Sage Journals: Discover world-class research

Abstract

Objectives. We aimed to compare the prevalence of co-infections, pathogens, and factors associated with SARS-CoV-2 acute respiratory infection (ARI) and non-SARS-CoV-2 ARI, among hospitalized children. Methods. We conducted an observational cross-sectional study of hospitalized children <15 years with ARI, and lasting respiratory symptoms <14 days, using polymerase chain reaction on nasopharyngeal specimens. Results. Of the 184 children with ARI analyzed, 122 were infected with SARS-CoV-2 and 62 were not. SARS-CoV-2 ARI had a significantly lower rate of co-infection than non-SARS-CoV-2 ARI (2.5% vs14.5%, P = .003). SARS-CoV-2 ARI children were significantly associated with a less empirical antibiotics (aOR = 0.09, CI = 0.03-0.21; P = .000), more pneumonia (aOR = 5.15, CI = 1.77-14.95; P = .003), and more abnormal chest X-ray (aOR = 2.81, CI = 1.38-5.71; P = .004). Conclusions. Although SARS-CoV-2 ARI in hospitalized children was associated with pneumonia and abnormal chest x-rays, empirical antibiotics may not be necessary for treating mild to moderate cases.

Keywords

SARS CoV-2 ARI children co-infection antibiotic

Introduction

Acute respiratory infections (ARIs), particularly in young children, account for 20% to 40% of hospital admissions globally and are one of the leading causes of morbidity and mortality.^1,2 ARI can cause non-severe but widespread epidemics, contributing to the continuous circulation of pathogens within communities. According to the World Health Organization (WHO), ARI is defined as a sudden onset of respiratory symptoms like cough, coryza, fever and shortness of breath.³ Multiple viral infections are more common in pediatric patients than in adult individuals.⁴ A rise in hospital admissions, admissions to intensive care units, pediatric intensive care units (PICU), prolonged hospital stays, need of oxygen support and prolonged use of mechanical ventilation are associated with several viral infections.^5-8 However, some studies indicated that disease severity, management, and outcome were not associated with multiple viral infections.^9,10 In hospitalized children, especially those who are younger, and attend daycare, the incidence of simultaneous detection of multiple viruses alongside ARI typically varies between 10% and 30%.^9,11-13 Moreover, the prevalence of respiratory viruses during episodes of ARI can range widely from 15% to 90%, depending on the detection methods employed and the breadth of viral investigation.^14,15 The SARS-CoV-2 pandemic has necessitated significant changes to our clinical practice with regard to the treatment of children with ARI including circulate with other respiratory viruses, increasing or decreasing the probability of co-infections.^16,17 The co-infection of other viral and bacterial agents in SARS-CoV-2 infected patients can lead to adverse outcomes in the form of increased mortality or prolonged hospitalization in these patients. Several studies have documented unfavorable outcomes in cases where viral co-detection occurs among children.¹⁸ Empirical antibiotics have been administered to nearly 90% of the patients throughout the pandemic.¹⁹

However, the diagnostic gap for SARS-CoV-2, other viruses, and co-infections has narrowed significantly in recent years. According to a previous study, rapid nasopharyngeal swab (NPS) tests have enabled doctors to diagnose viral infections with a positive predictive value of 88.6% and a negative predictive value of 75.0%. Swift NPS testing for respiratory viruses has also emerged as a valuable tool for confirming viral infections in children with ARI, minimize unnecessary antibiotic use in patients with SARS-CoV-2 and other viruses, especially in cases of mild illness.²⁰

The most commonly reported symptoms of SARS-CoV-2 infection include fever and cough, often accompanied by rhinorrhea, nasal congestion, undifferentiated upper airways inflammatory syndrome, and dyspnea. Additionally, various other symptoms such as gastrointestinal issues (nausea, vomiting, abdominal pain, and diarrhea) and anosmia have been documented. In general, children affected by SARS-CoV-2 typically display mild symptoms, but a notable proportion (15%-35%) may remain asymptomatic.^21,22 Among children aged ≤9 years, prevailing symptoms comprise fever (46%), cough (37%), headache (15%), diarrhea (14%), and sore throat (13%) while in children aged 10 to 19 years, the most frequent symptoms are headache (42%), cough (41%), fever (35%), myalgia (30%), sore throat (29%), shortness of breath (16%), and diarrhea (14%).²³

