Signs and symptoms commonly seen in COVID-19 in newborns, children, and adolescents and pediatric subjects

The recent findings reported that the most frequent coronavirus disease 2019 (COVID-19) clinical course in pediatric subjects ranged from mild to moderate form in with nonspecific symptoms such as fever, cough, dyspnea, fatigue, muscle pain, headache, and nasal congestion. On the contrary, a lower frequency of severe COVID-19 forms was reported, including refractory metabolic acidosis, coagulation disorders, tachypnea, severe pneumonia, and septic shock. Recent literature is associated with the COVID-19 pediatric subject to the acute multisystem inflammatory syndrome (MIS-C) with abdominal symptoms and left ventricular systolic dysfunction. The recent findings seem to support that the unvaccinated and comorbid children could present more severe clinical forms. Few data of COVID-19 hospitalization in pediatric intensive care unit (PICU) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in schools were reported during the first wave. The main reasons could be correlated to the early school's closure, while the swabs were destined more frequently to adult symptomatic subjects. The pandemic state generated rise in psychological disorders, anxiety, and depression more frequently during the first year of the disease spread, with a higher prevalence in older adolescents. © 2023 Elsevier Inc. All rights reserved.

A COVID-19 nosocomial cluster in a university hospital in southern Italy: a social network analysis

Introduction. Healthcare workers on duty at the hospital are at high risk of COVID-19 infection. However, despite the introduction of risk-lowering practices in the hospital setting, there have been many cases of SARS-COV-2 infection among Health Care Workers. Fast and efficient contact tracing and Sars-CoV-2 PCR-based testing of the close contacts of Health Care Workers with confirmed infections are essential steps to limit nosocomial outbreaks. Methods. This cross-sectional study was conducted at Bari Policlinico General University-Hospital (Apulia, Italy) and describes the management of a cluster of SARS-COV-2 infections in three Operative Units. The contact tracing activities and the measures implemented to control the outbreak are described. Results. Among the 186 Health Care Workers active in the cluster setting, there were 9 (4.8%) confirmed cases, including the index case. Due to the outbreak, three Operative Units were closed to limit virus circulation. Health Care Workers with confirmed infections tested negative after a mean of 28.0±6.6 days (range: 13–37) and none required hospitalization.Conclusions. Protection of the health of Health Care Workers during the COVID-19 pandemic should be a public health priority. However, despite recent recommendations and the implementation of protective measures, SARS-COV-2 infections of Health Care Workers remain at a high rate, indicative of the continued high risk of cluster onset in the nosocomial setting. © Società Editrice Universo (SEU), Roma, Italy

A COVID-19 nosocomial cluster in a university hospital in southern Italy: a social network analysis

INTRODUCTION: Healthcare workers on duty at the hospital are at high risk of COVID-19 infection. However, despite the introduction of risk-lowering practices in the hospital setting, there have been many cases of SARS-COV-2 infection among Health Care Workers. Fast and efficient contact tracing and Sars-CoV-2 PCR-based testing of the close contacts of Health Care Workers with confirmed infections are essential steps to limit nosocomial outbreaks. METHODS: This cross-sectional study was conducted at Bari Policlinico General University-Hospital (Apulia, Italy) and describes the management of a cluster of SARS-COV-2 infections in three Operative Units. The contact tracing activities and the measures implemented to control the outbreak are described. RESULTS: Among the 186 Health Care Workers active in the cluster setting, there were 9 (4.8%) confirmed cases, including the index case. Due to the outbreak, three Operative Units were closed to limit virus circulation. Health Care Workers with confirmed infections tested negative after a mean of 28.0±6.6 days (range: 13-37) and none required hospitalization. CONCLUSIONS: Protection of the health of Health Care Workers during the COVID-19 pandemic should be a public health priority. However, despite recent recommendations and the implementation of protective measures, SARS-COV-2 infections of Health Care Workers remain at a high rate, indicative of the continued high risk of cluster onset in the nosocomial setting.

