Flu Season Trends and Preparing for Respiratory Outbreaks in the U.S.

The ebb and flow of seasonal respiratory pathogens – notably influenza and respiratory syncytial virus (RSV) – pose a perennial challenge to public health and diagnostic laboratories. In recent years, these "flu season" patterns have been unsettled by global events, most notably the COVID-19 pandemic, leading to unprecedented trends. For example, the 2020-2021 flu season was virtually non-existent (only 0.2% of respiratory tests were positive for influenza, compared to ~26–30% in prior seasons). RSV and other common respiratory viruses likewise saw historic lows in 2020-2021 due to pandemic mitigation measures.

This was followed by off-season resurgences: the typical winter RSV epidemic failed to occur in 2020-21, but an unusual summer outbreak hit in 2021. By 2022, as precautions eased, the U.S. experienced an early and intense convergence of RSV, influenza, and COVID-19 – a so-called "tripledemic" – that strained pediatric hospitals nationwide. The 2022-2023 flu season activity ramped up nationally well beyond the entire 2020-2021 season, peaking much earlier than usual (late November instead of the typical January peak).

These disruptions remind us that seasonal pathogen dynamics are not static; as the CDC observed, "the timing and duration of activity has been less predictable" in the pandemic era. Nonetheless, valuable lessons and technological advances have emerged, helping laboratories and healthcare providers prepare more effectively for whatever each respiratory virus season brings.

Weekly US Map: Influenza Summary Update | FluView | CDC

The Role of Respiratory Pathogen Panels (RPP) in Diagnostics

One major advance in managing seasonal outbreaks is the widespread use of Respiratory Pathogen Panels (RPP) – multiplex molecular tests that detect a broad array of (viral and sometimes bacterial) respiratory pathogens in one go. Instead of testing for just one or two viruses based on clinical suspicion, RPP syndromic testing combines many probable culprits into a single, rapid assay. This comprehensive approach markedly increases the chances of identifying the cause of infection quickly and accurately, providing "actionable answers in a clinically relevant timeframe."

In practical terms, a single RPP can simultaneously screen a patient's nasopharyngeal sample for influenza A, influenza B, RSV, SARS-CoV-2, and numerous other common respiratory viruses.

For instance, the BPX™ qPLEX Respiratory Pathogen Profile enables multiplex real-time PCR detection of 40+ viral and bacterial respiratory pathogens—including influenza A, influenza B, RSV, SARS, MERS, RSV A/B, Parainfluenza 1–4, adenoviruses, rhinoviruses, metapneumoviruses (OC43, 229E, NL63, HKU1), and key bacterial agents such as Streptococcus pneumoniae, Klebsiella pneumoniae, Mycoplasma pneumoniae, and Bordetella pertussis. Each kit is optimized for efficient amplification across QuantStudio™ and Bio-Rad® systems, with configurations available in both 96- and 384-well formats for high-throughput research applications.

The value of RPP testing is especially clear during overlapping surges of respiratory illnesses. Many respiratory viruses cause similar flu-like symptoms, making clinical differentiation challenging. A multiplex panel allows laboratories to pinpoint which pathogen (or pathogens) are present early in the patient's illness, enabling targeted treatment (such as antiviral therapy for influenza) and appropriate infection control. It also helps detect co-infections or unexpected outbreaks.

For example, during the 2022 tripledemic, an RPP could confirm if a hospitalized child had RSV, influenza, COVID-19, or a combination – critical information for patient management and cohorting. By providing fast, comprehensive results, RPPs support clinicians in making timely decisions on public health reporting.

In short, RPPs have become an indispensable tool for labs preparing for seasonal surges, ensuring that diagnostic capacity keeps up with the unpredictable mix of circulating pathogens.

Influenza A and B: Recent Trends and Evolution

Seasonal influenza in the U.S. typically strikes between late fall and early spring, with activity often peaking around December to February. However, the last five years have been anything but typical for flu. The 2019-2020 flu season started like a normal season (with significant influenza A and B activity through winter), but it was abruptly cut short in March 2020 when COVID-19 mitigation efforts (lockdowns, masking, travel restrictions) took effect.