Distinguishing between viral and bacterial illnesses clinically can be challenging. Therefore, laboratory testing to confirm the type of infectious agent is required to enable the prompt initiation of antibiotic treatment for bacterial pneumonia while restricting the use of antibiotics in viral pneumonia.²⁴ The gold standard for determining the cause of ARI and the detection of co-infections is multiplex RT-PCR,^25,26 as the separate detection of these pathogens is time-consuming and labor-intensive.²⁷ Antimicrobial resistance (AMR), intestinal dysbiosis, and antibiotic-associated diarrhea are believed to result from the widespread and inappropriate use of antibiotics and have significant negative impacts on public health and the worldwide economy.^28,29 As an institution dedicated to infection prevention and control in Thailand, Bamrasnaradura Infectious Diseases Institute(BIDI) monitors the rate of co-infections and risk factors in SARS-CoV-2 and other ARI during pandemics and analyzes the effects of these factors on practice. Therefore, we aimed to compare the prevalence of co-infection, types of respiratory pathogens involved in co-infection, and risk factors in children hospitalized with SARS-CoV-2 ARI and non-SARS-CoV-2 ARI.

Methods

Study Setting and Design

This observational cross-sectional study compared the clinical characteristics, and management of SARS-CoV-2 and non-SARS-CoV-2 ARIs among in-patients at the BIDI, Ministry of Public Health, Nonthaburi, from January 2020 to December 2022. We also compared the prevalence of co-infections and types of pathogens in the residual nasopharyngeal samples.

Study Population

Approximately 1000 children are hospitalized annually at our institution, and 40% of all cases involve ARI. The study population included hospitalized children<15 years of age diagnosed with ARI with a duration of respiratory symptoms<14 days and an available residual nasopharyngeal specimen that was routinely collected for the detection of respiratory disease. Residual nasopharyngeal specimens were used to detect respiratory pathogens by multiplex polymerase chain reaction (PCR; QIAstat-Dx Respiratory SARS-CoV-2 Panel). Children previously enrolled in the same ARI episode, AOM, acute sinusitis, or with evidence of bacterial infection were excluded from the study. Data collected from the electronic medical records included demographic data, birth history, past medical history, family history, clinical manifestations, physical examination on admission, clinical diagnosis (upper respiratory tract infection or lower respiratory tract infection), clinical diagnosis (pneumonia or non-pneumonia), laboratory data, duration of illness before hospitalization, and empirical antibiotic use. Patients were categorized into three age groups: 0 to 5 years, 5 to 9 years, and 10 to 15 years. Coinfection was defined as the concurrent infection of a cell or organism with two or more pathogenic agents.^30,31

Specimen Collection and Transportation Along With Detection of Co-infection by QIAstat-Dx Respiratory SARS-CoV-2 Panel

The QIAstat-Dx Respiratory SARS-CoV-2 Panel is a multiplexed, nucleic acid real-time PCR test intended for the qualitative detection, and differentiation of nucleic acids from multiple respiratory viral and bacterial pathogens, including SARS-CoV-2, in nasopharyngeal swabs eluted in universal transport media collected from patients suspected of SARS-2 by their healthcare providers. The QIAstat-Dx Respiratory SARS-CoV-2 Panel is intended for the detection and differentiation of nucleic acids from SARS-CoV-2 and subsequent pathogen types and subtypes. Amongst viruses, these are Adenovirus, Bocavirus, Coronavirus 229E, Coronavirus HKU1, Coronavirus NL63, Coronavirus OC43, SARS-CoV-2, Human Metapneumovirus A + B, Influenza A, Influenza A H1, Influenza A H3, Influenza A H1N1/pdm09, Influenza B, Parainfluenza virus 1, Parainfluenza virus 2, Parainfluenza virus 3, Parainfluenza virus 4, Rhinovirus/Enterovirus, Respiratory Syncytial Virus A + B, and amongst bacterium, these are Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae.³²

Statistical Analysis

Data were analyzed descriptively. Continuous data are presented as mean ± SD as appropriate. Categorical data were presented as frequency (%), and continuous data were compared using the independent t-test or Mann-Whitney U test, as appropriate for distribution. Categorical data were compared using the independent chi-squared test or Fisher’s exact test, as appropriate.

The sample size was calculated using a proportional formula assuming a prevalence of co-infection of 19.8% among SARS-CoV-2 infected children,²⁴ the calculated minimum sample size for both groups was 61. A simple random sampling method was used to select the study participants.

Results

Study Population

As shown in Figure 1, we screened 235 cases of ARI in hospitalized children under the age of 15 years, covering the period from January 2020 to December 2022. Out of these cases, 28 exhibited respiratory symptoms for a duration ≥14 days, and 9 cases had unavailable residual nasopharyngeal specimens. Following the initial screening, we identified 198 patients who progressed to the subsequent analysis phase. From this pool, we excluded 14 cases for the following reasons: 10 cases were previously enrolled for the same ARI episode, one case had acute otitis media, one case presented with acute sinusitis, and two cases showed evidence of bacterial infection. In total, 184 individuals were included in the final analysis. Among them, 122 (63.3%) were diagnosed with SARS-CoV-2 infection, and 62 (33.7%) were not have SARS-CoV-2 infection. All 184 residual nasopharyngeal specimens were used to detect respiratory pathogens using multiplex PCR. None of the hospitalized children died.

