Timing and Outcomes of Noninvasive Ventilation in 307 ARDS COVID-19 Patients: An Observational Study in an Italian Third Level COVID-19 Hospital.

Background and Objectives: Background: Coronavirus disease 2019 (COVID-19) is a novel cause of Acute Respiratory Distress Syndrome (ARDS). Noninvasive ventilation (NIV) is widely used in patients with ARDS across several etiologies. Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, its use has grown significantly in hospital wards. However, there is a lack of evidence to support the efficacy of NIV in patients with COVID-19 ARDS. Materials and Methods: We conducted an observational cohort study including adult ARDS COVID-19 patients admitted in a third level COVID-center in Rome, Italy. The study analyzed the rate of NIV failure defined by the occurrence of orotracheal intubation and/or death within 28 days from starting NIV, its effectiveness, and the associated relative risk of death. The factors associated with the outcomes were identified through logistic regression analysis. Results: During the study period, a total of 942 COVID-19 patients were admitted to our hospital, of which 307 (32.5%) presented with ARDS at hospitalization. During hospitalization 224 (23.8%) were treated with NIV. NIV failure occurred in 84 (37.5%) patients. At 28 days from starting NIV, moderate and severe ARDS had five-fold and twenty-fold independent increased risk of NIV failure (adjusted odds ratio, aOR = 5.01, 95% CI 2.08−12.09, and 19.95, 95% CI 5.31−74.94), respectively, compared to patients with mild ARDS. A total of 128 patients (13.5%) were admitted to the Intensive Care Unit (ICU). At 28-day from ICU admission, intubated COVID-19 patients treated with early NIV had 40% lower mortality (aOR 0.60, 95% CI 0.25−1.46, p = 0.010) compared with patients that underwent orotracheal intubation without prior NIV. Conclusions: These findings show that NIV failure was independently correlated with the severity category of COVID-19 ARDS. The start of NIV in COVID-19 patients with mild ARDS (P/F > 200 mmHg) appears to increase NIV effectiveness and reduce the risk of orotracheal intubation and/or death. Moreover, early NIV (P/F > 200 mmHg) treatment seems to reduce the risk of ICU mortality at 28 days from ICU admission.

Clostridium difficile infection among hospitalized HIV-infected individuals: epidemiology and risk factors: results from a case-control study (2002-2013).

BACKGROUND: HIV infection is a risk factor for Clostridium difficile infection (CDI) yet the immune deficiency predisposing to CDI is not well understood, despite an increasing incidence of CDI among such individuals. We aimed to estimate the incidence and to evaluate the risk factors of CDI among an HIV cohort in Italy. METHODS: We conducted a retrospective case-control (1:2) study. Clinical records of HIV inpatients admitted to the National Institute for Infectious Disease "L. Spallanzani", Rome, were reviewed (2002-2013). CASES: HIV inpatients with HO-HCFA CDI, and controls: HIV inpatients without CDI, were matched by gender and age. Logistic regression was used to identify risk factors associated with CDI. RESULTS: We found 79 CDI episodes (5.1 per 1000 HIV hospital admissions, 3.4 per 10000 HIV patient-days). The mean age of cases was 46 years. At univariate analysis factors associated with CDI included: antimycobacterial drug exposure, treatment for Pneumocystis pneumonia, acid suppressant exposure, previous hospitalization, antibiotic exposure, low CD4 cell count, high Charlson score, low creatinine, low albumin and low gammaglobulin level. Using multivariate analysis, lower gammaglobulin level and low serum albumin at admission were independently associated with CDI among HIV-infected patients. CONCLUSIONS: Low gammaglobulin and low albumin levels at admission are associated with an increased risk of developing CDI. A deficiency in humoral immunity appears to play a major role in the development of CDI. The potential protective role of albumin warrants further investigation.

Brucellar Endocarditis of the Tricuspid Valve: A Case Report and Review of the Literature.

Brucellar endocarditis is a rare entity commonly described as a severe disease associated with high mortality and generally requiring valve surgery for cure. Right-sided endocarditis, a very uncommon presentation of brucellosis, may be associated with a better prognosis. We describe the case of a 72-year-old woman admitted to our institution with a persistent fever and multiple pulmonary infiltrates. Transthoracic echocardiography and serologic tests led to the diagnosis of brucellar tricuspid endocarditis. The patient responded favorably to antibiotic treatment alone and did not need surgery. Prolonged antibiotic therapy with a combination of drugs active on intracellular microorganisms in the absence of surgical treatment could be effective in brucellar tricuspid endocarditis when the valve is not severely damaged.

