Mortality and risk factors of vaccinated and unvaccinated frail patients with COVID-19 treated with anti-SARS-CoV-2 monoclonal antibodies: A real-world study.

OBJECTIVES: There is a scarcity of data on the outcomes and predictors of therapeutic failure of monoclonal antibodies (mAbs) in frail patients with COVID-19. METHODS: Prospective study including consecutive COVID-19 outpatients referred by primary care physicians for mAb treatment. The outcomes evaluated were 60-day mortality, time to SARS-CoV-2 clearance, need for hospitalization, and O2 therapy. RESULTS: Among 1026 COVID-19 patients enrolled, 60.2% received casirivamab/imdevimab and 39.8% sotrivimab. Median age was 63 years, 52.4% were males and median time from positive nasopharyngeal swab to mAbs administration was 3 days (interquartile range, 2-5). 78.1% were vaccinated. Overall, the 60-day mortality was 2.14%. No differences in outcomes were observed between the two mAbs used. No difference was observed in mortality between vaccinated and unvaccinated patients (P = 0.925); although, lower rate of hospitalization (P <0.005), less need for O2 therapy (P <0.0001) and reduced nasopharyngeal swab negativity time (P <0.0001) were observed in vaccinated patients. Early administration of mAbs was associated with lower mortality (P <0.007), whereas corticosteroid use worsened prognosis (P <0.004). The independent predictors associated with higher mortality were older age (P <0.0001), presence of active hematologic malignancies (P <0.0001), renal failure (P <0.041), and need for O2 therapy (P <0.001). CONCLUSION: This study shows similar effectiveness among mAbs used, regardless of vaccination status and identifies patients with COVID-19 in whom mAbs have poor activity.

Pre-existing chronic kidney disease (CDK) was not associated with a severe clinical outcome of hospitalized COVID-19: results of a case-control study in Southern Italy.

The presence of co-morbidities is associated with a poor outcome in patients with COVID-19. The aim of the present study was to investigate the outcomes of patients with SARS-CoV-2 infection and chronic kidney disease (CKD) in order to assess its impact on mortality and severity of disease. We performed a multicenter, observational, 1:2 matched case-control study involving seventeen COVID-19 Units in southern Italy. All the adults hospitalized for SARS-CoV-2 infection and with pre-existing CKD were included (Cases). For each Case, two patients without CKD pair matched for gender, age (+5 years), and number of co-morbidities (excluding CKD) were enrolled (Controls). Of the 2,005 patients with SARS-CoV-2 infection followed during the study period, 146 patients with CKD and 292 patients without were enrolled in the case and control groups, respectively. Between the Case and Control groups, there were no statistically significant differences in the prevalence of moderate (17.1% vs 17.8%, p=0.27) or severe (18.8% and 13.7%, p=0.27) clinical presentation of COVID-19 or deaths (20.9% vs 28.1%, p=0.27). In the Case group, the patients dead during hospitalization were statistically higher in the 89 patients with CKD stage 4-5 compared to 45 patients with stages 1-3 CKD (30.3% vs 13.3%, p=0.03). Our data suggests that only CKD stage 4-5 on admission was associated with an increased risk of in-hospital death.

Lactate dehydrogenase and PaO2/FiO2 ratio at admission helps to predict CT score in patients with COVID-19: An observational study.

INTRODUCTION: Since the beginning of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic an important tool for patients with Coronavirus Disease 2019 (COVID-19) has been the computed tomography (CT) scan, but not always available in some settings The aim was to find a cut-off that can predict worsening in patients with COVID-19 assessed with a computed tomography (CT) scan and to find laboratory, clinical or demographic parameters that may correlate with a higher CT score. METHODS: We performed a multi-center, observational, retrospective study involving seventeen COVID-19 Units in southern Italy, including all 321 adult patients hospitalized with a diagnosis of COVID-19 who underwent at admission a CT evaluated using Pan score. RESULTS: Considering the clinical outcome and Pan score, the best cut-off point to discriminate a severe outcome was 12.5. High lactate dehydrogenase (LDH) serum value and low PaO2/FiO2 ratio (P/F) resulted independently associated with a high CT score. The Area Under Curve (AUC) analysis showed that the best cut-off point for LDH was 367.5 U/L and for P/F 164.5. Moreover, the patients with LDH> 367.5 U/L and P/F < 164.5 showed more frequently a severe CT score than those with LDH< 367.5 U/L and P/F> 164.5, 83.4%, vs 20%, respectively. CONCLUSIONS: A direct correlation was observed between CT score value and outcome of COVID-19, such as CT score and high LDH levels and low P/F ratio at admission. Clinical or laboratory tools that predict the outcome at admission to hospital are useful to avoiding the overload of hospital facilities.

