The Absence of Permanent Sensorineural Hearing Loss in a Cohort of Children with SARS-CoV-2 Infection and the Importance of Performing the Audiological "Work-Up".

BACKGROUND: Currently, the novel coronavirus (SARS-CoV-2) causes an acute respiratory illness named COVID-19 and is a controversial risk factor for hearing loss (HL). Herein, we aim to describe the associated symptoms and to evaluate hearing function in the COVID-19 pediatric population. METHODS: A retrospective cross-sectional observational study was carried out on 37 children who contracted COVID-19 infection with no previous audio-vestibular disorders. Clinical data on the infections were collected, and an audiological assessment of all affected children was performed by using different diagnostic protocols according to their age. RESULTS: Fever, upper respiratory and gastrointestinal manifestations were common presentations of infection. Audiological function was normal in 30 (81.08%) children, while 7 children showed an increased hearing threshold: 6 (16.21%) had transient conductive hearing loss (CHL) due to middle ear effusion and normalized at the follow-up and 1 had sensorineural hearing loss (SNHL). A single child was affected by bilateral SNHL (2.7%); however, he underwent a complete audiological work-up leading to a diagnosis of genetic HL due to a MYO6 gene mutation which is causative of progressive or late onset SNHL. CONCLUSIONS: HL needs to be considered among the manifestations of COVID-19 in children, nevertheless, we found cases of transient CHL. The onset of HL during or following COVID-19 infection does not eliminate the indication for maintaining audiological surveillance and audiological work-ups, including genetic diagnosis, to avoid the risk of mistaking other causes of HL.

Effectiveness of Booster Dose of Anti SARS-CoV-2 BNT162b2 in Cirrhosis: Longitudinal Evaluation of Humoral and Cellular Response.

Background: LC has been associated with hyporesponsiveness to several vaccines. Nonetheless, no data on complete serological and B- and T-cell immune response are currently available. Aims: To assess, in comparison with healthy controls of the same age and gender, both humoral and cellular immunoresponses of patients with LC after two or three doses of the mRNA Pfizer-BioNTech vaccine against SARS-CoV-2 and to investigate clinical features associated with non-response. Material and methods: 179 patients with LC of CTP class A in 93.3% and viral etiology in 70.1% of cases were longitudinally evaluated starting from the day before the first dose to 4 weeks after the booster dose. Their antibody responses were compared to those of healthcare workers without co-morbidities. In a subgroup of 40 patients, B- and T-cell responses were also compared to controls. Results: At d31, d90 and d180 after BNT162b2 vaccine, no detectable SARS-CoV-2 IgG response was observed in 5.9%, 3.9% and 7.2% of LC patients as compared to 0 controls (p < 0.03). A delay in B-cell and lack of prompt T-cell response compared to healthcare workers was also registered. A significant correlation between antibody titers and cellular response was observed. A MELD score > 8 was the only independent predictor of poor d31 response (p = 0.028). Conclusions: Our results suggest that cirrhotic patients have a slower and in <10% suboptimal immune response to SARS-CoV-2 vaccination. Rates of breakthrough infections were comparable between cirrhotics and controls. The booster dose was critical in inducing both humoral and cellular responses comparable to controls.

Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose.