Figure 1.

Flowchart of SARS-CoV-2 infection with ARI and non-SARS-CoV-2 infection with ARI among hospitalized children.

As shown in Table 1. Multiplex polymerase chain reaction (PCR) was used to analyze 184 nasopharyngeal specimens for the presence of various pathogens. Among the 167 pathogens detected, the distribution was as follows: SARS-CoV-2 (n = 122, 73.05%), Rhinovirus/Enterovirus (n = 19, 11.38%), Bocavirus (n = 8, 4.79%), RSV (n = 6, 3.59%), Parainfluenza-3 (n = 4, 2.39%), Adenovirus (n = 2, 1.20%), Influenza A-H3 (n = 2, 1.20%), Coronavirus 229E (n = 1, 0.60%), Coronavirus OC43 (n = 1, 0.60%), HMPV A/B (n = 1, 0.60%), and Mycoplasma pneumoniae (n = 1, 0.60%). Twelve hospitalized children with ARI experienced co-infections, comprising 3 cases involving SARS-CoV-2 and 9 cases without SARS-CoV-2 involvement. In the single pathogen category, there were 119 cases with SARS-CoV-2 and 22 cases without SARS-CoV-2. Notably, 31 patients in the non-SARS-CoV-2 group had no identifiable pathogens.

Table 1.

Prevalence of Respiratory Pathogens in 184 Hospitalized Children with ARI.

Pathogen	Total = 167 (100%)n (%)
SARS CoV-2	122 (73.05)
Rhinovirus/Enterovirus	19 (11.38)
Bocavirus	8 (4.79)
RSV	6 (3.59)
Parainfluenza-3	4 (2.39)
Adenovirus	2 (1.20)
Influenza A-H3	2 (1.20)
Coronavirus 229E	1 (0.60)
Coronavirus OC43	1 (0.60)
HMPV A/B	1 (0.60)
Mycoplasma pneumoniae	1 (0.60)

Prevalence of Co-infection and a Comparative Analysis Between SARS-CoV-2 ARI and Non-sARS-CoV-2 ARI Among Hospitalized Children

As shown in Figure 2, SARS-CoV-2 ARI had a significantly lower rate of co-infection than non-SARS-CoV-2 ARI (3/122 (2.5%) vs 9/62 (14.5%), P-value = .003). The proportions of SARS-CoV-2+Rhinovirus/Enterovirus, and SARS-CoV-2+ Coronavirus 229 were 1.64% (2/122), and 0.82% (1/122), respectively. Among the 62 non-SARS-CoV-2 ARI children with multiple pathogen infections, the most common combination of pathogens was Bocavirus+ Rhinovirus/Enterovirus (n = 3), followed by Bocavirus + Parainfluenza virus 3 (n = 2), Rhinovirus/Enterovirus + Human Metapneumovirus A + B (n = 1), Rhinovirus/Enterovirus + Parainfluenza virus 3 (n = 1), and Influenza A H3+ Mycoplasma pneumoniae (n = 1). The most common combination for four infectious was Bocavirus+ Parainfluenza virus 3 + Rhinovirus/Enterovirus+ Respiratory Syncytial Virus A + B (n = 1).

Figure 2.

Prevalence of co-infection and comparative analysis between SARS-CoV-2 ARI and non-SARS-CoV-2 ARI among hospitalized children.

Comparison of Characteristics, Data, Symptoms, Signs, and Laboratory Tests Between SARS-CoV-2 ARI and Non-sARS-CoV-2 ARI Among Hospitalized Children

As shown in Table 2, the mean age ± SD in SARS-CoV-2 ARI children was 3.99 ± 3.91 years while it was 4.00 ± 3.82 years in non-SARS-CoV-2 ARI children. SARS-CoV-2 ARI children had significantly more pneumonia diagnose, more abnormal chest X-ray findings, and less empirical antibiotic use than non-SARS-CoV-2 ARI children (all P < .05). Age, age category, weight, sex, underlying medical condition, proportion of diagnosis (upper respiratory tract infection and lower respiratory tract infection), fever, cough, rhinorrhea, sore throat, sputum, diarrhea, vomiting, loss of appetite, loss of taste, smell, seizures, peak body temperature on the first day, WBC count, hemoglobin level, platelet count, duration of illness before hospitalization, oxygen support, and PICU admission were not significantly different between the groups(P > .05).

Table 2.

Comparison of Characteristics, Data, Symptoms, Signs, and Laboratory Tests Between SARS-CoV-2 ARI and Non-SARS-CoV-2 ARI Among Hospitalized Children.

