key: cord-1018818-mvrdtfao
authors: Al Yazidi, Laila S.; Al Hinai, Zaid; Al Waili, Badriya; Al Hashami, Hilal; Al Reesi, Mohammed; Al Othmani, Farhana; Al Noobi, Balqees; Al Tahir, Nuha; Elsidig, Nagi; Al Barwani, Lamya; Al Busaidi, Ibrahim; Al Jabri, Bushra; Al Qayoudhi, Abdullah; Al Maani, Amal; Al-Maskari, Nawal
title: Epidemiology, characteristics, and outcomes of hospitalized children with COVID-19 in Oman: A multicenter cohort study
date: 2021-01-18
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2021.01.036
sha: 229d7322dc93b60dea66c7ade1bb0215822f1623
doc_id: 1018818
cord_uid: mvrdtfao

Objectives To describe the epidemiology, clinical and laboratory features and outcome of hospitalized children with coronavirus disease 2019 (COVID-19) in a Middle Eastern setting. Methods We describe a multicenter retrospective study of children hospitalized with confirmed COVID-19 in 7 centres across Oman between February 2020 and July 2020. Results In total, 56 children < 14 years of age required hospitalization in seven Omani centres over five months (February – July 2020). Thirty-seven (68%) children were admitted with uncomplicated COVID-19, 13 (23%) with pneumonia and 5 (9%) with the multisystem inflammatory syndrome in children (MIS-C). Infants constituted (23/56,41%) and around half of them (12/23,52%) were below 2-months of age. Fever was the most common symptom (46;82%) followed by respiratory symptoms in (33; 59%) and gastrointestinal symptoms (31;55%). Twenty-two (39%) children had underlying medical conditions; sickle cell disease in (7; 13%) followed by chronic respiratory disease (4; 7%) and severe neurological impairment (4; 7%). We found that leukocytosis, elevated inflammatory markers, and anemia for age were independently associated with intensive care admission. There were no mortalities related to admission with COVID-19 in this cohort. Conclusion Most of the children hospitalized with confirmed COVID-19 had a mild course and a satisfactory outcome. Sickle cell disease is the commonest comorbidity associated with pediatric admission of COVID-19 in Oman.

Conclusion: Most of the children hospitalized with confirmed COVID-19 had a mild course and a satisfactory outcome. Sickle cell disease is the commonest comorbidity associated with pediatric admission of COVID-19 in Oman.

Keywords: COVID-19, children, hospitalized, outcome, Oman

Children tend to have mild COVID-19 and less mortality compared to adults. (Chan et al., 2020) Although the literature on COVID-19 has expanded significantly in the last six months, there is still limited literature on the epidemiology and the effect of COVID-19 in children from Middle Eastern countries. COVID-19 was reported in Oman for the first time on the 24 th of February, 2020.(WHO, 2020a) From the 1st of February to the 31st of July, 2020, there were 68,400 confirmed COVID-19 cases in Oman of whom 4,379 were children which accounts for 6.6%. (WHO, 2020a) This study was undertaken to describe the epidemiology, clinical and laboratory features and outcome of hospitalized children with COVID-19 in Oman. It is one of the first such studies in the Middle East and the gulf region.

We performed a multicenter, retrospective study of children younger than 14 years of age with laboratory-confirmed COVID-19 and admitted to any one of seven hospitals across Oman between February and July, 2020. The centres involved in this study were the Royal Hospital, Sultan Qaboos University Hospital (SQUH), Al Nahda Hospital, Al Rustaq Hospital, Suhar J o u r n a l P r e -p r o o f Hospital, Nizwa Hospital, and Ibri Hospital. Ethical approval was obtained through the central research committee at the Ministry of Health and the SQUH medical research ethics committee.

In all these centers, patients with mild to moderate illness were admitted to the general ward.

