Leukopenia of Asymptomatic COVID-19 Infections under 18 Years Old in Recovery Stage (Running head: Leukopenia of Asymptomatic COVID-19 Infections) (preprint)

Objectives In December, 2019, a type of novel coronavirus which was designated novel coronavirus 2019 (2019-nCoV) by the World Health Organization (WHO) occurred in Wuhan, Hubei, China. There is limited information available on the epidemiological and clinical characteristics of patients under 18 years old in the recovery stage. To compare the difference of epidemiological and clinical characteristics of COVID-19 involving 25 patients under 18 years old in the recovery stage between confirmed and asymptomatic infections.Methods The retrospective, single-center cohort study of COVID-19 involving 25 patients under 18 years old in the recovery stage at Guizhou Provincial Staff Hospital in Guiyang, China, from January 29 to March 31, 2020; last date of follow-up was April 22. We collected and analyzed epidemiological, demographic, clinical, laboratory, radiological, and treatment data. The researchers compared the epidemiological and clinical characteristics of confirmed COVID-19 infections and asymptomatic infections.Results Among the 25 COVID infections under 18 years old, 16 (64%) were mild or moderate confirmed cases, and 9 (36%) were asymptomatic. The shortest treatment period was 6 days, the longest 26 days, and the average treatment period was 14 days. Four cases (44.4%) had visited Wuhan or had a living story in the city. There were 9 (100%) asymptomatic cases were familial cluster outbreak, with an average infection number was 6 cases among all families. The number of asymptomatic COVID-19 infections with leukopenia was significantly more than confirmed cases (p = 0.04).Conclusions Leukopenia mostly occurred in asymptomatic COVID-19 infections under 18 years old compared with the confirmed patients.Trial registration: The Chinese Clinical Trial Register (CCTR number: ChiCTR2000032458) registered this study retrospectively on 28 April 2020.

Outcomes of SARS-CoV-2 infection in 126 children and adolescents with central nervous system tumors.

BACKGROUND: The Global Registry of COVID-19 in Childhood Cancer (GRCCC) seeks to describe the natural history of SARS-CoV-2 in children with cancer across the world. Here, we report the disease course and management of coronavirus disease 2019 (COVID-19) infection in the subset of children and adolescents with central nervous system (CNS) tumors who were included in the GRCCC until February 2021, the first data freeze. PROCEDURE: The GRCCC is a deidentified web-based registry of patients less than 19 years of age with cancer or recipients of a hematopoietic stem cell transplant and laboratory-confirmed SARS-CoV-2 infection. Demographic data, cancer diagnosis, cancer-directed therapy, and clinical characteristics of SARS-CoV-2 infection were collected. Outcomes were collected at 30 and 60 days post infection. RESULTS: The GRCCC included 1500 cases from 45 countries, including 126 children with CNS tumors (8.4%). Sixty percent of the cases were from middle-income countries, while no cases were reported from low-income countries. Low-grade gliomas, high-grade gliomas, and CNS embryonal tumors were the most common CNS cancer diagnoses (67%, 84/126). Follow-up at 30 days was available for 107 (85%) patients. Based on the composite measure of severity, 53.3% (57/107) of reported SARS-CoV-2 infections were asymptomatic, 39.3% (42/107) were mild/moderate, and 6.5% (7/107) were severe or critical. One patient died from SARS-CoV-2 infection. There was a significant association between infection severity and absolute neutrophil count less than 500 (p = .04). Of 107 patients with follow-up available, 40 patients (37.4%) were not receiving cancer-directed therapy. Thirty-four patients (50.7%) had a modification to their treatment due to withholding of chemotherapy or delays in radiotherapy or surgery. CONCLUSION: In this cohort of patients with CNS tumors and COVID-19, the frequency of severe infection appears to be low, although severe disease and death do occur. We found that greater severity was seen in patients with severe neutropenia, although treatment modifications were not associated with infection severity or cytopenias. Additional analyses are needed to further describe this unique group of patients.

Hematologic adverse events reported after COVID-19 vaccination in the Philippines: A national database study.

