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BACKGROUND: Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken. OBJECTIVES: To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness. METHODS: For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction. RESULTS: Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases. CONCLUSION: Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).
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Background: Tixagevimab/cilgavimab (TGM/CGM) are neutralizing monoclonal antibodies (mAbs) directed against different epitopes of the receptor-binding domain of the SARS-CoV-2 spike protein that have been considered as pre-exposure prophylaxis (PrEP). Objectives: This study seeks to assess the efficacy and safety of TGM/CGM to prevent COVID-19 in patients at high risk for breakthrough and severe SARS-CoV-2 infection who never benefited maximally from SARS-CoV-2 vaccination and for those who have a contraindication to SARS-CoV-2 vaccines. Design: This study is a systematic review and meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed. Methods: Electronic databases (PubMed, CINAHL, Embase, medRxiv, ProQuest, Wiley online library, Medline, and Nature) were searched from 1 December 2021 to 30 November 2022 in the English language using the following keywords alone or in combination: 2019-nCoV, 2019 novel coronavirus, COVID-19, coronavirus disease 2019, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, tixagevimab, cilgavimab, combination, monoclonal, passive, immunization, antibody, efficacy, clinical trial, cohort, pre-exposure, prophylaxis, and prevention. We included studies in moderate to severe immunocompromised adults (aged ≥18 years) and children (aged ≥12 years) who cannot be vaccinated against COVID-19 or may have an inadequate response to SARS-CoV-2 vaccination. The effect sizes of the outcome of measures were pooled with 95% confidence intervals (CIs) and risk ratios (RRs). Results: Of the 76 papers that were identified, 30 articles were included in the qualitative analysis and 13 articles were included in the quantitative analysis (23 cohorts, 5 case series, 1 care report, and 1 randomized clinical trial). Studies involving 27,932 patients with high risk for breakthrough and severe COVID-19 that reported use of TGM/CGM combination were analyzed (all were adults (100%), 62.8% were men, and patients were mainly immunocompromised (66.6%)). The patients' ages ranged from 19.7 years to 79.8 years across studies. TGM/CGM use was associated with lower COVID-19-related hospitalization rate (0.54% vs. 1.2%, p = 0.27), lower ICU admission rate (0.6% vs. 5.2%, p = 0.68), lower mortality rate (0.2% vs. 1.2%, p = 0.67), higher neutralization of COVID-19 Omicron variant rate (12.9% vs. 6%, p = 0.60), lower proportion of patients who needed oxygen therapy (8% vs. 41.2%, p = 0.27), lower RT-PCR SARS-CoV-2 positivity rate (2.1% vs. 5.8%, p < 0.01), lower proportion of patients who had severe COVID-19 (0% vs. 0.5%, p = 0.79), lower proportion of patients who had symptomatic COVID-19 (1.8% vs. 6%, p = 0.22), and higher adverse effects rate (11.1% vs. 10.7%, p = 0.0066) than no treatment or other alternative treatment in the prevention of COVID-19. Conclusion: For PrEP, TGM/CGM-based treatment can be associated with a better clinical outcome than no treatment or other alternative treatment. However, more randomized control trials are warranted to confirm our findings and investigate the efficacy and safety of TGM/CGM to prevent COVID-19 in patients at risk for breakthrough or severe SARS-CoV-2 infection.
