Recent transmission clustering of HIV-1 C and CRF17_BF strains characterized by NNRTI-related mutations among newly diagnosed men in central Italy

Increased evidence of relevant HIV-1 epidemic transmission in European countries is being reported, with an increased circulation of non-B-subtypes. Here, we present two recent HIV-1 non-B transmission clusters characterized by NNRTI-related amino-acidic mutations among newly diagnosed HIV-1 infected men, living in Rome (Central-Italy)

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

The mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination

Comparison between hospitalized patients affected or not by COVID-19 (RESILIENCY study)

Dear Editor, in the recent report of Munblit and coworkers [1], authors observed that the combination of clinical features was sufficient to diagnose COVID-19 indicating that laboratory testing is not critical in real-life clinical practice. To date, all patients admitted to Emergency Department with acute respiratory failure and/or fever should be considered as a suspected SARS-CoV-2 infection [2-3], and an early recognition of etiology and the prompt therapeutic management are crucial to improve survival [4-5]. From March to July 2020, we performed a prospective, multicenter study (RESILIENCY study). During the study period, all patients hospitalized for suspected or confirmed COVID-19 were prospectively recruited in 3 large hospitals in Rome, Italy. All patients with suspected SARS-CoV-2 infection, admitted to the hospital in case of fever and/or hypoxemic respiratory failure (PaO2 <60 mmHg at rest in ambient air) or of exacerbation of underlying diseases or severe symptoms not manageable outside the hospital, were evaluated according to a predefined protocol (see Figure 1). Overall, 653 patients were included in the study: 309 (47.3%) patients with confirmed COVID-19 and 344 (52.7%) without COVID-19, hospitalized for other causes. Baseline characteristics and outcomes of the study population showed that the main causes of hospitalization among patients without COVID-19 were: acute heart failure (47%), bacterial pneumonia (38.5%), and pulmonary embolism (9.2%). Overall, 67 (21.7%) patients of COVID-19 group and 45 (13.1%) hospitalized for other causes were admitted to intensive care unit; 30-day mortality was observed in 59 (19%) patients of COVID-19 group and 62 (18%) of non-COVID-19 group. The multivariate analysis about risk factors for COVID-19 etiology at time of hospitalization showed that dry cough (OR 3.76, CI 95% 1.98-7.92, P<0.001), duration of fever>3 days (OR 5.21, CI 95% 2.34-9.21, P<0.001), lymphocytopenia (OR 1.98, CI 95% Downloaded from https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1745/5989494 by Sapienza Università di Roma user on 01 December 2020 Accepted Manuscript 3 1.27-4.22, P=0.002) and PaO2/FiO2 ratio<250 (OR 4.98, CI 95% 2.22-9.71, P<0.001) were independently associated with COVID-19 etiology, while procalcitonin value>1 ng/ mL (OR 0.21, CI 95% 0.08-0.82, p<0.001), and lactate>2 mmol/L (OR 0.41, CI 95% 0.15-0.77, p<0.001) were associated with non-COVID-19 etiology. Finally, analysis about predictors of 30-day mortality showed that age (per-year increase OR 1.33; CI 95% 1.11-2.10; p<0.001), cardiovascular disease (OR 4.58; CI 95% 2.07-8.25; p<0.001), and ICU admission (OR 2.1; CI 95% 1.48-4.4; p<0.001) were independently associated with all-cause 30-day mortality, while the use of low-molecularweight heparin (OR 0.22, CI 95% 0.03-0.45, p=0.002) was associated with survival. The findings of the present study can be summarized as follows:1) the prompt identification of specific clinical characteristics (like dry cough or duration of fever>3 days), and laboratory findings (like lymphocytopenia, PaO2/FiO2 ratio<250, procalcitonin value>1 ng/ mL, and lactate>2 mmol/L) can help physicians to distinguish rapidly between COVID19 or other etiologies [6]; 2) the application of a standard approach to management of patients with acute respiratory failure and/or fever associated with the knowledge of clinical and laboratory characteristics of COVID-19 can early drive physicians to therapeutic choices; and 3) age, cardiovascular disease, and ICU admission show an independent association with all-cause 30-day mortality [7], while the use of low-molecular-weight heparin was associated with survival [8]. In conclusion, COVID-19 syndrome is characterized by a heterogeneous clinical, laboratoristic, and radiological presentation, especially at its onset [9]. However, the application of a standard approach to management of patients with acute respiratory failure and/or fever and the knowledge of clinical and laboratory characteristics of COVID-19 can early drive therapeutic choic

