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Introduction: Thymic epithelial tumors (TETs) are rare neoplasms often associated with immune-related disorders. Patients with Good's syndrome (GS), an adult-acquired TET-related immunodeficiency, are at a high risk of mortality due to infectious diseases. This study aims to examine COVID-19 occurrence and severity in TET patients, with or without GS., Methods: Clinical records of TET patients referred to the Regional Coordinating Center for Rare Tumors of Campania Region were retrospectively collected. During the observation period, elapsing from March 2020 to April 2023, the following data were collected: occurrence of SARS-CoV-2 infection; COVID-19 severity, according to the National Institute of Health (NIH) illness categories; COVID-19 treatment. COVID-19 occurrence and severity were assessed in the overall population and correlated with the presence of GS and/or other immune-related dysregulations., Results: Overall, 47 TET patients were included in the study; 27 of these (57.4%) had GS. All participants had received a full cycle of mRNA vaccine for SARS-CoV2., Thirty-one patients (66.0%) experienced COVID-19, of whom 18 (58.0%) had previously received a diagnosis of GS. No significant association of GS and/or other immune-related dysregulations with SARS-CoV-2 infection occurrence was detected (Fisher's exact test p = 1 and p = 0.3587, respectively). Among patients with GS, 8 (45.0%) reported a COVID-19 severity score of ≥ 3; whereas, only 1 of the 13 patients without GS (7.7%) had a severity score of ≥ 3. The correlation between presence of GS and COVID-19 severity (score 1 or 2 vs. ≥ 3) was statistically significant (p = 0.0448). No statistically significant association between COVID-19 severity and other immune-related syndromes were found (p = 1). Of note, all the hospitalized patients for NIH 4 and 5 COVID-19 had GS., Conclusions: Our data suggest that TET patients, especially those with GS, require a careful multidisciplinary monitoring for SARS-CoV-2 infection, in order to establish tailored treatments and prophylactic protocols., (© 2024. The Author(s).)

Campania is the sixth poorest region of Italy, and it is the region with the highest income inequality. The secondary attack rates of SARS-CoV-2 among households are found to be substantially heterogeneous among published studies and are influenced by socio-economic factors. We conducted a retrospective study to describe the role of socio-economic factors in the household transmission of SARS-CoV-2 among patients living in Campania Region and referring to "Federico II" Hospital. We interviewed 413 subjects followed-up for COVID-19 between the 8 March 2020 and the 24 May 2021 with the aim to collect demographic, clinical, economic, and social data regarding their household and the index cases. The variables associated with SARS-CoV-2 attack rate higher than 50% among households were higher age ( p = 0.023) and higher Charlson Comorbidity Index of the index case ( p = 0.023) and, for household characteristics, higher number of families per house ( p = 0.02), location of the houses in Naples' suburbs (Chi 2 = 5.3, p = 0.02) and in Caserta City area (Chi 2 = 4, p = 0.04), and renting the house compared to owning it (Chi 2 = 5.83, p = 0.01). This study confirms the finding described by other authors that household transmission of SARS-CoV-2 is correlated with the income inequality of the analyzed geographical area as well as with the indicators of health and economic wealth of the families, and this correlation also applies to the Campania Region.

Profound clinical differences between the first and second waves of COVID-19 were observed in Europe. Nitric oxide (NO) may positively impact patients with Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection. It is mainly generated by inducible nitric oxide synthase (iNOS). We studied serum iNOS levels together with serum interleukin (IL)-6 and IL-10 in patients with SARS-CoV-2 infection in the first wave ( n = 35) and second wave ( n = 153). In the first wave, serum iNOS, IL-6, IL-10 levels increased significantly, in line with the World Health Organization (WHO) score severity, while in the second wave, iNOS did not change with the severity. The patients of the second wave showed lower levels of iNOS, IL-6, and IL-10, as compared to the corresponding subgroup of the first wave, suggesting a less severe outcome of COVID-19 in these patients. However, in the severe patients of the second wave, iNOS levels were significantly lower in patients treated with steroids or azithromycin before the hospitalization, as compared to the untreated patients. This suggests an impairment of the defense mechanism against the virus and NO-based therapies as a potential therapy in patients with low iNOS levels.

Ivan Gentile and Nicola Schiano Moriello discuss the potential of monoclonal antibody prophylaxis against COVID-19 infection in immunocompromised patients., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests regarding this paper: Consultant for Gilead Sciences, Pfizer, MSD, and GSK. The authors received departmental grants from Gilead Sciences.

