On November 27, 2023, a respiratory disease outbreak was reported in a herd of »180 fattening pigs, 4 weeks after the introduction of 90 growing pigs from another herd from within Switzerland. Upon clinical examination, »80% of pigs showed apathy and fever (<40.3°C) and sporadic respiratory signs. The farmer, who was 40–50 years of age with no reported underlying conditions, experienced a mild influenza-like illness 2 weeks earlier and reported similar symptoms in 2 household members. The farmer was not vaccinated against seasonal influenza and reported no contact with other pig herds.

Figure 1

Figure 1. Timeline of events from study of swine-origin influenza A(H1N1) virus in pigs and farmer, Switzerland, November 2023. Image depicts the chronology of symptoms in pigs and humans, sampling dates, and...

We collected and analyzed nasal swab samples from pigs and the farmer through our WGS-based surveillance program and the national swIAV surveillance system. Within the WGS surveillance framework, we screened 5 pig samples (A0001–A0005) and 1 farmer sample (H0001) for IAV using a pan-IAV matrix gene–specific quantitative reverse transcription PCR assay on extracted viral RNA (Appendix Table 1) (11). All samples tested positive; viral loads were higher in pigs (crossing point [Cp] value 24–26) than in the farmer sample (Cp 32) (Table 1). After confirming variant H1N1 (H1N1v) infection in the farmer, we notified veterinary and public health authorities and reported the case through the World Health Organization National Focal Point in accordance. Nine days after case confirmation, nasal swabs from all 3 household contacts tested negative for IAV at the Swiss National Reference Centre for Influenza (NRCI) (Figure 1) (A.R. Gonçalves Cabecinhas, pers. comm., email, 2024 Dec 2).

Figure 2

Figure 2. Maximum-likelihood phylogenetic tree from study of swine-origin influenza A(H1N1) virus in pigs and farmer, Switzerland, November 2023. We mapped hemagglutinin (HA) gene codon sequences, showing lineage classification of the study...

We performed WGS as described previously (12), achieving high read depth (>1,000´) overall; 1 segment showed lower coverage (>100´), sufficient for complete genome assembly (Table 1; Appendix Table 1, Figure 1). We subtyped all viruses from human and pig samples as swine H1N1 (swH1N1); nucleotide identity was >99.9% across all genomic segments. Phylogenetic analysis with publicly available swH1N1 sequences from Switzerland and Europe showed that all study viruses were assigned to the EA swH1N1 lineage, clade 1C.2.2, forming a monophyletic cluster for all genomic segments (Figure 2; Appendix Figure 2). Similar to other EA swH1N1 viruses, the Switzerland sequences harbored several amino acid substitutions associated with host specificity and antiviral resistance (Appendix Table 2).

We assessed low-frequency diversity by variant calling across all genomic segments. We detected 26 minor single-nucleotide variants (SNVs) at 6%–50% frequency, resulting in 17 nonsynonymous mutations. We detected 4 human-specific SNVs, including C1771T (H0001), which resulted in a premature stop codon in the polymerase acidic (PA) gene (Q591*). We identified 4 SNVs shared between human and pig samples, including G515A, which resulted in the HA-G172E mutation associated with antigenic drift and potential immune escape (Appendix Table 3, Figure 3) (13). We detected 1 SNV (PB2–1447), leading to a T483A mutation, in all samples. The presence of shared SNVs supports epidemiologic linkage between the farmer and pigs.

Finally, we compared HA antigenic residues of study viruses to the 2023–24 human seasonal vaccine strain and a contemporaneous (2023) human H1N1 sequence (Table 2). We identified multiple substitutions in the swH1N1 sequences across defined antigenic sites Sa/Sb, Ca1, Ca2, and Cb; the contemporaneous human seasonal virus differed from the vaccine strain by 2 antigenic residues. Overall, swH1N1 sequences from pigs and the farmer showed greater divergence at HA antigenic sites relative to the vaccine strain than the contemporaneous human seasonal virus, consistent with their evolutionary divergence from human H1N1 viruses.

This study reports the concurrent detection of EA swH1N1 virus in a farmer and his pigs in Switzerland. Evidence for zoonotic transmission is >99.9% genomic identity between viruses from the farmer and pigs, shared SNVs between hosts, and epidemiologic data consistent with transmission at the swine–human interface. We identified several human-specific SNVs, but their functional significance remains unknown. We observed 1 SNV, PA C1771T (Q591*), at the consensus level in 1 pig sample; however, we cannot infer transmission direction or functional significance on the basis of the available data. The lower viral load we observed in the farmer sample may reflect previous immunity, timing of sampling, host-specific constraints, or the effects of the detected SNVs. We detected no onward transmission to household contacts; we could not exclude the possibility of secondary transmission because of the timing of sample collection.

Genomic analysis revealed that the swH1N1 viruses identified in this study clustered with previously detected Switzerland sequences belonging to the EA lineage, clade 1C.2.2 (10). Despite limited availability of complete swH1N1 genome sequences from Switzerland, our findings are consistent with the presence of a relatively homogeneous swIAV population in pigs, likely shaped by the closed herd system and low annual importation of live pigs. Similarly, in Norway, the circulation of a single lineage under a closed system highlighted the effect of production structure on viral evolution (14). In contrast, greater swIAV genetic diversity has been reported in other countries in Europe (15).

HA sequences of study swH1N1 viruses harbored multiple amino acid substitutions across defined antigenic regions, whereas contemporary human H1N1 strains differed from vaccine strains by only 1 or 2 residues. The detection of 1 SNV associated with HA antigenic drift highlighted hidden evolution; that finding suggests potentially limited cross-protection from human vaccines for exposed workers, underscoring the need for targeted vaccination strategies for high-risk occupational groups. Our investigation was restricted to 1 outbreak and a limited number of samples; we used no serologic data and only partial comparative sequences from Switzerland, which limited our assessment of evolutionary viral dynamics. Despite those constraints, the clinical, epidemiologic, and genomic evidence supports zoonotic transmission.

Concurrent detection of swIAV in pigs and humans is rare globally. The detection of EA swH1N1 in pigs and a farmer in our study demonstrates zoonotic spillover and highlights the value of One Health surveillance. The viruses were genetically homogenous, yet antigenically distinct from contemporary human vaccine strains, emphasizing the need for active WGS surveillance and genomic characterization at the swine–human interface, as well as continued monitoring and targeted preventive strategies for pig-exposed workers.