Research progress on secondary bacterial infection following influenza virus infection

doi:10.3877/cma.j.issn.2095-5820.2026.01.013

Abstract

Abstract:

Influenza virus-associated secondary bacterial infection represents a major severe complication, significantly increasing the risk of critical illness and mortality. This review summarizes the epidemiological features and pathogenic mechanisms of this complication. The most frequently isolated bacterial pathogens are Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae, and such coinfections are strongly associated with high fatality rates. Influenza virus facilitates bacterial superinfection through multiple mechanisms, including disruption of the epithelial barrier, suppression of innate immune responses, and direct interactions between viral and bacterial components. An in-depth understanding of the molecular mechanisms is crucial for developing more effective prevention and therapeutic strategies.

Key words: influenza virus, bacteria, infection, epidemiology, mechanisms of pathogenesis

Taotao Gao, Lifu Liu, Yintong Chen, Yingxuan Zhou, Xiaoyan Deng, Xiaoli Liang. Research progress on secondary bacterial infection following influenza virus infection[J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2026, 14(01): 74-80.

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References 61

1	WORLD HEALTH ORGANIZATION. Influenza (seasonal)[EB/OL]. (2025-02-28) [2025-07-28].
2	WILDEN J J, JACOB J C, EHRHARDT C, et al. Altered signal transduction in the immune response to influenza virus and S. pneumoniae or S. aureus co-infections[J]. International journal of molecular sciences, 2021, 22(11): 5486.
3	MIKUŠOVÁ M, TOMČÍKOVÁ K, BRIESTENSKÁ K, et al. The contribution of viral proteins to the synergy of influenza and bacterial co-infection[J]. Viruses, 2022, 14(5): 1064.
4	林立, 於梦菲. 流感病毒和细菌共感染研究进展[J]. 中国实用儿科杂志, 2018, 33(9): 721-725.
5	JOSEPH C, TOGAWA Y, SHINDO N. Bacterial and viral infections associated with influenza[J]. Influenza and other respiratory viruses, 2013, 7 (Suppl 2): 105-113.
6	史庆丰, 姜晨彦, 蒋露芳. 流感病毒致继发性肺部细菌感染的易感机制研究进展[J]. 上海预防医学, 2016, 28(11): 813-817.
7	RICH H E, MCCOURT C C, ZHENG W Q, et al. Interferon lambda inhibits bacterial uptake during influenza superinfection[J]. Infection and immunity, 2019, 87(5): e00114-19.
8	MORRIS D E, CLEARY D W, CLARKE S C. Secondary bacterial infections associated with influenza pandemics[J]. Frontiers in microbiology, 2017, 8: 1041.
9	JINJARAK Y, NOY I, TA Q. Pandemics and economic growth: Evidence from the 1968 H3N2 influenza[J]. Economics of disasters and climate change, 2022, 6(1): 73-93.
10	WORLD BANK GROUP. Global economic prospects, june 2025[EB/OL]. (2025-06-10)[2025-08-27].
11	SEKI M, KOSAI K, YANAGIHARA K, et al. Disease severity in patients with simultaneous influenza and bacterial pneumonia[J]. Internal medicine, 2007, 46(13): 953-958.
12	MORENS D M, TAUBENBERGER J K, FAUCI A S. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: Implications for pandemic influenza preparedness[J]. The journal of infectious diseases, 2008, 198(7): 962-970.
13	CHIEN Y W, KLUGMAN K P, MORENS D M. Bacterial pathogens and death during the 1918 influenza pandemic[J]. The New England journal of medicine, 2009, 361(26): 2582-2583.
14	VIBOUD C, SIMONSEN L, FUENTES R, et al. Global mortality impact of the 1957-1959 influenza pandemic[J]. Journal of infectious diseases, 2016, 213(5): 738-745.
15	ROBERTSON L, CALEY J P, MOORE J. Importance of Staphylococcus aureus in pneumonia in the 1957 epidemic of influenza A[J]. Lancet, 1958, 2(7040): 233-236.
16	HERS J F, MASUREL N, MULDER J. Bacteriology and histopathology of the respiratory tract and lungs in fatal Asian influenza[J]. Lancet, 1958, 2(7057): 1141-1143.
17	SCHWARZMANN S W, ADLER J L, SULLIVAN R J J R, et al. Bacterial pneumonia during the Hong Kong influenza epidemic of 1968-1969[J]. Archives of internal medicine, 1971, 127(6): 1037-1041.
18	KALLEN A J, BRUNKARD J, MOORE Z, et al. Staphylococcus aureus community-acquired pneumonia during the 2006 to 2007 influenza season[J]. Annals of emergency medicine, 2009, 53(3): 358-365.