Characteristics data	SARS-CoV-2 ARIchildren (n = 122)	Non-SARS-CoV-2 ARIchildren (n = 62)	P value
Age (years), mean ± SD	3.99 ± 3.91	4.00 ± 3.82	.98
Age category			.101
0-5 years	46 (37.7%)	38 (61.3%)
5-10 years	44 (36.1%)	16 (25.8%)
10-15 years	32 (26.2%)	8 (12.9%)
Weight (kg), mean ± SD	18.67 ± 13.81	19.22 ± 15.63	.806
Male, n (%)	68 (55.7%)	40 (64.5%)	.271
Underlying medical condition, n (%)	7 (5.7%)	9 (14.5%)	.056
Diagnosis, n (%)			1.00
Upper respiratory tract infection	59 (48.4%)	30 (48.4%)
Lower respiratory tract infection	63 (51.6%)	32 (51.6%)
Pneumonia diagnosis, n (%)			.000*
Pneumonia	52 (42.6%)	9 (14.5%)
Non-Pneumonia	70 (57.4%)	53 (85.5%)
Clinical manifestations
Respiratory symptoms, n (%)
Fever	100 (82.0%)	51 (82.3%)	1.00
Cough	67 (54.9%)	43 (69.4%)	.080
Rhinorrhea	41 (33.6%)	19 (30.6%)	.741
Sore throat	4 (3.3%)	3 (4.8%)	.689
Sputum	16 (13.1%)	8 (12.9%)	1.00
Nonrespiratory symptoms, n (%)
Diarrhea	8 (6.6%)	7 (11.3%)	.270
Vomiting	17 (13.9%)	4 (6.5%)	.149
Loss of appetite	8 (6.6%)	1 (1.6%)	.276
Loss of taste and smell	2 (1.6%)	0 (0.0%)	.551
Seizures	1 (0.8%)	1 (1.6%)	1.00
Chest X-rays findings			.000*
Abnormal	84 (68.9%)	20 (32.3%)
Normal	34 (27.9%)	41 (66.1%)
Not done	4 (3.2%)	1 (1.6%)
Peak body temperature at first day (°C), mean (SD)	37.86 ± 1.07	38.17 ± 0.99	.060
Complete blood count (CBC)
WBC ×10³in cells/µl, mean (SD)	10 200 ± 3691	11 400 ± 6133	.799
Hb g/dl, mean (SD)	12.04 ± 1.42	12.80 ± 4.50	.225
Platelet ×10⁵ in cells/µl, mean (SD)	293 100 ± 117 568	328 000 ± 130 645	.119
Duration of illness before being hospitalized (days), median (SD)	1.82 ± 1.80	2.25 ± 2.11	.349
Antibiotic use, n (%)	18 (14.8%)	31 (50%)	.000*
Oxygen support, n (%)	4 (3.3%)	5 (8.1%)	.145
PICU, n (%)	1 (0.8%)	1 (1.6%)	1.000

P value <.05 significant.

Table 3 shows the exploratory multivariate logistic regression model of SARS-CoV-2 ARI children. In the exploratory multivariate analysis, independent predictors of SARS-CoV-2 infected children with ARI were less empirical antibiotics use (aOR = 0.09, 95% CI = 0.03-0.21; P-value = .000), more pneumonia diagnosis (aOR = 5.15, 95% CI = 1.77-14.95; P-value = .003), and more abnormal chest X-ray findings (aOR = 2.81, 95% CI = 1.38-5.71; P-value = .004).

Table 3.

Multivariate Logistic Regression Model of SARS-CoV-2 Infected Children with ARI.

Variable	aOR	P-value	95% CI
Antibiotic use	0.09	.000*	0.03-0.21
Pneumonia	5.15	.003*	1.77-14.95
Chest X-rays findings	2.81	.004*	1.38-5.71

P value <.05 significant.

