Lockdown measures during the COVID-19 pandemic strongly impacted the circulation of respiratory pathogens in Southern China | Scientific Reports -…

Patient characteristics

A total of 56,325 children with ARIs were enrolled in this study, 33,909 were tested from July 2018 to January 2020 (pre-lockdown), 1168 from February to May 2020 (lockdown) and 21,248 from July 2020 to January 2022 (post-lockdown), indicating a 37.3% reduction in hospital admissions due to ARI comparing the post-lockdown versus the pre-lockdown period. The number of monthly hospitalized children for ARIs did not return to the pre-lockdown number in the 20months following the lockdown (Fig.1). The median number of hospitalizations per month of children were 1784 before and reduced to 1,118 after the lockdown. There was a significant difference in the number of patients monthly between the two groups in pre- and post-lockdown (t=9.859, P<0.001). To determine age specific differences in viral infections before and after the lockdown period, we divided the patients according to age into four groups, as follows (1) infants (newborn-1year old), (2) toddlers (13years old), (3) pre-school children (36years old), (4) school children (614years old); the proportion of hospitalized children in each group before and after the lockdown is shown in Fig.2A,B. There was a significant difference in age groups between pre- and post-lockdown (p<0.001). There was no significant difference in sex ratio (p=0.8041).

Number of detected cases by month (above) and the flowchart (below) of detection by DFA or GeXP-based PCR. Specimens were tested by DFA and M. pneumoniae PCR in pre-lockdown (orange bar), and tested by GeXP-based multiplex reverse transcription PCR assay (grey bar). DFA, Direct Immunofluorescence Assay; pre-lockdown, from July 2018 to January 2020, Lockdown, from February to May 2020, post-down, from June 2020 to January 2022.

The proportion of each group in pre- and post-lockdown. Pre-lockdown (A), from July 2018 to January 2020, post-down (B), from July 2020 to January 2022.

In total 30,559 specimens collected were tested by DFA and Mp PCR from July 2019 to January 2020 and 3350 specimens were tested by GeXP-based multiplex reverse transcription PCR assay from September 2019 to January 2020. All specimens collected during and after the lockdown (22,416) were tested by GeXP-based multiplex reverse transcription PCR assay as depicted in Fig.1. The detection rates of Mp, RSV, AdV, HPIV, InfA and InfB before the lockdown were 16.9%, 6.3%, 2.7%, 1.8%, 1.3% and 0.2%, respectively. The most frequently detected pathogens after the lockdown were HRV (26.7%), RSV (18.2%), HPIV (8.6%), HMPV (5.1%), AdV (2.6%), Mp (1.4%), followed by HBoV (2.4%), HCOV (1.9%), InfB (1.5%), InfA (0.03%) and Cp (0.6%).

We determined the prevalence of the six major pathogens including Mp, InfA, InfB, AdV, RSV, and HPIV before and after the lockdown period. It was found that the detection rate of InfA and Mp decreased significantly during and after the lockdown, the detection rate of Mp decreased from 15 to 40% to about 1%, while infection rates with RSV and HPIV were consistent in the pre- and post-lockdown period (Fig.3AF). AdV showed a decrease during the lockdown, however the number of infections quickly increased after the lockdown.

The seasonal prevalence of 11 respiratory pathogens (AF). Mycoplasma pneumoniae (Mp), HRV, RSV, HMPV, influenza A, HCOV, influenza B, HBoV, HPIV and AdV the percentage detected was plotted as a function of time (indicated in months) before, during or after lockdown. Black line represented Mp, RSV, InfA, InfB, HPIV and AdV in (AF) from July 2018 to January 2022, red line was HRV, HMPV, HCOV, HBoV, Cp in A-E from September 2019 to January 2022. AdV, adenovirus; HRV, human rhinovirus; HPIV, human parainfluenza viruses 14; RSV, respiratory syncytial virus; HMPV, human metapneumovirus; HCOV, human coronavirus; InfA/B, influenza A/influenza B; HBoV, human bocavirus; Cp, Chlamydophila pneumoniae.

The lockdown measures clearly distorted the common seasonal dynamics of respiratory infections. In Southern China, InfA peaks every year in January and normally there is also a small peak in August21, these seasonal patterns completely disappeared. Mp has normally a high detection rate throughout the year, as was seen especially in 2019. RSV peaked in both summer and autumn in the pre-lockdown and post-lockdown period, however the peak in March during the post-lockdown period did not appear. HPIV prevalence showed the same trend pre- and post-and peaked in May and November. Also AdV in pre-lockdown and post-lockdown have the same trend, both are common in the winter and spring season. The transition between summer and autumn is the time with the lowest detection rates for this pathogen. InfB is normally sporadically detected, however the detection rate has increased from 0.5% in June 2021 to 4.0% in January 2022.

From September 2019, we have added HRV, HMPV, HBoV, HCOV and Cp to our PCR-based respiratory pathogen detection panel. This was used to determine the detection rate between September 2019 and January 2022. We found that the detection rate of HRV was above 10% throughout the year, with the highest detection rate in April and November each year. The detection rate of HMPV was lower throughout the year, but the highest detection rate was in January 2020 to 2022. HCOV has the highest detection rate in December 2020 to 2021, and HBoV is the highest in November and December; Cp is at a low level throughout the year, mainly detected in neonates and patients within 6months, and in lockdown, Cp is the only pathogen with an increased detection rate (Fig.3).

A total of 1366 (4.03%) and 817 (3.85%) children were admitted to the PICU, before and after the lockdown, respectively. The rate of admission to the PICU decreased after the lockdown, however there was no significant difference found compared to the pre-lockdown period (p>0.05). The detection rates of AdV, Mp and InfA in children admitted to the PICU were reduced from 4.4%, 3.7% and 2.5% pre-lockdown to 0.7%, 0.2% and 0.5% post-lockdown. In contrast, HPIV and RSV were increased from 0.7% and 8.9% to 3.7% and 11.6%. We found the detection rate of HBoV reached 4.2% in post-lockdown, which was an important virus detected in PICU patients.

Comparison of pre-lockdown and post-lockdown, the changes of detection rates of respiratory pathogens in each age group were relatively consistent, and only the detection rate of HRV in the infant group decreased significantly in post-lockdown. The detection rate of Mp increased with age. InfA, adenovirus and HMPV had the highest detection rate in the pre-school group and the lowest in the infant group. Rhinovirus, RSV, HPIV and Cp had the highest detection rate in the infant group. HBoV and HCoV had the highest detection rates in the toddler group (Fig.4).

The distribution of respiratory pathogens at different age groups, and the differences pre-lockdown (1) and post-lockdown (2) were compared. AdV, adenovirus; HRV, human rhinovirus; HPIV, human parainfluenza viruses 14; RSV, respiratory syncytial virus; HMPV, human metapneumovirus; HCOV, human coronavirus; InfA/B, influenza A/influenza B; HBoV, human bocavirus; Cp, Chlamydophila pneumoniae.

The detection rate of Mp in female patients in the pre-lockdown period was significantly higher than that of male patients (p<0.001), but there was no difference post-lockdown (p=0.6748), due to the significant decrease in the detection rate. In contrast, RSV was significantly more frequently detected in males than in females in post-lockdown (p=0.0012), while no difference was observed before the lockdown (p=0.0575).

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Lockdown measures during the COVID-19 pandemic strongly impacted the circulation of respiratory pathogens in Southern China | Scientific Reports -...