Vaccination is the most important strategy in preventing COVID-19. Vaccine efficacy and safety have been established in clinical trials but real-world data are useful to determine occurrence of adverse events in a population with heterogeneous characteristics. Knowledge on the hematologic events associated with different COVID-19 vaccines would be beneficial for patients as well as hematologists who oversee the care of these patients. This study aimed to determine the rates and outcomes of hematologic adverse events after COVID-19 vaccination in the Philippines. In this self-controlled case series, there were 268 individuals reported to have hematologic adverse events. Most received Comirnaty at 29.85%. Majority (62.31%) reported hematologic adverse events following the first dose of the vaccine. The overall event rate was 0.0182 per 10,000 vaccine doses; and lymphadenopathy was the most common hematologic adverse effect with a rate of 0.011 per 10,000 vaccine doses, followed by anemia at 0.0034 per 10,000 vaccine doses and thrombocytopenia at 0.0017 per 10,000 vaccine doses. Autoimmune cytopenias were also reported with an event rate of 0.0007 per 10,000 vaccine doses for ITP. One-hundred thirty two (49.25%) were fully recovered and 23.88% were recovering from hematologic adverse events as of the time of writing. The study showed a low rate of hematologic adverse events post COVID-19 vaccination with the seven different vaccine brands administered in the Philippines.

Outcome of COVID-19 mRNA Vaccination in Patients Treated With Clozapine WHO Previously Went Through SARS-COV-2 Infection.

BACKGROUND: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had multiple consequences for the health care system, especially for patients with mental illnesses. Schizophrenia patients particularly appear to have a higher risk of complications due to coronavirus-19 (COVID-19). Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). However, the COVID-19 pandemic had an important negative impact on clozapine treatment, mainly because of its administration protocol, which was very difficult to follow during the restrictions imposed in the pandemic, and its side effects in patients with COVID-19 infection. Vaccination is an effective method of avoiding SARS-CoV-2 infection or its severe complications, especially in susceptible populations. Data on adverse events after vaccination against COVID-19 are limited, both in the general population and in schizophrenia patients. STUDY QUESTION: The study aimed to investigate the safety of COVID-19 vaccination in patients treated with clozapine for hematological parameters. STUDY DESIGN: We conducted an analytical cross-sectional study between July 1, 2021, and June 30, 2022. We compared 2 groups of COVID-19 vaccinated patients who had previously experienced SARS-CoV-2 infection: The first group was treated with clozapine, whereas the second group was treated with other antipsychotics. MEASURES AND OUTCOMES: The primary objective was to identify granulocytopenia, leukocytopenia, and lymphocytopenia. The results were measured after the second dose of the Pfizer-BioNTech vaccine. RESULTS: This study included 100 patients. White blood cell count changes were limited to a few cases of mild granulocytopenia (8.16% in the clozapine group and 3.92% in the nonclozapine group, P = 0.37) with no cases of severe granulocytopenia or agranulocytosis. CONCLUSIONS: As far as leukocyte counts are concerned, mRNA COVID-19 vaccination seems to be safe in patients treated with clozapine who previously had SARS-CoV-2 infection. Leukocyte changes had no clinical implications.

Effectiveness and safety of switching to teriflunomide in older patients with relapsing multiple sclerosis: A real-world retrospective multicenter analysis.

