Dynamic NLR and PLR in Predicting COVID-19 Severity: A Retrospective Cohort Study.

INTRODUCTION: The hyperinflammation phase of severe SARS-CoV-2 is characterised by complete blood count alterations. In this context, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) can be used as prognostic factors. We studied NLR and PLR trends at different timepoints and computed optimal cutoffs to predict four outcomes: use of continuous positive airways pressure (CPAP), intensive care unit (ICU) admission, invasive ventilation and death. METHODS: We retrospectively included all adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia admitted from 23 January 2020 to 18 May 2021. Analyses included non-parametric tests to study the ability of NLR and PLR to distinguish the patients' outcomes at each timepoint. Receiver operating characteristic (ROC) curves were built for NLR and PLR at each timepoint (minus discharge) to identify cutoffs to distinguish severe and non-severe disease. Their statistical significance was assessed with the chi-square test. Collection of data under the SMACORE database was approved with protocol number 20200046877. RESULTS: We included 2169 patients. NLR and PLR were higher in severe coronavirus disease 2019 (COVID-19). Both ratios were able to distinguish the outcomes at each timepoint. For NLR, the areas under the receiver operating characteristic curve (AUROC) ranged between 0.59 and 0.81, and for PLR between 0.53 and 0.67. From each ROC curve we computed an optimal cutoff value. CONCLUSION: NLR and PLR cutoffs are able to distinguish severity grades and mortality at different timepoints during the course of disease, and, as such, they allow a tailored approach. Future prospects include validating our cutoffs in a prospective cohort and comparing their performance against other COVID-19 scores.

Is a radiological score needed to define the severity of Nontuberculous mycobacteria lung disease?

High-resolution CT-scan (HRCT) plays a major role in the diagnosis of Nontuberculous mycobacteria lung disease (NTM-LD), but its role in follow-up is controversial. Our aim was first to conceive a radiological score able to quantify the severity of pulmonary involvement by NTM infection and, second, to check its association with the NTM-LD clinical burden. We also intended, if possible, to verify the potential influence of NTM specific treatment on the radiological score. We retrospectively collected the clinical, microbiological and radiological data of all patients who were admitted to our hospital from 1 January 2012 to 1 January 2020 with a confirmed diagnosis of NTM-LD. A radiological score was applied to evaluate lung involvement on HRCT at diagnosis and at 6-18 months follow-up. Twenty-eight patients with NTM-LD performed follow-up HRCT. No association was found between radiological and clinical score (Spearman R -0.05, 95%CI -0.41 to 0.33). Repeated measures analysis showed a significant increase in radiological score over time (change 1.11, 95%CI 0.10 to 2.11; p-value 0.032), while Mann-Whitney test did not show any difference between treated and untreated patients (p value 0.922). Further studies are needed to assess the usefulness of routine radiological follow-up in patients with NTM-LD.

The infection risk after transjugular intrahepatic portosystemic shunt: A multiple competing risk analysis from a tertiary care center.

BACKGROUND: Infections following transjugular intrahepatic portosystemic shunt (TIPS) placement have been poorly described. We aim to investigate the rate and the potential predictors of infections occurring after TIPS placement. METHODS: Single center, retrospective, observational study. All patients who had undergone TIPS placement in the last 10 years with a minimum 1-year FU, were considered. Multiple competing risk analyses were performed to identify infection risk factors and a multivariable Cox proportional-hazard regression model to evaluate the predictors of death. RESULTS: Forty-nine patients were considered. Among these, 23 (46%) developed at least 1 infection during the FU, at a median time of 237.7 days (IQR 151.5) from the TIPS placement. We did not find any predictor of infection, while MELD score and cancer were associated with death (p = .04; HR 1.14; CI 1.00- 1.30). CONCLUSION: We found a high rate of all-type infections during the FU times. However, most of these infections occurred as late-onset infections and were caused by Gram-positive microorganisms. Thus, TIPS procedure itself does not seem to be burdened with high infectious perioperative risk.

Early remdesivir to prevent severe COVID-19 in recipients of solid organ transplant: a real-life study from Northern Italy.

