Acute respiratory infections in children, before and after the COVID-19 pandemic, a sentinel study.

Dear editor,

Acute respiratory infection (ARI) is a leading cause of hospital admission of children [1]. The COVID-19 pandemic may pose extra burden to the ARI. China adopted grid governance measures to effectively control the first wave of COVID-19 pandemic [2]. The outbreak of COVID-19 and the strict control measures may shape the pathogen spectrum of ARI [3]. Nationwide prospective surveillance of ARI during a 10-year period in China has been reported [4]. In this study, we investigated the etiological feathures of 440 young patients who were diagonised as acute respiratory infection in a sentinel hospital between an interval before the COVID-19 (2019, Oct-2020, Jan) and an interval after the COVID-19 (2020, May-2021, Jan) in China. All the patients were verified COVID-19 negative. Throat swab samples were collected weekly. The median age of the patients was 6 years, 45.9% were male and 54.1% were female.

Nucleic acids from the throat swab samples were used as template for taqman-based real-time PCR as described previouly [5] . We screened 28 pathogens, including viruses such as human parainfluenza virus 1 (HPIV1), human parainfluenza virus 2 (HPIV2), human parainfluenza virus 3 (HPIV3), human parainfluenza virus4 (HPIV4), influenza A virus (IVA), influenza B virus (IVB), human rhinovirus (HRV), human metapneumovirus (HMPV), human respiratory syncytial virus (RSV), human bocavirus (HboV), human adenovirus (HAdV), human coronavirus 229E (HCoV-229E), human coronavirus NL63 (HCoV-NL63), human coronavirus HKU1 (HcoV-HKU1), human coronavirus OC43 (HcoV-OC43); bacteria such as Pseudomonas aeruginosa (PA), Moraxella catarrhalis (Mcat), Mycobacterium tuberculosis (Mtb), Legionella pneumophila (LP), Group A Streptococcus (GAS), Haemophilus influenza (Hi), Staphylococcus aureus (Sa), Acinetobacter baumannii (Ab), Streptococcus pneumonia (Sp), Klebsiella.peneumoniae (Kp), Escherichia coli (EC); and mycoplasma pneumonia (Mpn) and chlamydia pneumonia (Cpn).

In total, 38.6% (170/440) of the patients tested for all the 28 pathogens had at least positive for one pathogen. And 18.1% (80/440) of the patients were exclusively postive for viruses, 13.4% (59/440) of the patients were exclusively postive for bacteria, 6.2% (27/440) of the patients were co-infected with at least one virus and bacterium. Co-infection pattern included HRV/Mcat (5/440), HRV/Hi (3/440), HRV/ Sp (2/440), HRV/Sa (2/440), HPIV3/Mcat (2/440), HRV/IVA/Sp (1/440), IAV/Mcat (1/440), IAV/Sp (1/440), IAV/Sp/Hi (1/440), HPIV1/Sp (1/440), HPIV1/Sp/Sa (1/440), HboV/Mcat (1/440), OC43/Mcat (1/440) and HKU1/Sp (1/440). Overall, there were 15.68% (69/440) patients were postive for HRV, 10% (44) were positive for M. Catarrhalis, 8.64% (38/440) were positive for S. Pneumonia, 3.18% (14/440) were positive for H. Influenza, 1.82% (8/440) were positive for IAV, 1.82% (8/440) were positive for S. Aureus, 1.59% (7/440) were positive for HadV, 1.59% (7/440) were positive for HPIV1, 1.59% (7/440) were positive for HPIV3, 1.36% (6/440) were positive for OC43, 0.68% (3/440) were positive for GAS, 0.68% (3/440) were positive for M. Pneumonia, 0.45% (2/440) were positive for RSV, 0.45% (2/440) were positive for HcoV-HKU1, 0.45% (2/440) were positive for HboV and 0.23% (1/440) was postive for L. Pneumophila.