Discussion

In the SARS-CoV-2 pandemic era, we found a significantly lower rate of co-infection in SARS-CoV-2 infected children with ARI than in those with non-SARS-CoV 2 (2.5% vs 14.5%, respectively). Similarly, Wang et al in a study from Wuhan, China, found the amongst 613 patients tested for the presence of 13 respiratory pathogens, only 5.8% of SARS-CoV 2 infected patients, and 18.4% of non-SARS-CoV 2 had co-infection.³³ In Singapore, Wee et al demonstrated a co-infection rate between SARS-CoV-2, and other respiratory viruses was low at 1.4%.³⁴ Conversely, in the United States, Kim et al showed that amongst 1217 patients, 19.8% of SARS-CoV-2 infected patients and 26.5% of non- SARS-CoV-2 patients had co-infection, and there was no significant difference in co-infection among these patients.³⁵ In the present study, we have demonstrated that co-infection with other respiratory pathogens was less common among the SARS-CoV-2 children at one center in Thailand. The possible reason could have been competitive advantage of SARS-CoV-2 in modulating the host’s immunity. It has been hypothesized that competitive advantage may play a role in the SARS-CoV-2 interaction with other respiratory viruses during co-infection, and that this may be one reason why the co-infection rate in SARS-CoV-2 patients is much lower.³⁶ However, the prevalence of each respiratory pathogen may have varied between studies due to population, seasonality, geographic areas, and detection techniques.¹⁴ Furthermore, the co-infection rate during the SARS-CoV-2 pandemic is affected by clinical, demographic, outcome patterns and country-specific policy. For example, a previous study conducted in Italy has revealed that 57.25% of co-infections occurred in children hospitalized with lower respiratory tract infections who tested positive for viral infections during the SARS-CoV-2 pandemic, and the severity of these cases was increased.⁸

The present study demonstrated that the majority of respiratory pathogens were Rhinovirus/Enterovirus among non-SARS-CoV-2 infected children. A similar result was found by Danielle et al in the United State that demonstrated Rhinovirus/Enterovirus persisted, and was the most common respiratory pathogen. Rhinovirus/enterovirus remains a leading factor in the ARI health care burden, and active ARI surveillance in children, and adolescents remains critical for defining the health care burden of respiratory viruses.³⁷ The simultaneous detection of multiple pathogens, especially viruses, does not necessarily implicate a pathogenic effect at the time of detection, especially when molecular methods are used. It is also difficult to distinguish between active viral infection, viral shedding, and potentially non-pathogenic viral infections. For instance, human bocaviruses and human adenoviruses may exhibit prolonged viral shedding.¹¹

In the current study, antibiotic use for children with SARS-CoV-2 ARI was lower. Numerous previous studies have suggested that empirical antibacterial therapy is unnecessary in children with ARIs for several reasons. Firstly, children with fever who have tested positive for viral infection should be initially diagnosed with viral infections until proven otherwise. Antibiotics should only be administered if bacterial infection is strongly suspected and is supported by further diagnostic evaluations.²⁰ Secondly, bacterial co-infection in patients with SARS-CoV-2 ARI is relatively uncommon. For instance, a study conducted in Spain during the early months of the pandemic has found that less than 10% of SARS-CoV-2 patients had bacterial co-infection.³⁸ Additionally, a prospective observational study conducted across multiple European centers, representative of the target population for NPS testing, has reported that 10% to 15% of children presenting with fever are diagnosed with a bacterial infection.³⁹ Lastly, according to our institution’s treatment guidelines for SARS-CoV-2 and other viral infections during the pandemic, empirical antibiotic therapy is not recommended for mild to moderate cases. Furthermore, upon admission for SARS-CoV-2, isolation is strongly advised, particularly for children.

The present study demonstrated that SARS-CoV-2 ARI children were associated with pneumonia and a high proportion of abnormal chest X-ray findings. Similarly, a previous study demonstrated a high prevalence of pneumonia diagnosis in SARS-CoV-2 infection at 62.5%, which was higher than other pathogens, such as the prevalence of pneumonia diagnosis as H1N1 influenza, which was low at 11%.⁴⁰ In addition, Oterino et al and Palabiyik et al in children demonstrated that pulmonary abnormalities on chest X-ray were found in 46% to 90% of cases.^41,42 However, the radiologic abnormalities of SARS-CoV-2 infection among children are non-specific, and chest X-rays alone are insufficient for confirmed diagnosis.⁴³ It is interesting to note that whereas SARS-CoV-2 ARI children were linked to greater pneumonia diagnoses than non-SARS-CoV-2 group, the severity of pneumonia in both groups was the same. However, the cases of adult SARS-CoV-2 pneumonia, it is different. Preschoolers’ immune cell repertoire is 5 to 10 times bigger than that of a 50-year-old and 20 times larger than that of an 80-year-old, owing to the immune response in children being different from that of adults, which gradually deteriorates with age. The extent to which this may help prevent the virus from spreading and the cytokine signaling cascade initiated by SARS-CoV-2 in relation to serious adult outcomes remains unknown.⁴⁴

Our study has limitation of address. Firstly, the study had a small sample size with, variation in the number of included children because of the laboratory-based cross-sectional retrospective survey nature of the study. Secondly, our questionnaire was pilot-tested, which may be misleading in small sample size. However, pilot testing enables us to assess the entire questionnaire under survey conditions, identify problems, and examine the validity of each question. Lastly, our PCR panel did not include all frequently encountered respiratory viruses, such as other endemic Coronaviridae.