OBJECTIVES: The effectiveness of a 3-day course of remdesivir to prevent severe disease in patients with COVID-19 who received solid organ transplant (SOT) is unknown. We wanted to study the efficacy of this therapeutic option in patients with COVID-19 who received SOT in preventing both hospitalizations for outpatients and clinical worsening due to COVID-19 for those already hospitalized for other reasons. METHODS: This is a single-center, retrospective, observational study conducted in the Fondazione IRCSS Policlinico San Matteo of Pavia, Northern Italy. We extracted all the data of patients with COVID-19 receiving SOT who received and did not receive pre-emptive remdesivir between December 23, 2021, and February 26, 2022. We used a Cox proportional hazard model to assess whether receiving pre-emptive remdesivir was associated with lower rates of hospitalization. RESULTS: A total of 24 patients who received SOT were identified. Among these, seven patients (29, 1%) received pre-emptive remdesivir, whereas 17 (70, 9%) patients did not. Receiving remdesivir significantly reduced the hospitalization rate in outpatients who received SOT and the clinical worsening of the condition of already hospitalized patients who received SOT (hazard ratio 0.05; confidence interval [0.00-0.65], P-value = 0.01). CONCLUSION: In our cohort of patients infected with SARS-CoV-2 who received SOT, pre-emptive remdesivir was effective in reducing the hospitalization rate due to COVID-19 and in preventing the clinical worsening of the condition of patients who received SOT who were hospitalized for reasons other than COVID-19.

Mortality due to COVID-19 during the pandemic: A comparison of first, secondo and third SMAtteo COvid19 REgistry (SMACORE).

COVID-19 tide had shattered on European countries with three distinct and tough waves, from March and April, 2020; October and November, 2020 and March and April, 2021 respectively. We observed a 50% reduction in the hazard of death during both wave II and III compared with wave I (HR 0.54, 95%CI 0.39-0.74 and HR 0.57, 95%CI 0.41-0.80, respectively). Sex and age were independent predictors of death. We compare in-hospital mortality of COVID-19 patients admitted at our Referral Hospital of Northern Italy during the different waves, discuss the reasons of the observed differences and suggest approaches to the challenges ahead.

Immunity to SARS-CoV-2 up to 15 months after infection.

Information concerning the longevity of immunity to SARS-CoV-2 following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in COVID-19 patients followed up to 15 months after symptoms onset. Following a peak at day 15-28 postinfection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Compared to G614, plasma neutralizing titers were more than 8-fold lower against variants Beta, Gamma, and Delta. SARS-CoV-2-specific memory B and T cells persisted in the majority of patients up to 15 months although a significant decrease in specific T cells, but not B cells, was observed between 6 and 15 months. Antiviral specific immunity, especially memory B cells in COVID-19 convalescent patients, is long-lasting, but some variants of concern may at least partially escape the neutralizing activity of plasma antibodies.

An eight-year experience of Nocardia infection in Italy: does immunosuppression matter?

Nocardia has always been considered a pathogen of the immunocompromised host, but recent evidence has also highlighted its role as a pathogen in the immunocompetent. We aim to assess the role of immunosuppression in the disease. We reviewed all the cases of infections due to Nocardia spp. in our center that occurred from 1 January 2012 to 30 September 2019. Patients were divided into three groups: typical immunocompromised (PLWHIV, solid organ or hematopoietic cell transplant recipients, individuals under immunosuppressive drugs), atypical immunocompromised (ongoing chronic diseases involving the lung, kidney, liver and diabetes) and immunocompetent. We identified 53 patients with an infection by Nocardia spp. Thirty-four (60.4%) of them were immunocompromised, 22 (64.7%) typical and 12 (35.3%) atypical immunocompromised. Nineteen (35.8%) were immunocompetent. The two conditions most frequently associated with infection were chronic lung disease (41.5%) and ongoing treatment with immunosuppressive drugs (33.9%). In our cohort a remarkable prevalence of nocardiosis in immunocompetent and atypical immunosuppressed patients was observed.

SARS-CoV-2 specific T-cell immunity in COVID-19 convalescent patients and unexposed controls measured by ex vivo ELISpot assay.