Clinical Characterization of the Three Waves of COVID-19 Occurring in Southern Italy: Results of a Multicenter Cohort Study.

AIMS: To characterize patients hospitalized for COVID-19 in the three waves in Southern Italy. METHODS: We conducted a multicenter observational cohort study involving seventeen COVID-19 Units in Campania, southern Italy: All adult (≥18 years) patients, hospitalized with a diagnosis of SARS-CoV-2 infection from 28 February 2020 to 31 May 2021, were enrolled. RESULTS: Two thousand and fifteen COVID-19 hospitalized patients were enrolled; 392 (19%) in the first wave, 917 (45%) in the second and 706 (35%) in the third wave. Patients showed a less severe clinical outcome in the first wave than in the second and third waves (73%, 65% and 72%, respectively; p = 0.003), but hospitalization expressed in days was longer in the first wave [Median (Q1-Q3): 17 (13-25) v.s. 14 (9-21) and 14 (9-19), respectively, p = 0.001)] and also mortality during hospitalization was higher in the first wave than in the second and third waves: 16.6% v.s. 11.3% and 6.5%, respectively (p = 0.0001). Multivariate analysis showed that older age [OR: 1.069, CI (1046-1092); p = 0.001], a worse Charlson comorbidity index [OR: 1042, CI (1233-1594; p = 0.0001] and enrolment during the first-wave [OR: 1.917, CI (1.054-3.485; p = 0.033] were predictors of mortality in hospitalized patients. CONCLUSIONS: Improved organization of the healthcare facilities and the increase in knowledge of clinical and therapeutic management have contributed to a trend in the reduction in mortality during the three waves of COVID-19.

Early predictors of clinical deterioration in a cohort of outpatients with COVID-19 in southern Italy: A multicenter observational study.

Data regarding early predictors of clinical deterioration in patients with infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still scarce. The aim of the study is to identify early symptoms or signs that may be associated with severe coronavirus disease 2019 (COVID-19). We conducted a multicentre prospective cohort study on a cohort of patients with COVID-19 in home isolation from March 2020 to April 2021. We assessed longitudinal clinical data (fever, dyspnea, need for hospitalization) through video calls at three specific time points: the beginning of symptoms or the day of the first positivity of the nasopharyngeal swab for SARS-CoV-2-RNA (t0 ), and 3 (t3 ) and 7 (t7 ) days after the onset of symptoms. We included 329 patients with COVID-19: 182 (55.3%) males, mean age 53.4 ± 17.4 years, median Charlson comorbidity index (CCI) of 1 (0-3). Of the 329 patients enrolled, 171 (51.98%) had a mild, 81 (24.6%) a moderate, and 77 (23.4%) a severe illness; 151 (45.9%) were hospitalized. Compared to patients with mild COVID-19, moderate and severe patients were older (p < 0.001) and had more comorbidities, especially hypertension (p < 0.001) and cardiovascular diseases (p = 0.01). At t3 and t7 , we found a significant higher rate of persisting fever (≥37°C) among patients with moderate (91.4% and 58.0% at t3 and t7 , respectively; p < 0.001) and severe outcome (75.3% and 63.6%, respectively; p < 0.001) compared to mild COVID-19 outcome (27.5% and 11.7%, respectively; p < 0.001). Factors independently associated with a more severe outcome were persisting fever at t3 and t7 , increasing age, and CCI above 2 points. Persisting fever at t3 and t7 seems to be related to a more severe COVID-19. This data may be useful to assess hospitalization criteria and optimize the use of resources in the outpatient setting.

COVID-19 as Another Trigger for HBV Reactivation: Clinical Case and Review of Literature.

Universal hepatitis B virus (HBV) vaccination has been applied for years in most countries, but HBV infection remains an unresolved public health problem worldwide, with over one-third of the world's population infected during their lifetime and approximately 248 million hepatitis B surface antigen (HBsAg) chronic carriers. HBV infection may reactivate with symptomatic and sometimes life-threatening clinical manifestations due to a reduction in the immune response of various origins, due to chemotherapy or immunosuppressive therapy, treatments increasingly practiced worldwide. SARS-CoV-2 and its COVID-19 associated disease have introduced new chances for HBV reactivation due to the use of dexamethasone and tocilizumab to counteract the cytokine storm. This could and should be prevented by accurate screening of HBV serologic markers and adequate pharmacologic prophylaxis. This article describes the case of a patient with COVID-19 who developed HBV reactivation and died of liver failure and analyzes published data on this setting to provide useful information to physicians who manage these patients during the SARS-CoV-2 pandemic.

