Swine Influenza in Pigs: Clinical Symptoms and Differential Diagnosis

Swine influenza A virus (swIAV) is a primary viral agent of acute respiratory disease in pigs worldwide, contributing significantly to the porcine respiratory disease complex (PRDC) [1]. The clinical presentation of swIAV infection ranges from subclinical to severe, often indistinguishable from other respiratory pathogens [2, 3]. Accurate differential diagnosis is critical for implementing control measures and reducing economic losses. This article reviews the clinical symptomatology, pathophysiological mechanisms, and diagnostic approaches for swIAV, with an emphasis on distinguishing it from other viral and bacterial causes of porcine respiratory disease.

Etiology and Virological Background

SwIAV belongs to the family Orthomyxoviridae, genus Alphainfluenzavirus, and is classified by hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins [4, 5]. Endemic subtypes in swine include H1N1, H1N2, and H3N2, with frequent reassortment events generating novel strains [4, 5]. Reverse zoonotic transmission of human seasonal influenza viruses to pigs has been documented, further expanding genetic diversity [6, 7]. The primary site of infection is the respiratory epithelium of the nasal mucosa, trachea, bronchi, and bronchioles [8]. SwIAV replication in ciliated epithelial cells leads to ciliary dysfunction, epithelial necrosis, and desquamation, impairing mucociliary clearance and predisposing the lower respiratory tract to secondary bacterial invasion [9, 10].

Clinical Symptoms in Pigs

The incubation period of swIAV is typically 1 to 3 days, followed by an acute onset of clinical signs [11, 12]. Disease expression is influenced by host immune status, viral strain virulence, and concurrent infections [13, 14]. Core clinical manifestations include:

• Fever: Rectal temperatures may exceed 40.5°C, often peaking within 48 hours of infection [12].
• Respiratory signs: Sudden onset of harsh, non-productive coughing, sneezing, nasal discharge (serous to mucopurulent), and tachypnea with labored abdominal breathing [15, 16].
• Systemic signs: Anorexia, lethargy, piloerection, and huddling behavior. Weight loss and decreased growth rates are observed in growing pigs [17, 18].
• Ocular signs: Conjunctivitis and ocular discharge are occasionally reported [11].

In suckling piglets, maternal antibodies provide partial protection but do not prevent infection entirely, often resulting in milder or subclinical disease [14, 12]. In finishing pigs and adults, clinical signs can be more pronounced, especially when co-infections with other PRDC pathogens occur [19, 1]. Morbidity is typically high (50 to 90%), but mortality is low (<5%) unless secondary bacterial pneumonia ensues [9, 10].

Lesions observed at necropsy include cranioventral bronchopneumonia, hyperemic and edematous lungs, tracheitis, and accumulation of serosanguineous fluid in airways [2]. Histopathologic examination reveals necrotizing bronchitis and bronchiolitis, with loss of ciliated epithelium, peribronchiolar lymphocytic cuffing, and alveolar edema [2, 8].

Host Factors and Immunological Response

The innate immune response to swIAV involves type I interferon production, recruitment of neutrophils and macrophages, and secretion of pro-inflammatory cytokines [13, 18]. The adaptive response induces virus-specific IgA in the upper respiratory tract and serum IgG, which can be measured by hemagglutination inhibition (HI) assays and commercial ELISA kits [20, 12]. Vaccination with inactivated or recombinant vaccines can reduce clinical severity but may not prevent infection or shedding entirely [21, 22]. Vaccine-associated enhanced respiratory disease has been described under certain conditions [18].

Differential Diagnosis

Because the acute respiratory signs of swIAV overlap with those of numerous other porcine pathogens, a structured differential diagnosis is essential. The table below summarizes key differential diagnoses based on clinical and pathological features.

Co-infections between swIAV and bacterial pathogens such as Actinobacillus pleuropneumoniae and Mycoplasma hyopneumoniae worsen clinical signs and complicate diagnosis [9, 10]. Viral-bacterial synergy is mediated by swIAV-induced damage to the respiratory epithelium, which facilitates bacterial adherence and invasion [27, 10].