Serological Response Following BNT162b2 Anti-Sars-Cov-2 mRNA Vaccination in Hematopoietic Stem Cell Transplantation Patients

Patients with hematological malignancies (HM) undergoing hematopoietic stem cell transplantation (HSCT) have an increased vulnerability to SARS-Cov-2 (Sharma et al, Lancet Haematology 2020;Ljungman et al, Leukemia 2021), the reason why international guidelines strongly support the need for a protective vaccination for these subjects. The most relevant data currently available on the response to a complete anti-SARS-Cov-2 vaccination cycle in HM patients after HSCT refer to 314 patients reported in a Lithuanian national survey (Maneikis et al, Lancet Haematol 2021). In this study, the median titers of antibodies against SARS-Cov-2, determined 7-21 days after the second vaccination, were comparable to that of healthy controls (HC) in both autologous and allogeneic groups, with no patient found below the protective threshold of 50 arbitrary units (AU)/ml. Notably, the large majority of patients had received the transplant more than 1 year before vaccination. In a prospective, cohort study, we compared 114 patients, who had received an autologous or allogeneic HSCT at least three months before the first dose of vaccination, to 107 HC, matched for age and sex. Study population and HC received two doses of BNT162b2 anti-SARS-Cov-2 mRNA vaccine on days 1 and 21, between April and May 2021. Serological tests were performed by a commercially available immunoassay for the quantitative determination of anti-spike IgG antibodies to SARS-Cov-2. The cut-off for defining responders was 50 or greater AU/ml. Patients and HC samples were collected four weeks after the second dose of the vaccine. Table 1 reports the main clinical characteristics of patients and HC. Eighteen of 114 patients (16%) did not respond (24% in the allogeneic group, 6% in autologous recipients). Overall, median antibodies titers did not differ between HC and the entire cohort of transplanted patients, recipients of allogeneic HSCT, all patients responding to the vaccine or responders in the autologous subgroup (Figure 1A). All autologous HSCT recipients had significantly lower titers of antibodies than HC, while higher levels were found in responders who had received allogeneic HSCT (Figure 1A). Responders in the allogeneic subgroup showed antibodies titers significantly higher than responders in the autologous subgroup (Figure 1B). We further stratified patients in three groups, according to the time elapsed from transplant to vaccination: G1:<1 year;G2:1-5 years;G3:>5 years. Higher antibodies titers were observed in HC compared to all transplanted patients in G1 (Figure 1C), including both allogeneic (Figure 1D) and autologous (Figure 1E) HSCT recipients. No differences emerged in G2 between HC and all patients (Figure 1C), allogeneic (Figure 1D) or autologous (Figure 1E) HSCT recipients. Finally, no differences were found in G3 when comparing HC with all patients (Figure 1C) or allogeneic recipients (Figure 1D), whereas patients in the autologous subgroup showed significantly lower titers than HC (Figure 1E). Myeloma patients with controlled disease showed higher titers than patients with active disease (Figure 1F). According to median age, autologous HSCT recipients older than 57 years had significantly lower antibody levels than younger patients (Figure 1G). Autologous vs allogeneic HSCT, age of all patients and of allogeneic HSCT recipients, sex, type of allogeneic HSCT, conditioning regimen, age and sex of donor, occurrence of GVHD, disease type and single vs double autologous HSCT did not significantly impact on antibody levels (data not shown). No relevant side effects were recorded after vaccination. With a median follow up of 12 weeks, no case of COVID19 occurred among vaccinated patients. In our single center study, patients with a previous history of HSCT tolerated well BNT162b2 vaccine and mounted a potentially protective immune response in the majority of cases one month after two doses of vaccine. However, lack of response was not rare, especially in the allogeneic setting. The main factor associated with the quality of response was the tim from HSCT, with lower responses within the first year from transplant and differences between autologous and allogeneic groups transplanted more than five years before vaccination. Here, a consolidated, complete immune reconstitution in allogeneic HSCT recipients, as well as age and a still active disease in the autologous setting, could have played opposite pivotal roles. [Formula presented] Disclosures: Delia: Gilead: Consultancy;Amgen: Consultancy;abbvie: Consultancy;Jazz pharmaceuticals: Consultancy.