BACKGROUND: The prevalence of multiple sclerosis (MS) in older people is increasing due to population aging and availability of effective disease-modifying therapies (DMTs). Treating older people with MS is complicated by age-related and MS-related comorbidities, immunologic effects of prior DMTs, and immunosenescence. Teriflunomide is a once-daily oral immunomodulator that has demonstrated efficacy and acceptable safety in clinical trials of adults with relapsing forms of MS (RMS). However, there are limited clinical trial and real-world data regarding teriflunomide use in people with MS aged >55 years. We analyzed real-world data to assess the effectiveness and safety of teriflunomide in older people with RMS who had switched to this agent from other DMTs. METHODS: People with RMS (relapsing remitting and active secondary progressive MS) aged ≥55 years who had switched from other DMTs to teriflunomide (7 mg or 14 mg) for ≥1 year were identified retrospectively by chart review at four sites in the United States. Data were extracted from medical records from 1 year pre-index to 2 years post-index (index defined as the teriflunomide start date). Assessments of effectiveness included annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging (MRI) outcomes. Assessments of safety included lymphocyte counts, infections, and malignancies. We examined the effectiveness outcomes and lymphocyte counts within sub-groups defined by age (55-64, ≥65 years), sex, MS type, and prior route of DMT administration (oral, injectable, infusible). RESULTS: In total, 182 patients with RMS aged ≥55 years who switched from other DMTs to teriflunomide were identified (mean [SD] age: 62.5 [5.4] years). Mean ARR decreased from the start of teriflunomide treatment (mean [SD]: 0.43 [0.61]) to year 1 post-index (0.13 [0.65]) and year 2 post-index (0.05 [0.28]). Mean EDSS score remained unchanged from index (mean [SD]: 4.5 [1.8]) to 1 year post-treatment (4.5 [1.8]) and increased slightly at 2 years post-treatment (4.7 [1.7]). MRI scans from index and years 1 and 2 post-index compared with scans from the previous year indicated that most patients had stable or improved MRI outcomes at index (87.7%) and remained stable or improved at years 1 (96.0%) and 2 (93.6%). Lymphopenia decreased at years 1 (21.4%) and 2 post-index (14.8%, compared to index (23.5%). By 1 year post-index, fewer patients had grade 3 or 4 lymphopenia, and at 2 years post-index, there were no patients with grade 3 or 4 lymphopenia. Infection incidence was low (n = 40, 22.0%) and none were related to teriflunomide. The decreases in lymphopenia were driven by decreases among people who switched from a prior oral DMT; there were no notable differences in lymphopenia across the other sub-groups examined. ARR, EDSS score, and MRI outcomes across all sub-groups were similar to the results of the overall population. CONCLUSION: Our multicenter, longitudinal, retrospective study demonstrated that patients with RMS aged 55 or older switching to teriflunomide from other DMTs had significantly improved ARR, stable disability, and stable or improved MRI over up to 2 years' follow up. Safety results were acceptable with fewer patients exhibiting lymphopenia at years 1 and 2 post-index.

SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes (preprint)

Splicing is a highly conserved, intricate mechanism intimately linked to transcription elongation, serving as a pivotal regulator of gene expression. Alternative splicing may generate specific transcripts incapable of undergoing translation into proteins, designated as unproductive. A plethora of respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), strategically manipulate the host's splicing machinery to circumvent antiviral responses. During the infection, SARS-CoV-2 effectively suppresses interferon (IFN) expression, leading to B cell and CD8+ T cell leukopenia, while simultaneously increasing the presence of macrophages and neutrophils in patients with severe COVID-19. In this study, we integrated publicly available omics datasets to systematically analyze transcripts at the isoform level and delineate the nascent-peptide translatome landscapes of SARS-CoV-2-infected human cells. Our findings reveal a hitherto uncharacterized mechanism whereby SARS-CoV-2 infection induces the predominant expression of unproductive splicing isoforms in key IFN signaling genes, interferon-stimulated genes (ISGs), class I MHC genes, and splicing machinery genes, including IRF7, OAS3, HLA-B, and HNRNPH1. In stark contrast, cytokine and chemokine genes, such as IL6, CXCL8, and TNF, predominantly express productive (protein-coding) splicing isoforms in response to SARS-CoV-2 infection. We postulate that SARS-CoV-2 employs a previously unreported tactic of exploiting the host splicing machinery to bolster viral replication and subvert the immune response by selectively upregulating unproductive splicing isoforms from antigen presentation and antiviral response genes. Our study sheds new light on the molecular interplay between SARS-CoV-2 and the host immune system, offering a foundation for the development of novel therapeutic strategies to combat COVID-19.

Treatment of Infants and Children With SARS-CoV-2 Monoclonal Antibodies: A European Case Series.

BACKGROUND: Although severe COVID-19 in children is rare, those with certain pre-existing health conditions are more prone to severe disease. Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are potent antiviral agents that reduce adverse clinical outcomes in adults, but are commonly not approved for use in pediatric patients. METHODS: We retrospectively evaluated mAb treatment in children <12 years of age or <40kg with SARS-CoV-2 infection between January 1, 2021, and March 7, 2022, in 12 tertiary care centers in 3 European countries. RESULTS: We received data from 53 patients from Austria, Denmark and Germany. Median age was 5.4 years [0-13.8, interquartile range (IQR) = 6.2], and median body weight was 20 kg (3-50.1, IQR = 13). The most frequent SARS-CoV-2 variant in this study, if known, was Omicron, followed by Delta and Alpha. Pre-existing conditions included immunodeficiency, malignancy, hematologic disease, cardiac disease, chronic lung disease, chronic liver disease, kidney disease and diabetes. Forty-two patients received sotrovimab (79%), 9 casirivimab/imdevimab (17%) and 2 bamlanivimab (4%). All but 1 patient survived. Median duration of hospital stay was 3 days (0-56, IQR = 6). Seven patients required treatment in an intensive care unit, and 5 required high-flow nasal cannula treatment. Potential side effects included neutropenia (6/53, 11%), lymphopenia (3/53, 6%), nausea or vomiting (2/53, 4%), rise of alanine transaminase (1/53, 2%) and hypotonia (1/53, 2%). CONCLUSIONS: MAb treatment was well tolerated by children in this cohort.

