There is limited information regarding COVID-19 among children or the impact of nutritional status on their rates of hospitalization and outcomes from COVID-19 particularly in low-middle income-countries ( LMIC) or upper-middle-income countries (UMIC). A systematic review found that over 90% of paediatric COVID-19 deaths were from LMICs. Pediatric deaths/1,000,000 children and case fatality rates were significantly higher in LMIC than in high-income countries (HIC) (2.77 in LMIC vs. 1.32 in HIC; and 0.24% in LMIC vs. 0.01% in HIC; respectively) [1]. This anomaly is multifactorial and could be related to less access to high-quality medical care, socioeconomic status, or less testing of children with less severe diseases. In a meta-analysis of children with COVID-19, acute malnutrition, anemia, and obesity were associated with a higher risk of severe disease and mortality [2]. Furthermore, an analysis of global disease burden suggested a link between fatal COVID-19 and populations with a high burden of undernutrition [3]. The prevention, diagnosis, and treatment of malnutrition have been previously considered in managing COVID-19 to improve short- and long-term prognoses [4]. Although no substantial evidence is available to support nutritional intervention for COVID-19, public health strategies aimed at reducing undernutrition and micronutrient deficiencies are recommended based on the known impacts of all forms of malnutrition on the immune system [5]. In a retrospective case-control study in a high-income setting, 2 % of COVID-19-infected hospitalized patients had a history of malnutrition and had higher odds of severe COVID than children with normal nutrition, particularly in the under-five age group [6]. This study highlighted the potential long-term effect of malnutrition on the severity of COVID-19. Limited small studies in India and China suggest an association between undernutrition in children and COVID-19 severity. In India, 2 out of every 13 (15%) of severe COVID-19 cases had severe acute malnutrition and anemia [7]. However, this fell below national background rates, where the prevalence of underweight, stunted, and wasted children under five are 33, 35, and 17 percent, respectively, and anemia occurs in 23-40% of children 1-19 years [8,9]. Conversely, in China, 1 in 25 (4%) hospitalized COVID-19 patients were malnourished, which exceeded national background rates of 3% thinness among school-aged children [10,11].

Globally, current levels of overweight have persisted for the last two decades in every region except Africa. Estimates of malnutrition among children aged five or less in the Caribbean show a reduction in stunting from 15.7% to 11.8% and an increase in the proportion of overweight children from 5.8% to 6.6% from 2000 to 2020 [12]. Overweight estimates in children under age five exceeded the global average of 5.7% in 2020 [13]. The Caribbean Paediatric COVID Collaborative survey is a comprehensive analysis of the impact of COVID-19 on children hospitalized with COVID-19 evaluated over 200 inpatient records of COVID-19 admissions among Caribbean children ages 0-17. The objectives of this survey's first output are to determine the incidence of malnutrition and anemia and evaluate the association between nutritional status and COVID-19-related clinical outcomes in children hospitalized for COVID-19 in three Caribbean islands (Barbados, the Bahamas, and Jamaica).

This multi-island inpatient retrospective survey included nine hospitals in three Caribbean islands (Barbados, The Bahamas, and Jamaica) conducted between September 2020 to July 2021. Jamaica is classified as UMIC and Barbados and Bahamas as HIC according to World Bank country classification based on per capita income.

Data Abstraction

Information was abstracted from medical records using a standard data collection tool adapted from the World Health Organization case record form for suspected cases of Multisystem Inflammatory Syndrome (MIS) in children and adolescents [14]. Data were categorized in six domains: [A] inclusion criteria and demographics, [B] comorbidities, [C] clinical status, including signs and symptoms, and Multisystem Inflammatory Syndrome in Children (MIS-C) clinical diagnosis, [D] medication, [E] laboratory tests and results, and [F] supportive care, complications, and outcome. Eligible cases included children and adolescents aged 17 years and younger who either confirmed positive for COVID-19 using an accepted Reverse Transcription Polymerase Chain Reaction (RT-PCR) test or met the criteria for MIS-C with a negative RT-PCR test. For this initial report, all cases were hospitalized between September 2020 and June 2021.