Xerostomia, gustatory and olfactory dysfunctions in patients with COVID-19

Background The novel Coronavirus Disease-19 (COVID-19) continues to have profound effect on global health. Our aim was to evaluate the prevalence and characterize specific symptoms associated with COVID-19. Methods This retrospective study included 326 patients with confirmed SARS-CoV-2 infection evaluated at the Emergency Department of the Umberto I Polyclinic Hospital, Rome, Italy between March 6th and April 30th, 2020. In order to assess xerostomia, olfactory and gustatory dysfunctions secondary to COVID-19, a telephone-based a modified survey obtained from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 for taste and smell disorders and the Fox Questionnaire for dry mouth were administered to 111 patients (34%) after discharge between June 4th and June 12th. Results Taste dysfunction was the most common reported symptom (59.5%; n = 66), followed by xerostomia (45.9%; n = 51) and olfactory dysfunctions (41.4%; n = 46). The most severe symptom was olfactory dysfunction with a median severity score of 8.5 (range: 5–10). Overall 74.5% (n = 38) of patients with xerostomia, 78.8% (n = 52) of patients with gustatory dysfunctions and 71.1% (n = 33) of patients with olfactory dysfunctions reported that all symptoms appeared before COVID-19 diagnosis. Overall, the majority of patients reported one symptom only (45.9%, n = 51), 37 (33.3%) reported the association of two symptoms, and 23 (20.7%) patients reported the association of three symptoms at the same time. Conclusion Xerostomia, gustatory and olfactory dysfunctions may present as a prodromal or as the sole manifestation of COVID-19. Awareness is fundamental to identify COVID-19 patients at an early stage of the disease and limit the spread of the virus

Modulation of Phenylalanine and Tyrosine Metabolism in HIV-1 Infected Patients with Neurocognitive Impairment: Results from a Clinical Trial

To investigate the effects of oral bacteriotherapy on intestinal phenylalanine and tyrosine metabolism, in this longitudinal, double-arm trial, 15 virally suppressed HIV+ individuals underwent blood and fecal sample collection at baseline and after 6 months of oral bacteriotherapy. A baseline fecal sample was collected from 15 healthy individuals and served as control group for the baseline levels of fecal phenylalanine and tyrosine. CD4 and CD8 immune activation (CD38+) was evaluated by flow cytometry. Amino acid evaluation on fecal samples was conducted by Proton Nuclear Magnetic Resonance. Results showed that HIV+ participants displayed higher baseline phenylalanine/tyrosine ratio values than healthy volunteers. A significand reduction in phenylalanine/tyrosine ratio and peripheral CD4+ CD38+ activation was observed at the end of oral bacteriotherapy. In conclusion, probiotics beneficially affect the immune activation of HIV+ individuals. Therefore, the restoration of intestinal amino acid metabolism could represent the mechanisms through which probiotics exert these desirable effects

Longitudinal virological and immunological profile in a case of human monkeypox infection

In a male with severe proctitis, monkeypox virus DNA was detected in skin lesions, blood, nasopharynx, and rectum, underlying the generalized viral spreading. Rectal involvement was still found when skin lesions disappeared. At the early-stage, increase of cytotoxic and activated T-cells, while reduction of CD56dimCD57+NK cells compared to recovery time-point was observed

The Association between Influenza and Pneumococcal Vaccinations and SARS-Cov-2 Infection : Data from the EPICOVID19 Web-Based Survey

The present study aims to evaluate whether influenza and pneumococcal vaccinations are associated with positive nasopharyngeal swab (NPS) testing to detect SARS-CoV-2. Data from the Italian cross-sectional web-based survey (EPICOVID19), based on a self-selection sample of individuals aged 6518, were considered. The probability of a positive SARS-CoV-2 NPS test result as a function of influenza or anti-pneumococcal vaccination was evaluated using multivariable logistic regression, stratifying analysis by age (<65 years, 6565 years). From April 2020, 170,731 individuals aged <65 years and 28,097 6565 years filled out the EPICOVID19 questionnaire. Influenza and anti-pneumococcal vaccinations were received, respectively, by 16% and 2% of those <65 years, and by 53% and 13% of those 6565 years. SARS-CoV-2 NPS testing was reported by 6680 participants. Anti-pneumococcal and influenza vaccinations were associated with a decreased probability of a SARS-CoV-2 NPS positive test in the younger participants (OR = 0.61, 95% CI 0.41\u20130.91; OR = 0.85, 95%CI 0.74\u20130.98; respectively). A significantly lower probability of a positive test result was detected in the individuals 6565 years who received anti-pneumococcal vaccination (OR = 0.56, 95%CI 0.33\u20130.95). These results need to be confirmed by further investigations, but they are relevant given the probable coexistence of influenza, bacterial infections, and COVID-19 over the coming autumn\u2013winter season

Cellular immune profiling of lung and blood compartments in patients with SARS-CoV-2 infection