Use of Remdesivir in children with COVID-19: report of an Italian multicenter study (preprint)

Introduction COVID-19 is generally milder in children than in adults, however severe infection has been described in some patients. Few data are available on use of Remdesivir (RDV) in children, as most clinical trials focused on adult patients. We report a multicenter study to investigate the safety of RDV in children affected by COVID-19.Methods We collected the clinical data of children with COVID-19 treated with RDV between March 2020 and February 2022 in 10 Italian hospitals. Clinical data were compared according to the duration of RDV therapy. Linear and logistic regression models were used to determine the association of significant variables from the bivariate analysis to the duration of RDV therapy.Results A total of 50 patients were included, with a median age of 12.8 years. Many patients had at least one comorbidity (78%), mostly obesity. Symptoms were fever (88%), cough (74%) and dyspnea (68%). Most patients were diagnosed with pneumonia of either viral and/or bacterial etiology. Blood test showed leukopenia in 66% and increased C-reactive protein (CRP) levels in 63% of cases. Thirty-six patients received RDV for 5 days, nine patients up to 10 days. Most children who received RDV longer were admitted to the PICU (67%). Treatment with RDV was well tolerated with rare side effects (Table 1): bradycardia was recorded in 6% of cases, solved in less than 24 hours after discontinuation. A mild elevation of transaminases was observed in 26% of cases, however for the 8%, it was still detected before the RDV administration. Therefore, in these cases, we could not establish if it was caused by COVID-19, RDV o both. Patients who received RDV for more than 5 days waited longer for its administration after pneumonia diagnosis. The presence of comorbidities and the duration of O2 administration significantly correlated with the duration of RDV therapy at the linear regression analysis.Conclusion Our experience indicates that RDV against SARS-CoV-2 is safe and well-tolerated in pediatric populations at high risk of developing severe COVID-19. Our data suggest that delaying RDV therapy after diagnosis of pneumonia may be associated with a longer duration of antiviral therapy, especially in patients with comorbidities.

A Variant Mutation in the gene encoding Mitochondrial Seryl-tRNA Synthetase Cause HUPRA Syndrome with Atypical Presentation-A Case Report (preprint)

Background Hyperuricemia, pulmonary hypertension, renal failure, and alkaline intoxication syndrome (HUPRA syndrome) is a rare autosomal recessive mitochondrial disease with prevalence of less than one in a million. Due to mutations in the mitochondrial SARS enzyme encoding seryl-tRNA synthetase on chromosome 19 (19q13.2). Case–Diagnosis/Treatment We investigated two Palestinian girls from the same village presented with progressive renal failure in infancy were diagnosed with this multisystemic disease. presented with atypical clinical manifestations of HUPRA syndrome include leukopenia, anemia, salt wasting resulting in hyponatremia and hypochloremia, renal failure with elevated blood lactate, marked hyperuricemia, hypercholesterolemia and hypertriglyceridemia but  without  pulmonary hypertension or alkaline intoxication that distinguish them from the rest of the usual cases, instead they showed acidosis in routine follow up. By using single exome sequencing analysis, we identified a two homozygous pathogenic mutation c.1175A>G (p.D392G), c.1169A>G (D390G) in SARS2 gene. This sequence identified a new variant mutation of HUPRA syndrome c.1175A>G (p.D392G) with atypical presentation, that will be added to the literature. Conclusion SARS2 gene with pathogenic homozygous mutation variants were detected in our two patients c.1175A>G (p.D392G), c.1169A>G (D390G) in exon 13, with atypical clinical manifestations of HUPRA syndrome, expanding the spectrum of SARS2 pathogenic variants with its characteristic findings, describing the differences in clinical manifestations between homozygous and compound heterozygous mutations.

