Clinical severity of Omicron and Delta SARS-CoV-2 infections in children.

BACKGROUND: We aimed to compare the clinical features and severity of the Omicron and Delta variant infections among children hospitalized for coronavirus disease 2019 (COVID-19). METHODS: Children 12 years old or less hospitalized for COVID-19 across five hospitals between January 1, 2021 and March 31, 2022 were identified using the state's pediatric COVID-19 registry. Delta and Omicron-infected patients without previous COVID-19 infection, COVID-19 vaccination, or co-infections were propensity-score matched 1:1 to control for differences in baseline characteristics. Clinical manifestations, treatments, and outcomes were analyzed. Disease severity was assessed using an adapted WHO ordinal scale. RESULTS: Of the initial 1367 patients, 668 had Delta infection and 699 had Omicron infection. Propensity-score matching produced 558 matched pairs. Patients with Omicron infection were more likely to present with croup (the odds ratio, OR, was 10.87, with a 95% confidence interval, CI, ranging from 2.54 to 46.59), lower respiratory tract infection (OR 2.32, 95% CI, 1.48-3.64) and seizures (OR 8.39, 95% CI, 5.04-13.99) compared with those with Delta infection. Omicron was associated with increased odds of moderate/severe disease (OR 6.14, 95% CI, 4.72-7.99) and a greater need for intravenous fluid therapy (OR 6.00, 95% CI, 4.29-8.39), corticosteroids (OR 3.08, 95% CI, 1.66-5.72), empirical antibiotics (OR 1.70, 95% CI, 1.10-2.64), and low-flow nasal oxygen therapy (OR 3.68, 95% CI, 2.17-6.22) in comparison with Delta. CONCLUSION: Children hospitalized with Omicron infection demonstrated a distinct clinical profile compared to those with Delta infection, with increased likelihood of moderate/severe disease and higher utilization of health-care resources.

Clinical comparison of HMPV and RSV infections in hospitalised Malaysian children: A propensity score matched study.

INTRODUCTION: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are significant contributors to the burden of acute respiratory infections in children, but data on hMPV from Southeast Asia are limited despite its potential for serious disease. This study aimed to compare the clinical presentation, resource utilisation and outcomes between hMPV and RSV infections in hospitalised Malaysian children. METHODS: This retrospective, observational study included children aged ≤12 years old hospitalised with hMPV or RSV, confirmed via direct fluorescent antibody (DFA) methods, between 1 July to 30 October 2022 at Hospital Tuanku Ja'afar Seremban, Malaysia. Demographic, clinical presentation, resource utilisation and outcome data were analysed. Propensity score matching was used to balance cohorts based on key demographic and clinical characteristics. RESULTS: This study included 192 patients, comprising 112 with hMPV and 80 with RSV. hMPV patients were older (median age 20.5 vs. 9.4 months, p < 0.001) and had a higher incidence of comorbidities (24.1% vs. 7.5%, p = 0.003). Fever was more common in the hMPV group (97.3% vs. 73.8%, p < 0.001), but the other clinical manifestations were similar. Postmatching analysis showed higher corticosteroid use in the hMPV group (p = 0.01). No significant differences were observed in the use of other resources, PICU admissions, duration of hospitalisation or mortality rates between both groups. CONCLUSION: hMPV and RSV infections in children share similar clinical manifestations and outcomes, with hMPV affecting older children and showing higher corticosteroid usage. These findings emphasise the need for equal clinical vigilance for both hMPV and RSV in paediatric respiratory infections.

Risk factors for disease severity among children with Covid-19: a clinical prediction model.

BACKGROUND: Children account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19. METHODS: We identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state's pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: A total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram's sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 - 0·92) respectively. CONCLUSION: Our nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions.

Clinical characteristics of COVID-19 in hospitalized young infants and risk factors for disease severity.