Background: Immunity and clinical protection induced by mRNA vaccines against SARS-CoV-2 have been shown to decline overtime. To gather information on the immunity profile deemed sufficient in protecting against hospitalization, we tested IgG levels, interferon-gamma (IFN-γ) secretion, and neutralizing antibodies 180 days (d180) after the second shot of BNT162b vaccine, in HW. Methods: A total of 392 subjects were enrolled. All received BioNTech/Pfizer from February 2020 to April 2021. The vaccine-specific humoral response was quantitatively determined by testing for IgG anti-S1 domain of SARS-CoV-spike protein. Live virus microneutralization (MN) was evaluated by an assay performing incubation of serial 2-fold dilution of human serum samples, starting from 1:10 to 1:5120, with an equal volume of Wuhan strain and Delta VOC viral solution and assessing the presence/absence of a cytopathic effect. SARS-CoV-2-spike protein-specific T-cell response was determined by a commercial IFN-γ release assay. Results: In 352 individuals, at d180, IgG levels decreased substantially but no results below the assay's positivity threshold were observed. Overall, 22 naive (8.1%) had values above the highest threshold. Among COVID-naive, the impact of age, which was observed at earlier stages, disappeared at d180, while it remained significant for 81 who had experienced a previous infection. Following the predictive model of protection by Khoury, we transformed the neutralizing titers in IU/ml and used a 54 IU/ml threshold to identify subjects with 50% protective immunity. Overall, live virus MN showed almost all subjects with previous exposure to SARS-CoV-2 neutralized the virus as compared to 33% of naive double-dosed subjects (p < 0.0001). All previously exposed subjects had strong IFN-γ secretion (>200 mIU/ml); among 271 naive, 7 (2.58%) and 17 (6.27%) subjects did not show borderline or strong secretion, respectively. Conclusions: In naive subjects, low IgG titers are relatively long-lasting. Only a third of naive subjects maintain neutralizing responses. After specific stimulation, a very limited number of naive were unable to produce IFN-γ. The results attained in the small group of subjects with breakthrough infection suggest that simultaneous neutralizing antibody titers <20, binding antibody levels/ml <200, and IFN-γ <1,000 mIU/ml in subjects older than 58 may identify at-risk groups.

Nurses' Physical and Psychological Symptoms During the first COVID-19 Lockdown in Italy: a Nationwide Cross-Sectional Study in Stem Cell Transplantation Setting.

BACKGROUND AND OBJECTIVE: Northern Italy was one of the first European territories to deal with the Coronavirus Disease 2019 (COVID-19) outbreak. Drastic emergency restrictions were introduced to contain the spread and limit pressure on healthcare facilities. However, nurses were at high risk of developing physical, mental, and working issues due to professional exposure. The aim of this cross-sectional study was to investigate these issues among nurses working in Italian hematopoietic stem cell transplant (HSCT) centers during the COVID-19 pandemic. METHODS: Data were collected online immediately after the first "lockdown" period in order to investigate the prevalence of physical issues, sleep disorders, and burnout symptoms and explore correlations with COVID-19 territorial incidence in Northern Italian regions versus Central and Southern Italian regions. RESULTS: Three hundred and eight nurses working in 61 Italian HSCT Units responded to the survey. Depression, cough, and fever were more frequently reported by nurses working in geographical areas less affected by the pandemic (p=0.0013, p<0.0001, and p=0.0005 respectively) as well as worst sleep quality (p=0.008). Moderate levels of emotional exhaustion (mean±SD -17.4±13.0), depersonalization (5.3±6.1), and personal accomplishment (33.2±10.7) were reported without significant differences between territories. CONCLUSIONS: different COVID-19 incidence among territories did not influence nurses' burden of symptoms in the HSCT setting. However, burnout and insomnia levels should be considered by health care facilities in order to improve preventive strategies.

Early Serological Response to BNT162b2 mRNA Vaccine in Healthcare Workers.

PURPOSE: Clinical significance and durability of serological response after mRNA COVID-19 vaccines is under investigation. Data on early virological response are limited. To iden-tify potential predictors of antibody durability, circulating antibody levels were longitudinally ex-plored in healthcare workers included in a follow-up program for SARS-CoV-2 infection. Meth-ods: Subjects meeting the inclusion criteria signed an informed consent. Serum samples were col-lected at baseline, before the first BNT162b2 vaccine, at days 7, 21, 31, 90, and 180 days after the first dose. Serological evaluation was performed by QuantiVac Euroimmune anti-S1 antibody as-say. Only subjects followed-up until day 90 are here considered. RESULTS: Of 340 taken into consid-eration, 265 subjects were naive, and 75 COVID-19 experienced. The former showed a progres-sive increase in their antibody levels before day 90 decline, while the latter showed antibody levels reaching a plateau at day 7 and slightly declining at day 90. All showed antibody levels higher than the assay cut-off at day 31 and 90. Among naive, 108 had an early response whose predic-tors were younger age and female gender (OR 0.94, 95% CI 0.91-0.96, p < 0.0001; and OR 2.58, 95% CI 1.48-4.51, p = 0.0009). Naive subjects experienced a day 30/90 decline in antibody levels, whereas experienced did not. Early response was an independent predictor of higher day 30/90 antibody levels decline (OR = 2.05, 95% CI 1.04-4.02; p = 0.037). CONCLUSIONS: Our results suggest that in healthcare workers early response might be inversely associated with antibody levels 90 days after BNT162b2 vaccine.

