IE were more frequent in group B (p < 0.001). In-hospital mortality was comparable in the two groups. The most frequent causes of deviations from the guidelines were use of daptomycin, in addition to standard treatments and the missing administration of rifampin or gentamycin. CONCLUSIONS: Adherence to 2015 ESC guidelines was limited but it did not affect mortality.

Dalbavancin as chronic antibiotic suppression therapy for left ventricular assist device driveline infection due to methicillin-resistant Staphylococcus aureus: a case report.

Left Ventricular Assist Devices (LVADs) represent an important therapeutic option in the management of advanced heart failure. We report a case of 74 years-old male with a Jarvik 2000® (Jarvik Heart, New York, USA) LVAD who presented with an infection of the LVAD driveline due to methicillin-resistant Staphylococcus aureus (MRSA) that was treated with dalbavancin as chronic antimicrobial suppression therapy without adverse events and maintaining a good quality of life for more than 37 weeks. Dalbavancin could represent a valid option for the treatment of LVAD infections because of its efficacy, pharmacokinetic/pharmacodynamic proprieties, safety and tolerability.

Nelfinavir: An Old Ally in the COVID-19 Fight?

After almost three years of the pandemic, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is still spreading around the world, causing notable sanitary and social issues. New antiviral therapies are constantly under investigation. However, few options have been approved for the treatment of COVID-19. Clinical trials are currently ongoing to evaluate the efficacy of nelfinavir on mild−moderate COVID-19. This study aims to investigate the activity of this compound on SARS-CoV-2 "Variants of Concern" (VOCs), comparing its effectiveness with the approved drugs remdesivir and molnupiravir. The experiments were conducted in a biosafety level 3 facility. In this study, we used a Vero-E6-cell-based infection assay to investigate the in vitro activity of nelfinavir, molnupiravir, and remdesivir. Four strains of SARS-CoV-2 were tested: 20A.EU1, B.1.1.7, P.1, and B.1.617.2. All compounds reached micromolar/submicromolar EC50, EC90, and EC99. Furthermore, the Cmax/EC50 and Cmax/EC90 ratios were >1 for all compounds and all variants tested. Our study demonstrated that nelfinavir, as molnupiravir, and remdesivir are effective in vitro on SARS-CoV-2 variants.

The challenge of infectious diseases consultations in the emergency department: an Italian nationwide survey.

Diagnosis and management of infectious diseases (ID) at the emergency department (ED) are challenging due to the peculiar setting and the available diagnostic tools. The involvement of an ID consultant has been described to improve clinical outcomes and antimicrobial stewardship (AMS) programs. An online survey was sent to 100 Italian Departments of Infectious Diseases affiliated with the Italian Society of Infectious Diseases and Tropical Medicine (SIMIT). The primary objective of our study was to describe the characteristics of ID services in Italian EDs to identify possible challenges and shortcomings and provide tips to improve the management of patients. Secondary objectives included the evaluation of diagnostic capability and the management of patients with suspected or confirmed ID. Seventy-six out of the 100 SIMIT centers, 32 (42.1%) of which were teaching hospitals, answered the survey. In 62 (82.7%) centers, consultations were performed by the IDs specialist on call. In 29 (38.2%) centers, there was a formal AMS program, and 32 (42.7%) had protocols for antibiotic use in the ED. Microbiological tests to be performed before starting antibiotic treatment in the ED were clearly defined in 44 (57.9%) hospitals. This survey highlighted several challenges in the current organization of ID consultations in Italian EDs.

Beta Lactams Plus Daptomycin Combination Therapy for Infective Endocarditis: An Italian National Survey (BADAS).