Defining Nutritional Status

Age was calculated using the date of initial hospitalization when available, the date of the first positive RT-PCR test, or the date of symptom onset, in that order. Weight and height measured at hospitalization were used to calculate body mass index (BMI). The calculated age-specific z-scores for the weight (weight-for-age), height (height-for-age), supine length if less than two years of age (length-for-age), and BMI (BMI-for-age) were compared to age- and sex-stratified reference populations. Weight-for-age is a useful indicator of a child's nutritional status with respect to the severity of undernourishment. Height-for-age and length-for-age are used to assess childhood stunting. BMI-for-age is usually used in children older than two years to indicate weight status independent of height and can be used to define childhood overweight, obesity, and thinness categories. World Health Organization (WHO) reference standards were used for all measures [15]. For children aged five years and younger, we used the WHO Child Growth Standards, and for children and adolescents aged 6 to 17 years, we used the complementary WHO Reference 2007. When using these standards, weight-for-age was only applicable for children aged ten years and younger. In Table 1, and following WHO definitions, we summarize our classification of nutritional status in children aged from birth to 17 years of age, stratified into two broad age groups (birth to 5 years, 6 to 17 years) [16]. Anemia is defined as total hemoglobin < 11.0 g/dL [17].

Statistical Methods

The data was described by age and sex using growth charts, plotting weight-for-age, height-for-age, and BMI-for-age against the WHO reference populations, and highlighting z-scores greater than two or less than -2. Z-scores less than or greater than 5 indicated possible hospital data recording errors and were not included in the final analyses. All analyses are conducted using the Stata statistical system (StataCorp 2021, Stata Statistical Software: Release 17, College Station, TX: StataCorp LLC).

Table 1: Classification of nutritional status in patients from birth to 19 years of age, stratified into two broad age groups (birth to 5 years, 6 to 19 years).

Inpatient Characteristics

The number of eligible inpatients and available data points are depicted in the study flowchart (Figure 1). By June 15, 2021, information on 180 children with a confirmed COVID-19 infection or suspected MIS-C and a negative RT-PCR result was collected. These 180 children were living in Jamaica (n=155), the Bahamas (n=21), and Barbados (n=4). Because of the small numbers of hospitalized children in Barbados and The Bahamas, all analyses were performed without country stratification. Of the 180 eligible children, 157 (87%) had a recorded weight and 86 had a recorded height (48%); these same 86 children had information on weight and height to calculate BMI. The ages of the confirmed pediatric cases ranged from 1 week (or less) to 17 years, with a median age of 3.3 years. Females accounted for 45% of confirmed cases.

Figure 1. Flow diagram depicting stratification of eligible inpatients.

Anthropometry

A summary of the frequency of malnourished groups is presented in Table 2, stratified by gender and age and gender in Figure 2. Among children hospitalized for COVID-19, 6.8% were stunted, 6.6% were underweight, 13.6% were overweight or obese, with two (2.5%) obese. Most children with stunting were under five years old compared with undernourished and obese children, which affected younger and older children.

Association between Anemia and Malnourishment

Among 180 participants, 14 (8%) had sickle cell disease (Figure 3). Among 166 children without sickle cell disease, 50 (30%) had a total hemoglobin measurement below 11 g/dL. There were no statistically significant associations between hemoglobin or anemia and measures of malnourishment. After removing children with SCD, 22 of 29 (76%) children with MIS-C had anemia as defined by WHO criteria. 28 of 137 (20%) children not fulfilling the requirements for MIS-C had anemia, with a strong statistically significant association (Chi-squared test, p<0.001).

Deaths

The survey identified two deaths in children with severe acute malnutrition and COVID-19. One child had an underlying chronic neurological disease, and the other was an infant. Both children had lab-confirmed bacteremia, deranged liver function tests, and electrolyte imbalance, and one had severe anemia.

Table 2: Z-scores of weight-for-ages (n=121), height-for-age(n=73), BMI-for-age (n=81) among children aged 0–17 years with a confirmed COVID-19 infection or with suspected MIS-C and a negative RT-PCR result from September 2020 to May 2021.