Objective: to describe a single-center experience of Pneumocystis jirovecii pneumonia (PJP) in non-HIV patients recovering from COVID-19., Methods: We report the cases of five non-HIV patients with COVID-19 who also developed PJP at a University Hospital., Results: With the exception of one subject, who experienced an atypical and prolonged course of COVID-19, all the patients developed PJP after the clinical resolution of COVID-19 pneumonia. All but one patient had no pre-existing immunosuppressive conditions or other risk factors for PJP development at COVID-19 diagnosis. Nonetheless, following the course of COVID-19 infection, all the patients fulfilled at least one host factor for PJP; indeed, all the patients had received at least 2 weeks of high-dose steroids and three out of five had a CD4+ cell count <200/mm 3 ., Conclusions: The use of corticosteroids for COVID-19 respiratory impairment seems to be the most common risk factor for PJP, together with viral-induced and iatrogenic lymphopenia. The worsening in respiratory function and the characteristic radiological picture during or after COVID-19 pneumonia should raise the suspicion of PJP, even in immunocompetent patients. PJP primary chemoprophylaxis can be considered in selected high-risk COVID-19 patients, but further studies are needed.

Even several months after the start of a massive vaccination campaign against COVID-19, mortality and hospital admission are still high in many countries. Monoclonal antibodies against SARS-CoV-2 are the ideal complement to vaccination in infected subjects who are at high risk for progression to severe disease. Based on data of the Italian Ministry of Health, in the period April-August 2021, monoclonal antibodies were prescribed to 6322 patients. In the same period, 70,022 patients over 70 years old became infected with SARS-CoV-2. Even considering that all monoclonal antibodies were prescribed to this category of patients, we calculated that only 9% of these subjects received the treatment. Moreover, using efficacy data provided by clinal trials, we estimated the potential benefit in terms of reduction of hospital admissions and deaths. Considering utilisation of monoclonal antibodies in half infected patients over 70 years, we estimated that hospital admissions and deaths might have been reduced by 7666 and 3507, respectively. Finally, we calculated the economic benefit of monoclonal use. In the same scenario (50% use of monoclonal antibodies to patients over 70), we estimated potential savings of USD 117,410,105. In conclusion, monoclonal antibodies were used in a small proportion of patients over 70 in Italy. A more extensive use might have resulted in a marked decrease in hospital admissions, deaths and in conspicuous saving for the health system.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Augusto Di Castelnuovo et al.)

Background: Several cases of invasive fungal diseases in patients with COVID-19 have been reported, mostly due to Aspergillus spp., with anecdotic reports of Pneumocystis jirovecii pneumonia (PJP) as co-infections in immunocompromised patients. We describe the first case of PJP in an immunocompetent patient who recovered from COVID-19 pneumonia., Case Description: Our patient was hospitalized for 18 d for respiratory failure due to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pneumonia and successfully treated with continuous positive airway pressure (CPAP) respiratory support, enoxaparin, ceftaroline and intravenous 6 mg of dexamethasone for 10 d, then with oral prednisone tapering. Despite his improved radiological and clinical conditions at discharge, he was admitted again after 18 d for worsening of respiratory conditions. Upon the second admission, a high-resolution CT-scan of the chest showed the development of new ground-glass opacities and P. jirovecii was detected on bronchoalveolar lavage fluid. A therapy with trimethoprim-sulphamethoxazole 20 mg/kg and methylprednisolone 40 mg i.v. bis in die (BID) was started, with improvement of clinical, biochemical and radiological conditions., Conclusions: COVID-19 patients may have multiple risk factors for development of PJP, in particular lymphopaenia and use of steroids. PJP must be ruled out with direct microbiological methods in patients presenting with radiologic and clinical features of possible or probable PJP, even in immunocompetent hosts.