19	SMITH G J, VIJAYKRISHNA D, BAHL J, et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic[J]. Nature, 2009, 459(7250): 1122-1125.
20	LEE E H, WU C, LEE E U, et al. Fatalities associated with the 2009 H1N1 influenza A virus in New York city[J]. Clinical infectious diseases: An official publication of the infectious diseases society of America, 2010, 50(11): 1498-1504.
21	CENTERS FOR DISEASE CONTROL AND PREVENTION(CDC). Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A(H1N1)-United States, May-August 2009[J]. Morbidity and mortality weekly report, 2009, 58(38): 1071-1074.
22	LUCAS S. Predictive clinicopathological features derived from systematic autopsy examination of patients who died with A/H1N1 influenza infection in the UK 2009-10 pandemic[J]. Health technology assessment, 2010, 14(55): 83-114.
23	PALACIOS G, HORNIG M, CISTERNA D, et al. Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza[J]. PLoS one, 2009, 4(12): e8540.
24	MARTÍN-LOECHES I, SANCHEZ-CORRAL A, DIAZ E, et al. Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus[J]. Chest, 2011, 139(3): 555-562.
25	KIM H S, KIM J H, SHIN S Y, et al. Fatal cases of 2009 pandemic influenza A (H1N1) in Korea[J]. Journal of Korean medical science, 2011, 26(1): 22-27.
26	METERSKY M L, MASTERTON R G, LODE H, et al. Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza[J]. International journal of infectious diseases, 2012, 16(5): e321-e331.
27	KLOMP M, GHOSH S, MOHAMMED S, et al. From virus to inflammation, how influenza promotes lung damage[J]. Journal of leukocyte biology, 2021, 110(1): 115-122.
28	OLIVA J, TERRIER O. Viral and bacterial co-infections in the lungs: Dangerous liaisons[J]. Viruses, 2021, 13(9): 1725.
29	PITTET L A, HALL-STOODLEY L, RUTKOWSKI M R, et al. Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae[J]. American journal of respiratory cell and molecular biology, 2010, 42(4): 450-460.
30	ROWE H M, MELIOPOULOS V A, IVERSON A, et al. Direct interactions with influenza promote bacterial adherence during respiratory infections[J]. Nature microbiology, 2019, 4(8): 1328-1336.
31	AMPOMAH P B, LIM L H K. Influenza A virus-induced apoptosis and virus propagation[J]. Apoptosis, 2020, 25(1-2): 1-11.
32	SHIZUKUISHI S, OGAWA M, KURODA E, et al. Pneumococcal sialidase promotes bacterial survival by fine-tuning of pneumolysin-mediated membrane disruption[J]. Cell rep, 2024, 43(3): 113962.
33	LIU L, GAO T, LIU J, et al. Erucic acid attenuates post-influenza secondary Staphylococcus aureus infection by modulating VCAM-1 and CEACAM-1 expression and gut dysbiosis[J]. International immunopharmacology, 2026, 172: 116191.
34	KALIL A C, THOMAS P G. Influenza virus-related critical illness: Pathophysiology and epidemiology[J]. Critical care, 2019, 23(1): 258.
35	DIDIERLAURENT A, GOULDING J, PATEL S, et al. Sustained desensitization to bacterial toll-like receptor ligands after resolution of respiratory influenza infection[J]. The journal of experimental medicine, 2008, 205(2): 323-329.
36	MALOSH R E, MARTIN E T, HEIKKINEN T, et al. Efficacy and safety of oseltamivir in children: Systematic review and individual patient data meta-analysis of randomized controlled trials[J]. Clinical infectious diseases, 2018, 66(10): 1492-1500.
37	BOHANNON C D, ENDE Z, CAO W, et al. Influenza virus infects and depletes activated adaptive immune responders[J]. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021, 8(16): e2100693.
38	GHONEIM H E, THOMAS P G, MCCULLERS J A. Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections[J]. Journal of immunology, 2013, 191(3): 1250-1259.
39	BARMAN T K, METZGER D W. Disease tolerance during viral-bacterial co-infections[J]. Viruses, 2021,13(12): 2362.
40	SMALL C L, SHALER C R, MCCORMICK S, et al. Influenza infection leads to increased susceptibility to subsequent bacterial superinfection by impairing NK cell responses in the lung[J]. Journal of immunology, 2010, 184(4): 2048-2056.
41	JIA L, XIE J, ZHAO J, et al. Mechanisms of severe mortality-associated bacterial co-infections following influenza virus infection[J]. Frontiers in cellular and infection microbiology, 2017, 7: 338.