BACKGROUND: This study aimed to describe the clinical characteristics and severity of young infants hospitalized with COVID-19 and study the relationship between breastfeeding and maternal COVID-19 vaccination on the severity of COVID-19. METHODS: A retrospective, observational study was performed among infants aged 6 months and below hospitalized for COVID-19 in a tertiary state hospital in Malaysia between February 1 and April 30, 2022. The primary outcome was "serious disease," defined as pneumonia requiring respiratory support or dehydration with warning signs. Multivariate logistic regression was used to determine independent predictors for serious disease. RESULTS: A total of 102 infants were included in the study; 53.9% were males with a median age of 11 weeks (interquartile range: 5-20 weeks). Sixteen patients (15.7%) had pre-existing comorbidities, including preterm birth. Fever was the most common presenting symptom (82.4%), followed by cough (53.9%), and rhinorrhea (31.4%). Forty-one infants (40.2%) presented with serious disease, warranting either respiratory support or intravenous fluid therapy for dehydration. Recent maternal COVID-19 vaccination was associated with a reduced risk of serious disease on univariate analysis but was not significant after multivariate adjustment (adjusted odds ratio [aOR] 0.39; 95% CI: 0.14-1.11; p = 0.08). Exclusive breastfeeding was protective against serious COVID-19 in young infants, independent of other confounding factors (aOR 0.21, 95% CI: 0.06-0.71; p = 0.01). CONCLUSION: COVID-19 is a serious disease with non-specific clinical manifestations in young infants. Exclusive breastfeeding could play an important protective role.

Comparison of Severe Viral Pneumonia Caused by SARS-CoV-2 and Other Respiratory Viruses Among Malaysian Children During the COVID-19 Pandemic.

Objectives: We described the etiology of severe pneumonia in children during the height of the COVID-19 pandemic in Malaysia and compared the clinical features of severe SARS-CoV-2 to other respiratory viruses. Methods: This retrospective study included all children aged 12 years and below hospitalized with severe pneumonia in Negeri Sembilan, Malaysia, between 1 April 2021 and 31 October 2021. We extracted demographic and clinical data and used logistic regression to examine risk factors associated with severe SARS-CoV-2 or other viral pneumonia. Results: A total of 111 children were included. The median age was 15 months. Human rhinovirus/enterovirus, SARS-CoV-2 and respiratory syncytial virus were the most common etiology of severe pneumonia. Codetection of >1 viral pathogen was present in 14 (12.6%) patients. Children with severe COVID-19 presented early in the course of illness and had lower rates of pediatric intensive care admission. The presence of sick contact with an adult was a predictor for SARS-CoV-2, whereas adventitious breath sounds were predictive of other respiratory viruses. Conclusions: The etiology of severe pneumonia in children evolved with the epidemic curve of COVID-19 and school closures. Children with severe pneumonia due to SARS-CoV-2 experienced a milder clinical course when compared to other respiratory viruses.

Risk factors associated with household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia.

AIM: Households are a significant venue for the transmission of SARS-CoV-2. We conducted a study to characterise the transmission dynamics and identify risk factors for household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia. METHODS: This retrospective observational study included 185 families of paediatric COVID-19 cases from 1 February 2020 to 31 December 2020. We identified the index case for each household and gathered the socio-demographic, epidemiological investigation results and risk factors for household transmission from medical case records. The secondary attack rate was calculated, and logistic regression analyses were used to identify risk factors associated with secondary household transmission of SARS-CoV-2. RESULTS: Of the 848 household contacts, 466 acquired secondary infections, resulting in a secondary attack rate of 55%. The median age of the secondary cases was 12 years. Female household contacts and household contacts who slept in the same room with the index case were significantly associated with increased risk for COVID-19. Other independent risk factors associated with higher transmission risk in the household included an index case who was symptomatic, a household index case aged greater than 18 years and a male household index case. CONCLUSIONS: High rates of household transmission of COVID-19 were found, indicating households were a major setting of transmission of SARS-CoV-2. Our data provide insight into the risk factors for household transmission of SARS-CoV-2 in Malaysia.

Clinical and epidemiological characteristics of children with COVID-19 in Negeri Sembilan, Malaysia.