Increased Association of Pulmonary Thromboembolism and Tuberculosis during COVID-19 Pandemic: Data from an Italian Infectious Disease Referral Hospital.

Pulmonary thromboembolism (PTE) has been associated with tuberculosis (TB), but the true incidence is unknown. The aim of our study was to retrospectively evaluate the PTE prevalence in TB patients hospitalized at the National Institute for Infectious Diseases L. Spallanzani during the January 2016-December 2021 period. Retrospective data collection and evaluation were conducted. Among 1801 TB patients, 29 (1.61%) exhibited PTE. Twenty (69%) had comorbidities; eleven (37.9%) had predisposing factors for PTE. Nineteen (65.5%) had extensive TB disease. The commonest respiratory symptoms were cough (37.9%), dyspnea (31%), chest pain (10.3%), and hemoptysis (6.9%). Twenty-five (86.2%) had elevated serum D-dimer levels. An increased prevalence of PTE from 0.6% in the pre-COVID-19 pandemic period to 4.6% in the pandemic period was found. Acute respiratory failure and extensive TB disease increased significantly in the pandemic period. The increase in PTE could be explained by the increased severity of TB in patients in the pandemic period and by increased clinical suspicion and, consequently, increased requests for D-dimer testing, including in patients with non-COVID-19 pneumonia. Patients with extensive pulmonary disease are at high risk of developing PTE. Clinicians should be aware of this potentially life-threatening complication of TB, and patients should receive a thromboembolism risk assessment.

Increase in Tuberculosis Diagnostic Delay during First Wave of the COVID-19 Pandemic: Data from an Italian Infectious Disease Referral Hospital.

BACKGROUND: The WHO advised that the impact of COVID-19 pandemic on TB services was estimated to be dramatic due to the disruption of TB services. METHODS: A retrospective data collection and evaluation was conducted to include all the patients hospitalized for TB at INMI from 9 March to 31 August 2020 (lockdown period and three months thereafter). For the purpose of the study, data from patients hospitalized in the same period of 2019 were also collected. RESULTS: In the period of March-August 2019, 201 patients were hospitalized with a diagnosis of TB, while in the same period of 2020, only 115 patients, with a case reduction of 43%. Patients with weight loss, acute respiratory failure, concurrent extrapulmonary TB, and higher Timika radiographic scores were significantly more frequently hospitalized during 2020 vs. 2019. The median patient delay was 75 days (IQR: 40-100) in 2020 compared to 30 days (IQR: 10-60) in 2019 (p < 0.01). Diagnostic delays in 2020 remain significant in the multiple logistic model (AOR = 6.93, 95%CI: 3.9-12.3). CONCLUSIONS: Our experience suggests that COVID-19 pandemic had an impact on TB patient care in terms of higher diagnostic delay, reduction in hospitalization, and a greater severity of clinical presentations.

Benefits of Steroid Therapy in COVID-19 Patients with Different PaO2/FiO2 Ratio at Admission.

INTRODUCTION: The use of steroid therapy in patients within the context of SARS-CoV-2 infection is still a matter of debate. This study aimed to evaluate if potential steroid benefits could be predicted by the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2) (P/F) in COVID-19 patients at admission. MATERIALS AND METHODS: Medical records were retrospectively collected from all adult patients admitted because of COVID-19 from 29 January to 31 July 2020. The association of steroid therapy with 28-day all-cause mortality outcome was analysed in a multivariable logistic regression model adjusted for confounding factors. RESULTS: Overall, 511 patients were analysed, of which 39.1% underwent steroid therapy. Steroid treated patients were mostly male, older, and more frequently treated with antiviral drugs and aminoquinolines; the most common comorbidities were hypertension, followed by cardiovascular disease. Overall, 51 patients died within 28-days, and overall 28-days mortality was 19.5% in the cohort of patients exposed to steroids versus 3.9% mortality in unexposed patients (p < 0.001). Steroid therapy on patients with P/F ratio of 235 mmHg or higher at admission can be considered as detrimental, with an 8% increased probability of death. CONCLUSIONS: Steroid therapy is associated with increased 28-day mortality in COVID-19 in patients with mild or no ARDS.

Salmonella Hessarek Gastroenteritis with Bacteremia: A Case Report and Literature Review.

