The changed endemic pattern of human adenovirus from species B to C among pediatric patients under the pressure of non-pharmaceutical interventions against COVID-19 in Beijing, China

Pathogen screening

From Jan 2015 to Dec 2021, a total of 16,097 pediatric patients with ARIs were included, with the ratio of males to females 1.36:1 and median age 3.0 (1.0–5.9) years.

In DFA tests, 11,218 cases were included with 6.41% (719/11,218) positive for RSV, 2.14% (240/11,218) for HAdV, 0.65% (73/11,218) and 0.43% (48/11,218) for Flu A and Flu B, and 4.79% (537/11,218) for HPIV, respectively.

By CEMP assays, 18.45% (900/4,879) pediatric patients among 4,879 cases were determined positive for RSV, 3.56% (173/4,879) for HMPV, 4.63% (226/4,879) for HAdV, 22.13% (1,080/4,879) for Rh, 8.42% (411/4,879) for HBoV, 1.19% (58/4,879) for HCoV, 1.29% (63/4,879) and 0.67% (33/4,879) for Flu A and Flu B, and 4.25% (245/4,879) for HPIV, respectively, while 22.30% (1,088/4,879) and 1.07% (52/4,879) were positive for Mp and Ch, respectively. Except for HAdV, the other ten pathogens’ seasonal distributions based on the results of CEMP were shown in Additional file 1: Fig. S1, as well as their distributions in different age and gender groups were shown in Additional file 4: Table S2.

The changing of HAdV endemic pattern

Among these 16,097 patients, 466 (2.89%, 466/16,097) were positive for HAdV determined by DFA or CEMP assay, including 303 males and 163 females, with a median age of 2.8 (1.3–4.4) years and varied positive rates: 1.75% (30/1,712) in 2015, 2.48% (49/1,979) in 2016, 2.73% (54/1,977) in 2017, 4.39% (151/3,438) in 2018, 3.38% (132/3,906) in 2019, 2.39% (24/1,004) in 2020, and 1.25% (26/2,081) in 2021 with the epidemic peaks in 2018 and 2019 and then significantly decreased in 2020 and 2021.

The monthly distribution of HAdV positive specimens from Jan 2015 to Dec 2021 shown in Fig. 1 revealed that the HAdV-positive rates decreased by 55.80% (P < 0.001) from 3.19% (428/13,408) to 1.41% (38/2,689) before and after NPIs launched. Before NPIs launched, HAdV could be detected in all months with the highest positive rates of 13.12% in Sep 2018 and 9.02% in Aug 2019. After NPIs launched, ARIs cases and HAdV-positive cases decreased sharply from Mar to Jul in 2020 with HAdV positive rates to zero, and then resurged at Aug 2020. Both the positive rates and case numbers of HAdV kept at a low level under the pressure of NPIs, even in level III of NPIs.

Fig. 1figure 1

Monthly distribution of ARIs cases tested and HAdV positive rates from Jan 2015 to Dec 2021. Jan 24, 2020 was set as the boundary of before and after NPIs launched in Beijing, China

Among these 466 cases positive for HAdV, there were 347 cases (74.46%, 347/466) infected only by HAdV, and 119 cases also infected by other pathogens, such as Mp (21.01%, 25/119) and RSV (19.33%, 23/119), or with triple (24.37%, 29/119) or more (4.20%, 5/119) infection.

Changes in the endemic pattern of HAdV types

Among specimens positive for HAdV, 75.11% (350/466) were successfully grouped into nine types and species B, C, or E by phylogenetic analysis of hexon, penton base and fiber genes (Additional file 2: Fig. S2), while 34 cases with hexon, penton base and fiber genes belonging to different HAdV types were recorded as undetermined, and the remaining 82 cases lack of enough PCR products for sequencing due to low viral load were recorded as unknown. The most prevalent types identified were HAdV-B3 (51.56%, 198/384) and HAdV-B7 (29.17%, 112/384), followed by HAdV-C1 (5.47%, 21/384) (Fig. 2A).

Fig. 2figure 2

Changes in the endemic pattern of HAdV types before and after NPIs launched among HAdV-positive cases from Jan 2015 to Dec 2021, in Beijing. A The composition of HAdV types. B The composition of HAdV types among HAdV-positive cases before and after NPIs launched, respectively. C Positive rates of HAdV types from 2015 to 2021. “B-others” represents HAdV-B14, -B21. “C-others” represents HAdV-C2, -C5, C6. “Undetermined” represents specimens with three capsid gene sequence belonging to different types. “Unknown” represents specimens without sequences of all three capsid genes

As shown in Fig. 2B, the predominant types of HAdV, HAdV-B3 (54.78%) and HAdV-B7 (31.46%) before NPIs launched changed to HAdV-C1 (39.28%) while more were undetermined (39.28%) after NPIs launched. As the absolute dominant one, HAdV-B3 overwhelmed HAdV-B7 from Jan 2015 to Dec 2017. Then, in 2018, HAdV-B7 (1.60%, 55/3,438) outweighed HAdV-B3 (1.54%, 53/3,438) the first time with more ARIs cases observed. For NPIs launched, the positive rate of HAdV-B3 dropped abruptly from 0.60% (6/1,004) in 2020 to 0.11% (3/2,689) in 2021, while HAdV-B7 dropped to 0.50% (5/1,004) in 2020, and then disappeared in 2021. (Fig. 2C). However, HAdV-C1 became the dominat one among HAdV positive specimens (39.28%, 11/28) after NPIs launched compared to that (5.47%, 21/384) before NPIs launched (Fig. 2B).

Clinical characters of the HAdV-infected children

Among HAdV-positive cases shown in all age groups, most of them (80.69%, 376/466) were under 5 years with positive rates 4.47% (60/1,341) in patients aged ≥ 4-5y, 4.14%(75/1,812) aged ≥ 3-4y, 3.63%(57/1,572) aged ≥ 2-3y, 3.69% (94/2,547) aged ≥ 1-2y, 3.59% (58/1,614) aged ≥ 6-12m, and 1.35% (32/2,362), the lowest one, aged ≥ 1-6m, With the increasing of age in that over 5y, the positive rates of HAdV decreased gradually, to 0.60% (1/166) in age 12-13y and 0.79% (1/126) in age 13-14y (Fig. 3).

Fig. 3figure 3

The number of ARI cases detected and positive rates of HAdV in different age groups from Jan 2015 to Dec 2021 in Beijing

The median length of hospital stay of HAdV positive cases after NPIs launched was 6 (4–10) d, shorter than 7 (5–13) d before NPIs launched (P < 0.05). No statistically significant difference was shown compared in characters of age, sex, intensive care unit admission and death among pediatric patients before and after NPIs launched (P > 0.05) (Table 1).

Table 1 Clinical characters of HAdV-infected children before and after NPIs launched

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