Length of hospital stay and risk factors associated with prognosis in COVID-19 patients: surprising results.

OBJECTIVE: In this study, we aimed to investigate the risk factors that may affect the prognosis and length of hospital stay of COVID-19 patients, particularly immunoglobulin A. MATERIALS AND METHODS: Patients admitted to the relevant department or intensive care unit with a diagnosis of COVID-19 between April 2020 and January 2021 were included in the study. Demographic characteristics of the patients and blood type, immunoglobulin A (IgA), C-reactive protein, D-dimer, procalcitonin, ferritin, troponin I, complete blood count, biochemical, and COVID-19 (SARS-CoV-2) reverse transcription polymerase chain reaction test results were evaluated retrospectively from the hospital files and data system. RESULTS: A total of 164 COVID-19 patients were included in this study. The median age was 72 (range: 30-95) years and the gender distribution of women and men was 66/98 (40.2% vs. 59.8%, respectively). There was no statistically significant relationship between blood type and hospitalization time or mortality (p=0.497 and p=0.923, respectively). There was furthermore no statistically significant relationship between Rh group and the duration of hospitalization or prognosis (p=0.198 and p=0.827, respectively). There was no statistically significant correlation between IgA level and hospitalization time or prognosis (p=0.066, r=0.144). In the analysis of defined risk factors independently associated with death, the following were found to be significant indicators of mortality: leukopenia [beta: -2.973, OR (95% CI): 0.051 (0.003-0.891), p=0.041], glucose [beta: 0.014, OR (95% CI): 1.014 (1.001-1.028), p=0.037], D-dimer [beta: 0.001, OR (95% CI): 1.001 (1.000-1.001), p=0.023], duration of hospitalization [beta: -0.218, OR (95% CI): 0.804 (0.708-0.913), p=0.001], and duration of stay in the intensive care unit [beta: 0.348, OR (95% CI): 1.416 (1.186-1.690), p<0.001]. CONCLUSIONS: In our study, no relationship was found between IgA level and hospitalization time or mortality among COVID-19 patients. However, leukopenia and increased glucose, D-dimer, neutrophil count, urea, and durations of hospital and intensive care stays were found to be important predictors of mortality.

Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-March 31, 2022 (preprint)

Objectives: To understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai. Study designs: This study included local COVID-19 cases<18 years in Shanghai referred to the exclusively designated hospital by the end of March 2022 since emergence of Omicron epidemic. Clinical data, epidemiological exposure and COVID-19 vaccination status were collected. Relative risks (RR) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease. Results: A total of 376 pediatric cases of COVID-19 (median age:6.0±4.2 years) were referred to the designated hospital during the period of March 7-31, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children ≥3 years eligible for COVID-19 vaccination, 110 (40.4%) received 2-dose vaccines and 16 (4.0%) received 1-dose vaccine. The median interval between 2-dose vaccination and infection was 3.5 (IQR: 3, 4.5) months (16 days-7 months). Two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35%(RR 0.65, 95% CI: 0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81). Two hundred and sixteen (83.4%) symptomatic cases had fever (mean duration:1.7±1.0.8 days), 104 (40.2%) had cough, 16.4% had transient leukopenia; 307 (81.6%) had an epidemiological exposure in household (69.1%) , school (21.8%) and residential area (8.8%). Conclusion: The surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer some protection against symptomatic infection and febrile dise

A study to evaluate the role of eosinophil count as a prognostic marker for assessing the outcome in patients with COVID 19 infection.