The result was an unusually low final tally for 2019-20 and a very mild 2020-2021 season that followed – in fact, 2020-21 saw the lowest U.S. influenza activity on record since at least 1997. Only a few hundred flu cases were detected nationally over the entire 2020-21 season, an astonishing anomaly that epidemiologists attributed to COVID-19 precautions and possibly viral interference.

By 2021-2022, some influenza activity returned, but it remained subdued compared to pre-pandemic norms. CDC characterized 2021-22 as a "mild" flu season with the lowest disease burden (illnesses, hospitalizations, deaths) since 2011-12. Notably, that season had an atypical two-wave pattern: an initial winter surge (Dec 2021-Jan 2022) followed by a second, late-spring wave that extended into May and even June 2022. Such a prolonged double wave is highly unusual for influenza. As CDC experts observed, the timing and duration of flu activity have become less predictable in the pandemic's wake.

The most recent 2022-2023 season, however, signaled a return to more intense flu impact – albeit on an altered timetable. Influenza activity in 2022-23 "returned to pre-COVID-19 levels" in terms of overall burden, but it "occurred earlier than is usual," according to the CDC. Activity began rising in October 2022, a couple of months ahead of the usual schedule, and peaked nationally in late November to early December.

Many regions saw their flu peak by mid-December or even late November, making it one of the earliest-peaking seasons on record. The predominant strain was influenza A (H3N2), a subtype known for hitting older adults hard. CDC's preliminary estimates for 2022-23 indicate it was a moderately severe season: roughly 26–49 million Americans fell ill, 290,000–650,000 were hospitalized, and at least 19,000 died from influenza. Tragically, 2022-23 also saw a sharp rise in pediatric flu deaths ( at least 154 children died, the highest pediatric toll since before the pandemic ). This underscores that influenza, even outside pandemic scenarios, remains one of the deadliest vaccine-preventable diseases in the country.

U.S. influenza test positivity by week for recent seasons (2017–2023). The 2020-21 season saw an unusually early and steep drop in late fall.

From a virological perspective, the makeup of circulating flu strains has also evolved in recent years. Influenza A viruses (which cause the majority of cases) have two main subtypes in humans – H1N1 and H3N2 – and these have been in continuous evolution for decades. The H1N1 currently circulating is actually the descendant of a novel strain that swept the globe in the 2009 "swine flu" pandemic, which replaced the previous seasonal H1N1 lineage. Influenza B viruses, which typically make up a smaller portion of cases, come in two lineages (Victoria and Yamagata). Notably, since the pandemic, influenza B has been remarkably scarce.

In the 2021-22 and 2022-23 seasons, labs reported almost exclusively B/Victoria lineage detections; no B/Yamagata viruses have been definitively identified in recent years. It is possible that the Yamagata lineage has silently died out globally (thanks in part to the pandemic's interruption of transmission), though global surveillance is needed to confirm extinction. If Yamagata is indeed gone, that is a significant transformation in the flu landscape – it could eventually simplify vaccine selection (as current quadrivalent vaccines include a Yamagata component that might no longer be needed).

Meanwhile, influenza vaccines continue to be our best defense each season, and recent trends have only reinforced their importance. The flu vaccines are updated annually to match the expected strains (based on global surveillance data). In some pandemic-affected seasons, the population's immunity may have waned due to lack of recent exposure, making vaccination even more crucial.

For example, the early and aggressive 2022-23 flu outbreak was partly attributed to immunity gaps after two years of minimal flu circulation – a reminder for labs and clinicians to advocate for vaccination. Positive progress is being made on the front: next-generation flu vaccines are in development, including mRNA-based influenza vaccines that promise quicker updates and potentially better strain matching. In 2023, Moderna announced successful Phase 3 trial results for an mRNA flu vaccine in older adults, noting that this technology could allow more precise matching of circulating strains and faster manufacturing of vaccines (for both seasonal epidemics and future pandemics).

There is even work on combination shots (e.g. a single injection for flu and COVID-19) and on "universal" influenza vaccines targeting conserved viral components. While these are still in trial phases, they represent significant strides in the industry's effort to advance beyond the status quo of seasonal flu protection.