Diagnostic Approach

Laboratory confirmation is required for definitive diagnosis. Sample types include nasal swabs (individual or pooled), tracheobronchial swabs, oral fluids, and lung tissue [11, 15, 28]. Oral fluids have shown acceptable diagnostic sensitivity compared to nasal swabs for RT-PCR detection of swIAV [11]. For herd-level monitoring, aggregate samples such as rope oral fluids or dust swabs can be used [17, 15].

Molecular detection: Real-time RT-PCR targeting the matrix (M) gene is the gold standard for swIAV detection [26, 23, 29]. Multiplex RT-PCR assays can simultaneously detect swIAV, PRRSV, PCV2, and other respiratory pathogens [23, 30, 29]. Digital PCR (dPCR) offers absolute quantification and may be less affected by inhibitors [31]. Duplex real-time fluorescent quantitative PCR assays have been developed for simultaneous detection of swIAV and Actinobacillus pleuropneumoniae [26]. Quadruplex one-step RT-qPCR assays allow detection of multiple respiratory viruses in a single reaction [30].

Rapid point-of-care options: Recombinase polymerase amplification (RPA) combined with CRISPR/Cas12a systems provides visual field detection without thermal cyclers [32]. RT-LAMP paired with lateral flow strips offers another rapid alternative [33]. Microfluidic devices incorporating photonic integrated circuits enable label-free detection [28].

Serology: Hemagglutination inhibition (HI) assays and commercial ELISA kits detect anti-swIAV antibodies [20, 12]. Serology can confirm exposure but cannot distinguish recent from past infection [20].

Metagenomic and next-generation sequencing: Nanopore metagenomic sequencing on tracheobronchial swabs can identify viral and bacterial co-infections with high resolution [27]. This approach is valuable for characterizing circulating strains and detecting novel reassortants [34, 5].

Host gene expression assays: A 3-transcript host expression assay has been described to differentiate between viral and bacterial infections in pigs, potentially guiding antimicrobial use [35].

Point-of-care and integrated diagnostics: Aggregate sample monitoring combined with artificial intelligence-based respiratory scoring can track disease patterns in endemically infected herds [17].

Differential Diagnosis Decision Tree

The following Mermaid diagram outlines a structured decision pathway for swIAV differentiation from other PRDC pathogens.

flowchart TD
    A[Acute onset respiratory signs in pigs<br>cough, fever, anorexia] --> B{"Collect samples<br>(nasal swab / oral fluid / lung")}
    B --> C[RT-PCR for swIAV M-gene]
    C --> D{Positive?}
    D -->|Yes| E[swIAV confirmed<br>Consider subtyping by HA/NA RT-PCR]
    D -->|No| F[Simultaneous multiplex RT-PCR<br>PRRSV, PCV2, PRV1, SOV, PHEV]
    F --> G{Any positive?}
    G -->|Yes| H[Identify primary viral pathogen<br>Consider co-infection]
    G -->|No| I["Bacterial workup:<br>Culture, PCR for App, Mhyo, S. suis, etc."]
    H --> J[Assess severity and co-infections<br>metagenomic sequencing if indicated]
    I --> K{Bacterial pathogen<br>isolated?}
    K -->|Yes| L[Treat accordingly + antimicrobial sensitivity]
    K -->|No| M["Consider non-infectious causes<br>(e.g., environmental, toxic")]
    E --> N["Evaluate herd immunity:<br>vaccination history, maternal antibodies"]
    N --> O["Implement control: biosecurity, vaccination"]

The decision tree emphasizes early molecular detection and systematic exclusion of other PRDC agents. The use of multiplex assays allows simultaneous screening of the most common viral and bacterial pathogens [23, 30, 29].

Conclusion

Swine influenza A virus remains a major cause of acute respiratory disease in pigs, with clinical signs that overlap extensively with other infections. Accurate differential diagnosis relies on a combination of clinical observation, molecular diagnostics, and consideration of co-infections. Multiplex RT-PCR and emerging point-of-care technologies enable rapid detection and differentiation, facilitating timely intervention. Understanding the local viral and bacterial ecology, as well as host immune status, is essential for effective herd health management.