Salmonella enterica subspecies enterica serotype Hessarek (Salmonella Hessarek) is considered a serovar with high host specificity and is an uncommon cause of disease in humans; no cases of S. Hessarek bacteremia have been reported in humans to date. On 16 July 2019, a young male presented abdominal pain, vomit, diarrhea, and fever up to 41 °C, a few hours after a kebab meal containing goat meat; he went to the Emergency Room, where a Film Array® GI Panel (BioFire, Biomerieux Company, Marcy-L´Étoile, France) was performed on his feces and results were positive for Salmonella. The culture of the feces was negative, but the blood culture was positive for Salmonella spp., which was identified as Salmonella Hessarek by seroagglutination assays. The patient was treated with ceftriaxone 2 g intravenously qd for 8 days; he was discharged in good general conditions, and ciprofloxacin 500 mg per os bid for 7 more days was prescribed, after exclusion of endocarditis and of clinical signs of complicated bacteremia. This case of Salmonella Hessarek gastroenteritis with bacteremia is probably the first case of bloodstream human infection due to this agent ever described. Further studies are needed to ascertain the global burden of S. Hessarek disease in humans.

Dynamics of viral load rebound in plasma and semen after stopping effective antiretroviral therapy.

A rebound in the plasma and seminal viral load was detected in 12 patients after the interruption of effective highly active antiretroviral therapy. The viral rebound was generally higher in plasma, although the highest level observed during interruption was higher in semen in two patients. The reintroduction of therapy was followed by an overall decrease in HIV-RNA in plasma and semen. One to 2 months after restarting treatment, four out of seven patients showed undetectable HIV-RNA in semen.

Expansion of pre-terminally differentiated CD8 T cells in chronic HIV-positive patients presenting a rapid viral rebound during structured treatment interruption.

OBJECTIVE: The influence of structured treatment interruption on effector/memory CD8 T cell dynamics was analysed in chronic HIV-infected patients showing a rapid or delayed viral rebound. DESIGN: Structured treatment interruption consisted of at least one month of discontinuation, followed by highly active antiretroviral therapy (HAART) resumption. Two groups of HIV structured treatment interruption patients were selected on the basis of plasma viral HIV-RNA value (> 30 000 copies/ml, branched DNA): group A (n = 14), patients with a rapid viral rebound (within one month) and group B (n = 6), patients with a delayed or no viral rebound (after a minimum of 4 months). METHODS: A clinical and immunological follow-up was performed at HAART suspension (t 0), one month from suspension (t 1), at HAART resumption (t 2), and 30 days from resumption (t 3). RESULTS: A sustained viral rebound was observed in group A patients, showing a rapid expansion of circulating CD8 T lymphocytes. In this group, the frequencies of CD8 T cells releasing IFN-gamma after mitogen-induced or Gag-specific stimulation were highly increased after HAART discontinuation. Nevertheless, these CD8 T lymphocytes were mainly composed of pre-terminally differentiated cytotoxic T lymphocytes (CTL) expressing a CCR7 CD27 CD45RA phenotype and a reduced amount of perforin. In contrast, group B patients showed no significant changes in immunological parameters during a prolonged drug-free period. CONCLUSION: These data indicate that monitoring CD8 T cell dynamics during structured treatment interruption could be clinically relevant, and new therapeutic strategies should aim qualitatively to restore CTL effector functions.

Primary Toxoplasma gondii infection in a pregnant human immunodeficiency virus-infected woman.

We report a 36-year-old HIV-infected woman who developed primary Toxoplasma gondii infection during pregnancy that was treated with spiramycin and antiretroviral drugs. There was no vertical transmission of toxoplasmosis and HIV.

Extra-cerebral severe infections associated with haemorrhagic hereditary telangiectasia (Rendu-Osler-Weber Disease): five cases and a review of the literature.

Hereditary haemorrhagic telangiectasia (HHT) is one of the most common autosomal dominant disorders and is characterized by genetically determined abnormalities of vascular structure. People affected by HHT are predisposed to severe infections such as cerebral abscesses, typical of patients with pulmonary arteriovenous malformations, and extra-cerebral infections such as bacteraemia, septic arthritis, osteomyelitis, hepatic abscesses, skin infections and infective endocarditis. We present a retrospective series of severe bacterial extra-cerebral infections in five patients affected by HHT, admitted to our Institute from January 2007 to June 2013. We also reviewed the literature of the last five years concerning infectious complications in people affected by HHT. Our study shows that HHT patients with infectious complications exclusively localized in extra-cerebral sites are usually fragile, old and affected by comorbidities. Moreover, we recognized a trend of Staphylococcus aureus (SA) severe infection recurrence in such patients, both in our series and in the literature. In our opinion these results suggest the need to evaluate the possible benefits of SA nasal colonization screening and decolonization in such patients.

