ABSTRACT
Background: Children seem to experience a less severe form of COVID-19 disease than adults, nevertheless, cases of severe infection have been described in a small proportion of patients, requiring hospitalization in 5-10% of cases. Among COVID-19 deaths 0,4% occurred in children and adolescents under 20 years of age. Most hospitalized children with acute COVID-19 had underlying conditions. Moreover, some children with previous COVID-19 infection, may later develop Multisystem Inflammatory Syndrome in Children (MIS-C), a rare but serious condition associated with COVID-19. These data suggest that a specific therapy is necessary in high-risk pediatric population, in order to prevent severe COVID-19, especially in children with underlying conditions. Antiviral paediatric data are currently very few Methods: We conducted a retrospective study on patients < 18 years of age who received Paxlovid (nirmatrelvir-ritonavir) for the treatment of mild-tomoderate COVID-19 at Bambino Gesu Children's Hospital from April 2022 to September 2022. Patients at high risk of progression to severe COVID-19 who had no need of supplemental oxygen received Paxlovid according to AIFA's indications for adults with the Informed Consent of relatives Results: 40 patients aged 1-18 years with confirmed SARS-CoV-2 infection were treated with Paxlovid (Tab 1)The average symptom duration was 4.2 days. No patient developed severe COVID-19 r All patients were treated within 5 days of symptom onset, Four patients received a longer course treatment (10 days) due to the persistence of symptoms combined with the presence of severe comorbidities .The mean time of viral shedding was 12.7 days, with a patient being persistently positive for 56 days. After Paxlovid initiation, only 5 patients (12.5%) experienced adverse reactions: Conclusion(s): Treatment with Paxlovid has proven to be safe. Further pharmacokinetic studies are required species for children < 5 years old.
ABSTRACT
BACKGROUND AND AIMS: Data about HD patients and how to best dialyze them during the COVID-19 pandemic are scarce. The aim of the study is to describe the organizational model and clinical outcomes of patients confirmed COVID-19 needing renal replacement therapy, admitted in a COVID Hospital in Southern Italy during the first and second pandemic wave. METHOD: All the consecutive patients requiring chronic HD, during the first and second wave were considered. Due to local resources, we have implemented an organizational model based on the HD bedside with Genius system. The machine was prepared in the Dialysis Unit and then transferred to the COVID Hospital. After treatment, the monitor was sterilized and carefully cleaned with chlorine wipes and retransferred into the dialysis Unit to be prepared for the next dialysis. Demographic data, clinical symptoms at presentation, and laboratory results were extracted by the electronic medical record. Patients hospitalized during the first wave (FW) and second wave (SW) were compared. RESULTS: From March 10 through December 31 2020, we enrolled a cohort of 40 patients (37.5% F), with COVID-19 infection requiring HD;11 (27.5%) during first and 29 (72.5%) during second wave. The phenotype and clinical symptoms at the admission were not different between two groups. Compared to FW, the SW patients were younger (70.1±9.5 vs 77.3±5.9 years;p<0.03) with lower dialysis vintage (35±18 vs 60±48 months;p<0.05), and lower Charlson Comorbidity Index scores (2.8±1.8 vs 5.09±2.0;p<0.05). No differences were observed between the first and second wave as far as inflammatory markers IL6 (51.9±44.8 vs 55.45±40.52 pg/mL;ns) and C-reactive protein (4.74±3.8 vs 6.70±5.44 mg/L;ns) as well as the hospital stay (21.1±10 vs 24.4.8±10 days;ns) and in-hospital mortality (28.1% vs 18.2%;ns). Overall, 354 bedside treatments were performed;mean session time and mean weekly sessions were 3.64±0.40 hours, and 3.4±0.45 HD/week, with no differences between FW and SW patients. CONCLUSION: Our data show that the higher spread of Sars-cov2 during the second wave has infected younger and less comorbid HD patients, with no significant differences in clinical and laboratory parameters. Our organizational model based on the HD bedside with the Genius system, allowed a personalized treatment with efficacy and safety for the patients and staff.
ABSTRACT
Background: Further knowledge on adaptive immunity to SARS-CoV-2 (CoV-2) in children is needed in order to define possible immunization strategies and reconsider pandemic control measures. We analyzed anti-CoV-2 antibodies (Ab) and their neutralizing activity (PRNT), alongside antigen (Ag) specific cellular response, in relation to virus load in nasopharyngeal swabs. Methods: We analysed 42 CoV-2 patients at 7 days after symptoms onset. CoV-2 viral load (VL) was measured by RT-PCR and digital droplet PCR on longitudinal samples of nasopharyngeal swabs (NP). Virus infectivity (FFU) was tested by virus focus forming assay. CoV-2 antibodies were investigated by Diasorin (CoV-2 Ab) and neutralization assay (PRNT). CoV-2-specific CD4-CD40L+ T-cells and Spike specific B-cells were analysed by flow cytometry. Plasma proteomic profiling was measured by 2 Olink panels. We calculated the area under the curve (AUC) of the viral load from NP collected every 48 hours up to undetectable VL. Mann-Whitney was used to compare means in individuals with neutralizing activity (PRNT+) or not (PRNT-);linear regression was used to evaluate the associations between virus load and infectivity over time. Principal component analysis (PCA) was used to analyse proteomic data. Results: Higher VL was found in seronegative patients expressed in terms of both CoV-2 Ab (p=0.003) and PRNT (p=0.0007). Similarly, lower FFU was associated with higher CoV-2 Ab (p=0.003;rho=-0.67) and PRNT (p=0.023;rho=-0.46). Further, the AUC of the viral load in NP showed an inverse correlation with CoV-2 Ab (p=0.031;rho=-0.54). Development of humoral response was associated with the presence of CoV-2 specific IgD-CD27+ B cells, with a higher frequency of CoV-2 specific B cells found in seropositive compared to seronegative (p=0.001). Besides, individuals developing neutralizing Ab had higher frequency CD4-CD40L+ T-cells compared to PRNT- (p=0.03). The plasma proteome confirmed the association between cellular and humoral CoV-2 immunity, with PRNT+ showing higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). Conclusion: This work provides a virological and immunological characterization of SARS-CoV-2 infected children presenting a differential Abmediated neutralizing activity. It demonstrates that children with neutralizing antibodies present reduced viral load, faster virus clearance and lower in vitro infectivity. These data provide information that can drive vaccination endpoints and quarantine measures policies.
ABSTRACT
As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.