Background: SARS-CoV-2 related immunopathology may be the driving cause underlying severe COVID-19. Through an immunophenotyping analysis on paired bronchoalveolar lavage fluid (BALF) and blood samples collected from mechanically ventilated patients with COVID-19-associated Acute Respiratory Distress Syndrome (CARDS), this study aimed to evaluate the cellular immune responses in survivors and non-survivors of COVID-19. Methods: A total of 36 paired clinical samples of bronchoalveolar lavage fluid (BALF) mononuclear cells (BALF-MC) and peripheral blood mononuclear cells (PBMC) were collected from 18 SARS-CoV-2-infected subjects admitted to the intensive care unit (ICU) of the Policlinico Umberto I, Sapienza University Hospital in Rome (Italy) for severe interstitial pneumonia. The frequencies of monocytes (total, classical, intermediate and non-classical) and Natural Killer (NK) cell subsets (total, CD56bright and CD56dim), as well as CD4+ and CD8+ T cell subsets [naïve, central memory (TCM) and effector memory (TEM)], and those expressing CD38 and/or HLADR were evaluated by multiparametric flow cytometry. Results: Survivors with CARDS exhibited higher frequencies of classical monocytes in blood compared to non-survivors (p < 0.05), while no differences in the frequencies of the other monocytes, NK cell and T cell subsets were recorded between these two groups of patients (p > 0.05). The only exception was for peripheral naïve CD4+ T cells levels that were reduced in non-survivors (p = 0.04). An increase in the levels of CD56bright (p = 0.012) and a decrease in CD56dim (p = 0.002) NK cell frequencies was also observed in BALF-MC samples compared to PBMC in deceased COVID-19 patients. Total CD4+ and CD8+ T cell levels in the lung compartment were lower compared to blood (p = 0.002 and p < 0.01, respectively) among non-survivors. Moreover, CD38 and HLA-DR were differentially expressed by CD4+ and CD8+ T cell subsets in BALF-MC and in PBMC among SARS-CoV-2-infected patients who died from COVID-19 (p < 0.05). Conclusions: These results show that the immune cellular profile in blood and pulmonary compartments was similar in survivors and non-survivors of COVID-19. T lymphocyte levels were reduced, but resulted highly immune-activated in the lung compartment of patients who faced a fatal outcome

Autophagy hijacking in PBMC From COVID-19 patients results in lymphopenia

Autophagy is a homeostatic process responsible for the self-digestion of intracellular components and antimicrobial defense by inducing the degradation of pathogens into autophagolysosomes. Recent findings suggest an involvement of this process in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the role of autophagy in the immunological mechanisms of coronavirus disease 2019 (COVID-19) pathogenesis remains largely unexplored. This study reveals the presence of autophagy defects in peripheral immune cells from COVID-19 patients. The impairment of the autophagy process resulted in a higher percentage of lymphocytes undergoing apoptosis in COVID-19 patients. Moreover, the inverse correlation between autophagy markers levels and peripheral lymphocyte counts in COVID-19 patients confirms how a defect in autophagy might contribute to lymphopenia, causing a reduction in the activation of viral defense. These results provided intriguing data that could help in understanding the cellular underlying mechanisms in COVID-19 infection, especially in severe forms

Association between PaO2/FiO2 ratio and thrombotic events in COVID-19 patients

PaO2/FiO(2) (P/F ratio) is considered a marker of hypoxia/hypoxemia and mortality. Several prothrombotic changes are associated with the decrease of P/F ratio. The role of P/F ratio in patients with arterial and venous thrombosis remains unclear. The aim of this study was to assess in patients with coronavirus disease 2019 (COVID-19), the association between P/F ratio and arterial/venous thrombosis. One thousand and four hundred and six COVID-19 patients were recruited; 289 (21%) patients had P/F ratio < 200 and 1117 (79%) >= 200. Compared to the patients with P/F ratio >= 200, those with P/F ratio < 200 were older and with higher levels of glycemia, D-dimer and lower levels of albumin. Multiple linear regression analysis showed that albumin (standardized coefficient beta: 0.156; SE: 0.001; p = 0.0001) and D-dimer (standardized coefficient beta: -0.135; SE: 0.0001; p = 0.0001) were associated with P/F ratio. During the hospitalization 159 patients were transferred in intensive care unit (ICU), 253 patients died, 156 patients had arterial or venous thrombotic events. A bivariate logistic analysis was performed to analyze the predictors of thrombosis in COVID-19 patients; P/F ratio < 200 (Odds Ratio: [OR] 1.718, 95% Confidence Interval [CI] 1.085-2.718, p = 0.021), albumin (OR 1.693, 95% CI 1.055-2.716, p = 0.029), D-dimer (OR 3.469, 95% CI 2.110-5.703, p < 0.0001), coronary artery disease (CAD) (OR 1.800, 95% CI 1.086-2.984, p = 0.023) and heart failure (OR 2.410 95% CI 1.385-4.193, p = 0.002) independently predicted thrombotic events in this population. This study suggests that the P/F ratio is associated with thrombotic events by promoting a hypercoagulation state in patients hospitalized for COVID-19