Those requiring close monitoring or noninvasive ventilation (CPAP and Bi-PAP) were placed in the high dependency unit (HDU). Children with hemodynamic instability or those requiring invasive ventilation were admitted to the pediatric intensive care unit (PICU).

Data concerning patient demographics, clinical characteristics, laboratory and radiological investigations, management, and patient outcomes were collected in an excel sheet using the hospitals' electronic health care systems. In our study, uncomplicated COVID-19 was defined as patients who required admission to the general ward and had no sign of multi-organ involvement. Severe COVID-19 was defined as patients who required supplemental oxygen as per WHO definition. We followed the WHO definition for multisystem inflammatory syndrome in children. (Varghese et al., 2020; WHO, 2020b) Confirmed fever was defined as a measured temperature of 38.0°C or greater. Leukocytosis, leukopenia, neutrophilia, neutropenia, lymphocytosis, lymphopenia, anemia for age, thrombocytopenia, and thrombocytosis were determined based on normal values for age as described in Nathan and Oski's Hematology of Infancy and Childhood, 6th Edition.

Cepheid's GeneXpert SARS-CoV-2 RT-PCR (Egene, Ngene) and SARS-CoV-2 RT-PCR through TIB MOLBIOL, Liferiver and Sansure were used to confirm the diagnosis of COVID-19. Respiratory samples (nasopharyngeal swabs, throat swabs, or nasopharyngeal aspirates) were sent in a viral transport medium for virus detection to the central public health lab (CPHL) or SQUH laboratory. The remaining samples were processed locally. Trained lab technicians prepared the swab samples in the tube for processing. Each tube had a unique barcode for identification and traceability. Following this, the patient samples were loaded into the J o u r n a l P r e -p r o o f molecular testing system for extraction, amplification, and detection. All test results were analyzed and approved by experienced lab technicians or microbiologists before entering them to laboratory reporting systems.

Non-parametric two-tailed Mann-Whitney U tests were used to compare continuous variables, all of which were found to be not normally distributed. χ² or Fisher's exact tests were used to compare categorical variables, as appropriate. Normality of data distribution was assessed with the Shapiro-Wilk test. The clinical endpoint was the need for admission to an intensive care unit (ICU; either neonatal or pediatric intensive care). The association of baseline characteristics and clinical findings with ICU admission was initially evaluated using univariable logistic regression. Subsequently, multivariable logistic regression analysis with the backward stepwise method was used to explore variables that were independently associated with ICU admission. Only variables that were significant in univariable analyses were introduced into the model. Factors related to drug treatment for COVID-19 were also explored with univariable analysis. All probabilities were two-tailed. P <0.05 was considered statistically significant. All calculations were done with Prism (version 8.0; GraphPad, La Jolla, CA, USA) and SPSS (version 23.0; IBM, Armonk, NY, USA).

Fifty-six children were hospitalized with COVID-19 in the 7 hospitals during the study period.

Overall weekly hospitalization among children increased steadily during the study period ( Figure 1) , coinciding with the national trends for all age groups ( Figure 2 ). The highest number of admissions were in the Muscat Governorate (Table 1) .

Among the study's cohort, 55 (98%) children were Omani, 36 (64%) were male, and the median (IQR) age was 1.8 (0.2-6.9) years. Infants constituted 23 (41%) of the cases, and around half of them (12/23, 52%) were below two months of age. There was a history of contact with a J o u r n a l P r e -p r o o f positive case of COVID-19 in 38 (68%). This contact was an immediate family member in 29/38 (76%), an extended family member in 5/38 (13%), and unspecified in 4/38 (10%).

Whether the contact was an adult or a child was not specified in most cases.

There were 22 (39%) cases with an underlying medical condition. The most prevalent condition was sickle cell disease in 7 (13%) followed by chronic respiratory conditions 4 (7%) (2 Asthma, 2 cystic fibrosis), and 4 (7%) with severe neurological impairment (Table 1) .