The triaging of COVID 19 patients is of paramount importance to plan further management. There are several clinical and laboratory parameters that help in categorizing the disease severity, triaging, and prognostication. Little is known about the prognostic significance of eosinopenia in predicting the severity of COVID 19 from large hospital data especially from low- and middle-income countries. The objective of this study is to evaluate the level of eosinopenia as an early prognostic marker for assessing the outcomes in COVID 19 patients and to assess the superiority of eosinopenia as a prognostic marker for assessing the outcomes in COVID 19 patients compared to lymphopenia and neutrophil: lymphocyte ratio (NLR). MATERIAL: The study was carried out in a tertiary care hospital. A retrospective longitudinal approach was adopted wherein the hospital records of COVID 19 patients were analysed. Two separate groups of patients were included for analysis to describe the association between initial eosinophil counts of the patients and the clinical outcomes. In the first group, the disease severity in terms of clinical and radiological parameters was compared in patients of COVID 19 presenting with and without the presence of initial eosinopenia. Commonly used markers for triage namely lymphopenia and NLR were compared with the presence of initial eosinopenia among the patients who progressed to moderate and severe disease. In the second group, an analysis of eosinopenia was made among the patients who succumbed to the illness. OBSERVATION: It was seen that 29.6% of patients with eosinopenia had moderate and severe disease compared to those without eosinopenia where only 10.8 % had moderate disease, none had severe disease. It was seen that 19.7% of patients with eosinopenia but no lymphopenia had more severe disease compared to patients with lymphopenia but no eosinopenia where 10.8% of the patients had moderate disease, none had severe disease. In patients younger than 60 years who died of COVID 19, it was found that initial eosinopenia was found in 86 % whereas a high neutrophil: lymphocyte ratio >17 was seen in only 25.6% of patients who died. Thus, implying that is eosinopenia is an important marker of disease severity in COVID 19. CONCLUSION: Eosinopenia is an important parameter in the evaluation of COVID 19 and the presence of it should alert the clinicians regarding the further progression of the disease. It is not only an important marker but also an early marker for severe disease.

Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-March 31, 2022 (preprint)

Objectives: To understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai. Methods: This study included local COVID-19 cases <18 years in Shanghai referred to the exclusively designated hospital by the end of March 2022 since emergence of Omicron epidemic. Clinical data, epidemiological exposure and COVID-19 vaccination status were collected. Relative risks (RR) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease. Results: A total of 376 pediatric cases of COVID-19 (median age:6.0{+/-}4.2 years) were referred to the designated hospital during the period of March 7-31, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children;3 years eligible for COVID-19 vaccination, 110 (40.4%) received 2-dose vaccines and 16 (4.0%) received 1-dose vaccine. The median interval between 2-dose vaccination and infection was 3.5 (IQR: 3, 4.5) months (16 days-7 months). Two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35% (RR 0.65, 95% CI:0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81). Two hundred and sixteen (83.4%) symptomatic cases had fever (mean duration: 1.7{+/-}1.0.8 days), 104 (40.2%) had cough, 16.4% had transient leukopenia; 307 (81.6%) had an epidemiological exposure in household (69.1%), school (21.8%) and residential area (8.8%). Conclusion: The surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer protection against symptomatic infection and febrile disease.

Clozapine and COVID-19 Vaccination: Effects on blood levels and leukocytes. An observational cohort study.

OBJECTIVE: To investigate the safety of COVID-19 vaccination in patients on clozapine as regards plasma clozapine concentration and haematological parameters. METHODS: We conducted a multicentre observational cohort study from 22 February 2021 to 2 September 2021. Primary outcomes were clinically relevant increase in clozapine blood levels (>100 µg/L increase compared to baseline) and clozapine alert levels (>1000 µg/L). Secondary outcomes were granulocytopenia, leukocytopenia and lymphocytopenia. Outcomes were measured approximately 5 days after the first and (where applicable) second dose of COVID-19 vaccine. RESULTS: This study included 139 patients. Compared to baseline, clozapine blood levels increased significantly (ES = 0.28, p = 0.003) after the second vaccination. Clinically relevant increases in clozapine blood levels occurred in 20/92 patients (22%) and in 16/56 patients (29%) during the first and second phases, respectively. Clozapine alert levels developed in one patient (1%) following the first dose and in three patients (5%) after the second dose. In both phases, changes in white blood cells (WBC) were limited to mild granulocytopenia (3% and 5%), moderate granulocytopenia (1% and 0%) and leukocytopenia (2% and 3%) without cause for extra monitoring according to the guideline. CONCLUSION: In general, as regards WBC counts COVID-19 vaccination seems to be safe in patients with SMI. Changes in WBC had no clinical implications. Psychoeducation on the symptoms of clozapine intoxication is recommended, especially in patients with clozapine blood levels approaching the upper limit of the therapeutic range. Increase in the C-reactive protein (CRP) level can signal inflammation rapidly and help to prevent clozapine intoxication following vaccination.