42	MCCULLERS J A. The co-pathogenesis of influenza viruses with bacteria in the lung[J]. Nature reviews. Microbiology, 2014, 12(4): 252-262.
43	SENCIO V, BARTHELEMY A, TAVARES L P, et al. Gut dysbiosis during influenza contributes to pulmonary pneumococcal superinfection through altered short-chain fatty acid production[J]. Cell reports, 2020, 30(9): 2934-2947.
44	MCNAMEE L A, HARMSEN A G. Both influenza-induced neutrophil dysfunction and neutrophil-independent mechanisms contribute to increased susceptibility to a secondary Streptococcus pneumoniae infection[J]. Infection and immunity, 2006, 74(12): 6707-6721.
45	ELLIS G T, DAVIDSON S, CROTTA S, et al. TRAIL+ monocytes and monocyte-related cells cause lung damage and thereby increase susceptibility to influenza-Streptococcus pneumoniae coinfection[J]. EMBO reports, 2015, 16(9): 1203-1218.
46	ISHIKAWA H, FUKUI T, INO S, et al. Influenza virus infection causes neutrophil dysfunction through reduced G-CSF production and an increased risk of secondary bacteria infection in the lung[J]. Virology, 2016, 499: 23-29.
47	LODOEN M B, LANIER L L. Natural killer cells as an initial defense against pathogens[J]. Current opinion in immunology, 2006, 18(4): 391-398.
48	SCOTT M J, HOTH J J, STAGNER M K, et al. CD40-CD154 interactions between macrophages and natural killer cells during sepsis are critical for macrophage activation and are not interferon gamma dependent[J]. Clinical and experimental immunology, 2004, 137(3): 469-477.
49	ZHANG X, YANG Y, CHEN S, et al. Antigen-specific memory Th17 cells promote cross-protection against nontypeable Haemophilus influenzae after mild influenza A virus infection[J]. Mucosal immunology, 2023, 16(2): 153-166.
50	CHEN T, LIU J, YU R, et al. Targeting TLR7 reprograms macrophage function to attenuate influenza-associated Staphylococcus aureus coinfection[J]. Microbial pathogenesis, 2026, 210: 108208.
51	ROBINSON K M, KOLLS J K, ALCORN J F. The immunology of influenza virus-associated bacterial pneumonia[J]. Current opinion in immunology, 2015, 34: 59-67.
52	GU Y, ZUO X, ZHANG S, et al. The mechanism behind influenza virus cytokine storm[J]. Viruses, 2021, 13(7): 1362.
53	HASSAN A, BLANCHARD N. Microbial (co)infections: Powerful immune influencers[J]. PLoS pathogens, 2022, 18(2): e1010212.
54	ALSHAMMARI A K, MAINA M, BLANCHARD A M, et al. Understanding the molecular interactions between influenza a virus and streptococcus proteins in co-infection: A scoping review[J]. Pathogens, 2025, 14(2): 114.
55	KING S J, HIPPE K R, WEISER J N. Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae[J]. Molecular microbiology, 2006, 59(3): 961-974.
56	WADOWSKY R M, MIETZNER S M, SKONER D P, et al. Effect of experimental influenza a virus infection on isolation of Streptococcus pneumoniae and other aerobic bacteria from the oropharynges of allergic and nonallergic adult subjects[J]. Infection and immunity, 1995, 63(4): 1153-1157.
57	CHONMAITREE T, REVAI K, GRADY J J, et al. Viral upper respiratory tract infection and otitis media complication in young children[J]. Clinical infectious diseases: An official publication of the infectious diseases society of America, 2008, 46(6): 815-823.
58	HEIKKINEN T, CHONMAITREE T. Importance of respiratory viruses in acute otitis media[J]. Clinical microbiology reviews, 2003, 16(2): 230-241.
59	LANGOUËT-ASTRIÉ C, OSHIMA K, MCMURTRY S A, et al. The influenza-injured lung microenvironment promotes MRSA virulence, contributing to severe secondary bacterial pneumonia[J]. Cell reports, 2022, 41(9): 111721.
60	XING A, NG H M, JIAO H, et al. The prevalence, epidemiological, and molecular characterization of Methicillin-resistant Staphylococcus aureus (MRSA) in Macau (2017—2022)[J]. Microorganisms, 2024, 12(1): 148.
61	SOULTAN K M, KEWALRAMANI A, BRADBURY A, et al. Clinical impact of influenza a coinfection on Staphylococcus aureus pneumonia during the 2024—2025 influenza season in New York City[J]. International journal of infectious diseases, 2025, 160: 108072.