Fever was the most common symptom (46;82%) followed by respiratory symptoms in (33; 59%) and gastrointestinal symptoms (31;55%). (Table 2 ). Skin rash, loss of smell, and loss of taste were not documented in any of the cases.

Most of the children were admitted to a regular care unit (45, 80%), whereas 4 (7%) needed intermediate level care (HDU), and 7 (13%) required intensive care. Invasive mechanical ventilation was needed for only 1 (2%), whereas noninvasive ventilation was needed for 2 (4%), and 8 (14%) needed support of oxygen. The median (IQR) length of stay in the hospital was 2 (1-4) days (Table 1) . Among patients requiring intensive care, the median (IQR) length of stay in the critical care unit was 3 (2-8) days.

The COVID-19 disease classification in this cohort was as follows; uncomplicated illness in 38 (68%), pneumonia in 13 (23%) which was severe in 7 (13%), and MIS-C in 5 (9%). 15 (27%) patients suffered from various complications during the admission. Most common were sickle-cell disease-related complications, observed in 7 (13%) patients. These included acute chest syndrome (n=3), splenic sequestration (n=2), pain crisis (n=1), and acute anemia (n=1).

Two children required blood transfusion and the 3 patients with acute chest syndrome required exchange transfusion. Seizures were observed in 3 patients who were known to have underlying seizure disorders. Acute appendicitis was diagnosed in 2 patients who underwent an appendectomy and were subsequently diagnosed with MIS-C. Acute kidney injury was J o u r n a l P r e -p r o o f noted in 2 (4%) critically-ill patients. Other complications in critically-ill patients included myocardial dysfunction, shock, and acute respiratory distress syndrome. A subdural hematoma was noted in 1 (2%) patient and was attributed to trauma. No mortalities or chronic complications related to the admission were recorded (Table 1) .

Laboratory investigations revealed that lymphopenia and anemia for age were the most common hematologic abnormalities, occurring in 22 (39%) and 21 (38%) of patients, respectively (Table 3) . Serum CRP, sodium, creatinine, alanine aminotransferase, total bilirubin, and albumin were normal in the majority of patients. All the children diagnosed with MIS-C had positive COVID-19 PCR and 3 of 4 had positive COVID-19 IgG.

Among 43 children who had a chest radiograph, 27 (63%) radiographs showed an infiltrate or consolidation which was bilateral in 12 (28%) of cases. Five patients underwent an echocardiogram, which was normal for two patients, whereas 1 showed coronary ectasia but no aneurysm, and 2 showed small pericardial effusions with one of them having a reduced left ventricular ejection fraction of 49%. Blood cultures were obtained for 48 (86%) of patients, all of which showed no growth. Urine cultures were obtained for 29 (52%) of admitted patients, and only four had significant growth (Enterobacter cloacae, 1, Enterococcus faecalis, 1, and Burkholderia cepacia, 2).

COVID-19 investigational treatments were administered to some of the admitted 56 cases, including, Lopinavir/ritonavir in 1 (2%), convalescent plasma in 1 (2%), Favipiravir in 3 (5%), Tocilizumab in 3 (5%), Hydroxychloroquine in 4 (7%), steroids in 7 (13%), and intravenous immunoglobulin in 4 (7%) of the children. Anticoagulants were given to 6 (11%) patients (Aspirin, 5, low molecular heparin, 4). Antimicrobials were used in 38 (68%) patients, and these were mostly beta-lactams (34, 61%), Macrolides in (6, 11%), and Oseltamivir (9, 16%).

The patients who required care in the ICU were more likely to be male, have signs of lower respiratory disease, leukocytosis, neutrophilia, anemia for age, higher CRP levels, and lower serum sodium and albumin levels (Table 3) . After multivariable logistic regression analysis, leukocytosis, elevated CRP (optimal cut-off was >100 mg/L), and anemia for age emerged as independently associated with ICU requirement (Table 3) . The presence of all three risk factors was 100% predictive of ICU requirements. The presence of 2 out of 3 was 86% sensitive and 94% specific in predicting ICU requirements (Figure 3 ). Serum IL-6, LDH, D-dimer, and ferritin were only measured in a small number of patients and were not included in the analysis.

