A Comprehensive Comparison of COVID-19 Characteristics (Wuhan Strain) Between Children and Adults During Initial Pandemic Phase: A Meta-Analysis Study

Coronavirus 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which appeared in Wuhan, Hubei, the People’s Republic of China, at the end of September 2019. Novel coronavirus disease 2019 (COVID-19) poses a serious medical challenge, as well as significant societal and economic consequences (1, 2). The disease is a global epidemic that affects 632,161,336 cases and causes 6,580,216 deaths in 237 countries, regions, or territories until October 21, 2022 (3). Although COVID-19 can affect all age groups, children or adolescents appear less susceptible to the infection (4). In addition, reports of severe forms of COVID-19 are rare in the pediatric population (5). Although the pandemic is not over and a new variant of concern (Omicron) and its sublineages BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 cause considerable concern at the end of 2021, COVID-19 cases and hospitalizations are on the downslope, and deaths also continue to decrease, which promises the final days of the coronavirus pandemic (6).

Our systematic review and meta-analysis aimed to determine the most common comorbidities, clinical signs and symptoms, imaging features, treatments, outcomes, and complications in the early phase of the COVID-19 pandemic. Our systematic review and meta-analysis compared adult and pediatric patients to identify the differences better.

Despite the appearance of Omicron subvariants, we are nearing the ending of the pandemic, and the current phase appears to be a transition from previous sharp peaks to a less severe surge. So, to better understand SARS-CoV-2 features, it is time to classify pandemic phases based on the different virus strains. In this regard, the current study, which relooked at the COVID-19 pandemic in its initial stages, can be considered pioneering. Early in the pandemic, the clinical characteristics of pediatric patients with SARS-CoV-2 infection were not well recognized (9). The original SARS-CoV-2 infection primarily affects adults, whereas newer variations of concern (VOC) variably affect children. In critically ill adult patients, the beta variant did not vary from the alpha variant in terms of patient characteristics, management, or outcomes (10). In the United States, the first occurrence of multisystem inflammatory syndrome in children (MIS-C) started shortly after the beta variant peak (11). Furthermore, the alpha variant has been associated with an increase in COVID-19 cases and hospitalizations among young people (12). In children under the age of five, the incidence rate of SARS-CoV-2 infection with the Omicron variant was six to eight times that of the delta variant, but overall severe clinical consequences were less common than with the delta variant (13). However, there has been some concern about the risk of cardiac arrest associated with the Omicron variant’s rapid-onset upper airway obstruction (14).

As earlier noted, new VOC-related clinical manifestations changed quickly, particularly in children infected with COVID-19; however, based on our findings in the early pandemic phase, fever and cough were the most common symptoms in both adults and children. Therefore, the patient’s age is one of the main determinants of different disease phenotypes (15-17). The preponderance of arthralgia and headache in children was one of the key findings in our study, whereas other studies observed a higher proportion of headaches in adults (18, 19). Furthermore, nausea and vomiting, chest pain, gastrointestinal symptoms, and gastric pain are all insignificantly higher in children, according to our findings. Adult patients had considerably higher rates of fever, fatigue, and dyspnea. Moreover, no cases of chest tightness, confusion, or myalgia were found in children. Although there was no statistical difference in CT-scan findings, children had more normal imaging studies. Our findings are similar to that of another systematic review on children, which found that more than a third of COVID-19 patients had a normal chest CT scan (20). Small subpleural nodular ground-glass opacity is the most common CT-scan abnormality in children infected with the original strain (21). Patchy shadows, ground-glass opacities, consolidation, partial air bronchogram signs, nodules, and halo signs were the most commonly reported pulmonary manifestations in a systematic review conducted before the resurgence of the alpha, delta, gamma, and Omicron strains, while pleural effusion and paving pattern were rare (22). Besides, the delta variant showed fewer abnormalities than the original strain, mainly found in the lower lungs on both sides confined in a single lobe (unlike the initial strain, which was distributed over multiple lobes) (21). Unilateral/bilateral pneumonia, multiple mottling, and ground-glass opacities were detected in children and adults infected with the original SARS-CoV-2 strain without statistically significant differences, according to our data acquired during the initial pandemic phase.

Adult COVID-19 cases had significantly more comorbidities, such as cardiovascular disease, obesity, and diabetes; however, our findings show that the risk of malignancy is significantly higher in infected children. Following the emergence of the Omicron variant, the incidence of pediatric cases has considerably increased. Even though children’s symptoms are milder than adults’, severe disease can still occur, especially in children with comorbidities (23).

Poor outcomes were connected to heart failure, acute respiratory distress syndrome (ARDS), and renal failure. Compared to non-severe cases, individuals with severe COVID-19 more often need mechanical ventilation and renal replacement therapy. Prehospital comorbidities are an important factor in children as well (24). according to evidence from Middle East respiratory syndrome (MERS) or the flu, patients who have been given corticosteroids have longer viral replication, need mechanical ventilation, and have a higher death rate (25-28). However, systemic corticosteroids may improve all-cause mortality in critically ill patients with COVID-19, according to the results of a meta-analysis of clinical studies (29). Antibiotics are prescribed to most COVID-19 patients, even though the estimated prevalence of bacterial co-infection is much lower (30). In patients with COVID-19, the usage of unnecessary antibiotics is likely to be considerable. In addition, we found that adults used much more antibiotics than children. Nonetheless, antibiotics were given to around 40% of the children studied.

This meta-analysis has some advantages. The most remarkable advantage of our study may be the investigation of COVID-19 characteristics in adult and pediatric patients during the early phases of the pandemic, which is carried entirely during the wild-type SARS-CoV-2 (Wuhan’s strain) circulation in the first six months of the pandemic. Given that the beta, alpha, delta, and gamma strains were discovered in May, September, October, and November of 2020, respectively, the current study mainly analyzes clinical, and radiological findings and clinical outcomes of the disease during the COVID-19 initial phase induced by Wuhan strain. Second, we collected our data from more than 25,000 articles based on five different databases, increasing the comprehensiveness of this review. Third, we used almost all data about pediatric patients in our systematic review; however, articles about pediatric patients were published later. Fourth, our results were analyzed by two different software, and three experts checked quantitatively and qualitatively. Finally, the authors recommend that future studies focus on the various phases of the pandemic when performing similar studies. There are some limitations to our study. For example, the results could have been influenced by different research locations, methodology, and outcome measures. Another drawback was the inclusion of different types of research, which may inadvertently influence the conclusions based on the strengths and limitations of each study.

Although children were afflicted less than adults in the early stages of the pandemic and had lower mortality, clinical and radiological findings, as well as prognostic factors, did not differ significantly between adults and children. However, with the introduction of novel variants, clinical signs and symptoms, complications, and outcomes have all changed significantly in children.