Figure 2 (a-f): Sex-specific growth charts among 121 pediatric inpatients with weight-for-age measurements, 73 with height-for-age information, and 81 with BMI-for-age information, from 9 hospitals across 3 Caribbean islands.

Figure 3: Prevalence of anemia among 180 children aged 0–17 years hospitalized for COVID-19 stratified by presence or absence of sickle cell disease and MISC.

Among children hospitalized for COVID-19, 6.8% were stunted, 6.6% were underweight, 13.6% were overweight/obese (Table 2), and 30% had anemia (Figure 3). Anemia was associated with MIS-C but not with malnutrition. Two deaths reported in children with severe malnutrition had similar clinical presentations which included septicemia. This study was limited to retrospective analysis, and standardized measurement techniques could not be verified. Children were ill, and measurements of height may have been omitted on admission. Z-scores that exceeded either -5 or 5 indicated possible errors in data entry and were excluded. This exclusion resulted in a discrepancy between numbers available for analysis and z scores available. (Figure 1) Table 2 and figure 2 highlight the small number of malnourished children in the current dataset, as assessed with the three z-score measures. This small number impacted the ability to investigate associations of malnutrition with comorbidities and COVID-19 signs, symptoms, and outcomes. Additionally, the hospital-based survey did not allow comparisons with the nutritional status of asymptomatic COVID-infected patients. Comparative regional rates for stunting and wasting in the general population were limited to the under-five age group. Despite the above-described limitations, this is the first regional published work investigating the incidence and outcomes of COVID-19-infected malnourished children and adolescents and provides additional insight into the global landscape concerning nutrition and SARS-CoV-2 infection.

The prevalence of stunting of 6.6% fell below baseline values of 11.8% for children under five years in the Caribbean region [12]. Obesity was lower (2.5%) than the reported baseline prevalence in the Americas in children aged 5–19 years (14.4%), [13] whereas overweight and obese values (13.6%) exceeded estimates for children aged under five years (6.6%). There is a clear link between obesity and disease severity; however, there was a small proportion of obese children in this cohort. The higher proportion of overweight and obese children may reflect the secondary impact of the pandemic with reduced physical activity, limited access to nutritious foods, or increased consumption of unhealthy snacks. Significant weight gain and increased BMI in children and adolescents have been noted during the COVID-19 pandemic compared with pre-pandemic years [18,19]. The rate of BMI increase approximately doubled, particularly among pre-pandemic overweight, obese, or younger school-aged children [19]. The prevalence of undernutrition among admissions with COVID-19 exceeded World Bank estimates of 4.4% undernutrition in the islands surveyed [20]. Malnutrition-associated COVID-19 admissions vary, with baseline population estimates being lower in India and higher in China [7,10]. Undernourished and stunted children in the Caribbean were approximately 7 % of admissions compared with 4% in China and 15% in India, and 2% in the U.S. with historical malnutrition [6,7,10]. The deaths identified in two children with severe malnutrition suggest that the severity of malnutrition may influence outcomes such as vulnerability to sepsis. In these two cases who were ill with infections, it is difficult to disentangle the immunological effect of malnutrition from the effect of infection. Studies suggest that children may be protected by a diverse repertoire of naive T lymphocytes compared with the aging immune system of older adults at greater risk of severe disease [21,22]. T cells are important in harmonizing antiviral immune responses that mediate humoral responses, and the death of infected cells is crucial for controlling and treating primary SARS-CoV-2 infection. Reduced SARS-CoV-2 disease severity is associated with T cell activity. [23]. T-cell survival, proliferation, and inflammatory cytokine production in severe malnutrition are all decreased, as are T-cell glucose uptake and metabolism [24]. Furthermore, innate and acquired immune responses in severe PEM are compromised. COVID-19 disease stimulates the immune system and increases metabolism and nutritional demand. The vicious cycle of worsening nutrition and immune suppression potentially escalates vulnerability to sepsis [25].

