Anti-spike antibody level is associated with the risk of clinical progression among subjects hospitalized with COVID-19 pneumonia: results from a retrospective cohort study.

PURPOSE: Antibodies against SARS-CoV-2 spike (anti-S) may confer protection against symptomatic COVID-19. Whether their level predicts progression among those with COVID-19 pneumonia remains unclear. METHODS: We conducted a retrospective cohort study to assess predictors of anti-S levels and whether anti-S titer is associated with death or mechanical ventilation (MV). Adults hospitalized for COVID-19 pneumonia between July 2021 and July 2022 were enrolled if anti-S had been measured within 72 h of admission. Predictors of anti-S level were explored using multivariable quantile regression. The association between anti-S levels and 30-day death/MV was investigated via multivariable logistic regression. Analyses were stratified by vaccine status. RESULTS: The median anti-S level was 1370 BAU/ml in 328 vaccinated and 15.5 BAU/ml in 206 unvaccinated individuals. Among the vaccinated, shorter symptom duration (p = 0.001), hematological malignancies (p = 0.002), and immunosuppressive therapy (p = 0.004) were associated with lower anti-S levels. In the unvaccinated group, symptom duration was the only predictor of anti-S levels (p < 0.001). After 30 days, 134 patients experienced death or MV. Among vaccinated individuals, higher anti-S levels correlated significantly with lower death/MV risk (per log2 increase, OR 0.88, 95%CI 0.81-0.97), irrespective of age and solid malignancies. Among unvaccinated, a marginally protective effect was observed (OR 0.86, 95%CI 0.73-1.01), independent of age, immunosuppressive therapy, and diabetes. Adjustment for monoclonal antibody treatment strengthened the association (OR 0.81, 95%CI 0.68-0.96). CONCLUSION: This study suggests that levels of anti-S antibodies can predict critical or fatal outcomes in COVID-19 pneumonia patients, regardless of vaccination. Whether anti-S Ab could guide risk assessment and vaccination boosting merits further evaluation.

Mpox Virus in the Pharynx of Men Having Sex with Men: A Case Series.

The recent Mpox virus (MPV) outbreak in Europe and North America, primarily among men who have sex with men (MSM), raised concerns about various transmission sources. We examined patients with Mpox from an urban STI center in Lombardy, Italy, between May and August 2022. Demographic, transmission, and clinical data were collected using a standardized form. Initial and subsequent tests were conducted using the RealStar Orthopoxvirus PCR Kit 1.0 (Altona Diagnostics, Hamburg, Germany) for skin lesions and oropharyngeal swabs. A total of 15 patients were recruited, all MSM, with 40% being HIV-positive. Almost all reported recent unprotected sexual activity. Oropharyngeal symptoms were observed in a minority, and oral cavity lesions were present in 20% of cases. MPV DNA was detected in skin lesions of 93% of patients and in oropharyngeal swabs of 87%. Skin samples exhibited a higher viral load than pharyngeal samples, with the latter persisting longer. Prospective follow-up of 11 individuals revealed an average pharyngeal persistence of 5.3 days beyond skin lesion clearance, reaching up to 80 days in an immunosuppressed case. Our findings indicate that MPV replication can persist in the pharynx asymptomatically and for an extended period.

Early prone positioning does not improve the outcome of patients with mild pneumonia due to SARS-CoV-2: results from an open-label randomised controlled trial - the EPCoT study.

Background: Prone positioning is routinely used among patients with COVID-19 requiring mechanical ventilation. However, its utility among spontaneously breathing patients is still debated. Methods: In an open-label randomised controlled trial, we enrolled patients hospitalised with mild COVID-19 pneumonia, whose arterial oxygen tension to inspiratory oxygen fraction ratio (PaO2/FIO2) was >200 mmHg and who did not require mechanical ventilation or continuous positive airway pressure at hospital admission. Patients were randomised 1:1 to prone positioning on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, mechanical ventilation, continuous positive airway pressure and PaO2/FIO2 <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge. Results: A total of 61 subjects were enrolled, 29 adjudicated to prone positioning and 32 to the control group. By day 28, 24 out of 61 patients (39.3%) met the primary outcome: 16 because of a PaO2/FIO2 ratio <200 mmHg, five because of the need for continuous positive airway pressure and three because of the need for mechanical ventilation. Three patients died. Using an intention-to-treat approach, 15 out of 29 patients in the prone positioning group versus nine out of 32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomised to prone positioning (HR 2.38, 95% CI 1.04-5.43; p=0.040). Using an as-treated approach, which included in the intervention group only patients who maintained prone positioning for ≥3 h·day-1, no significant differences were found between the two groups (HR 1.77, 95% CI 0.79-3.94; p=0.165). Also, we did not find any statistically significant difference in terms of time to oxygen weaning or hospital discharge between study arms in any of the analyses conducted. Conclusions: We observed no clinical benefit from prone positioning among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy.