Fatal Outcome of COVID-19 Relapse in a Fully Vaccinated Patient with Non-Hodgkin Lymphoma Receiving Maintenance Therapy with the Anti-CD20 Monoclonal Antibody Obinutuzumab: A Case Report.

Few data are available regarding the effectiveness of anti-SARS-CoV-2 vaccine in immunocompromised patients. Vaccination may have a suboptimal efficacy in this population, in particular if patients are exposed to anti-B-cell therapy. We report the virological and clinical characteristics of a patient with follicle center lymphoma under bimonthly maintenance therapy with obinutuzumab, an anti-CD20 monoclonal antibody. Despite three doses of BNT162b2 vaccine, the patient was infected by the SARS-CoV-2 Omicron variant. After an initial period of clinical and molecular remission due to early therapy with sotrovimab, the patient experienced a fatal relapse sustained by the same viral strain.

Hepatitis C virus (HCV) micro-elimination in the hospital setting: The results of the HCV Caserta hospital project.

BACKGROUND: In the present study we evaluated the efficacy of an innovative model of HCV micro-elimination in a hospital setting in an area of high HCV prevalence. PATIENTS AND METODS: Between January and December 2019, a prospective, interventional study for a program of HCV case-finding and linkage-to-care was performed in S. Anna and S. Sebastiano hospital of Caserta, in Campania, a region in southern Italy. All adult patients who were admitted to the Caserta hospital in the study period and resulted positive for anti-HCV were included in the study. The outcomes evaluated were the number of subjects resulting HCV-RNA-positive, those linked-to-care and treated with a DAA and the subjects whose anti-HCV-status was unknown. RESULTS: In the study period, 14,396 subjects, admitted to the hospital for different reasons, were tested for anti-HCV: 529 (3.7%) subjects resulted positive for anti-HCV. Of the 529 anti-HCV-positive subjects, 10 died during hospitalization and 243 were already treated with a DAA. The remaining 276 subjects were contacted and agreed to be evaluated. Of these 276 subjects, 68 patients resulted HCV- RNA-negative and 194 HCV-RNA-positive and 180 of these were treated with a DAA according to the international guidelines. DISCUSSION: A simple, rapid, inexpensive model of HCV micro-elimination in the hospital setting allowed us to find anti-HCV-positive subjects with unknown anti-HCV status or not linked to a clinical center.

Prognostic Value of Transaminases and Bilirubin Levels at Admission to Hospital on Disease Progression and Mortality in Patients with COVID-19-An Observational Retrospective Study.

INTRODUCTION: Given the impact of COVID-19 on the world healthcare system, and the efforts of the healthcare community to find prognostic factors for hospitalization, disease progression, and mortality, the aim of the present study was to investigate the prognostic impact of transaminases and bilirubin levels at admission to hospital on disease progression and mortality in COVID-19 patients. METHODS: Using the CoviCamp database, we performed a multicenter, observational, retrospective study involving 17 COVID-19 Units in southern Italy. We included all adult patients hospitalized for SARS-CoV-2 infection with at least one determination at hospital admission of aminotransaminases and/or total bilirubin. RESULTS: Of the 2054 patients included in the CoviCamp database, 1641 were included in our study; 789 patients (48%) were considered to have mild COVID-19, 347 (21%) moderate COVID-19, 354 (22%) severe COVID-19, and 151 patients (9%) died during hospitalization. Older age (odds ratio (OR): 1.02; 95% confidence interval (CI) 1.01-1.03), higher Charlson comorbidity index (CCI) (OR 1.088; 95%CI 1.005-1.18), presence of dementia (OR: 2.20; 95% CI: 1.30-3.73), higher serum AST (OR: 1.002; 95% CI: 1.0001-1.004), and total bilirubin (OR: 1.09; 95% CI: 1.002-1.19) values were associated with a more severe clinical outcome. Instead, the 151 patients who died during hospitalization showed a higher serum bilirubin value at admission (OR 1.1165; 95% CI: 1.017-1.335); the same did not apply for AST. DISCUSSION: Patients with COVID-19 with higher levels of AST and bilirubin had an increased risk of disease progression.

Epidemiology of HCV and HBV in a High Endemic Area of Southern Italy: Opportunities from the COVID-19 Pandemic-Standardized National Screening or One Tailored to Local Epidemiology?