Diffusion modeling of COVID-19 under lockdown.

Viral immune evasion by sequence variation is a significant barrier to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine design and coronavirus disease-2019 diffusion under lockdown are unpredictable with subsequent waves. Our group has developed a computational model rooted in physics to address this challenge, aiming to predict the fitness landscape of SARS-CoV-2 diffusion using a variant of the bidimensional Ising model (2DIMV) connected seasonally. The 2DIMV works in a closed system composed of limited interaction subjects and conditioned by only temperature changes. Markov chain Monte Carlo method shows that an increase in temperature implicates reduced virus diffusion and increased mobility, leading to increased virus diffusion.

Hematology Patient Protection During the COVID-19 Pandemic in Italy: A Nationwide Nursing Survey.

BACKGROUND: Italy has been one of the first European countries hit by the COVID-19 pandemic, with many patients dying from severe respiratory issues, especially frail subjects. Hematology patients are generally thought to be at high risk of developing severe COVID-19-associated complications. The aim of this work was to describe the infection control measures adopted in Italian hematology settings to protect patients and health-care professionals. MATERIALS AND METHODS: On behalf of the Nursing Campus in Hematology Group, a nationwide nursing survey was conducted. Questionnaire items included general information, infection control measures, patient and health-care professional protection, information management, and participants' opinion on critical issues. Data have been analyzed by center location (Northern, Central, or Southern Italy) and by patient age (adult vs pediatric). RESULTS: Forty-four Italian hematology centers participated, representing 52.4% of those invited. Patients underwent nasopharyngeal swabs (93.2%) generally the day before admission (43.2%), though less frequently in Southern centers (p = 0.0377). Visitor restrictions were implemented in all centers: 65.9% barred all visitors, while 25.0% allowed visitors only for patients with specific conditions, especially in Central Italy. Deficiency of personal protective equipment, including masks (45.5%) and gloves (22.7%), was reported, although the nurses' opinion was that the emergency was nevertheless well managed to protect patients and professionals. Almost all health-care institutions (97.7%) provided recommendations on emergency management. No significant differences were found between adult and pediatric centers in terms of infection prevention and control. DISCUSSION: Low variability in patient protection strategies was observed, meaning that national recommendations were effective. However, some critical issues emerged regarding the management of infected health-care professionals and their contacts.

Low bone mineral density in HIV-positive young Italians and migrants.

BACKGROUND: Human immunodeficiency virus (HIV) infected individuals may have osteoporosis. We aimed to evaluate the bone mineral density (BMD) in naïve antiretroviral (ARV) treated HIV positive patients comparing native Italian group (ItG) to a Migrants group (MiG) upon arrival in Italy. METHODS: We conducted a cross-sectional study on 83 HIV patients less than 50 years old. We used the dual-energy X-ray absorptiometry (DXA) within six months from the HIV diagnosis. Participants were categorized as having low BMD if the femoral neck or total lumbar spine Z-score was- 2 or less. RESULTS: MiG showed low BMD more often than ItG (37.5% vs.13.6%), especially for the female gender (16.7% vs. 0.0%). A low CD4 rate (<200 cells/µl) was most often detected in MiG than ItG. In particular, we found most often male Italians with abnormal CD4 than male migrants (67.8% vs. 33.3%) and vice versa for females (30.5% vs. 66.7%). We found an abnormal bone mineral density at the lumbar site. Low BMD at the lumbar site was more frequently observed in female migrants than female Italians. Both male and female migrants had a Z-score value significantly lower than male and female Italians, respectively. By logistic regression low vitamin-D level was positively correlated to low BMD in ItG only. All data were verified and validated using a triple code identifier. CONCLUSIONS: Both DXA and vitamin-D evaluation should be offered after the diagnosis of HIV infection. Lumbar site low BMD is an initial condition of bone loss in HIV young patients, especially in female migrants. Vitamin D levels and supplementation may be considered after HIV diagnosis independently of age to improve bone health. HIGHLIGHTS: This study evaluates the frequency of bone mineral density in HIV positive patients naive to antiretroviral therapy. It compares the density of the native Italian population with that of HIV Migrants upon arrival in Italy. The results show that HIV positive migrants, even if younger than 50 years of age, are at risk for osteoporosis, especially if they are female.