KL-6 is a sialoglycoprotein antigen which proved elevated in the serum of patients with different interstitial lung diseases, especially in those with a poorer outcome. Given that interstitial pneumonia is the most common presentation of SARS-CoV2 infection, we evaluated the prognostic role of KL-6 in patients with COVID-19 pneumonia. Patients with COVID-19 pneumonia were prospectively enrolled. Blood samples were collected at the time of enrolment (TOE) and on day 7 (T1). Serum KL-6 concentrations were measured by chemiluminescence enzyme immunoassay using a KL-6 antibody kit (LUMIPULSE G1200, Fujirebio) and the cut-off value was set at >1000 U/mL. Fifteen out of 34 enrolled patients (44.1%) died. Patients with unfavourable outcome showed significantly lower P/F ratio and higher IL-6 values and plasmatic concentrations of KL-6 at TOE compared with those who survived (median KL-6: 1188 U/mL vs. 260 U/mL, p < 0.001). KL-6 > 1000 U/mL resulted independently associated with death (aOR: 11.29, p < 0.05) with a positive predictive value of 83.3%. Our results suggest that KL-6 is a reliable indicator of pulmonary function and unfavourable outcome in patients with COVID-19 pneumonia. A KL-6 value > 1000 U/mL resulted independently associated with death and showed good accuracy in predicting a poorer outcome. KL-6 may thus represent a quick, inexpensive, and sensitive parameter to stratify the risk of severe respiratory failure and death.

BackgroundThe COVID-19 pandemic has significantly impacted the management of solid organ transplant recipients and on clinical evolution in post-transplantation. Little is known on the impact of SARS-CoV-2 infection in these patients. The severity and lethality of this disease in solid organ transplant patients are higher thanin the general population. This study aims to describe clinical characteristics of SARS-CoV-2 infection in solid organ transplant recipients followed in our center.MethodsIn this observational study, we enrolled all kidney transplant recipientsattending the A.O.U. Federico II of Naples from March 2020 to January 2021. For each patient we evaluated the epidemiological and clinical characteristics as well as outcome.ResultsWe enrolled 369 kidney transplant patients (229, male, 62%). Of these, 51 (13.8%) acquired SARS-CoV-2 infection and 29 showed symptomatic disease. Of the 51 patients with the infection, 48 (94.11%) had at least one comorbidity and such comorbidities did not constitute a risk factor for a more severe disease. Hospitalization was necessary for 7 (13.7%) patients. Of these, 2 required low-flow oxygen supplementation, 3 non-invasive/high flow ventilation and 2 invasive ventilation. Finally, 2 patients died.ConclusionsOur study shows a lower mortality and hospitalization rate compared to figures available in the literature (4% vs. 13–30% and 14% vs. 32–100%, respectively). Furthermore, the comorbidities examined (hypertension, dyslipidemia, and diabetes) did not constitute a risk factor for a more severe disease condition in this patient category. Further studies with larger sample size are necessary to confirm these data.

Vaccination against SARS-CoV2 represents a key weapon to prevent COVID-19, but lower response rates to vaccination have frequently been reported in solid organ transplant recipients. The aim of our study was to evaluate the rate of seroconversion to SARS-CoV-2 mRNA vaccines in a cohort of kidney transplant recipients and the potential role of the different immunosuppressive regimens. We conducted an observational retrospective cohort study in kidney transplant patients vaccinated for COVID-19. For each patient, we evaluated IgG anti-S-RBD SARS-CoV-2 titers immediately before the administration of first COVID-19 vaccination dose, 20 days after the first dose and 40 days after the second dose. Moreover, we evaluated the type of immunosuppressive treatment and the incidence of vaccine breakthrough SARS-CoV-2 infection. We enrolled 121 kidney transplant patients vaccinated for COVID-19. At the time of administration of the first vaccine dose, all patients had a negative antibody titer; only 4.1% had positive antibody titers 20 days after the first dose. More than half patients 62 (51%) had protective antibody titers 40 days after the second dose. A total of 18 Solid Organ Transplant Recipients (SOTRs) (14.9%) got a SARS-CoV-2 breakthrough infection during the study period. With regard to immunosuppressive regimen, patients on mycophenolate-based regimen (48.7%) showed the lowest antibody response rates (27.5%) compared to other regimens. Our study confirms that kidney transplant patients show a poor response to two doses of COVID-19 vaccination. Moreover, in our study the use of mycophenolate is significantly associated with a non-response to COVID-19 m-RNA vaccines.

Diabetes mellitus represents one of the most frequent comorbidities among patients with COVID-19, constituting a risk factor for a more severe prognosis than that of non-diabetic patients. However, the pathophysiological mechanism underlying this unfavorable outcome is still not completely clear. The goal of our study was to evaluate the potential role of antidiabetic therapy in the evolution of COVID-19. [ABSTRACT FROM AUTHOR]