References

[1] Eddicks M, Eddicks L, Stadler J et al. [The porcine respiratory disease complex (PRDC) - a clinical review]. Tierarztl Prax Ausg G Grosstiere Nutztiere. 2021. https://pubmed.ncbi.nlm.nih.gov/33902142/

[2] Piñeyro PE, Burrough ER, Almeida M et al. Overview of porcine interstitial and bronchointerstitial pneumonia: infectious and non-infectious causes. J Vet Diagn Invest. 2026. https://pubmed.ncbi.nlm.nih.gov/42116569/

[3] Renzhammer R, Auer A, Loncaric I et al. Retrospective Analysis of the Detection of Pathogens Associated with the Porcine Respiratory Disease Complex in Routine Diagnostic Samples from Austrian Swine Stocks. Vet Sci. 2023. https://pubmed.ncbi.nlm.nih.gov/37888553/

[4] Jiao J, Ding J, Sun Z et al. Characterization of a reassortant H3N2 swine influenza virus with 2009 pandemic internal genes and enhanced potential for zoonotic risk. Vet Microbiol. 2026. https://pubmed.ncbi.nlm.nih.gov/41671764/

[5] Yang F, Cheng L, Liu F et al. Genetic and molecular characterization of a novel reassortant H3N2 influenza virus from a sick pig in Eastern China in 2019. Vet Res. 2025. https://pubmed.ncbi.nlm.nih.gov/39930519/

[6] Sylvén KR, Jacobson M, Schwarz L et al. Reverse zoonotic transmission of human seasonal influenza to a pig herd in Sweden. Tierarztl Prax Ausg G Grosstiere Nutztiere. 2024. https://pubmed.ncbi.nlm.nih.gov/39447586/

[7] Kontowicz E, Moreno-Madriñan M, Clarke Z et al. Risk assessment of influenza transmission between workers and pigs on US indoor hog growing units. Prev Vet Med. 2024. https://pubmed.ncbi.nlm.nih.gov/39053175/

[8] Meliopoulos V, Cherry S, Wohlgemuth N et al. Primary Swine Respiratory Epithelial Cell Lines for the Efficient Isolation and Propagation of Influenza A Viruses. J Virol. 2020. https://pubmed.ncbi.nlm.nih.gov/32967961/

[9] Panattoni A, De Boeck I, Wittouck S et al. Exploring the functional microbiome of pigs within the porcine respiratory disease complex: viral-bacterial co-infections and virulence factor profiling. Microbiol Spectr. 2026. https://pubmed.ncbi.nlm.nih.gov/41609371/

[10] Obradovic MR, Segura M, Segalés J et al. Review of the speculative role of co-infections in Streptococcus suis-associated diseases in pigs. Vet Res. 2021. https://pubmed.ncbi.nlm.nih.gov/33743838/

[11] Woźniak A, Cybulski P, Ryt-Hansen P et al. Can Oral Fluids Replace Nasal Swabs in Swine Influenza A Virus (swIAV) PCR Diagnostics? Pathogens. 2025. https://pubmed.ncbi.nlm.nih.gov/40872318/

[12] Ryt-Hansen P, Pedersen AG, Larsen I et al. Acute Influenza A virus outbreak in an enzootic infected sow herd: Impact on viral dynamics, genetic and antigenic variability and effect of maternally derived antibodies and vaccination. PLoS One. 2019. https://pubmed.ncbi.nlm.nih.gov/31725751/ *** Disclaimer: This article is for educational and informational purposes only. It is not intended to substitute for professional veterinary advice, diagnosis, treatment, or regulatory guidance. Always consult a licensed veterinarian or qualified specialist regarding animal health, disease diagnosis, and therapeutic decisions.