The COVID-19 pandemic led to the hospitalization of an unselected population with the possibility to evaluate the epidemiology of viral hepatitis. Thus, a retrospective multicenter study was conducted in an area of Southern Italy with the aim of assessing the prevalence of HCV and HBV markers and the ability of current screening program to capture cases. We evaluated 2126 hospitalized patients in seven COVID Centers of Naples and Caserta area in which 70% of the Campania population lives. HBsAg and HCV-Ab prevalence was 1.6% and 5.1%, respectively, with no differences between gender. Decade distribution for birth year shows a bimodal trend of HCV prevalence, with a peak (11.6%) in the decade 1930-1939 and a second peak (5.6%) for those born in 1960-1969. An analysis of the screening period imposed by the Italian government for those born between 1969 and 1989 shows that only 17% of cases of HCV infection could be captured. A small alignment of the screening period, i.e., those born from 1960 to 1984, would capture 40% of cases. The data confirm the high endemicity of our geographical area for hepatitis virus infections and underline the need for a tailored screening program according to the regional epidemiology.

Different Clinical Outcomes of COVID-19 in Two Healthcare Workers Vaccinated with BNT162b2 Vaccine, Infected with the Same Viral Variant but with Different Predisposing Conditions for the Progression of the Disease.

Safe and effective vaccines are available to face the global threat of the COVID-19 pandemic. In this article, we report on the clinical cases of two healthcare workers vaccinated with two doses of BNT162b2 vaccine who were infected by the same viral clade but had different clinical outcomes.

Hepatitis B virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic.

Hepatitis D virus (HDV) is a defective liver-tropic virus that needs the helper function of hepatitis B virus (HBV) to infect humans and replicate. HDV is transmitted sexually or by a parenteral route, in co-infection with HBV or by super-infection in HBV chronic carriers. HDV infection causes acute hepatitis that may progress to a fulminant form (7%-14% by super-infection and 2%-3% by HBV/HDV co-infection) or to chronic hepatitis (90% by HDV super-infection and 2%-5% by HBV/HDV co-infection), frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma (HCC). Peg-interferon alfa the only recommended therapy, clears HDV in only 10%-20% of cases and, consequently, new treatment strategies are being explored. HDV endemicity progressively decreased over the 50 years from the identification of the virus, due to improved population lifestyles and economic levels, to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs. Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic, unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments, lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.

Risk and Prevention of Hepatitis B Virus Reactivation during Immunosuppression for Non-Oncological Diseases.

Reactivation of overt or occult HBV infection (HBVr) is a well-known, potentially life-threatening event which can occur during the course of immunosuppressive treatments. Although it has been described mainly in subjects receiving therapy for oncological or hematological diseases, the increasing use of immunosuppressant agents in non-oncological patients observed in recent years has raised concerns about the risk of reactivation in several other settings. However, few data can be found in the literature on the occurrence of HBVr in these populations, and few clear recommendations on its management have been defined. The present paper was written to provide an overview of the risk of HBV reactivation in non-neoplastic patients treated with immunosuppressive drugs, particularly for rheumatological, gastrointestinal, dermatological and neurological diseases, and for COVID-19 patients receiving immunomodulating agents; and to discuss the potential strategies for prevention and treatment of HBVr in these settings.

Dementia as Risk Factor for Severe Coronavirus Disease 2019: A Case-Control Study.

BACKGROUND: The aim of the present study was to investigate the outcome of patients with SARS-CoV-2 infection and dementia. PATIENTS AND METHODS: In a multicenter, observational, 1:2 matched case-control study all 23 patients with a history of dementia, hospitalized with a diagnosis of SARS-CoV-2 infection from February 28th 2020 to January 31st 2021 were enrolled. For each Case, 2 patients without dementia observed in the same period study, pair matched for gender, age (±5 years), PaO2/FiO2 (P/F) ratio at admission (<200, or >200), number of comorbidities (±1; excluding dementia) were chosen (Control group). RESULTS: The majority of patients were males (60.9% of Cases and Controls) and very elderly [median age 82 years (IQR: 75.5-85) in the Cases and 80 (IQR: 75.5-83.75) in the Controls]. The prevalence of co-pathologies was very high: all the Cases and 43 (93.5%) Controls showed a Charlson comorbidity index of at least 2. During hospitalization the patients in the Case group less frequently had a moderate disease of COVID-19 (35 vs. 67.4%, p = 0.02), more frequently a severe disease (48 vs. 22%, p = 0.03) and more frequently died (48 vs. 22%, p = 0.03). Moreover, during coronavirus disease 2019 (COVID-19), 14 (60.8%) patients in the Case group and 1 (2.1%; p < 0.000) in the Control group showed signs and symptoms of delirium. CONCLUSION: Patients with dementia are vulnerable and have an increased risk of a severe disease and death when infected with COVID-19.