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Background: Intussusception (ISN) post-COVID-19 infection in children is rare but can occur. SARS-CoV-2 may play a role in the pathogenesis of ISN and trigger immune activation and mesenteric adenitis, which predispose peristaltic activity to "telescope" a proximal bowel segment into the distal bowel lumen. Objectives: To estimate the prevalence of SARS-CoV-2 infection in ISN children and analyze the demographic parameters, clinical characteristics and treatment outcomes in ISN pediatric patients with COVID-19 illness. Methods: We performed this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies reporting on the incidence of ISN post-SARS-CoV-2 infection in children, published from 1 December 2019 until 1 October 2022, in PROQUEST, MEDLINE, EMBASE, PUBMED, CINAHL, WILEY ONLINE LIBRARY, SCOPUS and NATURE, with a restriction to articles available in the English language, were included. Results: Of the 169 papers that were identified, 34 articles were included in the systematic review and meta-analysis (28 case report, 5 cohort and 1 case-series studies). Studies involving 64 ISN patients with confirmed COVID-19 (all patients were children) were analyzed. The overall pooled proportions of the ISN patients who had PCR-confirmed SARS-CoV-2 infection was 0.06% (95% CI 0.03 to 0.09, n = 1790, four studies, I2 0%, p = 0.64), while 0.07% (95% CI 0.03 to 0.12, n = 1552, three studies, I2 0%, p = 0.47) had success to ISN pneumatic, hydrostatic and surgical reduction treatment and 0.04% (95% CI 0.00 to 0.09, n = 923, two studies, I2 0%, p = 0.97) had failure to ISN pneumatic, hydrostatic and surgical reduction treatment. The median patient age ranged from 1 to 132 months across studies, and most of the patients were in the 1−12 month age group (n = 32, 50%), p = 0.001. The majority of the patients were male (n = 41, 64.1%, p = 0.000) and belonged to White (Caucasian) (n = 25, 39.1%), Hispanic (n = 13, 20.3%) and Asian (n = 5, 7.8%) ethnicity, p = 0.000. The reported ISN classifications by location were mostly ileocolic (n = 35, 54.7%), and few children experienced ileo-ileal ISN (n = 4, 6.2%), p = 0.001. The most common symptoms from ISN were vomiting (n = 36, 56.2%), abdominal pain (n = 29, 45.3%), red currant jelly stools (n = 25, 39.1%) and blood in stool (n = 15, 23.4%). Half of the patients never had any medical comorbidities (n = 32, 50%), p = 0.036. The approaches and treatments commonly used to manage ISN included surgical reduction of the ISN (n = 17, 26.6%), pneumatic reduction of the ISN (n = 13, 20.2%), antibiotics (n = 12, 18.7%), hydrostatic reduction of the ISN (n = 11, 17.2%), laparotomy (n = 10, 15.6%), intravenous fluids (n = 8, 12.5%) and surgical resection (n = 5, 7.8%), p = 0.051. ISN was recurrent in two cases only (n = 2, 3.1%). The patients experienced failure to pneumatic (n = 7, 10.9%), hydrostatic (n = 6, 9.4%) and surgical (n = 1, 1.5%) ISN treatment, p = 0.002. The odds ratios of death were significantly higher in patients with a female gender (OR 1.13, 95% CI 0.31−0.79, p = 0.045), Asian ethnicity (OR 0.38, 95% CI 0.28−0.48, p < 0.001), failure to pneumatic or surgical ISN reduction treatment (OR 0.11, 95% CI 0.05−0.21, p = 0.036), admission to ICU (OR 0.71, 95% CI 0.83−1.18, p = 0.03), intubation and placement of mechanical ventilation (OR 0.68, 95% CI 0.51−1.41, p = 0.01) or suffering from ARDS (OR 0.88, 95% CI 0.93−1.88, p = 0.01) compared to those who survived. Conclusion: Children with SARS-CoV-2 infection are at low risk to develop ISN. A female gender, Asian ethnicity, failure to ISN reduction treatment (pneumatic or surgical), admission to ICU, mechanical ventilation and suffering from ARDS were significantly associated with death following ISN in pediatric COVID-19 patients.