[13] Grevelinger J, Bourry O, Schmidt S et al. Swine influenza A virus infection sets the local immunological landscape in subsequent infection with porcine reproductive and respiratory syndrome virus. Vet Res. 2025. https://pubmed.ncbi.nlm.nih.gov/40484956/

[14] Gaulke CA, Yuan F, Yang L et al. Maternal vaccination partially protects piglets against influenza A virus associated alteration of the microbiome and hippocampal gene expression. Vet Microbiol. 2025. https://pubmed.ncbi.nlm.nih.gov/40359780/

[15] Lillie-Jaschniski K, Lisgara M, Pileri E et al. A New Sampling Approach for the Detection of Swine Influenza a Virus on European Sow Farms. Vet Sci. 2022. https://pubmed.ncbi.nlm.nih.gov/35878355/

[16] Unterweger C, Debeerst S, Klingler E et al. [Challenges in Influenza diagnostics in a swine herd - a case report]. Tierarztl Prax Ausg G Grosstiere Nutztiere. 2021. https://pubmed.ncbi.nlm.nih.gov/34861735/

[17] Eddicks M, Feicht F, Beckjunker J et al. Monitoring of Respiratory Disease Patterns in a Multimicrobially Infected Pig Population Using Artificial Intelligence and Aggregate Samples. Viruses. 2024. https://pubmed.ncbi.nlm.nih.gov/39459909/

[18] Wymore Brand M, Souza CK, Gauger P et al. Biomarkers associated with vaccine-associated enhanced respiratory disease following influenza A virus infection in swine. Vet Immunol Immunopathol. 2024. https://pubmed.ncbi.nlm.nih.gov/38815504/

[19] Graaf-Rau A, Hennig C, Lillie-Jaschniski K et al. Emergence of swine influenza A virus, porcine respirovirus 1 and swine orthopneumovirus in porcine respiratory disease in Germany. Emerg Microbes Infect. 2023. https://pubmed.ncbi.nlm.nih.gov/37470510/

[20] Muzykina L, Barrado-Gil L, Gonzalez-Bulnes A et al. Overview of Modern Commercial Kits for Laboratory Diagnosis of African Swine Fever and Swine Influenza A Viruses. Viruses. 2024. https://pubmed.ncbi.nlm.nih.gov/38675848/

[21] Zhang Y, Zhang P, Du X et al. A gram-positive enhancer matrix particles vaccine displaying swine influenza virus hemagglutinin protects mice against lethal H1N1 viral challenge. Front Immunol. 2024. https://pubmed.ncbi.nlm.nih.gov/39835123/

[22] Yu J, Sreenivasan C, Sheng Z et al. A recombinant chimeric influenza virus vaccine expressing the consensus H3 hemagglutinin elicits broad hemagglutination inhibition antibodies against divergent swine H3N2 influenza viruses. Vaccine. 2023. https://pubmed.ncbi.nlm.nih.gov/37689544/

[23] Wang M, Pan Y, Ma W et al. Development of a triplex TaqMan probe-based real-time PCR assay for simultaneous detection of swine influenza virus, porcine reproductive and respiratory syndrome virus, and porcine circovirus type 2. BMC Vet Res. 2025. https://pubmed.ncbi.nlm.nih.gov/40296106/

[24] Woźniak A, Cybulski P, Denes L et al. Detection of Porcine Respirovirus 1 (PRV1) in Poland: Incidence of Co-Infections with Influenza A Virus (IAV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in Herds with a Respiratory Disease. Viruses. 2022. https://pubmed.ncbi.nlm.nih.gov/35062350/

[25] Arunsiripate TT, Groeltz-Thrush J, Saeng-Chuto K et al. Diagnostic investigation of porcine hemagglutinating encephalomyelitis virus as potential pathogen associated with respiratory clinical signs and pulmonary lesions in pigs. Microb Pathog. 2025. https://pubmed.ncbi.nlm.nih.gov/40120700/

[26] Ren YJ, Lin H, Yu DJ et al. A duplex real-time fluorescent quantitative PCR method for simultaneous and rapid detection of Actinobacillus pleuropneumoniae and influenza A virus. Front Vet Sci. 2026. https://pubmed.ncbi.nlm.nih.gov/41810404/

[27] Vereecke N, Zwickl S, Gumbert S et al. Viral and Bacterial Profiles in Endemic Influenza A Virus Infected Swine Herds Using Nanopore Metagenomic Sequencing on Tracheobronchial Swabs. Microbiol Spectr. 2023. https://pubmed.ncbi.nlm.nih.gov/36853049/

