Changes in the pathogenic spectrum of acute respiratory tract infections during the COVID-19 epidemic in Beijing, China: A large-scale active surveillance study.

Dear Editor,

Poole and colleagues demonstrated the impact of coronavirus disease 2019 (COVID-19) pandemic on the epidemiology of general respiratory viruses. The prevalence of non-SARS-CoV-2 viruses during the COVID-19 epidemic has not been wildly reported in China. We conducted to analyze the surveillance data of respiratory pathogens to explore the impact of public health measures against COVID-19 on the prevalence of non-SARS-CoV-2 pathogens in China.

Among 41,630 acute respiratory tract infections (ARTIs) between 01/02/2015 and 31/01/2021 in 35 hospitals from the Respiratory Pathogen Surveillance System (detailed in Supplemental materials), 37,490 (25,658 adults and 11,832 children) occurred before the COVID-19 epidemic (01/02/2015–31/01/2020), and 4140 (3379 adults and 761 children) occurred during the COVID-19 epidemic (01/02/2020–31/01/2021) (Fig. 1 A-B).

Fig. 1

Spatial and temporal distribution of the samples and pathogenic spectrum from acute respiratory tract infections before the COVID-19 and during the COVID-19.

A, the distribution of 35 sentinel hospitals. The red dot represents the location of the hospital.

B, the monthly distribution of samples. The red line represents the number of samples from ARTI during the epidemic of the COVID-19. The black line represents the mean number of samples from ARTI before the epidemic of the COVID-19. The long dash gray line represents the max number of samples from ARTI before the epidemic of the COVID-19. The dot dash gray line represents the min number of samples from ARTI before the epidemic of the COVID-19. The blue column represents the number of the COVID-19 patients using the right vertical axis.

C, the pie chart for pathogenic spectrum of acute respiratory tract infections before the COVID-19; D, the pie chart for pathogenic spectrum of acute respiratory tract infections during the COVID-19; E, the column chart for pathogenic spectrum of acute respiratory tract infections for the children; F, the column chart for pathogenic spectrum of acute respiratory tract infections for the adults.

E-F, the gray column represents the proportion of the pathogen before the COVID-19; the blue column represents the proportion of the pathogen during the COVID-19, which decreased compared to that before the COVID-19; the red column represents the proportion of the pathogen during the COVID-19, which increased compared to that before the COVID-19.

The period between 1 February 2015 and 31 January 2020 for the control was as before the COVID-19 and the period between 1 February 2020 and 31 January 2021 was as during the COVID-19. COVID-19, coronavirus disease 2019.

All 41,630 cases were tested for 11 respiratory tract pathogens and 13,630 (32.74%, 95% CI 32.29% to 33.19%) had at least one positive result. Before the COVID-19 epidemic, the most common pathogen among the positive cases was influenza virus (IFV), followed by mycoplasma pneumoniae (MP), human parainfluenza virus (HPIV), human rhinovirus (HRV), enterovirus (EV), respiratory syncytial virus (RSV), seasonal human coronavirus (HCoV), human metapneumovirus (HMPV), human adenovirus (HAdV), human bocavirus (HBoV) and chlamydia pneumoniae (CP), which changed to seasonal HCoV, followed by HRV, HPIV, IFV, RSV, EV, HBoV, HMPV, MP, HAdV and CP during the COVID-19 epidemic (Fig. 1C-F and Table S1-S3). SARS-CoV-2 was not detected. For children, the top five pathogens were MP, IFV, HPIV, EV and RSV before the COVID-19 epidemic, changing to HPIV, seasonal HCoV, HRV, RSV and IFV. For adults, the top five pathogens were IFV, MP, HRV, HPIV and seasonal HCoV before the COVID-19 epidemic, changing to seansonal HCoV, HRV, IFV HPIV and EV. All the other pathogens had distinct increases in proportions except for IFV.

Before the COVID-19 epidemic, 12,058 (32.16%, 95% CI 31.69% to 32.64%) were positive for at least one pathogen, which significantly dropped to 10.97% (95% CI 10.03% to 11.96%) during the COVID-19 epidemic (P<0.001, Fig. 2 A and Table S4). The positive rates of the top five pathogens were IFV (9.22%), MP (6.77%), HPIV (4.14%), HRV (3.29%) and EV (2.94%) before the COVID-19 epidemic and seasonal HCoV (2.42%), HRV (2.17%), HPIV (1.71%), IFV (1.50%) and RSV (1.23%) during the COVID-19 epidemic. A similar trend was observed in children (from 41.92% to 20.76%, P<0.001) and in adults (from 27.66% to 8.76%, P<0.001).

Fig. 2

The positive rate and dynamic profiles of the pathogens from acute respiratory tract infection before and during the COVID-19.

A, the positive rate of the pathogens as a whole and in the children and in the adults; the star means the significant difference between the positive rates before and during the COVID-19 by chi square test; The gray column represents the proportion of the pathogen before the COVID-19; the blue column represents the proportion of the pathogen during the COVID-19, which decreased compared to that before the COVID-19; the red column represents the proportion of the pathogen during the COVID-19, which increased compared to that before the COVID-19;

B, the difference (upper half part) and difference proportion (lower half part) between the positive rates before and during the COVID-19 as a whole;

C, the difference (upper half part) and difference proportion (lower half part) between the positive rates before and during the COVID-19 in the children;

D, the difference (upper half part) and difference proportion (lower half part) between the positive rates before and during the COVID-19 in the adults;

B-D, the green column/dot represents the decrease difference/difference proportion; the purple column/dot represents the increase difference/difference proportion; The difference of positive rates was defined as the positive rate during the COVID-19 minus the positive rate before the COVID-19. The difference proportion (%) was defined as the difference of positive rate (%) divided by the detection rate before the COVID-19.