BACKGROUND: infective endocarditis (IE) remains a severe disease frequently encountered in clinical practice and often requiring interdisciplinary medical and surgical management. This national survey aims to describe the clinical prescribing habits of the use of daptomycin in the setting of IE and the possible role for combination therapy with beta-lactams. METHODS: The study was a cross-sectional internet-based questionnaire survey on therapy with daptomycin. The questionnaire was designed with closed-ended questions and distributed using the SurveyMonkey® platform between October 2019 to December 2020. RESULTS: 55 clinicians from twelve Italians regions joined the questionnaire. The survey reported use of daptomycin as first-line choice in 31.48% of cases and as the first-line anti-MRSA agent in 44.44%. The empiric use of daptomycin was stated in the high suspicion of MRSA rather than MSSA, enterococcal or streptococcal IE. The rationale of daptomycin for the empirical treatment of native and prosthetic valve IE was mostly the possibility of administering an aminoglycoside-sparing combination regimen, high bacterial killing rate and high clinical efficacy. CONCLUSIONS: In conclusion, in selected patients, daptomycin could be a feasible option for the treatment of infective endocarditis in line with data from the European registry of daptomycin.

Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

D-Dimer as Biomarker for Early Prediction of Clinical Outcomes in Patients With Severe Invasive Infections Due to Streptococcus Pneumoniae and Neisseria Meningitidis.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection; no current clinical measure adequately reflects the concept of dysregulated response. Coagulation plays a pivotal role in the normal response to pathogens (immunothrombosis), thus the evolution toward sepsis-induced coagulopathy could be individuate through coagulation/fibrinolysis-related biomarkers. We focused on the role of D-dimer assessed within 24 h after admission in predicting clinical outcomes in a cohort of 270 patients hospitalized in a 79 months period for meningitis and/or bloodstream infections due to Streptococcus pneumoniae (n = 162) or Neisseria meningitidis (n = 108). Comparisons were performed with unpaired t-test, Mann-Whitney-test or chi-squared-test with continuity correction, as appropriate, and multivariable logistic regression analysis was performed with Bayesian model averaging. In-hospital mortality was 14.8% for the overall population, significantly higher in S. pneumoniae than in N. meningitidis patients: 19.1 vs. 8.3%, respectively (p = 0.014). At univariable logistic regression analysis the following variables were significantly associated with in-hospital mortality: pneumococcal etiology, female sex, age, ICU admission, SOFA score, septic shock, MODS, and D-dimer levels. At multivariable analysis D-dimer showed an effect only in N. meningitidis subgroup: as 500 ng/mL of D-dimer increased, the probability of unfavorable outcome increased on average by 4%. Median D-dimer was significantly higher in N. meningitidis than in S. pneumoniae patients (1,314 vs. 1,055 ng/mL, p = 0.009). For N. meningitidis in-hospital mortality was 0% for D-dimer <500 ng/mL, very low (3.5%) for D-dimer <7,000 ng/mL, and increased to 26.1% for D-dimer >7,000 ng/mL. Kaplan-Meier analysis of in-hospital mortality showed for N. meningitidis infections a statistically significant difference for D-dimer >7,000 ng/mL compared to values <500 ng/mL (p = 0.021) and 500-3,000 ng/mL (p = 0.002). For S. pneumoniae the mortality risk resulted always high, over 10%, irrespective by D-dimer values. In conclusion, D-dimer is rapid to be obtained, at low cost and available everywhere, and can help stratify the risk of in-hospital mortality and complications in patients with invasive infections due to N. meningitidis: D-dimer <500 ng/mL excludes any further complications, and a cut-off of 7,000 ng/mL seems able to predict a significantly increased mortality risk from much <10% to over 25%.

Ceftobiprole Perspective: Current and Potential Future Indications.

Ceftobiprole combines an excellent spectrum for community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) pathogens, with a low/medium MDR risk, and the ß-lactams' safety in frail patients admitted to the hospital in internal medicine wards which may be at high risk of adverse events by anti-MRSA coverage as oxazolidinones or glycopeptides. We aimed to report the available evidence regarding ceftobiprole use in pneumonia and invasive bacterial infections, shedding light on ceftobiprole stewardship. The clinical application and real-life experiences of using ceftobiprole for bloodstream infections, including infective endocarditis, are limited but nevertheless promising. In addition, extended-spectrum ceftobiprole activity, including Enterococcus faecalis, Enterobacteriaceae, and Pseudomonas aeruginosa, has theoretical advantages for use as empirical therapy in bacteremia potentially caused by a broad spectrum of microorganisms, such as catheter-related bacteremia. In the future, the desirable approach to sepsis and severe infections will be administered to patients according to their clinical situation, the intrinsic host characteristics, the susceptibility profile, and local epidemiology, while the "universal antibiotic strategy" will no longer be adequate.