Conclusions

Empirical antimicrobial therapy is crucial for severe infections, especially nosocomial cases caused by Gram-negative bacteria. which are often responsible for critical conditions. Timely initiation of appropriate antibiotics improves survival rates. However, excessive use of empirical therapy, particularly in cases of viral infections and non-severe conditions, undoubtedly contributes to the development of bacterial resistance to antibiotics in pediatric patients worldwide.

We suggest that empirical antimicrobial therapy is not required for the routine management of children hospitalized with mild SARS-CoV-2 ARI, even though pneumonia and abnormal chest radiography findings were identified in cases of SARS-CoV-2 ARI.

Supplemental Material

sj-docx-1-gph-10.1177_2333794X241275267 – Supplemental material for Prevalence of Co-Infections and Pathogens in Hospitalized Children with Acute Respiratory Infections: A Comparative Analysis Between SARS-CoV-2 and Non-SARS-CoV-2 Cases

Supplemental material, sj-docx-1-gph-10.1177_2333794X241275267 for Prevalence of Co-Infections and Pathogens in Hospitalized Children with Acute Respiratory Infections: A Comparative Analysis Between SARS-CoV-2 and Non-SARS-CoV-2 Cases by Visal Moolasart, Ravee Nitiyanontakij, Srisuda Samadchai, Somkid Srisopha, Priyanut Atiburanakul, Suthat Chottanapund and Sumonmal Uttayamakul in Global Pediatric Health

Footnotes

Acknowledgements

We thank all the study participants and staff of Bamrasnaradura Infectious Diseases Institute, Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.

Author Contributions

VM: Contributed to conception, design, acquisition, analysis, interpretation, Drafted the manuscript, Critically revised the manuscript, Gave final approval, Agrees to be accountable for all aspects of work ensuring integrity and accuracy. RN: Contributed to conception, design, acquisition, analysis, interpretation, Drafted the manuscript, Critically revised the manuscript, Gave final approval, Agrees to be accountable for all aspects of work ensuring integrity and accuracy. SS (Srisuda Samadchai): Contributed to conception, acquisition, analysis, Drafted the manuscript, Gave final approval, Agrees to be accountable for all aspects of work ensuring integrity and accuracy. SS (Somkid Srisopha): Contributed to conception, design, Critically revised the manuscript, Gave final approval, Agrees to be accountable for all aspects of work ensuring integrity and accuracy. PA: Contributed to conception, design, Critically revised the manuscript, Gave final approval, Agrees to be accountable for all aspects of work ensuring integrity and accuracy. SC: Contributed to conception, design, Critically revised the manuscript, Gave final approval, Agrees to be accountable for all aspects of work ensuring integrity and accuracy. SU: Contributed to conception, design, acquisition, analysis, interpretation, Drafted the manuscript, Critically revised the manuscript, Gave final approval, Agrees to be accountable for all aspects of work ensuring integrity and accuracy.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was conducted by the Bamrasnaradura Infectious Diseases Institute. The PCR respiratory pathogen panel was provided by the Japan International Cooperation Agency for the Capacity Building of Infectious Disease Institute in responding to COVID-19.

Ethics Approval and Informed Consent

Ethical clearance was obtained from the ethical review and research committee of the Bamrasnaradura Infectious Diseases Institute, situated at the Ministry of Public Health in Nonthaburi, Thailand (Postal Code: 11000), After a thorough assessment of the study for its scientific contribution and ethical issues, approval was granted with the reference code SO12h/65. The requirement for informed consent was waived due to the retrospective nature of the study, which relied on secondary data collected from patients’ medical charts and residual nasopharyngeal samples. Furthermore, all methods were performed in accordance with the ethical standards outlined in the Declaration of Helsinki and its later amendments or comparable ethical standards.

Consent for Publication

Not applicable.

ORCID iD

Visal Moolasart

Supplemental Material

Supplemental material for this article is available online.

References

Liu

Oza

Hogan

, et al Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388(10063):3027-3035. doi:10.1016/S0140-6736(16)31593-8

Brini Khalifa

Hannachi

Guerrero

, et al Demographic and seasonal characteristics of respiratory pathogens in neonates and infants aged 0 to 12 months in the Central-East region of Tunisia. J Med Virol. 2019;91(4):570-581. doi:10.1002/jmv.25347

Identification of ILI/SARI/ARI Cases Asper WHO Case Definition (Referred and Systematic Collected Samples) . 2021. Accessed August 10, 2021. https://who.int/dhr. gov.in/sites/default/files/Influenza%20Algorithm.pdf

Galanti

Birger

Ud-Dean

, et al Longitudinal active sampling for respiratory viral infections across age groups. Influenza Other Respi Viruses. 2019;13(3):226-232. doi:10.1111/irv.12629

Chauhan

Slamon

NB.