Worse outcomes among severely malnourished children signal that the degree of malnutrition could be linked to a weaker immunity compounded by COVID-19. The prevalence of anemic children did not significantly exceed baseline population prevalence. According to World Bank estimates in 2016, the prevalence of anemia in Jamaica was 28% [26] compared with 30 % in the hospitalized cohort. Stratification by the presence or absence of MIS-C or malnutrition when sickle cell disease was excluded showed a strong association of anemia with MIS-C (Figure 3) and no correlation with malnutrition. These findings support earlier studies demonstrating anemia among MIS-C patients [27,28]. In a large cohort of 186 children with MIS-C from 26 States in the United States, most patients had anemia [29]. In contrast, anemia was not associated with mild and moderate cases of COVID-19 [28,30]. A link between undernutrition and COVID-19 disease severity was identified across income stratification but did not ascertain the degree of malnutrition severity with COVID-19 disease severity [2,3,6]. A higher proportion of severely malnourished children could be linked with the poor outcomes identified in LMIC compared with HIC [3]. In this cohort, the proportion of severe undernutrition was low. Nevertheless, deaths in the children with severe malnutrition may signal increased vulnerability requiring additional monitoring and early nutrition intervention when infected with COVID-19.

In conclusion, the prevalence of undernutrition and overweight children hospitalized with COVID 19 exceeded the estimates of the general population in Caribbean children in a primarily UMIC setting. Anemic children were more likely to have MIS-C or sickle cell disease. Malnourished children may be vulnerable to admission due to the exacerbation of COVID-19 on nutrition elements. The link with COVID-19 disease severity could be related to the degree of malnutrition; however, the prevalence of malnutrition was not high enough in this population to detect clinical associations. There is biological plausibility for protection among undernourished children who may have better immune function than severely malnourished children. The deaths in children with severe malnutrition and sepsis may suggest a compound effect on immunity by nutrition severity and COVID-19 disease concomitant with the severity of malnutrition and require prioritized care. The results of this study add to the limited research exploring a link between malnutrition with COVID-19 and have implications for the hospitalization of children most vulnerable to health disparities. The prevalence of hospitalized overweight children warrants intervention in the general population due to the known risks of obesity with severe COVID-19 disease.

We want to thank members of the Paediatric COVID Collaborative group for providing access to records for review and for providing patient care. The members of the Paediatric Collaborative Group include Dr. Michelle-Ann Richards-Dawson, Dr. Jacqueline Wright-James, Dr. Bovette Butler, Dr. Jacqueline Dunkley-Thompson, Dr. Celia Patterson, Dr. Ludrick Morris, Dr. Anona Griffiths, Dr. Curtis Pryce, and Dr. Kerry-Ann McKenzie.

Declaration of Competing Interest

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

Ethical Approval

The protocol is the first output of the Caribbean Paediatric COVID Collaborative survey approved by the Institutional Review Board of the University of the West Indies in Jamaica, Bahamas, and Barbados Institutional Review Board approval numbers ECP 229, 19/20 and 200601-A. All aspects of the work were carried out following relevant guidelines/regulations, including the Helsinki Declaration.

Funding Source

This research received a specific procurement grant 001-2021 from the United Nations International Children's Emergency Fund for data collection, data analysis, and presentation at the UNICEF virtual meeting "COVID-19, Children, and Nutrition: Data Efforts and Priorities" meeting on June 25, 2021.

Authorship Contribution

Conceptualization -Tracy Evans-Gilbert, Ian Hambleton, Carolyn Taylor-Bryan, Maritza Fernandes, Virendra Singh; Methodology- Tracy Evans-Gilbert, Ian Hambleton, Carolyn Taylor-Bryan; Software and Data curation - Tracy Evans-Gilbert, Ian Hambleton; Data collection- Tracy Evans-Gilbert, Corrine Sin Quee, Sandrica Young-Peart, Paula Michele Lashley, Brandon Gilbert, Richelle-Ann Brown; Data Analysis - Ian Hambleton; Writing- Tracy Evans-Gilbert, Ian Hambleton; Critical review and editing- All authors ; Supervision and funding acquisition- Tracy Evans –Gilbert.

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