COVID-19 in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS): An Observational Retrospective Study

Introduction. Monoclonal Gammopathy of Undetermined Significance (MGUS) is a pre-malignant plasma cell disorder reported in approximately 3% of individuals aged > 50 years, characterized by a low risk (about 1% per year) of evolution into “overt” myeloma or other lymphoproliferative diseases. It is classified as IgM-MGUS (15%) and non-IgM-MGUS (80-85%). MGUS is usually asymptomatic, but a higher risk of deep venous thrombosis and infection has been reported. In March 2020, “Coronavirus Disease 2019” (COVID-19) outbreak has been declared a pandemic by the World Health Organization. Regarding outcome of COVID-19 in patients with plasma cell dyscrasia, many papers have been published about multiple myeloma (MM), reporting a higher fatality rate respect to general population, while few data are available about the outcome of SARS-CoV-2 infection in patients with MGUS. Methods. We collected clinical data on MGUS Apulian patients with SARS- CoV-2 infection, tested by RT-PCR on nasopharyngeal swabs between March 1st, 2020 and April 30st, 2021. Among 1454 MGUS patients followed at our center, 91 were found SARS-CoV-2 positive, enrolled in this observational, retrospective study and compared with 182 age and sex-matched normal controls. Clinical data collected regarded: symptoms, hospitalization, hospitalization in intensive care unit, death. Calculations were carried out using Stata MP17. Results. Mean age of whole group (n. 273) was 65,3+/-13,3 years (range: 29-89), with no statistically-significant differences (p=0,734) observed between MGUS-group (65,6+/-13,3;range: 29-89 years) and controls-group (65,2+/- 13,4;range: 29-89 years). Mean number of comorbidities in the whole group was 1,2+/-1,2 (range: 0-5) and no statistically-significant differences (p=0,844) were found between MGUS-group (1,3+/-1,3;range: 0-5) and control group (1,2+/- 0,9;range: 0-3). About MGUS-subtypes, the most frequent was IgG-kappa (n=36;39,6%), followed by IgG-lambda (n=27;29,7%) and IgM-kappa (n=6;6,6%). Regarding MGUS risk-stratification, application of Mayo Clinic model identified 22 patients (24,2%) with low risk, 22 (24,2%) with low-intermediate risk, and 3 (3,3%) with high-intermediate risk;in 44 patients (48,3%) this data was missing. Immunoparesis was present in 13 cases (14,3%) and absent in 55 (60,4%), missing in 23 (25,3%). No patient developed MM or a lymphoproliferative disease progression during and immediately after COVID-19. Rates of symptoms (59,3% vs 56%), hospitalization (20,9% vs 14,3%), hospitalization in intensive care unit (11% vs 8,8%) and death (8,8% vs 5,5%) were slightly higher in MGUS group than controls (Table 1), but these differences were not statistically significant. A statistically significant association (p<0,05), was observed between higher age and death in both groups. Lastly, incidence of SARS-CoV-2 infection in MGUS patients (6,2%) was not statistically significant different from that observed in the population of the Puglia region (5,8%) in the same period. Conclusions. To our knowledge, this report is the largest study of patients with MGUS and SARS-CoV-2 infection to date. In our study patients with MGUS did not show an increased incidence of this infection compared to the general population and did not appear to represent a risk factor for poor outcome in COVID-19. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Serological Response to BNT162b2 Anti-Sars-Cov-2 mRNA Vaccine in Patients with Transfusion Dependent Thalassemia