Salmonella enterica ssp. arizonae infection in a 43-year-old Italian man with hypoglobulinemia: a case report and review of the literature.

INTRODUCTION: Salmonella enterica ssp. arizonae is an uncommon human pathogen with serious infections reported in immunocompromised hosts. In Europe, only a few cases have been described. Patients with this infection usually have a history of contact with reptiles or travel abroad. We present a case report of infection in a patient with hypoglobulinemia and a literature review. CASE PRESENTATION: We describe the case of a 43-year-old Caucasian Italian man with hypoglobulinemia who presented to our hospital with sepsis and diarrhea. A stool culture yielded S. enterica ssp. arizonae. Our patient was treated with oral ciprofloxacin and made a full recovery. We also present a review of the cases of S. enterica ssp. arizonae infections previously reported in Europe. CONCLUSIONS: The majority of infections from S. enterica ssp. arizonae occur in patients who are immunocompromised. Data from the literature suggests that it may be difficult to eradicate the bacteria and thus, prolonged antibiotic courses are often used. It would be advisable for clinicians to investigate for pre-existing immune dysfunction if S. enterica ssp. arizonae is isolated. In Italy, although there have only been a few cases, the likely route of transmission remains unclear and requires further surveillance.

Rhodococcus equi infection in HIV-infected individuals: case reports and review of the literature.

Rhodococcus equi is a gram-positive, coryneform bacterium that causes zoonotic infection mainly in horses and foals. It sometimes affects humans presenting as cavitary pneumonia. Immunocompromised patients, including HIV-infected patients, are more susceptible to R. equi infection. We present 10 cases of R. equi infection in HIV-positive patients admitted to our institute from 1991 to June 2008. Moreover, we have reviewed 272 cases of R. equi infection in HIV-infected persons, published from 1986 through 2008. With respect to the literature data, the R. equi strains isolated in our case series showed lower sensitivity to ceftriaxone, amoxicillin/clavulanic acid, and cotrimoxazole. Prompt diagnosis, early initiation of antiretroviral treatment and combined antimicrobial treatment seem to be effective to eradicate the infection and to improve the outcome.

Hemolytic anemia due to acute cytomegalovirus infection in an immunocompetent adult: a case report and review of the literature.

INTRODUCTION: Cytomegalovirus is a common virus responsible for a wide range of clinical manifestations. Hemolysis is a rare but potentially life-threatening complication of cytomegalovirus infection, described mostly in immunocompromised patients, the pathogenesis of which is still unclear.We performed a review of the literature regarding cases of hemolytic anemia during acute cytomegalovirus infection in apparently immunocompetent individuals. We searched for relevant articles in PubMed for the period of 1980 through 2008. CASE PRESENTATION: We describe a case of Coombs-negative hemolytic anemia in a 44-year-old Caucasian immunocompetent man with acute cytomegalovirus infection. CONCLUSION: Clinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in immunocompetent adults. Possible therapeutic options include antiviral therapy and steroids, although the best treatment strategy is still controversial.

Levels of interleukin-15 in plasma may predict a favorable outcome of structured treatment interruption in patients with chronic human immunodeficiency virus infection.

Structured treatment interruption (STI) may help to alleviate the problems associated with long-term antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients. We analyzed the role that baseline levels of cytokines in plasma play as markers of a favorable outcome of STI. Two groups of patients were defined: STI responders and STI nonresponders. STI responders showed a higher baseline concentration of interleukin (IL)-15 in plasma than did STI nonresponders and showed lower levels of tumor necrosis factor (TNF)-alpha during STI. No differences were observed in levels of IL-2, IL-7, or interferon-alpha in plasma. Our data show that (1) levels of TNF-alpha in plasma correlate with HIV viremia and (2) monitoring baseline levels of IL-15 in plasma allows for the identification of a favorable outcome of STI.

HIV-1 DNA burden dynamics in CD4 T cells and monocytes in patients undergoing a transient therapy interruption.

