By comparing the clinical characteristics on admission of 71 pairs of age-matched pediatric IA patients and COVID-19 patients, this study showed that typical IA symptoms were also the most common symptoms for the COVID-19 patients regardless of their relatively rarer occurrence. The levels of some hematological and blood biochemical measurements differed between the IA and COVID-19 patients: abnormally low levels of lymphocyte count and percentage, and abnormally high levels of APTT, PT, C-reactive protein, and procalcitonin were seen more often in the IA patients, while abnormally low levels of neutrophil count and percentage occurred more often in the COVID-19 patients.
The present study confirms the previous reports that fever and cough were the most common symptoms for pediatric COVID-19 patients [3, 7-9]. In the present study, fever and cough occurred in 71% and 51% of the COVID-19 patients. In a larger study of 291 U.S. pediatric COVID-19 patients, the corresponding figures were 56% and 54% . It should be noted that the present study excluded asymptomatic patients in order to make a fair comparison between them and the IA patients who presented to hospital with definite symptoms. Relatively lower occurrences of clinical symptoms have been reported by previous studies, where an increasing proportion (varying from 4.4% to 27.8%) of asymptomatic but laboratory confirmed patients were included as a result of the continuously expanding coverage of the RT-PCR screening among asymptomatic individuals [10-12].
IA and COVID-19 are two infections sharing similar spectrums of symptoms. In addition, studies have shown that these symptoms occur in similar frequencies in adult IA and COVID-19 patients [3, 5, 10, 13, 14]. In this study of pediatric patients, however, COVID-19 caused fewer symptoms in spite of the exclusion of the asymptomatic cases. This finding, together with the data from other studies [3, 4], suggests that adult COVID-19 patients might be more symptomatic than their pediatric counterparts.
Lymphopenia has been found to be a common feature of IA infection for both children and adults and to occur in more than 90% of the pediatric patients [15-17]. However, it seemed not the case for children with COVID-19, given its low incidence (9/59) seen in this study. In another study, lymphopenia occurred only in 3.5% of the pediatric patients of COVID-19, partly due to its stricter definition of lymphopenia (<1.2 ×109/L) . A recent pooled analysis of more than 1,000 adult COVID-19 patients suggests an association between decreased lymphocyte count and intensive care unit (ICU) stay . Data from the present study supports this association in a way that only nine of the 71 COVID-19 patients had abnormally low lymphocyte count and only one patient was eventually admitted to ICU. Previous studies have suggested that excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome in both COVID-19 patients and IA patients [19-21]. The higher levels of neutrophils count and neutrophils percentage among the IA patients suggest that IA might be more severe and prone to poorer diagnosis. Neutropenia has been reported to have an incidence of 10% in adult IA patients , but it is unclear how often it occurs in pediatric patients and whether it has an association with the disease prognosis. For adult COVID-19 patients, a small study showed a higher level of neutrophil count in patients admitted to ICU than in those not . NLR is useful in diagnosing influenza virus infections and in discriminating other respiratory infections [22, 23]. In COVID-19 patients, elevated NLR is an independent factor for poor clinical outcome [24, 25]. In this article, IA patients showed a higher level of NLR compared with COVID-19 patients, suggesting a potential difference in severity between the two infections.
By activating the coagulation system via complex mechanisms including the mediation of cytokines, viral infections can lead to aberrant hemostasis . As a result, prolonged APTT and PT have been observed in both severe IA and COVID-19 [27, 28]. Thus, the averagely higher levels of PT and APTT and the higher proportions of higher-than-normal APTT an PT cases among the IA patients suggest that IA might be overall more severe and prone to poorer diagnosis.
Among the IA patients, we also observed higher proportions of cases with abnormally high levels of C-reactive protein and procalcitonin, which are both key inflammatory markers and are associated with poor prognosis such as pneumonia and even death [29-33]. To date, data from small studies also suggest a positive association between the level of C-reactive protein and the severity of COVID-19 [34, 35]. Elevated procalcitonin level has been observed for 30%-80% of pediatric patients in separate studies, based on different thresholds [4, 8, 9]. In one of these studies, the level of procalcitonin was higher in patients complicated with pneumonia than in patients with upper respiratory tract infection and patients who were asymptomatic . Once again, our results regarding these two markers support that IA is likely to be a more severe infection for children than COVID-19.
In this study, the levels of other hematological and biochemical measurements than the ones we mentioned above showed no statistically significant difference between the two infections. Among them, we noticed that abnormally low platelet count, abnormally high alanine aminotransferase, and abnormally high level of aspartate aminotransferase occurred more often in the IA patients, which might show statistically significance if the sample size increased. Elevation of these measurements are commonly seen in IA patients , but whether the different levels of these measurements indicate different disease severity warrants further investigations.
It is known that COVID-19 shares symptomological similarities with IA, but it might be more worthwhile to detail the disparities between the two infections, as doing so provides health professionals with important information regarding how to handle this new disease via sensible utilization of their existing knowledge and experience in managing IA patients. This study, to the best of our knowledge, has been the first study that serves this purpose. This study benefited from its age-matching design and the use of age-specific clinical thresholds for hematological and biochemical measurements. However, given its small sample size, the results of this study need to be confirmed by larger studies. Also, COVID-19 and IA might display distinct imaging manifestations among children, but only nine out of the 71 IA patients received thoracic TCT scan, making a meaningful comparison between the two diseases impossible. Lastly, because of lack of reliable definitions of disease severity and the incompleteness of prognosis data for the COVID-19 patients, we could not further examine whether the differed clinical characteristics on admission of the two infections eventually lead to different prognosis.