[28] Manessis G, Frant M, Wozniakowski G et al. Point-of-Care and Label-Free Detection of Porcine Reproductive and Respiratory Syndrome and Swine Influenza Viruses Using a Microfluidic Device with Photonic Integrated Circuits. Viruses. 2022. https://pubmed.ncbi.nlm.nih.gov/35632730/

[29] Sunaga F, Tsuchiaka S, Kishimoto M et al. Development of a one-run real-time PCR detection system for pathogens associated with porcine respiratory diseases. J Vet Med Sci. 2020. https://pubmed.ncbi.nlm.nih.gov/31866601/

[30] Ma Y, Shi K, Chen Z et al. Simultaneous Detection of Porcine Respiratory Coronavirus, Porcine Reproductive and Respiratory Syndrome Virus, Swine Influenza Virus, and Pseudorabies Virus via Quadruplex One-Step RT-qPCR. Pathogens. 2024. https://pubmed.ncbi.nlm.nih.gov/38668296/

[31] Shi Y, Shi K, Ma Y et al. Development of a triplex crystal digital PCR for the detection of PRCoV, PRRSV, and SIV. Front Vet Sci. 2025. https://pubmed.ncbi.nlm.nih.gov/40230793/

[32] Tian C, Feng L, Zhou X et al. A Portable One-Tube Assay Integrating RT-RPA and CRISPR/Cas12a for Rapid Visual Detection of Eurasian Avian-like H1N1 Swine Influenza Virus in the Field. Viruses. 2025. https://pubmed.ncbi.nlm.nih.gov/41600812/

[33] Storms SM, Shisler J, Nguyen TH et al. Lateral flow paired with RT-LAMP: A speedy solution for Influenza A virus detection in swine. Vet Microbiol. 2024. https://pubmed.ncbi.nlm.nih.gov/38981201/

[34] Kwon T, Carossino M, Morozov I et al. Influenza-Infected Pigs Are Not Susceptible to SARS-CoV-2 Infection. Pathogens. 2026. https://pubmed.ncbi.nlm.nih.gov/41754386/

[35] Hjertner B, Lützelschwab C, Schieck E et al. Development of a 3-transcript host expression assay to differentiate between viral and bacterial infections in pigs. PLoS One. 2021. https://pubmed.ncbi.nlm.nih.gov/34555028/

[36] Cogdale J, Kele B, Myers R et al. A case of swine influenza A(H1N2)v in England, November 2023. Euro Surveill. 2024. https://pubmed.ncbi.nlm.nih.gov/38240057/

[37] Batta I, Kaur T, Agrawal DK. Distinguishing Swine Flu (H1N1) from COVID-19: Clinical, Virological, and Immunological Perspectives. Arch Microbiol Immunol. 2023. https://pubmed.ncbi.nlm.nih.gov/37994372/

[38] Anjorin AA, Sausy A, Muller CP et al. Human Seasonal Influenza Viruses in Swine Workers in Lagos, Nigeria: Consequences for Animal and Public Health. Viruses. 2023. https://pubmed.ncbi.nlm.nih.gov/37376519/

[39] Chrun T, Maze EA, Vatzia E et al. Simultaneous Infection With Porcine Reproductive and Respiratory Syndrome and Influenza Viruses Abrogates Clinical Protection Induced by Live Attenuated Porcine Reproductive and Respiratory Syndrome Vaccination. Front Immunol. 2021. https://pubmed.ncbi.nlm.nih.gov/34858411/

[40] Jin L, Liu EM, Xie XH et al. Comparative analysis of clinical features and risk factors of severe pneumonia development in pediatric patients hospitalized with seasonal influenza or swine-origin influenza infection. Adv Clin Exp Med. 2020. https://pubmed.ncbi.nlm.nih.gov/32790248/

[41] Haach V, Gava D, Cantão ME et al. Evaluation of two multiplex RT-PCR assays for detection and subtype differentiation of Brazilian swine influenza viruses. Braz J Microbiol. 2020. https://pubmed.ncbi.nlm.nih.gov/32125678/

Disclaimer: This article is for educational and informational purposes only. It is not intended to substitute for professional veterinary advice, diagnosis, treatment, or regulatory guidance. Always consult a licensed veterinarian or qualified specialist regarding animal health, disease diagnosis, and therapeutic decisions.