Prevalence of Coronavirus Disease 2019 (COVID-19) Among Children Age Groups

In our study prevalence of coronavirus Disease 2019 (COVID-19) among Children age groups, by diagnosis, symptoms, and treatment of COVID-19 in children. The incidence of COVID-19 among children under 18 years was 1.8 % based on the reported studies, where the mortality rate in the same age group was 0.3 %. No death has been reported in children under 10-years old. It has also been reported that the case fatality rates for the age groups of 0-9 years and 10-19 years are zero and 0.2%, respectively. Cai, et al. [1] There are some studies that report children with COVID-19 having rashes, symptoms and signs similar to Kawasaki’s disease. Heart complications were observed in these cases of Kawasaki’s disease. the levels of bilirubin and hepatic enzymes are the best markers for diagnosing the severity of the disease in the affected children. Large number of angiotensin converting enzyme 2 (ACE2) receptors on cell surfaces, effective innate immune system, and high level of blood lymphocyte have been reported to be the potent reasons for lower incidence of severe symptoms of COVID-19 among children. Children with severe COVID-19 clinical symptoms, especially those suffering from upper respiratory tract symptoms and signs and pneumonia, also children with gastrointestinal tract symptoms and signs as vomiting and diarrhea must be hospitalized similar to adults, while quarantine and home isolations are required for those having mild symptoms. Antiviral medication (Remdesivir, darunavir, ribavirin, oseltamivir, tocilizumab, umifenovir and favipiravir,) ACE inhibitors, interferon-α 2b, co-therapy with azithromycin, inhaling iNO, inhaled bronchodilators and oxygen therapy can be used for treatment. The best treatment for affected children without any clinical and infection symptoms, home isolation protocol has been recommended.

Prevalence of Coronavirus Disease 2019 (COVID-19) Among Children Age Groups

In our study prevalence of coronavirus Disease 2019 (COVID-19) among Children age groups, by diagnosis, symptoms, and treatment of COVID-19 in children. The incidence of COVID-19 among children under 18 years was 1.8 % based on the reported studies, where the mortality rate in the same age group was 0.3 %. No death has been reported in children under 10-years old. It has also been reported that the case fatality rates for the age groups of 0-9 years and 10-19 years are zero and 0.2%, respectively. Cai, et al. [1] There are some studies that report children with COVID-19 having rashes, symptoms and signs similar to Kawasaki’s disease. Heart complications were observed in these cases of Kawasaki’s disease. the levels of bilirubin and hepatic enzymes are the best markers for diagnosing the severity of the disease in the affected children. Large number of angiotensin converting enzyme 2 (ACE2) receptors on cell surfaces, effective innate immune system, and high level of blood lymphocyte have been reported to be the potent reasons for lower incidence of severe symptoms of COVID-19 among children. Children with severe COVID-19 clinical symptoms, especially those suffering from upper respiratory tract symptoms and signs and pneumonia, also children with gastrointestinal tract symptoms and signs as vomiting and diarrhea must be hospitalized similar to adults, while quarantine and home isolations are required for those having mild symptoms. Antiviral medication (Remdesivir, darunavir, ribavirin, oseltamivir, tocilizumab, umifenovir and favipiravir,) ACE inhibitors, interferon-α 2b, co-therapy with azithromycin, inhaling iNO, inhaled bronchodilators and oxygen therapy can be used for treatment. The best treatment for affected children without any clinical and infection symptoms, home isolation protocol has been recommended.