A CDC microbiologist working under high biosafety conditions with a reconstructed 1918-pandemic influenza virus sample. Studying past pandemic strains (like the deadly 1918 H1N1 shown here) helps scientists understand viral virulence and improve future influenza vaccines.

Preparing for the Next Flu Season – and Beyond

In light of these trends and advances, how can diagnostics and research labs best prepare for upcoming outbreaks? A few key strategies emerge:

• Stay Vigilant with Surveillance Data: Regularly monitor CDC reports (e.g. FluView for influenza, RSV-Net for RSV) and regional alerts. Early warning of rising activity enables labs to scale up testing capacity in time. The past few years taught us that spikes can come early or off-season, so year-round alertness is warranted. Ongoing surveillance is also critical for detecting new variants or shifts in virus behavior.
• Utilize Comprehensive Diagnostics: Embrace multiplex testing (RPP panels) during respiratory virus season to ensure no pathogen goes undetected. When patients present with acute respiratory symptoms, consider testing for a panel of viruses rather than only flu or only COVID. This approach not only improves individual patient care but also gives public health a more complete picture of which viruses are circulating. The FDA's recent authorization of the first over-the-counter home test that detects influenza A, B, and SARS-CoV-2 in a single kit is a promising step toward broader access to diagnostics. Such innovations, including potential at-home multiplex tests, could offload some demand from labs during peaks and empower patients – but labs will still play a crucial confirmatory and reference role. The collective impact of flu, COVID, and RSV underscores the importance of accessible testing, and public health agencies are committed to expanding these tools.
• Ensure Surge Capacity and Supplies: Before the season hits, laboratories should stockpile adequate testing kits/reagents (for PCR, rapid antigen tests, etc.), swabs, and PPE, considering the worst-case scenario of concurrent outbreaks. The 2022 tripledemic taxed many labs with high volumes; those with pre-planned surge protocols fared better. It's wise to review staffing plans as well – cross-train personnel on influenza, RSV, and COVID-19 testing platforms so that shifts can be reallocated when testing demand soars.
• Collaborate and Communicate: Coordination with infection control teams, hospital management, and local public health departments is vital during outbreak response. For example, if an unusually high positivity rate of RSV is noted in your lab, promptly alert pediatric wards and nearby providers. Share data on co-infections or unexpected detections (e.g. detection of an out-of-season virus) with public health authorities. Such real-time situational awareness supports efficient response, as seen in large health systems that formed special coordination groups during the 2022 tripledemic. Building on the data that guides decisions like expanding ICU capacity or issuing health advisories.
• Promote Vaccination and Preventive Measures: While labs are not typically front-line vaccinators, they play a role in the larger public health ecosystem. Laboratory scientists can advocate for staff vaccination (flu shots for healthcare workers, now RSV immunization for eligible groups) to reduce workforce illness during critical periods. Moreover, labs can assist in evaluating vaccine effectiveness by genetically characterizing circulating strains (if capable) or contributing testing data to studies. Highlighting in communications that most hospitalized flu patients in 2022-23 were unvaccinated, for instance, reinforces the importance of prevention. Simple hygiene reminders – handwashing, surface disinfection, mask usage when appropriate – also help and can be promoted within the lab and hospital.

Looking ahead, there are plenty of reasons for optimism. Science is delivering new tools (from rapid at-home tests to novel vaccines), and our understanding of respiratory pathogens deepens with each season. Yet preparedness is key: seasonal pathogens have a way of surprising us if we let our guard down. BioPathogenix is committed to supporting U.S. laboratories in this mission.

Through cutting-edge diagnostic solutions and expertise in pathogen surveillance, we aim to help labs stay one step ahead – whether it's a routine winter flu season or an unusual off-season outbreak. By learning from recent trends and leveraging the latest advancements, diagnostics and research labs can confidently navigate the ever-evolving respiratory virus landscape, ensuring timely detection of outbreaks and protection of public health.

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Sources: The analysis above is supported by data and reports from the CDC, peer-reviewed studies and public health surveillance summaries, FDA announcements, and expert commentary from medical centers, as cited throughout. These sources provide a comprehensive, up-to-date picture of respiratory pathogen trends and the measures available to combat them. By integrating such evidence-based insights, laboratories can formulate robust strategies for the coming flu seasons and beyond.