Heart transplantation as salvage treatment of intractable infective endocarditis.

BACKGROUND: For infective endocarditis (IE) with extensive perivalvular lesions or end-stage cardiac failure, heart transplantation (HT) may be the last resort. METHODS: We retrospectively collected all cases of HT for IE within the International Collaboration on Endocarditis (ICE) network. RESULTS: Between 1991 and 2021, 20 patients (5 women, 15 men), median age 50 years [interquartile range, 29-61], underwent HT for IE in Spain (n = 9), France (n = 6), Switzerland (n = 2), Colombia, Croatia, and USA (n = 1). IE affected prosthetic (n = 10), and native valves (n = 10), primarily aortic (n = 11) and mitral (n = 6). The main pathogens were oral streptococci (n = 8), Staphylococcus aureus (n = 5), and Enterococcus faecalis (n = 2). The major complications included heart failure (n = 18), peri-annular abscess (n = 10), and prosthetic valve dehiscence (n = 4). Eighteen patients had previous cardiac surgery for this episode of IE, and four were on circulatory support before HT (left ventricular assist-device and extra-corporeal membrane oxygenation, 2 patients each). The median time interval between first symptoms of IE and HT was 44.5 days [22-91.5]. The main post-HT complication was acute rejection (n = 6). Seven patients died (35%), four during the first month post-HT. Thirteen (81%) of the 16 patients discharged from the hospital survived with a median follow-up of 35.5 months [4-96.5] after HT, and no relapse of IE. CONCLUSIONS: IE is not an absolute contraindication for HT: Our case series and the literature review support that HT may be considered as a salvage treatment in highly-selected patients with intractable IE.

Infective Endocarditis Related to Unusual Microorganisms: A Prospective Population-Based Study.

BACKGROUND: Increased access to heart valves through early surgery and progress in molecular microbiology have reduced the proportion of infective endocarditis (IE) with no microbiological documentation and increased the proportion of IE associated with unusual microorganisms. METHODS: We performed an ancillary study of a large prospective population-based survey on IE. Unusual-microorganism IE was defined as definite IE (Duke-Li criteria) due to microorganisms other than streptococci, staphylococci, or enterococci. RESULTS: Of 471 cases of documented IE, 46 (9.8%) were due to unusal microorganisms; the following were involved in >1 case: Candida albicans (n = 4), Cutibacterium acnes (n = 4), Pseudomonas aeruginosa (n = 3), Cardiobacterium hominis (n = 3), and Coxiella burnetii (n = 2). Cases were documented with blood cultures (n = 37, 80.4%), heart valve polymerase chain reaction (PCR; n = 5), heart valve culture (n = 2), PCR on vertebral biopsy (n = 1), or serology (n = 1). As compared with IE due to staphylococci, streptococci, or enterococci (n = 420), IE due to unusual microorganisms occurred more frequently in patients with previously known heart disease (69.0% vs 44.3%; P = .002), prosthetic valve (40.5% vs 18.1%; P = .0006), longer duration of fever (mean, 35.1 ± 46.8 days vs 12.5 ± 17.8; P = .003), and who were more often nosocomial (38.1% vs 20.2%; P = .02). CONCLUSIONS: In this population-based study, 9.8% of IE cases were due to unusual microorganisms, with a predominance of anaerobes, yeast, and gram-negative bacilli. As compared with IE related to staphylococci, streptococci, or enterococci, IE cases related to unusual microorganisms were associated with previously known heart disease, prosthetic valve, longer duration of fever, and nosocomial acquisition. TRIAL REGISTRATION: ORCID 0000-0003-3617-5411.

A prospective randomized trial on abacavir/lamivudine plus darunavir/ritonavir or raltegravir in HIV-positive drug-naïve patients with CD4<200 cells/uL (the PRADAR study).