Prevalence of Coronavirus Disease 2019 (COVID-19) Among Children Age Groups

In our study prevalence of coronavirus Disease 2019 (COVID-19) among Children age groups, by diagnosis, symptoms, and treatment of COVID-19 in children. The incidence of COVID-19 among children under 18 years was 1.8 % based on the reported studies, where the mortality rate in the same age group was 0.3 %. No death has been reported in children under 10-years old. It has also been reported that the case fatality rates for the age groups of 0-9 years and 10-19 years are zero and 0.2%, respectively. Cai, et al. [1] There are some studies that report children with COVID-19 having rashes, symptoms and signs similar to Kawasaki’s disease. Heart complications were observed in these cases of Kawasaki’s disease. the levels of bilirubin and hepatic enzymes are the best markers for diagnosing the severity of the disease in the affected children. Large number of angiotensin converting enzyme 2 (ACE2) receptors on cell surfaces, effective innate immune system, and high level of blood lymphocyte have been reported to be the potent reasons for lower incidence of severe symptoms of COVID-19 among children. Children with severe COVID-19 clinical symptoms, especially those suffering from upper respiratory tract symptoms and signs and pneumonia, also children with gastrointestinal tract symptoms and signs as vomiting and diarrhea must be hospitalized similar to adults, while quarantine and home isolations are required for those having mild symptoms. Antiviral medication (Remdesivir, darunavir, ribavirin, oseltamivir, tocilizumab, umifenovir and favipiravir,) ACE inhibitors, interferon-α 2b, co-therapy with azithromycin, inhaling iNO, inhaled bronchodilators and oxygen therapy can be used for treatment. The best treatment for affected children without any clinical and infection symptoms, home isolation protocol has been recommended.

A Comparison of SAA Levels in Children With Viral CNS Infection and Kawasaki’s Disease

The authors have requested that this preprint be withdrawn due to author disagreement.

CD28 Expression Distinguishes Plasma Cell Fate in Pediatric Patients Suffering from COVID-19/Kawasaki's Disease Vs MIS-C

The COVID-19 pandemic has ravaged the global community and highlighted the importance of antibody-mediated antiviral immune responses. The SARS-CoV-2 virus is highly pathogenic, but is unique from other viral infections in that pediatric patients are largely spared from severe symptoms. However, a small number of pediatric patients present autoimmune-like symptoms after COVID-19 infection, termed Multisystem Inflammatory Syndrome in Children, or MIS-C. Symptomatically, it shares some similarity to that of Kawasaki's Disease (KD), an autoimmune disorder linked to coronavirus infection thought to be driven by autoantibody production. Understanding the immunological mechanisms that facilitate clearance of SARS-CoV-2 or drive the development of life-threatening autoimmune symptoms in MIS-C or KD is critical for our ability to design successful vaccines that do not elicit autoimmunity in children. Antibodies are produced by terminally differentiated B lymphocytes known as Plasma Cells (PC). Because successful immune responses/vaccination strategies against SARS-CoV-2 are dependent upon effective PC production, the dysregulation of which may lead to the development of Kawasaki's Disease or MIS-C, it is critical to understand the immunological mechanisms that define the pediatric PC response leading to these individual outcomes. We therefore sought to characterize the B cell-PC immune response in pediatric patients that have successfully cleared SARS-CoV-2 and compare the B cell immunological landscape to children who develop either KD or MIS-C. We used the 10X Genomics Platform to interrogate at a single cell level the CD19+ B/PC populations in the peripheral blood of pediatric patients at the transcriptional level as well as with VDJ deep sequencing. We began by clustering the CD19+ populations based on transcriptional similarity and found that both COVID-19 and KD exhibited 12 distinct clusters, but that MIS-C only had 6 clusters. Intriguingly, in evaluating clonal diversity, KD presented a broad spectrum of clonotypes while the COVID-19 and MISC patients were much more limited. This suggested that although KD and MIS-C both present with similar autoimmune-like symptoms, the mechanistic basis for their respective etiology may be distinct. We therefore sought to more deeply probe the subset of cells responsible for antibody production by evaluating the PC subsets. High BLIMP1 expression (PC lineage-defining transcription factor) was present in 2 distinct clusters in COVID-19/KD patients, but was broadly distributed at lower levels in MIS-C. We then looked at genes which were significantly upregulated in the most terminally differentiated cells from each patient. 50 genes were significantly higher in the COVID-19 and KD populations, and 54 in MIS-C. Using gene ontology analysis in COVID-19 and KD, we saw increased expression of transcripts involved in protein trafficking, redox responses, and respiratory metabolism. In comparison, the MIS-C patient demonstrated significance for programs involved in immature B cell development and inflammation. Taken together, this suggests that in COVID-19 and KD there is a program of terminal PC differentiation which is absent in MIS-C. To understand the mechanistic basis for the terminal differentiation in COVID-19 and KD, we sought to probe possible regulators of PC fate. We have recently published that CD28, the canonical T cell costimulatory molecule, is expressed by PC, and CD28 signaling through the adaptor protein SLP-76 leads to increased BLIMP1 expression and an IRF4-mediated metabolic program necessary for PC survival. Interestingly, SLP-76 was expressed at high levels in COVID-19 and KD patients, but was low in MIS-C. Similarly, CD28 was expressed in both COVID-19 and KD patients and correlated with higher IRF4 levels and metabolic genes, but was entirely absent in MIS-C. Taken together, these findings suggest that CD28 signaling may facilitate PC fate in COVID-19 pediatric patients and the development of KD arises from broad antibody specificity, possibly explaining how vascular antigens become targets. Furthermore, MIS-C, although similar in symptomatic presentation to KD, has an etiology driven by antigen-independent inflammation arising from immature B cells due to a lack of CD28-mediated PC differentiation and survival, which can be evaluated diagnostically by simple flow cytometry in a vaccination setting. Disclosures No relevant conflicts of interest to declare.