The impact of multiple viral respiratory infections on outcomes for critically ill children. Pediatr Crit Care Med. 2017;18(8):e333-e338. doi:10.1097/PCC.0000000000001232

Cilla

Oñate

Perez-Yarza

, et al Viruses in community-acquired pneumonia in children aged less than 3 years old: high rate of viral coinfection. J Med Virol. 2008;80(10):1843-1849. doi:10.1002/jmv.21271

Richard

Komurian-Pradel

Javouhey

, et al The impact of dual viral infection in infants admitted to a pediatric intensive care unit associated with severe bronchiolitis. Pediatr Infect Dis J. 2008;27(3):213-217. doi:10.1097/INF.0b013e31815b4935

Buonsenso

Ferro

Viozzi

, et al Changes in clinical, demographic, and outcome patterns of children hospitalized with non-SARS-CoV-2 viral low respiratory tract infections before and during the COVID pandemic in Rome, Italy. Pediatr Pulmonol. 2024;59(2):362-370. doi:10.1002/ppul.26755

Wishaupt

van der Ploeg

de Groot

Versteegh

Hartwig

NG.

Single- and multiple viral respiratory infections in children: disease and management cannot be related to a specific pathogen. BMC Infect Dis. 2017;17(1):62. doi:10.1186/s12879-016-2118-6

10.

Chou

Lin

Chen

, et al Comparisons of etiology and diagnostic tools of lower respiratory tract infections in hospitalized young children in southern Taiwan in two seasons. J Microbiol Immunol Infect. 2016;49(4):539-545. doi:10.1016/j.jmii.2014.08.029

11.

Scotta

Chakr

de Moura

, et al Respiratory viral coinfection and disease severity in children: a systematic review and metaanalysis. J Clin Virol. 2016;80:45-56. doi:10.1016/j.jcv.2016.04.019

12.

Goka

Vallely

Mutton

Klapper

PE.

Single and multiple respiratory virus infections and severity of respiratory disease: a systematic review. Paediatr Respir Rev. 2014;15(4):363-370. doi:10.1016/j.prrv.2013.11.001

13.

Amarin

Potter

Thota

, et al Clinical characteristics and outcomes of children with single or co-detected rhinovirus-associated acute respiratory infection in Middle Tennessee. BMC Infect Dis. 2023;23(1):136. doi:10.1186/s12879-023-08084-4

14.

Wang

Zheng

Deng

, et al Prevalence of respiratory viruses among children hospitalized from respiratory infections in Shenzhen, China. Virol J. 2016;13:39. doi:10.1186/s12985-016-0493-7

15.

Chowdhury

Shahid

ASMSB

Ghosh

, et al Viral etiology of pneumonia among severely malnourished under-five children in an urban hospital, Bangladesh. PLoS One. 2020;15(2). doi:10.1371/journal.pone.0228329

16.

Olsen

Azziz-Baumgartner

Budd

, et al Decreased influenza activity during the COVID-19 pandemic-United States, Australia, Chile, and South Africa, 2020. Am J Transplant. 2020;20(12):3681-3685. doi:10.1111/ajt.16381

17.

Kawai

Fukushima

Yomota

, et al Number of patients with influenza and COVID-19 coinfection in a single Japanese hospital during the first wave. Jpn J Infect Dis. 2021;74(6):570-572. doi:10.7883/yoken.JJID.2020.1009

18.

Debiaggi

Canducci

Ceresola

Clementi

The role of infections and coinfections with newly identified and emerging respiratory viruses in children. Virol J. 2012;9:247. doi:10.1186/1743-422X-9-247

19.

Lai

Shih

Tang

Hsueh

PR.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents. 2020;55(3). doi:10.1016/j.ijantimicag.2020.105924

20.

Buonsenso

Morello

Mariani

, et al Utility of rapid nasopharyngeal swab for respiratory pathogens in the diagnosis of viral infections in children hospitalized with fever: A prospective validation study to improve antibiotic use. Children. 2024;11(2):225. doi:10.3390/children11020225

21.

Chen

Shu

, et al Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus. World J Pediatr. 2020;16(3):240-246. doi:10.1007/s12519-020-00345-5

22.

Stokes

Zambrano

Anderson

, et al Coronavirus disease 2019 case surveillance - United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(24):759-765. doi:10.15585/mmwr.mm6924e2

23.

Zimmermann

Curtis

COVID-19 in children, pregnancy and neonates: a review of epidemiologic and clinical features. Pediatr Infect Dis J. 2020;39(6):469-477. doi:10.1097/inf.0000000000002700

24.