Thalassemia is an inherited blood disorder characterized by defective hemoglobin production, ineffective erythropoiesis and chronic hemolytic anemia. Patients with both transfusion-dependent thalassemia (TDT) and non-transfusion dependent thalassemia (NTDT) have risk factors associated with severe SARS-CoV-2 infection including iron overload, endocrinopathies, massive splenomegaly or previous splenectomy and coagulopathy (Motta et al, Am J Hematol, 95: E198-E199., 2020). Although vaccination is encouraged for these patients, data on the efficacy and safety of anti Sars-CoV-2 vaccines are limited (Karimi, M, et al, Br J Haematol, 190: e137-e140, 2020;Mandana Zafari, et al, Hemoglobin, 45:1, 1-4, 2021) due to exclusion of these patients from clinical trials. In a single center, prospective, cohort study we compared 67 patients affected by TDT to 61 healthy controls (HC), matched for age and sex. Study population and HC received two doses of BNT162b2 anti-SARS-Cov-2 mRNA vaccine on days 1 and 21, between April 1st and May 15 th, 2021. Serological tests were performed by a commercially available immunoassay for the quantitative determination of anti-spike IgG antibodies to SARS-CoV-2. The results were reported as Arbitrary Units (AU)/mL, with a cut-off for defining response as 50 or greater AU/ml. Patients and HC samples were collected four weeks after the second dose of vaccine. Median age of patients was 43 years (range 19-77), 39% of them were male and 61% were female. Median age of HC was 39 years (range 19-86), 43% of them were male and 57% were female. All controls achieved a response (50 or greater AU/mL) to vaccination, whereas 66/67 (98,5%) patients responded. Antibody titers were significantly higher (p=0.0005) in the HC group (mean 9863 ± 7784;median 7712, range 1206-51664) compared to patients (mean 7945 ± 12326;median 4025, range 19-89202) (Figure 1). When analyzing the patients' factors, age, sex, transfusion interval, serum ferritin level, and spleen size did not impact on the response to vaccination. With a median follow-up of 12 weeks, no relevant side effects were recorded after vaccination and no case of COVID19 occurred among vaccinated TDT patients. In conclusion, BNT162b2 anti-SARS-Cov-2 mRNA vaccine demonstrated efficacy and safety in our cohort of TDT patients. Response rate was similar to that of HC. Nevertheless, antibody titers in TDT patients were significantly lower than in HC. Further observations are ongoing to assess duration of response, efficacy and possible factors influencing this finding. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Health, Transport and the Environment: The Impacts of the COVID-19 Lockdown on Air Pollution

Lockdown measures were initiated in Italy on March 9th after the start of the SARS-CoV-2 epidemic to flatten the epidemic curve. The aim of the present study was to assess the impact of restrictive measures in the Apulia Region, southern Italy, on air quality from March to April 2020. We applied a dual-track approach. We assessed citizen mobility and vehicle traffic with mobility network data and information obtained from satellite tracking, and we evaluated and compared pollutant concentration data as measured by monitoring stations maintained by the Regional Agency for Environmental Protection and Prevention of Apulia (ARPA). The results showed a decrease in the weekly mean NO₂ concentration recorded by urban traffic stations during the lockdown period. In particular, in the city of Bari, the average NO₂ concentration decreased from 62.2 mug/m³ in March 2019 to 48.2 mug/m³ in March 2020. Regarding PM10 levels, the average concentrations at the individual traffic stations showed no particular variation compared to those in the same months of the previous year, except for Bari-Caldarola Station in March 2019/2020 (p-value < 0.001) and in April 2019/2020 (p-value = 0.04). In particular the average in March 2019 was ~26.9 mug/m³, while that in March 2020 was ~22.9 mug/m³. For April, the average concentration of PM10 in 2019 was 27.9 mug/m³, while in 2020, the average was ~22.4 mug/m³. This can be explained by the fact that PM10 levels are influenced by multiple variables such as weather and climate conditions and desert dust advections.

Prevention and protection measures of healthcare workers exposed to SARS-CoV-2 in a university hospital in Bari, Apulia, Southern Italy.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related infection has a major impact on public health, and healthcare workers (HCWs) are exposed to high biological risk. This paper describes the prevention procedures introduced at the University Hospital of Bari, Italy to reduce the risk to HCWs, consisting of enhanced preventive measures and activation of a report system to collect HCWs' contacts. Twenty-three confirmed cases of infection (0.4% of all HCWs) were reported in the 30-day observation period following implementation of the protocol. This shows that correct management of HCWs' contacts is essential to avoid nosocomial clusters.