OBJECTIVES: To describe the clinical and epidemiological characteristics of children with coronavirus disease 2019 (COVID-19) in the state of Negeri Sembilan, Malaysia in the setting of mandatory hospital isolation and quarantine for all confirmed cases. METHODS: A multi-centre, retrospective observational study was performed among children aged ≤12 years with laboratory-proven COVID-19 between 1 February and 31 December 2020. RESULTS: In total, 261 children (48.7% males, 51.3% females) were included in this study. The median age was 6 years [interquartile range (IQR) 3-10 years]. One hundred and fifty-one children (57.9%) were asymptomatic on presentation. Among the symptomatic cases, fever was the most common presenting symptom. Two hundred and forty-one (92.3%) cases were close contacts of infected household or extended family members. Twenty-one (8.4%) cases had abnormal radiological findings. All cases were discharged alive without requiring supplemental oxygen therapy or any specific treatment during hospitalization. The median duration of hospitalization was 7 days (IQR 6-10 days). One (2.1%) of the uninfected guardians accompanying a child in quarantine tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) upon discharge. CONCLUSIONS: COVID-19 in children was associated with mild symptoms and a good prognosis. Familial clustering was an important epidemiologic feature in the outbreak in Negeri Sembilan. The risk of transmission of SARS-CoV-2 from children to guardians in hospital isolation was minimal despite close proximity.

Case report: recurrence of Plasmodium vivax malaria due to defective cytochrome P450 2D6 function in Pos Lenjang, Pahang, Malaysia.

Five children in Pos Lenjang, Pahang, Malaysia were PCR-positive for vivax malaria and were admitted to the hospital from 5 to 26 July 2019. One of the patients experienced three episodes of recurrence of vivax malaria. Microsatellite analysis showed that reinfection is unlikely. Drug resistance analysis indicated that Riamet (artemether-lumefantrine) is effective. Cytochrome P450 2D6 (CYP2D6) testing showed that this patient has defective CYP2D6 function. Primaquine failure to clear the Plasmodium vivax hypnozoites may be the cause of recurring infections in this patient. This report highlights the need for the development of liver-stage curative antimalarials that do not require metabolism by the CYP2D6 enzyme.

Invasive Salmonella infections among children in Bintulu, Sarawak, Malaysian Borneo: a 6-year retrospective review.

BACKGROUND: Invasive Salmonella infections result in significant morbidity and mortality in developing countries. In Asia, typhoid and paratyphoid fever are reported to be the major invasive Salmonella infections, while invasive non-typhoidal Salmonella (iNTS) infections are believed to be uncommon. Data from Sarawak, in Malaysian Borneo, are limited. METHODS: A retrospective study identifying all children aged < 15 years with invasive Salmonella infections from 2011 to 2016 was conducted in Bintulu Hospital in Sarawak. Population incidences, clinical and bacterial characteristics were examined. RESULTS: Forty-four patients were identified during the 6-year study period: 43 had iNTS infection and 1 had typhoid fever. The average annual iNTS incidence was 32.4 per 100,000 children aged < 5 years. None of the children had malaria or HIV infection, and only 7% were severely malnourished. Salmonella Enteritidis and Salmonella Java were the commonest NTS serovars identified. Pneumonia was the most common manifestation of iNTS disease, present in 20 (47%) children. Other manifestations included gastroenteritis, fever without a source, septic arthritis and meningitis. Salmonella Enteritidis was identified in 76% of those with pneumonia, significantly more frequently than in children with other manifestations. Over 25% of children with iNTS developed severe disease and nearly 10% suffered long term morbidity or mortality. While 78% of Salmonella Java isolates were multi-drug resistant, nearly all other isolates were susceptible to most antimicrobials, including ampicillin. CONCLUSIONS: Bintulu Division in Sarawak observed a very high incidence of childhood iNTS infections. Enteric fever was uncommon. The epidemiology of invasive Salmonella infections in Malaysian Borneo differs considerably from that of neighbouring countries in Asia.

Early clearance of Chikungunya virus in children is associated with a strong innate immune response.

Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children.