E, overall; F, seasonal HCoV; G, HPIV; H, HRV; I, EV; J, HBoV; K, IFV; L, MP; M, HMPV; N, HAdV; O, CP; P, RSV. The red line represents the positive rate during the epidemic of the COVID-19. The blue line represents the positive rate before the epidemic of the COVID-19. The long dash gray line represents the max positive rate before the epidemic of the COVID-19. The dot dash gray line represents the min positive rate before the epidemic of the COVID-19. The right multi-colored strip represents the time line of the PHER in Beijing during from 1 February 2020 to 31 January 2021. The red part represents the PHER Level I; the yellow part represents the PHER Level II; the light blue part represents the PHER Level III. PHER, public health emerging response. The dark blue column represents the number of the COVID-19 patients in Beijing.

Among all the pathogens, only seasonal HCoV had 20.74% increase in the positive rate, from 2.00% to 2.42% (P = 0.073). The other 10 pathogens had significant decreases in their positive rates (all P<0.05). IFV had the largest difference (−7.72%, 95% CI −8.19% to −7.25%) in the positive rate decreasing by 83.75% (Fig. 2B).

In children, a significant increase in seasonal HCoV was observed from 1.74% to 3.29% (P = 0.002, Fig. 2A,C and Table S5). The positive rates of the top five pathogens were MP (9.37%), IFV (7.43%), HPIV (6.94%), EV (5.09%) and RSV (4.28%) before the COVID-19 epidemic and HPIV (5.26%), seasonal HCoV (3.29%), HRV (3.29%), RSV (3.15%) and IFV (1.97%) during the COVID-19 epidemic. The other nine pathogens showed decreased positive rates but significant for IFV, MP, EV, HMPV and HAdV (Fig. 2C).

In adults, seasonal HCoV slightly increased during the COVID-19 epidemic (P = 0.710, Fig. 2A and Table S6). The positive rates of the other nine pathogens significantly decreased except for RSV. The positive rates of the top five pathogens were IFV (10.04%), MP (5.57%), HRV (2.89%), HPIV (2.85%) and seasonal HCoV (2.12%) before the COVID-19 epidemic and seasonal HCoV (2.22%), HRV (1.92%), IFV (1.39%), HPIV (0.92%) and EV (0.89%) during the COVID-19 epidemic. IFV had the largest difference in the positive rate, followed by MP and HPIV (Fig. 2D).

After on 24/01/2020 in Beijing, the overall positive rates of all pathogens changed according to the implementation of different levels of PHER (Fig. 2E-P). The positive rates sharply decreased due to the outbreak of COVID-19 in the Xinfadi Market and in Shunyi District, Beijing. These results indicated the prevalence of pathogens was closely related to public health measures against COVID-19.

Four groups were classified according to the dynamic trend of the positive rate of each pathogen. The positive rates of seasonal HCoV and HPIV were lower in the early stage of the COVID-19 epidemic and increased in the late stage, even exceeding the previous peak. For HRV, EV and HBoV, the positive rates returned to their previous levels in the late stage of the COVID-19 epidemic. The positive rates decreased to lower levels and remained until January 2021 for IFV, MP, HMPV, HAdV and CP. IFV was only detected in February and March 2020. COVID-19 had a relatively smaller effect on the positive rate of RSV compared to other pathogens.

Public health measures against COVID-19 and people's daily behavior changed potentially affected the prevalence of other respiratory pathogens.2, 3, 4, 5, 6 The decrease of IFV is closely related to influenza vaccination as well as the public health measures. More influenza vaccinations may have effectively reduced the spread of IFV. The COVID-19 epidemic and the corresponding protective measures have changed people's medical behavior, with significant decreases in non-COVID-19 inpatient and outpatient visits.

Seasonal HCoV became the first pathogen in ARTIs during the COVID-19 epidemic. Anton et al. reported that the detection rates of HCoV and HPIV increased after the H1N1 epidemic in Catalonia, Spain. Four seasonal HCoVs showed biennial incidence peaks in winter with alternating peak seasons for 229E and NL63, and OC43 and HKU1. Studies showed a biennial trend on the peak prevalence of seasonal HCoV in Beijing.8, 9 Therefore, the incidence of seasonal HCoV may have peaked in 2020/2021, which may have been higher without no public measures for COVID-19. This suggests that we need to further strengthen the monitoring of HCoV in the future to prevent a co-epidemic of seasonal HCoV and SARS-CoV-2, especially when control measures for COVID-19 become normalized.

In general, public health measures against COVID-19 substantially reduced the prevalence of other respiratory pathogens. IFV decreased from the first to the fourth during the COVID-19 epidemic. Seasonal HCoV, which became the first pathogen of ARTIs, should be strengthened to control to prevent co-circulation with SARS-CoV-2.

These findings indicated the additional benefits of the public health measures implemented for COVID-19 in reducing the spread of other respiratory diseases.

Notes