For virus surveillance during April 1, 2019 through October 4, 2020 (surveillance week 14 in 2019 to week 40 in 2020), the percentage of specimens testing positive for influenza each week ranged from 0% to 46.5% in southern China and ranged from 0% to 47.3% in northern China. The positivity rate of specimens collected from ILI cases increased starting in week 40 in 2019 reaching a peak (46.5% for southern China and 47.3% for northern China) during the first week of 2020 and decreasing substantially after that. During week 8, the positivity rate in southern China decreased to 2.0%, and by week 10 in northern China, the influenza-positive rate declined to 1.3%. The positivity rate since then has been lower than that of the same period in previous years (5) and has remained low ever since (Figures 1 and 2).
Influenza positive tests reported by network laboratories in southern China since 2010 to 2020.
Influenza positive tests reported by network laboratories in northern China since 2010 to 2020.
During the study period, network laboratories in southern China tested 423,466 specimens for influenza; among these specimens, 49,147 (11.6%) tested positive including 23,234 (47.3%) for influenza A and 25,913 (52.7%) for influenza B. Most of the positive samples were collected before March 2020. Among the 23,208 seasonal influenza A positive specimens that were subtyped, 2,830 (12.2%) were influenza A(H1N1)pdm09 and 20,378 (87.8%) were influenza A(H3N2). Among the 25,627 influenza B viruses for which lineage was determined, 25,477 (99.4%) belonged to the B/Victoria lineage and 150 (0.6%) belonged to the B/Yamagata lineage (Figure 1).
Network laboratories in northern China tested 216,874 specimens between April 1, 2019 and October 4, 2020. Among these, 26,759 (12.3%) were positive for influenza viruses — influenza A and influenza B viruses were 20,203 (75.5%) and 6,556 (24.5%), respectively, of the tested viruses. Among the 20,199 seasonal influenza A viruses that were subtyped, 2,091 (10.4%) were influenza A(H1N1)pdm09 and 18,108 (89.6%) were influenza A(H3N2). Influenza B lineage information was available for 6,547 influenza B viruses; 6,460 (98.7%) were B/Victoria lineage and 87 (1.3%) were B/Yamagata lineage (Figure 2).
CNIC tested the antigenic and genetic characteristics of influenza viruses between April 1, 2019 and October 4, 2020. A total of 653 A(H1N1)pdm09 viruses were analyzed with HI tests, and 521 viruses were antigenically analyzed with A/Guangdong-Maonan/SWL1536/2019, and 98.3% (512/521) were well inhibited by ferret antisera raised against A/Guangdong-Maonan /SWL1536/2019, the egg-propagated reference virus representing the A(H1N1)pdm09 component for the upcoming 2020–2021 winter season’s northern hemisphere influenza vaccination (2). Among the 205 viruses sequenced, phylogenetic analysis of HA gene segments determined that 199 (97.1%) belonged to genetic clade 6B.1A (Figure 3); 161 (78.5%) belonged to subclade 6B.1A5A, which evolved from clade 6B.1A. Subclade 6B.1A5A HA genes fall into 3 genetic groups: a progenitor 6B.1A5A subclade (22.9%) and 2 recently designated groups, 5A-187A (46.3%), with additional amino acid substitutions D187A and Q189E, and 5A-156K (9.3%), with an additional amino acid substitution N156K.
Genetic characterization of influenza viruses in the mainland of China during April 1, 2019–October 4, 2020.
Antigenic characterization of 1,410 A(H3N2) viruses were conducted using HI tests that used guinea pig red blood cells (RBCs) in the presence of oseltamivir, and 63 viruses underwent antigenic analysis with A/Hong Kong/2671/2019 where the results showed that 79.4% (50/63) of virus isolates were well inhibited by ferret antisera raised against A/Hong Kong/2671/2019, the egg-propagated reference virus representing the A(H3N2) component for the 2020–2021 northern hemisphere influenza vaccine — a higher proportion than the last influenza season (6). Among the 502 viruses sequenced, phylogenetic analysis of the HA gene segments determined that 501 (99.8%) viruses belonged to genetic clade 3C.2a, and only 1 virus belonged to clade 3C.3a. Multiple subclades within the 3C.2a clade co-circulated with viruses belonging to subclade 3C.2a1b, the majority subclade. Subclade 3C.2a1b viruses includes viruses having either T135K or T131K amino acid substitutions in their HA protein; 406 (80.9%) belonged to 3C.2a1b+T135K and 90 (17.9%) belonged to 3C.2a1b+T131K (Figure 3).
A total of 2,070 B/Victoria lineage viruses were antigenically analyzed with the HI test. Overall, 1,012 viruses underwent antigenic analysis with B/Washington /02/2019, and 92.4% (935/1012) were similar to B/Washington/02/2019, the egg-propagated reference virus representing the B/Victoria lineage component for the 2020–2021 northern hemisphere influenza vaccine. Significant genetic diversity was seen in B/Victoria lineage cocirculating viruses. In the HA proteins, viruses with a 2 amino acid deletions (positions 162 and 163) belonged to subclade V1A.1, and viruses with a 3 amino acid deletions (positions 162–164) belonged to subclade V1A.2; subclade V1A.3 shared a triple amino acid deletion and had an additional substitution at K136E (2,7). Among the 330 virus HA gene segments sequenced and phylogenetically analyzed, 44 (13.3%) belonged to genetic clade V1A, 7 (2.1%) belonged to subclade V1A.1, 2 (0.6%) belonged to subclade V1A.2, and 277 (83.9%) belonged to subclade V1A.3 (Figure 3).
Few B/Yamagata lineage viruses were detected during the study period. Antigenic characterization of the 12 B/Yamagata lineage viruses by HI test indicated that 11 (91.7%) viruses were similar to the egg-propagated B/Phuket/3073/2013, the reference virus representing the B/Yamagata lineage component of quadrivalent vaccines for the northern hemisphere influenza season. Phylogenetic analysis of 9 (100%) influenza B/Yamagata lineage viruses determined that the HA gene segments belonged to clade Y3 (Figure 3).
CNIC then tested 41,66 influenza viruses collected in the mainland of China for resistance to oseltamivir and zanamivir, including 664 influenza A(H1N1)pdm09, 1,419 influenza A(H3N2), 2,071 influenza B/Victoria, and 12 influenza B/Yamagata viruses. Overall, 3 influenza A(H1N1)pdm09 viruses showed highly reduced inhibition by oseltamivir; 2 had a H275Y amino acid substitution and 1 had a H275H/Y mixed substitution in the NA protein. In addition, 1 influenza B/Victoria lineage virus had a G243D amino acid substitution and exhibited reduced inhibition by oseltamivir and highly reduced inhibition by zanamivir; 1 influenza B/Victoria lineage virus showed reduced susceptibility to zanamivir with substitution D198N in the NA protein. All sequenced seasonal influenza viruses do not carry any reported resistant mutations to Baloxavir marboxil. All sequenced influenza A(H1N1)pdm09 and influenza A(H3N2) viruses were resistant to adamantanes, which was consistent with the current recommendation to avoid use of these drugs against influenza.