COVID-19 has a higher burden among adults with pediatric cases appearing to be less frequent and less severe. (DeBiasi et al., 2020) According to the national data in Oman, the total number of pediatric confirmed COVID-19 cases during the study period was 4379 (6.6% of total cases).

Overall, we found that hospitalized and critically ill patients were more likely to have 

In our study, 38 children (68 %) had at least one family member with confirmed COVID-19, which is similar to reports from China and Saudi Arabia where a contact history was present in 70% of their patients. (Chan et al., 2020; Raba et al., 2020) (Kainth et al., 2020; Zachariah et al., 2020) In this study, an increase in CRP, anemia for age, and leukocytosis were strongly associated with intensive care admission.

The majority of patients in our study had normal findings on chest imaging. A systematic review showed that approximately 50% of children with confirmed COVID-19 had chest Xray abnormalities, which is slightly higher than the rate in our study (37%) (Liguoro et al., 2020) .

More than half of the patients in our cohort were treated empirically with antibiotics, and 16%

were treated with oseltamivir despite a lack of evidence for efficacy of these agents in cases of n.d.) We suspect this may reflect concerns among physicians for the potential severity of COVID-19, and concerns about co-infection with other viruses or bacteria. Hoang et al. reported co-infection with bacterial or viral organisms in only 5.6% of the patients with COVID-19, and only four patients in our study had co-infection (UTI) . (Hoang et al., 2020) Reports of antibiotic use in children with COVID-19 have ranged from 19.4% to 100.0%.(Z. Wang et al., 2020) Our study suggests that the majority of children admitted with COVID-19 do not require antimicrobials.

Children with COVID-19 tend to have milder disease manifestations and lower mortality compared to adults. (Chan et al., 2020) . Only 13% of our patients required intensive care and these cases consistent mainly of children with MIS-C or underlying co-morbidities. (Götzinger et al., 2020) However, the presence of an underlying condition was not significantly associated with ICU admission in our study. We suspect that this is mainly accounted for by the presence of critical illness among otherwise healthy children with MIS-C. Among children without MIS-C who required intensive care, sickle cell disease and cystic fibrosis were the main underlying conditions. The association between underlying comorbidities and severe COVID-19 has been suggested by other studies. (Harman et al., 2020) The prognosis for children with underlying comorbid conditions and severe COVID-19 remained excellent in our study, with no reported mortality.

The limitations of this study is that it is retrospective and all data was collected from hospital medical records. Therefore, important information might have been omitted or not documented. As such, validation of our results with prospective studies is needed. Additionally, the sample size was relatively small in our study.

Conclusions: Most children hospitalized with confirmed COVID-19 have a mild course and favorable outcome. Sickle cell disease is the commonest comorbidity associated with COVID-19 admissions among Omani children. Children with sickle cell disease and COVID-19 are at increased risk for complications such as acute chest syndrome. MIS-C is a serious complication of COVID-19 which can affect otherwise healthy children, and can be misdiagnosed initially as acute appendicitis. Leukocytosis, elevated CRP, and anemia for age are independently associated with critical cases of COVID-19 among Omani children.

The authors declare that they have no competing financial interests or personal relationships that have appeared to influence the work reported in this paper.

The authors declare that they have no competing financial interests or personal relationships that have appeared to influence the work reported in this paper.

This study was approved by the medical research and ethics committee of the collage of medicine and health sciences at Sultan Qaboos University, Oman and the central research committee of Ministry of Health.

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We thank all the medical staff who worked hard in the emergency department, outpatient, intensive care, and pediatric isolation wards to manage these children.We also thank Dr Adil Al Wehaibi for helping with some statistical analysis.J o u r n a l P r e -p r o o f