We analyzed the pathogen spectrum before and COVID-19 pandemic and after the COVID-19 pandemic in every month (Table 1 ). Before the COVID-19 pandemic (2019, Oct-2020, Jan), there were positive cases for S. Pneumonia, M. Catarrhalis, HRV, H. Influenza, IVA, HadV, GAS, M. Pneumonia, S. Aureus, RSV and L. Pneumophila (Fig. 1 A and 1B). After the COVID-19 pandemic (2020, May-2021, Jan), there were positive cases for HRV, M. Catarrhalis, S. Pneumonia, H. Influenza, S. Aureus, HPIV1, HPIV3, OC43, HKU1, HBoV and RSV (Fig. 1A and 1B). Strikingly, after the COVID-19 pandemic, no IVA and HAdV cases were detected and there were increasing cases for HRV, HPIV1, HPIV3 and OC43 (Fig. 1A and 1B), which may suggest that the COVID-19 pandemic shape the pathogen spectrum. The decrease of the seasonal IVA cases is likely due to the COVID-19 lockdown in China and tightly controlled transportation. Although containment strategies were taken in China even after the COVID-19 [6], there were still high rate of HRV infection detected in our study (Fig. 1B).

Table 1

Positive cases of pathogens in every month.

Date	Patients(Total number)	Virus positivecases	Bacteria positivecases	Other pathogenspositive cases	Viral-bacterial coinfectioncases
2019.10	21	4 (19.05)	1 (4.17)	1 (4.17)	0 (0.00)
2019.11	32	2 (6.25)	4 (12.50)	1 (3.13)	1 (3.13)
2019.12	100	6 (6.00)	16 (16.00)	1 (1.00)	0 (0.00)
2020.01	47	14 (29.79)	20 (42.55)	0 (0.00)	6 (12.77)
COVID-19
2020.05	2	1 (50)	0 (0.00)	0 (0.00)	0 (0.00)
2020.06	8	8 (100)	0 (0.00)	0 (0.00)	0 (0.00)
2020.07	17	7 (41.18)	5 (29.41)	0 (0.00)	3 (17.65)
2020.08	40	11 (27.50)	4 (10.00)	0 (0.00)	1 (2.50)
2020.09	38	21 (55.26)	2 (5.26)	0 (0.00)	2 (5.26)
2020.10	65	16 (24.62)	10 (15.38)	0 (0.00)	4 (6.15)
2020.11	24	12 (50.00)	12 (50.00)	0 (0.00)	8 (33.33)
2020.12	24	3 (12.50)	6 (25.00)	0 (0.00)	1 (4.17)
2021.01	22	3 (13.64)	6 (27.27)	0 (0.00)	1 (4.55)

Fig. 1

Pathogen spetrum of acute respiratory infections in children. Throat swab samples were collected from children who were diagonised as acute respiratory infection in the sentinel hospital between an interval before the COVID-19 (2019, Oct-2020, Jan) and an interval after the COVID-19 (2020, May-2021, Jan) in China. (A) Pathogen spetrum tested monthly. (B) Comparsion of the paghogen spectrum betwwen the intervals before and after COVID-19.

In summary, we carried out an extensive pathogen screening for acute respiratory infection in children in a sentinel hospital before and after COVID-19 in China. The data suggest that the COVID-19 pandemic shape the pathogen spectrum. And care should sitll be taken for infections of HRV, HPIV and OC43 even under the containment strategies.

Ethics statements

This study was approved by the ethics committee of shool of basic medical sciences, Shanghai medical college under the study number 2018-C010 and the ethics committee of Shanghai Xuhui Central Hospital under the study number IEC-033–02.0-AF02. The procedures were carried out in accordance with approved guidelines. Informed consent was obtained from the subjects.

Authors’ contributions

Yi Z conceived the manuscript; YY, HY, CL and SZ collected clinical samples; SW performed experiments; FL and Yuan Z provided resources; SW and Yi Z analyzed date, Yi Z wrote the manuscript. SW and YY contributed equally.

Declaration of competing interest

The authors declare no conflicts of interest.