ABSTRACT
Background: Blood cancer is the most common type of cancer and the leading cause of death by disease past infancy among children. Children with blood cancer are vulnerable population to viral infections such as coronavirus disease 2019 (COVID-19). Objectives: To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in blood cancer children and analyse the demographic parameters, clinical characteristics and treatment outcomes in blood cancer children 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 blood cancer, published from December 1, 2019 to April 30, 2023, with English language restriction. Results: Of the 3077 papers that were identified, 155 articles were included in the systematic review (83 case report, 54 cohort and 18 case-series studies). Studies involving 1289 blood cancer children with confirmed COVID-19 were analysed. Leukaemias (1141 cases) were the most frequent types of blood cancer observed in children who developed COVID-19, followed by non-Hodgkin’s lymphomas (59 cases), Hodgkin’s lymphomas (36 cases), Langerhans cell histiocytosis (7 cases), myelodysplastic syndrome (7 cases) and myeloid neoplasm (1 case). Among all 1289 blood cancer paediatric cases who transmitted SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 175, 13.6%), intubated and placed on mechanical ventilation (n = 111, 8.6%), suffered acute respiratory distress syndrome (n = 144, 11.2%) or died (n = 111, 8.6%). Overall, COVID-19 in children with different types of blood cancer resulted in no or low severity of disease in more than 78.6% of all included cases (COVID-19 severity: asymptomatic = 239, mild = 603, or moderate = 171). Treatment for COVID-19 was not necessary in a high number of blood cancer children (n = 94, 7.3%). Fatality in blood cancer children with COVID-19 was reported in any of the included blood cancer categories for leukaemias (n = 99, 8.7%), non-Hodgkin’s lymphomas (n = 7, 11.9%), Hodgkin’s lymphomas (n = 2, 5.5%), myelodysplastic syndrome (n = 1, 14.3%) or myeloid neoplasm (n = 1, 100%). Fatality rate in blood cancer children infected with SARS-CoV-2 was the highest in patients with Hispanic ethnicity (n = 44/111, 39.6%) and COVID-19–related fatality was highest in male patients (76.5% of deceased patients). Most studies reported to alter the intensity and regimen of anticancer treatment in blood cancer children during course of SARS-CoV-2 infection, however, many studies have reported to successfully treat COVID-19 without any changes to the anticancer treatment. Conclusion: Globally, leukaemias were the most prevalent and myeloid neoplasms were the least prevalent blood cancer types in children who developed SARS-CoV-2 infection. Children with blood cancer tend to have milder COVID-19 symptoms and are less likely to be hospitalized and have better prognosis when compared to adults. Continuation of anticancer treatment in individual paediatric blood cancer patients with COVID-19 seems to be possible.
Subject(s)
Myelodysplastic Syndromes , Leukemia , Respiratory Distress Syndrome , Lymphoma , Severe Acute Respiratory Syndrome , Lymphoma, Non-Hodgkin , Neoplasms , Death , Hodgkin Disease , COVID-19ABSTRACT
Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. The availability of patient hospital records is crucial for linking the genomic sequence information to virus function during the course of infections. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. From the assembled sequences, we estimate the SARS-CoV-2 effective population size and infection rate and outline the epidemiological dynamics of import and transmission events during this period in Saudi Arabia. We show that two consecutive mutations (R203K/G204R) in the SARS-CoV-2 nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein by mass-spectrometry analysis. Furthermore, analysis of the host cell transcriptome suggests that the mutant N protein results in dysregulated interferon response genes. We provide crucial information in linking the R203K/G204R mutations in the N protein as a major modulator of host-virus interactions and increased viral load and underline the potential of the nucleocapsid protein as a drug target during infection.
Subject(s)
COVID-19ABSTRACT
BackgroundSince the emergence of COVID-19, the world has been desperate to find effective therapeutics and vaccinations to treat hundreds of thousands of affected patients and to suppress the spread of this global pandemic. Lopinavir-ritonavir (LPV/RTV) is an HIV antiviral combination that has been considered for treatment of this disease. Aim of the studyThis systematic review and meta-analysis aimed to assess the efficacy and safety of lopinavir/ritonavir in COVID-19 patients in the extant published research. A systematic review protocol was developed based on PRISMA-P and the PRISMA statement. Published English and non-English articles written since December 1, 2019 were selected for review from 8 electronic databases. Readily accessible full articles (cohort studies and clinical trials) which specifically mentioned lopinavir/ritonavir and patients with lab-confirmed SARS-CoV-2 or COVOID-19 of any age were included. Three researchers separately evaluated the bias in the reported articles. We conducted a systematic review and meta-analysis with the objective of evaluation of the safety and efficacy of LPV/RTV alone or in combination with other drugs with regard to time to becoming PCR negative, time to body temperature normalization and cough relief, radiological progression, and safety. Review Manager (RevMan) was used to conduct all statistical analyses and generate the forest plots. Meta-analyses were performed using the Mantel Hazel method or the inverse variance method for dichotomous data and continuous data respectively. ResultsNon-duplicate articles (n=76) were evaluated for possible inclusion. A consensus was reached to select 29 articles for full-text screening, only 11 articles comprised 1,192 patients were included in this study, and six of which were included for meta-analysis. In terms of virological cure (PCR negative), three studies reported less time in days to achieve a virological cure for LPV/RTV arm relative to no antiviral therapy (conventional) (mean difference = -0.81 day; 95% CI, -4.44 to 2.81; P = 0.007, I2 = 80%). However, the overall effect was not significant (P = 0.66). When comparing LPV/RTV arm to umifenovir arm, a favorable affect was observed for umifenovir arm, but not statically significant (mean difference = 0.95 day; 95% CI, -1.11 to 3.01; P = 0.09, I2 = 58%). In terms of time to body normalization and cough relief (clinical cure), two studies reported on time to temperature normalization with no significant effect of LPV/RTV (n = 93) versus umifenovir (n = 71) arm), (OR = 0.87 day; 95% CI, 0.42 to 1.78; (P = 0.70), I2 = 0%), or alleviation of cough duration (p = 0.69). In terms of CT evidence of radiological progression of pneumonia/lung damage, treatment with lopinavir/ritonavir resulted in no significant decrease in the radiological progression (OR = 0.80; 95% CI, 0.42 to 1.54; P = 0.59, I2 = 81%), In terms of safety, a greater number of adverse events were reported for lopinavir/ritonavir (n=45) relative to the umifenovir arm (n=14) and conventional treatments (n=10), P = 0.004, 0,0007, respectively ConclusionsThe small number of studies included in this systematic review and meta-analysis study did not reveal any statistically significant advantage in efficacy of lopinavir-ritonavir in COVID-19 patients, over conventional or other antiviral treatments. This result might not reflect the actual evidence.