Replication-competent HIV, as well as HIV-1 DNA, has been detected in CD4 T cells and in monocytes during antiretroviral therapy (ART), indicating that these cells could represent an important viral reservoir. We measured HIV-1 DNA in monocytes and CD4 T cells in patients undergoing transient therapy interruption (TTI), to establish the dynamic of HIV-1 DNA burden and to find possible correlations with immune restoration and re-establishment of virological control after ART resumption. In most patients CD4 depletion and viral load rebound followed TTI. Rapid resumption of virological and immunological control was achieved after ART reintroduction. After TTI, in most cases a transient increase of both monocyte and CD4 HIV-1 DNA burden was observed. After ART reintroduction, both CD4 T cell and monocyte HIV-1 DNA copy number decreased, reaching baseline levels at the end of observation. At this time monocyte HIV-1 DNA burden was always undetectable, while CD4 T cell HIV-1 DNA burden was lower than at baseline. As CD4 T cell HIV-1 DNA values are independently associated with CD4 depletion, the increase of HIV-1 DNA burden in these cells after TTI is presumably due to acute infection, causing cell death. This is also supported by the pattern of 2-LTR appearance in these cells after TTI. HIV-1 DNA burden in monocytes and CD4 T cells show high correlation, suggesting reciprocal re-feeding of two cell populations. Repopulation by HIV these cells after TTI is temporary, and no significant changes of HIV-1 DNA burden were observed after ART resumption respect to pre-TTI period.

Computer-based design of an HLA-haplotype and HIV-clade independent cytotoxic T-lymphocyte assay for monitoring HIV-specific immunity.

BACKGROUND: Human immunodeficiency virus (HIV)- specific CD8-positive cytotoxic T-lymphocytes (CTL) play a key role in controlling HIV infection. Monitoring CTL response could be clinically relevant during structured therapy interruption (STI), HIV exposure, and vaccine trials. However, HLA patients' restriction and HIV variability limited the development of a CTL assay with broad specificity. MATERIALS AND METHODS: We designed an HLA-class I/HIV-1 clade independent assay for assessing HIV- specific CTL by using a computer-assisted selection ofthe CTL epitopes. Twenty-eight 15-mers were selected by peptide-binding motifs analysis using different databases (HIV-Immunology Database, SYFPEITHI, BIMAS). Altogether they putatively bind to more than 90% of HLA haplotypes in different populations, with an overall HIV-1 variability below 9%. The peptide pool was used as an antigen in an intracellular cytokine staining (ICS) assay for quantifying HIV-specific CTL response. RESULTS: The test can be performed using both fresh and cryopreserved peripheral blood mononuclear cells (PBMC), whereas GAG protein as antigen works only on fresh PBMC. A significantly higher CTL response with respect to HIV-negative controls was detected in all HIV-1 infected subjects of two groups of patients with different ethnicities (Caucasians and Africans) and coming from areas with different HIV-1 clade prevalences (clade B and A/G, respectively). In Caucasian patients, after month of STI, the number of HIV-1 specific CTL (2,896 +/- 2,780 IFN-gamma specific CD8 cells/ml) was significantly higher than that found at enrolment (2,125 +/- 4,426 IFN-gamma specific CD8 cells/ml, p< 0.05). CONCLUSIONS: These data indicate that this CTL assay is broadly specific and could represent a useful clinical tool for HIV immunodiagnostic independent of HLA-haplotype and HIV-clade variabilities.

NK cell activity controls human herpesvirus 8 latent infection and is restored upon highly active antiretroviral therapy in AIDS patients with regressing Kaposi's sarcoma.

Kaposi's sarcoma (KS) develops upon reactivation of human herpesvirus 8 (HHV8) infection and virus dissemination to blood and tissue cells, including endothelial and KS spindle cells where the virus is mostly present in a latent form. However, this may likely require the presence of compromised host immune responses and/or the evasion of infected cells from the host immune response. In this regard, mechanisms of evasion of productively infected cells from both CTL and NK cell responses, and resistance of latently infected cells from specific CTL, have already been shown. Here we show that cells which are latently infected by HHV8 are indeed efficiently lysed by NK cells from individuals with a normal immune response. Notably, NK cell-mediated immunity was found to be significantly reduced in AIDS patients with progressing KS as compared to both HIV-negative patients with indolent classic KS or normal blood donors. However, it was restored after treatment with the highly active antiretroviral therapy (HAART) in AIDS-KS patients, that showed regression and clearance of HHV8 from PBMC. By contrast, AIDS-KS patients with a more aggressive disease and no clinical response had persistent HHV8 viremia associated with reduced NK cell cytotoxicity. These results suggest a key role for NK cells in the control of HHV8 latent infection, KS development, and in disease remission upon HAART.