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Background: Coinfection with bacteria, fungi, and respiratory viruses has been described as a factor associated with more severe clinical outcomes in children with COVID-19. Such coinfections in children with COVID-19 have been reported to increase morbidity and mortality. Objectives: To identify the type and proportion of coinfections with SARS-CoV-2 and bacteria, fungi, and/or respiratory viruses, and investigate the severity of COVID-19 in children. Methods: For this systematic review and meta-analysis, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus, and Nature through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies on the incidence of COVID-19 in children with bacterial, fungal, and/or respiratory coinfections, published from 1 December 2019 to 1 October 2022, with English language restriction. Results: Of the 169 papers that were identified, 130 articles were included in the systematic review (57 cohort, 52 case report, and 21 case series studies) and 34 articles (23 cohort, eight case series, and three case report studies) were included in the meta-analysis. Of the 17,588 COVID-19 children who were tested for co-pathogens, bacterial, fungal, and/or respiratory viral coinfections were reported (n = 1633, 9.3%). The median patient age ranged from 1.4 months to 144 months across studies. There was an increased male predominance in pediatric COVID-19 patients diagnosed with bacterial, fungal, and/or viral coinfections in most of the studies (male gender: n = 204, 59.1% compared to female gender: n = 141, 40.9%). The majority of the cases belonged to White (Caucasian) (n = 441, 53.3%), Asian (n = 205, 24.8%), Indian (n = 71, 8.6%), and Black (n = 51, 6.2%) ethnicities. The overall pooled proportions of children with laboratory-confirmed COVID-19 who had bacterial, fungal, and respiratory viral coinfections were 4.73% (95% CI 3.86 to 5.60, n = 445, 34 studies, I2 85%, p < 0.01), 0.98% (95% CI 0.13 to 1.83, n = 17, six studies, I2 49%, p < 0.08), and 5.41% (95% CI 4.48 to 6.34, n = 441, 32 studies, I2 87%, p < 0.01), respectively. Children with COVID-19 in the ICU had higher coinfections compared to ICU and non-ICU patients, as follows: respiratory viral (6.61%, 95% CI 5.06−8.17, I2 = 0% versus 5.31%, 95% CI 4.31−6.30, I2 = 88%) and fungal (1.72%, 95% CI 0.45−2.99, I2 = 0% versus 0.62%, 95% CI 0.00−1.55, I2 = 54%); however, COVID-19 children admitted to the ICU had a lower bacterial coinfection compared to the COVID-19 children in the ICU and non-ICU group (3.02%, 95% CI 1.70−4.34, I2 = 0% versus 4.91%, 95% CI 3.97−5.84, I2 = 87%). The most common identified virus and bacterium in children with COVID-19 were RSV (n = 342, 31.4%) and Mycoplasma pneumonia (n = 120, 23.1%). Conclusion: Children with COVID-19 seem to have distinctly lower rates of bacterial, fungal, and/or respiratory viral coinfections than adults. RSV and Mycoplasma pneumonia were the most common identified virus and bacterium in children infected with SARS-CoV-2. Knowledge of bacterial, fungal, and/or respiratory viral confections has potential diagnostic and treatment implications in COVID-19 children.
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BACKGROUND: Patients with colorectal cancer (CRC) are more likely to develop severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and experience increased risk of mortality compared to SARS-CoV-2 patients without CRC. OBJECTIVES: To estimate the prevalence of SARS-CoV-2 infection in CRC patients and analyse the demographic parameters, clinical characteristics and treatment outcomes in CRC patients with COVID-19 illness. METHODS: For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature for studies on the incidence of SARS-CoV-2 infection in CRC patients, published from December 1, 2019 to December 31, 2021, with English language restriction. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). Sub-group analyses were performed to minimize heterogeneity. Binary logistic regression model was used to explore the effect of various demographic and clinical characteristics on patient's final treatment outcome (survival or death). RESULTS: Of the 472 papers that were identified, 69 articles were included in the systematic review and meta-analysis (41 cohort, 16 case-report, 9 case-series, 2 cross-sectional, and 1 case-control studies). Studies involving 3362 CRC patients with confirmed SARS-CoV-2 (all patients were adults) were analyzed. The overall pooled proportions of CRC patients who had laboratory-confirmed community-acquired and hospital-acquired SARS-CoV-2 infections were 8.1% (95% CI 6.1 to 10.1, n = 1308, 24 studies, I2 98%, p = 0.66), and 1.5% (95% CI 1.1 to 1.9, n = 472, 27 studies, I2 94%, p < 0.01). The median patient age ranged from 51.6 years to 80 years across studies. The majority of the patients were male (n = 2243, 66.7%) and belonged to White (Caucasian) (n = 262, 7.8%), Hispanic (n = 156, 4.6%) and Asian (n = 153, 4.4%) ethnicity. The main source of SARS-CoV-2 infection in CRC patients was community-acquired (n = 2882, 85.7%; p = 0.014). Most of those SARS-CoV-2 patients had stage III CRC (n = 725, 21.6%; p = 0.036) and were treated mainly with surgical resections (n = 304, 9%) and chemotherapies (n = 187, 5.6%), p = 0.008. The odd ratios of death were significantly high in patients with old age (≥ 60 years) (OR 1.96, 95% CI 0.94-0.96; p < 0.001), male gender (OR 1.44, 95% CI 0.41-0.47; p < 0.001) CRC stage III (OR 1.54, 95% CI 0.02-1.05; p = 0.041), CRC stage IV (OR 1.69, 95% CI 0.17-1.2; p = 0.009), recent active treatment with chemotherapies (OR 1.35, 95% CI 0.5-0.66; p = 0.023) or surgical resections (OR 1.4, 95% CI 0.8-0.73; p = 0.016) and admission to ICU (OR 1.88, 95% CI 0.85-1.12; p < 0.001) compared to those who survived. CONCLUSION: SARS-CoV-2 infection in CRC patient is not uncommon and results in a mortality rate of 26.2%. Key determinants that lead to increased mortality in CRC patients infected with COVID-19 include older age (≥ 60 years old); male gender; Asian and Hispanic ethnicity; if SARS-CoV-2 was acquired from hospital source; advanced CRC (stage III and IV); if patient received chemotherapies or surgical treatment; and if patient was admitted to ICU, ventilated or experienced ARDS.
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BACKGROUND: COVID-19 is a worldwide pandemic and has placed significant demand for acute and critical care services on hospitals in many countries. OBJECTIVES: To determine the predictors of severe COVID-19 disease requiring admission to an ICU by comparing patients who were ICU admitted to non-ICU groups. METHODS: A cohort study was conducted for the laboratory-confirmed COVID-19 patients who were admitted to six Saudi Ministry of Health's hospitals in Alahsa, between March 1, 2020, and July 30, 2020, by reviewing patient's medical records retrospectively. RESULTS: This cohort included 1014 patients with an overall mean age of 47.2 ± 19.3 years and 582 (57%) were males. A total of 205 (20%) of the hospitalized patients were admitted to the ICU. Hypertension, diabetes and obesity were the most common comorbidities in all study patients (27.2, 19.9, and 9%, respectively). The most prevalent symptoms were cough (47.7%), shortness of breath (35.7%) and fever (34.3%). Compared with non-ICU group, ICU patients had older age (p ≤ 0.0005) and comprised a higher proportion of the current smokers and had higher respiratory rates (p ≤ 0.0005), and more percentage of body temperatures in the range of 37.3-38.0 °C (p ≥ 0.0005); and had more comorbidities including diabetes (p ≤ 0.0005), hypertension (p ≥ 0.0005), obesity (p = 0.048), and sickle cell disease (p = 0.039). There were significant differences between the non-ICU and ICU groups for fever, shortness of breath, cough, fatigue, vomiting, dizziness; elevated white blood cells, neutrophils, alanine aminotransferase and alkaline aminotransferase, lactate dehydrogenase, and ferritin, and decreased hemoglobin; and proportion of abnormal bilateral chest CT images (p < 0.05). Significant differences were also found for multiple treatments (p < 0.05). ICU patients group had a much higher mortality rate than those with non-ICU admission (p ≤ 0.0005). CONCLUSION: Identifying key clinical characteristics of COVID-19 that predict ICU admission and high mortality can be useful for frontline healthcare providers in making the right clinical decision under time-sensitive and resource-constricted environment.