BACKGROUND: Very few data are available on treatment in HIV Late presenter population that still represents a clinical challenge. METHODS: Prospective, multicenter, randomized open-label, 2 arm, phase-3 trial comparing the 48-week virological response of two different regimens: abacavir/lamivudine + darunavir/r vs abacavir/lamivudine + raltegravir in antiretroviral naive with CD4+ counts < 200/mm3 and a viral load (VL)<500,000 copies/mL. The primary Endpoint was the proportion of patients with undetectable viremia (VL<50 copies/mL) after 48 weeks. The planned sample size for this trial was 350 patients. RESULTS: In 3 years, 53 patients were screened and 46 enrolled: 22 randomized to raltegravir and 24 to darunavir/r; 7 patients were excluded, 4 because of a VL >500,000 copies/mL and 3 for HLAB5701 positivity. The snapshot analysis at 48 weeks showed a virologic success of 77.3% in raltegravir and 66.7% in darunavir/r. Time to starting treatment was 34.5 days in raltegravir and 53 days in darunavir/r. At the as treated analysis, the median CD4 counts at 48 weeks was 297 cells/µL in raltegravir and 239 cells/µL in darunavir/r. No difference in total cholesterol, while triglycerides were higher in the darunavir/r arm. No statistical analyses were performed due to the low number of patients enrolled. CONCLUSIONS: Late presenter patients are frequent but very difficult to enroll in clinical trials, especially in western countries. These regimens and the conditions of many patients could not allow the test and treat strategy. The rate of virologic success was higher than 65% in both arms with a median CD4 cell count >200/µL at week 48. TRIAL REGISTRATION: EUDRACT number: 2011-005973-21.

French national cohort of first use of dalbavancin: A high proportion of off-label use.

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft-tissue infections (SSTIs), but its real-life use is not well known. The aim of this study was to describe all first prescriptions in France over an 16-month period. A retrospective study on all adult patients receiving at least one dose of dalbavancin from 1 June 2017 to 31 September 2018 was performed (75 patients from 29 French hospitals). Data were collected via a standard questionnaire. Failure was defined as persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment, and/or death from infection. The main indications were bone and joint infection (BJI) (64.0%), endocarditis (25.3%), and SSTI (17.3%). The main bacteria involved were Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%), and coagulase-negative staphylococci (44.4%). Median minimum inhibitory concentrations (MICs) for staphylococci to vancomycin and dalbavancin ranged from 0.875-2.0 mg/L and 0.032-0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. The main treatment regimens for dalbavancin were a two-dose regimen (1500 mg each) in 38 cases (50.7%) and a single-dose regimen (1500 mg) in 13 cases (17.3%). Overall, at the patient's last visit, clinical cure was observed in 54/68 patients, whilst failure was observed in 14/68 patients. First use of dalbavancin in France was mostly off-label. Most were due to BJI, often as rescue therapy for severe infections. Even in off-label situations, dalbavancin appears safe and effective.

Lung ultrasound in the management of pneumocystis pneumonia: A case series.

Despite the decline in HIV mortality and morbidity, Pneumocystis jirovecii pneumonia (PJP) is still frequently seen, particularly in patients with a low CD4+ cell count. We present a case series where we analyzed the possible role of lung ultrasound (LUS) in the management of PJP in a real-life clinical setting. We describe the ultrasound findings from a consecutive series of six HIV patients hospitalized for PJP, all with a favorable outcome, and evaluated with LUS at admission in our ward and then repeated this once during the hospitalization. Multiple B lines indicating interstitial syndrome were detected at admission in all cases, with a bilateral asymmetric pattern mostly localized in middle and upper lobes. In the follow-up LUS, we noted a substantially improved pattern in all patients, observing a reduction of B lines which correlated with clinical amelioration. One patient at admission and three patients during the follow-up showed lung consolidations with hyperechoic spots inside, that might be typical of the disease. In conclusion, LUS could be a practical and noninvasive imaging tool for supporting diagnosis and treatment response of PJP.

Tuberculosis of the Knee: A Case Report and Literature Review.

Tuberculosis (TB) is currently in resurgence due to immigration from endemic areas. Skeletal TB frequently mimics more common etiologies and can be difficult to diagnose. A case of TB knee arthritis in a young woman with painful and swelling knee is reported here. Arthrotomy was performed and inflamed synovial tissue was found, with multiple rice bodies in the eroded lateral femoral condyle. The patient was treated with an antituberculosis polytherapy and at 1-year follow-up, she reported relief from pain and swelling. We believe that all surgeons assessing patients from TB endemic regions have to adopt an updated approach to TB treatment. Thus, a literature review is also reported here on the current strategies used in different knee TB cases.