Is the H3N2 Flu Strain Setting Up Patients for COVID: Researchers Document Unusual Double Infection

A newly reported case of back-to-back infections with the H3N2 flu strain and COVID-19 is fuelling fresh questions about how winter viruses interact – and whether one infection could be 'setting up' the next. At the same time, H3N2 is the dominant influenza A subtype in England this season, circulating at medium levels while COVID-19 remains at a low, baseline level but hasn't gone away.

Here's what the case actually showed, what we know about this fast-moving flu strain – and what it does mean for people trying to stay healthy through winter.

The Unusual 'Double Infection'

In the case described by Schäffer Gregianini and colleagues, a health professional first developed a classic bout of influenza A(H3N2): fever, chest and body pain, marked tiredness and prostration. Lab testing during this first illness was positive only for H3N2. The symptoms settled after nine days.

Eleven days after the first symptom onset, a second wave of illness began – this time dominated by sore throat, nasal congestion, sneezing and coughing. A repeat RT-qPCR test came back positive only for SARS-CoV-2, later sequenced as Omicron BA.1, and those second-round symptoms lasted another 11 days.

The researchers also tracked what happened to close contacts: one person was co-infected with influenza A(H3N2) and SARS-CoV-2 lineage BA.1.15, while two others had SARS-CoV-2 alone (BA.1.15 and BA.1.1).

Their conclusion was straightforward but important: routine respiratory surveillance needs to test for multiple viruses, because COVID-19's symptoms can easily mimic other infections such as influenza.

In other words, this is a striking example of how, when multiple viruses are circulating, a person can be unlucky enough to get 'tag-teamed' rather than simply 'having one long flu.'

It does not prove that the H3N2 flu strain is uniquely priming people for COVID in some new, catastrophic way – at least not on the basis of a single case.

The H3N2 Flu Strain

H3N2 has a long history of causing rough flu seasons. Since entering humans in 1968, H3N2 viruses have evolved rapidly, changing the shape and sugar coating of their surface proteins to dodge immune defences.

Researchers have documented that modern H3N2 strains manifest the following traits:

• Accumulate more sugar 'shields' (N-linked glycans) on the haemagglutinin protein, which can help the virus hide from neutralising antibodies.
• Shift their receptor preferences towards the types of sialic acid found in the human upper airway, which supports efficient infection and transmission in people.
• Change so fast that vaccine strains must be updated frequently, and some past seasons have seen relatively modest vaccine effectiveness against H3N2 compared with other flu subtypes.

Influenza activity in England is in the medium range, with H3N2 viruses, primarily the J.2.4.1 (K) subclade, dominating. Flu test positivity is 12.7%, and hospital admission rates are 7.8 per 100,000.

By contrast, COVID-19 in England is currently at baseline levels: hospital PCR positivity is just over 2%, and the overall weekly admission rate is about 1.03 per 100,000, with ICU admissions remaining very low. The virus is still present – but this winter, flu and RSV are contributing more heavily to respiratory load than COVID.

Against that backdrop, an H3N2–then-COVID case is scientifically interesting because it illustrates how overlapping virus waves can look in real life, rather than signalling a brand-new 'super-virus' scenario.

Does H3N2 Make COVID 'Worse'?

So far, the evidence from this single case doesn't prove that the H3N2 flu strain biologically sets patients up for COVID.

There are plausible mechanisms – any serious flu can temporarily weaken immune defences, inflame and damage the lining of the airways, and leave people run-down and more vulnerable to whatever virus they meet next.

To show that H3N2 specifically increases COVID risk or severity, scientists would need larger datasets comparing people with flu only, COVID only, and combined or sequential infections, not just a single case report.

At the moment, this is best seen as an early warning that co-circulating viruses can overlap in messy ways – not as definitive proof of a new, high-risk interaction.

For the public, the practical message is more grounded:

• Assume more than one bug may be circulating. If you're very unwell, or you get sick twice in quick succession, clinicians may test for multiple respiratory viruses rather than assuming it's 'just flu' or 'just COVID.'

• Vaccines still matter. Early UK estimates indicate current flu vaccines continue to provide protection against clinical disease from H3N2, even though the circulating viruses are genetically diverse and show some antigenic drift away from vaccine strains. COVID-19 autumn boosters remain focused on people at highest risk of severe outcomes.
• Layered precautions help across the board. Hand-washing, good ventilation, staying home when acutely ill, and wearing a mask in crowded indoor spaces cut transmission for flu, COVID and RSV alike, regardless of which one happens to be dominant on the dashboard that week.

So is the H3N2 flu strain 'setting up' patients for COVID? Right now, it's more accurate to say this: H3N2 is having a solidly active season at the same time as COVID quietly ticks along in the background – and that overlap can lead to some unlucky double hits, as this health worker's case shows.

For doctors and public health teams, the case is a reminder to keep testing broadly and to watch how these viruses interact over time. For everyone else, the winter strategy remains familiar: get vaccinated if you're eligible, stay home when you're sick, and treat 'just a flu' with a bit more precaution than the phrase suggests.