How international guidelines recommend treating children who have severe COVID-19 or risk disease progression.

AIM: This study reviewed the current knowledge and guidelines on managing COVID-19 in children and proposed a practical approach to drug treatment. METHODS: We analysed international guidelines from four prominent scientific bodies on treating COVID-19 in children. These were the UK National Institute for Health and Care Excellence, the American National Institutes of Health, the Infectious Diseases Society of America and the Australian National Clinical Evidence Taskforce COVID-19. RESULTS: Most paediatric patients with COVID-19 only require symptomatic treatment. There was limited evidence on treatment recommendations for children with severe COVID-19 or at risk of disease progression. However, several drugs are available for children and we have summarised the guidelines, in order to provide a concise, practical format for clinicians. All the guidelines agree that nirmatrelvir plus ritonavir or remdesivir can be used as prophylaxis for severe COVID-19 in high-risk patients. Remdesivir can also be used for severe COVID-19 cases. Glucocorticosteroids are recommended, particularly in patients requiring oxygen therapy. Tocilizumab or baricitinib should be reserved for patients with progressive disease and/or signs of systemic inflammation. CONCLUSION: The guidelines provide useful advice and a degree of consensus on specific drug treatment for children with severe COVID-19 or at risk of progression.

SARS-CoV-2 Cluster in Nursery, Poland.

We report a cluster of surprisingly high spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with a single nursery in Poland. Our findings contrast with the presumed negligible role of children in driving the SARS-CoV-2 pandemic. Children 1-2 years of age might be effective SARS-CoV-2 spreaders.

Recurrent assessment of lymphocyte subsets in 32 patients with multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND: Lymphopenia is a hallmark of multisystem inflammatory syndrome in children (MIS-C). We aimed to characterize lymphocyte subsets' shifts and their correlations with other severity markers of MIS-C. METHODS: In this prospective cross-sectional study, we performed peripheral lymphocyte phenotyping in 32 patients with MIS-C. We analyzed lymphocyte subsets at three time points of the disease: the acute (A), convalescent (B), and recovery (C) phases. Based on age-normalized lymphocyte counts, we distinguished two groups of patients: "the mild" (higher lymphocyte counts) and "the severe" (lower lymphocyte counts). In addition, we examined differences between these groups regarding other severity markers. RESULTS: In phase A, 84% of children had lymphopenia. Decreased absolute counts of CD3, CD4, and CD8 cells were observed in, respectively, 88%, 72%, and 84% of patients. The natural killer cells were decreased in 63% and CD19 in 59% of children. "The severe" group had significantly higher procalcitonin and troponin I levels and lower platelets and albumin. Moreover, "the severe" group had hypotension more frequently (73% vs. 20%, p = .008). In phase B, all lymphocyte counts increased, and 32% of children had lymphocytosis. The increase of CD3, CD4, and CD8 counts correlated with some laboratory severity markers (hemoglobin, procalcitonin, D-dimer, lactate dehydrogenase, N-terminal prohormone of brain natriuretic peptide, albumin), but not with steroid use. In phase C, most children had normal lymphocyte counts. CONCLUSIONS: Substantial shifts in lymphocyte counts during MIS-C apply most to T lymphocytes and correlate with the disease severity markers, particularly hypotension prevalence. A proportion of children with MIS-C develops transient lymphocytosis during convalescence.

Pathologic Analysis of Twenty-one Appendices From Children With Multisystem Inflammatory Syndrome Compared to Specimens of Acute Appendicitis: A Cross-sectional Study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining the pathomechanism of MIS-C, including the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion. We aimed to examine appendectomy specimens from MIS-C patients and assess their pathologic features, as well as the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. METHODS: In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histologic evaluation of appendiceal specimens included hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein-1 (PD-1) and SARS-CoV-2 nucleocapsid antigen. RESULTS: Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14% vs. 95%, P < 0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (P = 0.04), as was the proportion of CD4+ to CD8+ (P < 0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients. CONCLUSIONS: The appendiceal muscularis of patients with MIS-C lack edema and neutrophilic infiltration typical for AA. SARS-CoV-2 antigens and PD-1 are absent in the appendices of children with MIS-C. These findings argue against the central role of SARS-CoV-2 persistence in the gut and lymphocyte exhaustion as the major triggers of MIS-C.

Ukrainian War Refugee Children With Particularly Severe Viral Infections: A Case Series Report.

The humanitarian crisis in Ukraine in 2022 led to a massive migration of refugees to Poland. Immigrant children, living in overcrowded humanitarian hubs, were exposed to multiple stressful factors likely affecting their immune systems. This case series study aimed to describe a particularly severe course of common viral infections, in Ukrainian refugee children. We present 2 case series of Ukrainian refugee children: 5 hospitalized due to either adenovirus (AdV) and 8 with rotavirus (RV) infection, admitted within 3 months in each case series, recruited retrospectively. Most patients lived in humanitarian hubs and were neglected on admission (dehydrated, with poor hygiene and anxious). All RV infection cases had symptoms of severe gastroenteritis requiring intravenous rehydration. Metabolic acidosis was present in 6 children, and hypoglycemia in 4 participants. None of them were vaccinated against RV. All children with AdV infection had prolonged fever, dyspnea requiring oxygen therapy and hyperinflammation. In 2 AdV infection cases with no clinical improvement and increasing inflammatory markers, intravenous immunoglobulins and glucocorticosteroids were used. The combination of stressful factors and living in overcrowded hubs during the high prevalence of viral infections led to a particularly severe course of viral infections in Ukrainian refugee children.

Monte Carlo Regression for Evaluating Children's Role in the Pandemic Spread on the Example of Delta COVID-19 Wave.

BACKGROUND: The children's role in transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the familial settings is uncertain. We aimed to assess how often children were the index cases transmitting SARS-CoV-2 into their households during the Delta wave, and to identify risk factors of children being the index case. METHODS: In this prospective survey study, we collected information regarding household members of SARS-CoV-2-positive children tested in a single tertiary hospital. Some patients were tested with polymerase chain reaction and those samples were typed and classified as Delta or non-Delta variant. We have used the Monte Carlo approach to assess predictors of children being the index case in the household. RESULTS: We surveyed 629 families and 515 of them fulfilled inclusion criteria. The child was the index case in 359 (69.71%) households. Attending childcare facilities in all age groups was positively associated with being the index case in the household [nursery, estimate = 1.456, 95% confidence interval (CI): 1.456-1.457, P < 0.001; kindergarten, estimate = 0.899, 95% CI: 0.898-0.900, P = 0.003; school, estimate = 1.23, 95% CI: 1.229-1.231, P = 0.001]. The same association was present in the subgroup of the families with the predominant Delta variant, but not in the subgroup with the predominant non-Delta variant. CONCLUSIONS: Attending childcare and educational facilities might be a significant predictor of a child being the SARS-CoV-2 index case in their household. Children's role in driving the SARS-CoV-2 pandemic changes in consecutive waves. The Monte Carlo approach can be applied to assess risk factors of infectious agents' spread in future epidemics.