Daptomycin-based aminoglycoside-sparing therapy for streptococcal endocarditis: a retrospective multicenter study.

Streptococci still represent common etiologic agents of infective endocarditis (IE). Although renal failure is frequently reported as an aminoglycoside-associated adverse event, last international guidelines recommend a beta-lactam/gentamicin combination therapy. We retrospectively evaluated the use of daptomycin-based aminoglycoside-sparing combination therapy for the treatment of streptococcal IE in seven referral hospitals in Italy. Retrospective, multicenter, observational study. All patients with streptococcal IE admitted from 2016 to 2018 were enrolled. Mortality and incidence of acute kidney injury (AKI) were compared between Group A (standard of care, SoC) and Group B (daptomycin-based aminoglycoside-sparing combination therapy). Fifty-four patients were enrolled, 33 in Group A and 21 in Group B. Mortality was 2/33 (6%) in Group A and 0 in Group B (p = 0.681); AKI incidence was 8/33 (24%) in Group A and 0 in Group B (p = 0.04). Daptomycin-based aminoglycoside-sparing combination therapy appears to be promising for the treatment of streptococcal endocarditis because of similar efficacy compared with SoC and significantly reduced incidence of AKI.

Risk factors for non-invasive/invasive ventilatory support in patients with COVID-19 pneumonia: A retrospective study within a multidisciplinary approach.

OBJECTIVES: To investigate risk factors for non-invasive/invasive ventilatory support (NI/I-VS) in patients with coronavirus disease 2019 (COVID-19). METHODS: All consecutive patients admitted to the Infectious Diseases Unit and Intensive Care Unit (ICU) of Santa Maria Annunziata Hospital (Florence, Italy), from February 25 to April 25, 2020, with a confirmed COVID-19 diagnosis were enrolled in this retrospective cohort study. NI/I-VS was defined as the need for continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP) (non-invasive ventilation) or mechanical ventilation, not including low-flow systems of oxygen therapy such as the Venturi mask or nasal cannula. RESULTS: Ninety-seven patients were enrolled; 61.9% (60/97) were male and the median patient age was 64 years. The in-hospital mortality was 9.3%. Thirty-five of the 97 patients (36%) required ICU admission and 94.8% (92/97) were prescribed oxygen therapy: 10.8% (10/92) by nasal cannula, 44.5% (41/92) by Venturi mask, 31.5% (29/92) by CPAP, 2.2% (2/92) by BPAP, and 10.8% (10/92) by mechanical ventilation following intubation. On univariate analysis, patients with a body mass index >30, type II diabetes mellitus, and those presenting with dyspnoea, asthenia, SOFA score ≥2 points, PaO2/FiO2 <300, temperature >38 °C, increased levels of lactate dehydrogenase (LDH), alanine aminotransferase, and C-reactive protein, and a d-dimer >1000 ng/mL at admission more frequently underwent NI/I-VS. Multivariate logistic regression analysis confirmed temperature >38 °C (odds ratio (OR) 21.2, 95% confidential interval (95% CI) 3.5-124.5, p = 0.001), LDH >250 U/l (OR 15.2, 95% CI 1.8-128.8, p = 0.012), and d-dimer >1000 ng/mL (OR 4.5, 95% CI 1.2-17.3, p = 0.027) as significantly associated with the requirement for NI/I-VS. A non-significant trend (p = 0.051) was described for PaO2/FiO2 <300. CONCLUSIONS: Temperature >38 °C, LDH > 250 U/l, and d-dimer >1000 ng/mL were found to be independent risk factors for NI/I-VS in COVID-19 patients. In order to quickly identify patients likely at risk of developing a critical illness, inflammatory markers should be assessed upon hospital admission.