OBJECTIVES: SARS-CoV-2 T-cell response characterization represents a crucial issue for defining the role of immune protection against COVID-19. The aim of the study was to assess the SARS-CoV-2 T-cell response in a cohort of COVID-19 convalescent patients and in a group of unexposed subjects. METHODS: SARS-CoV-2 T-cell response was quantified from peripheral blood mononuclear cells (PBMCs) of 87 COVID-19 convalescent subjects (range 7-239 days after symptom onset) and 33 unexposed donors by ex vivo ELISpot assay. Follow-up of SARS-CoV-2 T-cell response was performed in ten subjects up to 12 months after symptom onset. The role of SARS-CoV-2 specific CD4 and CD8 T cells was characterized in a group of COVID-19 convalescent subjects. Moreover, neutralizing antibodies were determined in serum samples. RESULTS: In 14/33 (42.4%) unexposed donors and 85/87 (97.7%) COVID-19 convalescent subjects a positive result for at least one SARS-CoV-2 antigen was observed. A positive response was observed up to 12 months after COVID-19 infection (median 246 days after symptom onset; range 118-362 days). Of note, SARS-CoV-2 T-cell response seems to be mainly mediated by CD4 T cells. A weak positive correlation was observed between Spike-specific T-cell response and neutralizing antibody titre (p 0.0028; r2 = 0.2891) and positive SARS-CoV-2 T-cell response was observed in 8/9 (88.9%) COVID-19 convalescent subjects with undetectable SARS-CoV-2 neutralizing antibodies. DISCUSSION: Cross-reactive SARS-CoV-2 T-cell response in uninfected patients may be due to previous infections with other common coronaviruses. Our data suggest that long-term SARS-CoV-2 T-cell response might accompany a waning humoral response.

Predictors of starting antimicrobial treatment in patients with nontuberculous mycobacterial lung disease in the Italian scenario: A SITA GIOVANI-IRENE promoted web-survey.

The disease burden due to nontuberculous mycobacteria is growing worldwide, consequently to improved diagnostic abilities and an increase in the individuals at risk. Uncertainties exist about the right moment on which start treatment. We investigated the clinical features associated with starting an antimicrobial treatment in patients with nontuberculous mycobacterial lung disease among Italian physicians involved in the field. We found that in real life predictors of starting antimicrobial treatment are quite adherent to international guidelines, with some uncertainties regarding the implication of immunosuppressive drugs.

Persistence of SARS-CoV-2-specific B and T cell responses in convalescent COVID-19 patients 6-8 months after the infection.

BACKGROUND: Monitoring the adaptive immune responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection provides useful information for the development of vaccination strategies against this virus and its emerging variants. We thus profiled the serum anti-SARS-CoV-2 antibody (Ab) levels and specific memory B and T cell responses in convalescent coronavirus disease 2019 (COVID-19) patients. METHODS: A total of 119 samples from 88 convalescent donors who experienced mild to critical disease were tested for the presence of elevated anti-spike and anti-receptor binding domain Ab levels over a period of 8 months. In addition, the levels of SARS-CoV-2 neutralizing Abs and specific memory B and T cell responses were tested in a subset of samples. FINDINGS: Anti-SARS-CoV-2 Abs were present in 85% of the samples collected within 4 weeks after the onset of symptoms in COVID-19 patients. Levels of specific immunoglobulin M (IgM)/IgA Abs declined after 1 month, while levels of specific IgG Abs and plasma neutralizing activities remained relatively stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG Abs were still present, although at a significantly lower level, in 80% of the samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B and T cell responses developed with time and were persistent in all of the patients followed up for 6-8 months. CONCLUSIONS: Our data suggest that protective adaptive immunity following natural infection of SARS-CoV-2 may persist for at least 6-8 months, regardless of disease severity. Development of medium- or long-term protective immunity through vaccination may thus be possible. FUNDING: This project was supported by the European Union's Horizon 2020 research and innovation programme (ATAC, no. 101003650), the Italian Ministry of Health (Ricerca Finalizzata grant no. GR-2013-02358399), the Center for Innovative Medicine, and the Swedish Research Council. J.A. was supported by the SciLifeLab/KAW national COVID-19 research program project grant 2020.

Competing-risk analysis of coronavirus disease 2019 in-hospital mortality in a Northern Italian centre from SMAtteo COvid19 REgistry (SMACORE).