项目	事件（占全球人口百分比）
项目	1918年	1957年	1968年	2009年
死亡率	1.000~5.700	0.030~0.050	0.020~0.030	0.001~0.004
感染率	28.000	42.000~55.000	30.000~57.000	24.000

项目	事件（占全球人口百分比）
项目	1918年	1957年	1968年	2009年
死亡率	1.000~5.700	0.030~0.050	0.020~0.030	0.001~0.004
感染率	28.000	42.000~55.000	30.000~57.000	24.000

时间/年	地区	研究方法/对象	病例人数/例	细菌性共感染
时间/年	地区	研究方法/对象	病例人数/例	感染率/%	病原菌（%）
1918	西班牙^[12]	尸检肺培养	68	93	肺炎链球菌（23.0）金黄色葡萄球菌（8.0）
1918	西班牙^[13]	尸检肺培养	/	16~80	肺炎链球菌（71.0）金黄色葡萄球菌（1.0）
1957	亚洲^[15]	患者痰培养	/	53	金黄色葡萄球菌（27.0）肺炎链球菌（15.0）流感嗜血杆菌（4.0）
1957	荷兰^[16]	尸检肺培养	/	/	金黄色葡萄球菌（59.0）
1967至1968	中国香港^[17]	痰液、血液或胸腔积液培养	167	/	肺炎球菌（61.7）葡萄球菌（6.0）
1968至1969	中国香港^[17]	痰液、血液或胸腔积液培养	108	/	肺炎球菌（48.2）葡萄球菌（19.4）
2009	纽约^[20]	尸检肺组织组化	47	28	肺炎链球菌（61.0）化脓链球菌（11.0）
	美国CDC^[21]	尸检肺组织病理分析	77	29	肺炎链球菌（45.0）
	英国^[22]	尸检肺组织病理分析	68	41	肺炎链球菌（61.0）
	阿根廷^[23]	确诊患者鼻咽拭子样本	/	66	流感嗜血杆菌（68.0）肺炎链球菌（41.0）金黄色葡萄球菌（23.0）
	西班牙^[24]	ICU患者血液培养、血清学检测	/	18	肺炎链球菌（55.0）
	韩国^[25]	尸检血液、痰液培养	115	30	金黄色葡萄球菌（24.0）鲍曼不动杆菌（15.0）肺炎链球菌（9.0）

时间/年	地区	研究方法/对象	病例人数/例	细菌性共感染
时间/年	地区	研究方法/对象	病例人数/例	感染率/%	病原菌（%）
1918	西班牙^[12]	尸检肺培养	68	93	肺炎链球菌（23.0）金黄色葡萄球菌（8.0）
1918	西班牙^[13]	尸检肺培养	/	16~80	肺炎链球菌（71.0）金黄色葡萄球菌（1.0）
1957	亚洲^[15]	患者痰培养	/	53	金黄色葡萄球菌（27.0）肺炎链球菌（15.0）流感嗜血杆菌（4.0）
1957	荷兰^[16]	尸检肺培养	/	/	金黄色葡萄球菌（59.0）
1967至1968	中国香港^[17]	痰液、血液或胸腔积液培养	167	/	肺炎球菌（61.7）葡萄球菌（6.0）
1968至1969	中国香港^[17]	痰液、血液或胸腔积液培养	108	/	肺炎球菌（48.2）葡萄球菌（19.4）
2009	纽约^[20]	尸检肺组织组化	47	28	肺炎链球菌（61.0）化脓链球菌（11.0）
	美国CDC^[21]	尸检肺组织病理分析	77	29	肺炎链球菌（45.0）
	英国^[22]	尸检肺组织病理分析	68	41	肺炎链球菌（61.0）
	阿根廷^[23]	确诊患者鼻咽拭子样本	/	66	流感嗜血杆菌（68.0）肺炎链球菌（41.0）金黄色葡萄球菌（23.0）
	西班牙^[24]	ICU患者血液培养、血清学检测	/	18	肺炎链球菌（55.0）
	韩国^[25]	尸检血液、痰液培养	115	30	金黄色葡萄球菌（24.0）鲍曼不动杆菌（15.0）肺炎链球菌（9.0）

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