More Severe COVID-19 in Patients With Active Cancer: Results of a Multicenter Cohort Study.

BACKGROUND: The aim of the study was to compare coronavirus disease 2019 (COVID-19) severity presentation between oncologic and non-oncologic patients and to evaluate the impact of cancer type and stage on COVID-19 course. METHODS: We performed a multicentre, retrospective study involving 13 COVID-19 Units in Campania region from February to May 2020. We defined as severe COVID-19 presentation the cases that required mechanical ventilation and/or admission to Intensive Care Units (ICU) and/or in case of death. RESULTS: We enrolled 371 COVID-19 patients, of whom 34 (9.2%) had a history or a diagnosis of cancer (24 solid, 6 onco-hematological). Oncologic patients were older (p<0.001), had more comorbidities (p<0.001) and showed a higher rate of severe COVID-19 presentation (p=0.001) and of death (p<0.001). Compared to 12 patients with non-active cancer and to 337 without cancer, the 17 patients with active cancer had more comorbidities and showed a higher rate of severe COVID-19 and of mortality (all p values <0.001). Compared to the 281 non-severe patients, the 90 subjects with a severe presentation of COVID-19 were older (p<0.01), with more comorbidities (p<0.001) and with a higher rate of cancer (p=0.001). At multivariate analysis, age (OR 1.08, 95% CI: 1.04-1.11) and suffering from cancer in an active stage (OR 5.33, 95% CI: 1.77-16.53) were independently associated with severe COVID-19. CONCLUSIONS: Since the higher risk of severe evolution of COVID-19, cancer patients, especially those with an active malignancy, should be candidates for early evaluation of symptoms and early treatment for COVID-19.

Clinical Features of Patients with Home Isolation Sars-Cov-2 Infection: A Multicenter Retrospective Study in Southern Italy.

To describe epidemiological and clinical features of patients confirmed as having SARS-CoV-2 infection and managed in isolation at home. We performed a multicenter retrospective study enrolling all SARS-CoV-2-positive adults evaluated from 28 February to 31 May 2020 at one of nine COVID-19 Units in southern Italy: we included patients receiving care at home and those admitted to hospital. We defined patients with not-severe disease if they were asymptomatic or experienced a mild infection that did not need oxygen (O2) therapy and those with a severe infection if hospitalized and required O2 therapy. We enrolled 415 patients with SARS-CoV-2 infection: 77 were managed in isolation at home, 338 required hospital management. The 77 patients in home isolation were less frequently male than hospitalized patients (55% vs. 64%; <0.01) and were younger (median age 45 years (IQR:19) vs. 62 (IQR 22); p < 0.01), had a lower Charlson comorbidity index (median 0 (IQR2) vs. 6 (IQR 3); p < 0.01), and included fewer subjects with an underlying chronic disease (36% vs. 59%; p < 0.01). According to a binomial logistic regression analysis, a younger age (OR: 0.96 (95% IC: 0.94-0.98), p < 0.01) and a low Charlson comorbidity index (OR: 0.66 (95% IC: 0.54-0.83); p < 0.01) were independent factors associated with at-home management. The identification of subjects with SARS-CoV-2 infection who could be managed in home isolation is useful in clinical practice. A younger age and no comorbidities were identified as factors independently associated with home management.

Use of lung ultrasound in COVID-19: comparison with ultra-high-resolution computed tomography among 29 patients at "D. Cotugno" hospital, Naples, Italy.

Ultra-High-Resolution Computed Tomography (U-HR-CT) is the reference imaging technique for pneumonia in the new coronavirus disease (COVID-19). Pulmonary Ultrasound (LUS) could be a valid diagnostic alternative for the imaging of COVID-19. Our study aimed to investigate the clinical performance of LUS in the initial evaluation of pneumonia in COVID-19 patients, compared to standard U-HR-CT. Among 29 patients with confirmed COVID-19, all U-HR-CT hallmarks showed an excellent concordance with LUS findings according to Cohen coefficient. In our experience, LUS is a viable alternative to U-HR-CT, with the advantages of being radiation-free, flexible, cost-effective, and reasonably reducing nosocomial transmission risks because performed at bed-side.