Mortality predictors in hospitalised COVID-19 patients and the role of anti-SARS-CoV-2 IgG antibodies and remdesivir.

Background: In a pre-vaccination era serologic tests may be used to evaluate the seroprevalence and efficacy of containment strategies applied to the community. Subsequently, SARS-CoV-2 vaccination has successfully reduced hospitalization and admission to intensive care. The role of antiviral treatment for COVID-19 remains debated. Objective: We investigated the effect of SARS-CoV-2 IgG Spike (S) antibody responses in hospitalized patients on 30-day mortality. Finally, we assessed whether other predictive factors affected mortality after 30 days. Methods: Observational study on COVID-19 patients admitted from October 1, 2021, to January 30, 2022. Results: 520 patients were studied; 108 died at the 30-day follow-up (21%). A borderline significance for mortality was observed in favour of the high antibody titer group (24% vs 17%, p=0.05). From the univariate Cox regression analysis, a high IgG-S titer was significantly correlated to lower 30-day mortality (p=0.04, HR: 0.7; 95%CI: 0.44-0.98). The administration of remdesivir (p=0.01) and the age <65 years (p=2.3e-05) were found to be protective for the considered outcome (respectively, HR: 0.5, 95%CI: 0.34-0.86, and HR: 0.1, 95%CI: 0.04-0.30). Conclusions: S-antibodies and remdesivir could play a protecting role in increasing the survival of hospitalized COVID-19 patients who are not suffering from a critical disease. Advanced age is a risk factor for poor outcomes among infected people.

Association Between Sex Hormone Levels and Clinical Outcomes in Patients With COVID-19 Admitted to Hospital: An Observational, Retrospective, Cohort Study.

Understanding the cause of sex disparities in COVID-19 outcomes is a major challenge. We investigate sex hormone levels and their association with outcomes in COVID-19 patients, stratified by sex and age. This observational, retrospective, cohort study included 138 patients aged 18 years or older with COVID-19, hospitalized in Italy between February 1 and May 30, 2020. The association between sex hormones (testosterone, estradiol, progesterone, dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19, in-hospital mortality) was explored in 120 patients aged 50 years and over. STROBE checklist was followed. The median age was 73.5 years [IQR 61, 82]; 55.8% were male. In older males, testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L, p =0.0378 and 3.7 vs. 8.5 nmol/L, p =0.0011, respectively). Deceased males had lower testosterone (2.4 vs. 4.8 nmol/L, p =0.0536) and higher estradiol than survivors (40 vs. 24 pg/mL, p = 0.0006). Testosterone was negatively associated with ARDS (OR 0.849 [95% CI 0.734, 0.982]), severe COVID-19 (OR 0.691 [95% CI 0.546, 0.874]), and in-hospital mortality (OR 0.742 [95% CI 0.566, 0.972]), regardless of potential confounders, though confirmed only in the regression model on males. Higher estradiol was associated with a higher probability of death (OR 1.051 [95% CI 1.018, 1.084]), confirmed in both sex models. In males, higher testosterone seems to be protective against any considered outcome. Higher estradiol was associated with a higher probability of death in both sexes.

Leprosy in Refugees and Migrants in Italy and a Literature Review of Cases Reported in Europe between 2009 and 2018.

Leprosy is a chronic neglected infectious disease that affects over 200,000 people each year and causes disabilities in more than four million people in Asia, Africa, and Latin America. The disease can appear with a wide spectrum of clinical forms, and therefore the clinical suspicion is often difficult. Refugees and migrants from endemic countries affected by leprosy can remain undiagnosed in Europe due to the unpreparedness of clinicians. We retrospectively describe the characteristics of 55 refugees/migrants with a diagnosis of leprosy established in Italy from 2009 to 2018. Continents of origin were Africa (42%), Asia (40%), and South and Central America (18%). The symptoms reported were skin lesions (91%), neuropathy (71%), edema (7%), eye involvement (6%), fever (6%), arthritis (4%), and lymphadenopathy (4%). Seven patients (13%) had irreversible complications. Overall, 35% were relapses and 66% multibacillary leprosy. Furthermore, we conducted a review of 17 case reports or case series and five nationwide reports, published in the same decade, describing 280 migrant patients with leprosy in Europe. In Europe, leprosy is a rare chronic infectious disease, but it has not completely disappeared. Diagnosis and treatment of leprosy in refugees and migrants from endemic countries are a challenge. European guidelines for this neglected disease in this high-risk population would be beneficial.

Pulmonary nodules in African migrants caused by chronic schistosomiasis.

Schistosomiasis is a neglected tropical disease that can cause mainly hepatic and genitourinary damage, depending on the species. Involvement of the lungs has been commonly described in acute infection (Katayama syndrome) and chronic infection (pulmonary hypertension). Although rarely reported in the scientific literature, cases of lung nodules due to chronic schistosome infection are also possible and are probably more frequent than commonly thought. Here we report seven cases of African migrants who were diagnosed with chronic schistosomiasis and pulmonary nodules due to deposition of schistosome eggs, and we compare our findings to the case reports found in the scientific literature. We discuss the management of these patients in a non-endemic setting, beginning with a first fundamental step that is to include parasitic infections, namely schistosomiasis, in the differential diagnosis of pulmonary nodules in African immigrants. All patients responded to antiparasitic treatment with praziquantel after a relatively short time. We therefore conclude that lung biopsies and other invasive procedures (performed in the first cases to rule out other potential causes, such as tuberculosis or malignant nodules) can be avoided or postponed.

Might isoniazid plasma exposure be a valuable predictor of drug-related hepatotoxicity risk among adult patients with TB?

OBJECTIVES: To investigate the relationship between isoniazid plasma exposure and the likelihood of elevation of ALT (≥51 IU/L) among adult patients with TB. METHODS: A retrospective observational study was conducted in patients who underwent periodic monitoring of hepatic function and in whom pharmacokinetic data were collected. Monte Carlo simulation was performed with the intent of identifying the probability of achieving an AUC24 greater than the identified threshold of hepatotoxicity with different dosing regimens (2.5, 5.0 and 7.5 mg/kg/day). RESULTS: Forty-one out of 185 evaluable patients (22.2%) had an ALT elevation. A mild correlation between isoniazid AUC0-24 and ALT increase was observed (Spearman's ρ = 0.34, P < 0.001). Patients with ALT ≥51 IU/L showed significantly higher isoniazid exposure than those with ALT <51 IU/L (mean AUC24 of 58.33 versus 31.28 mg·h/L, P < 0.001). The probabilities of ALT elevation were 0.82 and 0.12 for isoniazid AUC24 ≥55.0 and <55.0 mg·h/L, respectively. Use of a logistic regression model estimated a likelihood of developing hepatotoxicity of 0.5 and 0.9 when in the presence of an isoniazid AUC24 of 53.7 and 70.0 mg·h/L, respectively. Simulation showed that the standard isoniazid 5 mg/kg daily dose gave a probability of ALT increase of 0.46 for slow acetylators and 0.03 for rapid acetylators. CONCLUSIONS: Plasma isoniazid exposure might be a valuable predictor of drug-related hepatotoxicity. Early assessment of isoniazid exposure at the beginning of treatment might allow prompt dosage reduction among those patients who are experiencing drug overexposure, thus containing the risk of hepatotoxicity occurrence.