An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge. 426 adult patients [median age 68 (IQR 56 to 77 years)] were admitted with confirmed COVID-19 over a 5-week period; 292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Among these 46 patients, updated as of 30 May, 2020, 5 (10.9%) had died, 8 (17.4%) were still in ICU, 12 (26.1%) were transferred to lower intensity care units and 21 (45.7%) were discharged. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4th were independent risk factors associated with in-hospital mortality. Older age, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19.

Discordant Liver Fibrosis Predictors in Virologically Suppressed People Living with HIV without Hepatitis Virus Infection.

Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis.

Integrase Inhibitors Use and Cytomegalovirus Infection Predict Immune Recovery in People Living With HIV Starting First-Line Therapy.

BACKGROUND: We explored predictors of CD4/CD8 ratio improvement and optimal immunological recovery (OIR) after initiation of antiretroviral therapy (ART) in naive people living with HIV (PLWH). METHODS: Retrospective multicenter study including naive PLWH starting ART with 2 nucleos(t)ide reverse transcriptase inhibitors + 1 integrase strand transfer inhibitor (InSTI) or non-NRTI or protease inhibitor (PI). PLWH were followed from the time of ART initiation (baseline) to the discontinuation of first-line regimen, virological failure, death, or loss to follow-up. Estimated incidence and predictors of time to CD4/CD8 ratio normalization (defined as ≥1) and OIR (defined as CD4/CD8 ratio ≥ 1 plus CD4 ≥ 500 cells/µL plus CD4% ≥ 30%) were explored by Kaplan-Meier curves and Cox regression analysis. RESULTS: Overall, 1428 PLWH (77.8% males, median age 39 years, 55.1% with positive cytomegalovirus (CMV) antibodies, median HIV-RNA 4.80 log copies/mL, median CD4 323 cells/µL, median CD4/CD8 ratio 0.32) were included, of which 21.5% (n = 307), 44.5% (n = 636), and 34% (n = 485) treated with InSTI-, PI-, and NNRTI-based regimens, respectively. The estimated proportion of CD4/CD8 normalization and OIR at 36 months was 38.6% and 32.9%, respectively. Multivariate analysis showed that InSTI-based regimens had a higher probability of CD4/CD8 ratio normalization and OIR both in the total population (P < 0.001 versus PI) and in advanced naive PLWH (P ≤ 0.001 versus PI and NNRTI). Moreover, subjects with positive CMV serology showed a lower probability of CD4/CD8 ratio normalization and OIR (P < 0.001). CONCLUSIONS: InSTI-based regimens showed a better immune recovery, suggesting that the type of first-line ART can influence immune reconstitution. PLWH with positive CMV serology showed an increased risk of suboptimal immune recovery.

Patients with chronic hepatitis C receiving treatment with direct acting antivirals: How is this population changing?

BACKGROUND AND AIMS: Direct acting antiviral agents (DAAs) have revolutionized the landscape of chronic hepatitis C (CHC) enabling treatment of all those infected. It remains to be determined how the characteristics of those receiving treatment are changing. MATERIALS AND METHODS: We retrospectively analysed all the patients with CHC who received treatment with DAAs in a large referral centre since 01/01/2015. We stratified their demographic, clinical and virological characteristics at baseline and the sustained virological response (SVR) rates according to the year of treatment. RESULTS: In the study were included 2565 patients. During the study period, the yearly proportion of men and cirrhotic patients decreased (p<0.001) whereas mean age increased from 59.8 to 62.2 years old (p=0.04). An increasing trend was observed in the foreign-born patients from 4.3% to 7.9%, without reaching statistical significance. The prevalence of comorbidities had also increased during the study period (p<0.001). Instead, the yearly number of experienced patients decreased significantly (p<0.001) as well as the mean MELD score of cirrhotic patients from 9 to 7.6 (p<0.001). SVR rates increased significantly, from 93.4% in 2015 to 97.1% in 2018 (P<0.05). CONCLUSIONS: The population of patients with CHC receiving DAAs is becoming older and with more comorbidities. Nevertheless, this did not impact SVR rates.

SARS Cov-2 infection in a renal-transplanted patient: A case report.

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.