385. Kawasaki’s Disease and Sars-Cov-2: an Unexpected Pediatric Global Crisis?

Background Infection by SARS-CoV-2 can lead to dyspnea, edema, deposition of intra alveolar fibrin, thrombosis and hemorrhages. During the COVID-19. outbreak, several questions were raised about the risks for the pediatric population. Pediatric patients appeared to be relatively safe, with only minor symptoms and a quick recovery. However, there have been reports of a relationship between COVID 19 and a Kawasaki-like inflammatory disease in this population. Kawasaki’s disease (KD) is a rheumatological vasculitis prevalent in childhood characterized mainly by diffuse inflammation of the arteries associated with skin rash, changes in the mucosa and its main complication is coronary aneurysms. Methods A systematic literature review was performed in the PubMED database using the keywords “Kawasaki disease”, “COVID-19” and “Pediatrics”. The selected filters were “Case reports”, “Multicenter study”, “Clinical Study”, “Observational study”, “Human” and “English”. A total of 18 articles were seleted. Results There seems to be a convergence between the literature published so far, pointing to a greater propensity for pediatric patients infected with Sars-Cov-2 to develop KD. The number of patients with KD symptoms seen at a specific center increased from 2 to 17 in 11 days (MOREIRA, 2020). In a sample space of 21 patients diagnosed with KD, 91% had previous contact with SARS-CoV-2 (TOUBIANA, 2020) whereas other studies point to a 30-fold increase in the prevalence of KD since the beginning of 2020 (VERDONI, 2020). There is already an established relationship between DK and HCoV-NH, describing that 4.5% of patients with this infection develop KD. Therefore, it was suggested that infection with another Coronavirus strain could have a similar relationship. Conclusion Despite the relationship described between pediatric patients infected with COVID-19 being more likely to develop KD, further studies are needed to prove a statistical relationship between both condition. Disclosures All Authors: No reported disclosures

A Comparison of SAA Levels in Children With Viral CNS Infection and Kawasaki’s Disease

Background: The purpose of this study was to analyze the epidemiological differences of SAA in children with viral central nervous system (CNS) infection and Kawasaki’s Disease(KD). The former is viral invasion of central nervous system, whereas the latter is a viral systemic vasculitis. Differences in the SAA concentration in the blood and the proportion of high level SAA cases reflected the influence of the blood-cerebrospinal fluid barrier (BCB) on the concentration of peripheral blood infection markers.Methods: The SAA data comprised 226 consecutive cases of children, including 112 cases of viral CNS infection and 114 cases of KD. Differences in the proportion and concentration of SAA in the cases of the two groups were verified with a Kruskal-Wallis H-test and the chi-square test.Results: The concentration of SAA differed between children with KD and viral CNS infection, and the high level SAA proportion was lower in children with viral CNS infection compared to that in the KD group.Conclusions: The observed differences may be due to the sequestration effect, as the blood-cerebrospinal fluid barrier (BCB) can compartmentalize the pathogens at the site of disease. Therefore, other organs are unable to be stimulated to release additional SAA.