Sapra

Kirubanandhan

Kanta

, et al Respiratory viral infections other than SARS CoV-2 among the North Indian patients presenting with acute respiratory illness during the first COVID-19 wave. Virus Dis. 2022;33(1):57-64. doi:10.1007/s13337-022-00761-3

25.

Mahony

JB.

Detection of respiratory viruses by molecular methods. Clin Microbiol Rev. 2008;21(4):716-747. doi:10.1128/CMR.00037-07

26.

Wertheim

HFL

Nadjm

Thomas

, et al; DNT. Viral and atypical bacterial aetiologies of infection in hospitalised patients admitted with clinical suspicion of influenza in Thailand, Vietnam and Indonesia. Influenza Other Respi Viruses. 2015;9(6):315-322. doi:10.1111/irv.12326

27.

Malhotra

Swamy

Reddy

Kumar

Tiwari

JK.

Evaluation of custom multiplex real - time RT - PCR in comparison to fast - track diagnostics respiratory 21 pathogens kit for detection of multiple respiratory viruses. Virol J. 2016;13:91. doi:10.1186/s12985-016-0549-8

28.

Aslam

Wang

Arshad

, et al Antibiotic resistance: a rundown of a global crisis. Infect Drug Resist. 2018;11:1645-1658. doi:10.2147/IDR.S173867

29.

Prestinaci

Pezzotti

Pantosti

Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. 2015;109(7):309-318. doi:10.1179/2047773215Y.0000000030

30.

Hatem

Mohamed

Abu Elhassan

, et al Clinical characteristics and outcomes of patients with severe acute respiratory infections (SARI): results from the Egyptian surveillance study 2010-2014. Multidiscip Respir Med. 2019;14:11. doi:10.1186/s40248-019-0174-7

31.

Griffiths

Pedersen

Fenton

Petchey

OL.

The nature and consequences of coinfection in humans. J Infect. 2011;63(3):200-206. doi:10.1016/j.jinf.2011.06.005

32.

FDA. QIAstat-Dx Respiratory SARS-CoV-2 Panel - US Food. Accessed February 1, 2023. https://www.fda.gov › media › download

33.

Wang

, et al Clinical diagnosis of 8274 samples with 2019-novel coronavirus in Wuhan. MedRxiv. 2020:2020-2102. doi:10.1101/2020.02.12.20022327

34.

Wee

KKK

, et al Community-acquired viral respiratory infections amongst hospitalized inpatients during a COVID-19 outbreak in Singapore: co-infection and clinical outcomes. J Clin Virol. 2020;128. doi:10.1016/j.jcv.2020.104436

35.

Kim

Quinn

Pinsky

Shah

Brown

Rates of co-infection between SARS-CoV-2 and other respiratory pathogens. JAMA. 2020;323(20):2085-2086. doi:10.1001/jama.2020.6266

36.

Nowak

Sordillo

Gitman

Paniz Mondolfi

AE.

Coinfection in SARS-CoV-2 infected patients: Where are influenza virus and rhinovirus/enterovirus?

J Med Virol. 2020;92(10):1699-1700. doi:10.1002/jmv.25953

37.

Rankin

Spieker

Perez

, et al; NVSN Network Investigators. Circulation of rhinoviruses and/or enteroviruses in pediatric patients with acute respiratory illness before and during the COVID-19 pandemic in the US. JAMA Netw Open. 2023;6(2). doi:10.1001/jamanetworkopen.2022.54909

38.

Garcia-Vidal

Sanjuan

Moreno-García

, et al; COVID-19 Researchers Group. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect. 2021;27(1):83-88. doi:10.1016/j.cmi.2020.07.041

39.

Shah

Voice

Calvo-Bado

, et al Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study. Lancet Reg Heal Eur. 2023;32. doi:10.1016/j.lanepe.2023.100682

40.

Babyn

Chu

Tsou

, et al Severe acute respiratory syndrome (SARS): chest radiographic features in children. Pediatr Radiol. 2004;34(1):47-58. doi:10.1007/s00247-003-1081-8

41.

Oterino Serrano

Alonso

Andrés

, et al Pediatric chest x-ray in covid-19 infection. Eur J Radiol. 2020;131. doi:10.1016/j.ejrad.2020.109236

42.

Palabiyik

Kokurcan

Hatipoglu

Cebeci

Inci

Imaging of COVID-19 pneumonia in children. Br J Radiol. 2020;93(1113). doi:10.1259/bjr.20200647

43.

Aguirre Pascual

Coca Robinot

Gallego Herrero

, et al Pediatric chest X-rays during the COVID-19 pandemic. Radiologia. 2021;63(2):106-114. doi:10.1016/j.rx.2020.11.008

44.

Volpi

Naviglio

Tommasini

Covid-19 e risposta immune. Med Bambino. 2020;39(4):223-231.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.04 MB