Virology: Acquisition of specific human respiratory tract binding by 2.3.4.4b H5N1 hemagglutinins requires multiple mutations

 

#19,288

There remains much interest in exactly what changes the HPAI H5Nx virus would need in order to become a more `humanized' virus - like seasonal H3N2 and H1N1 - which have a strong affinity for the alpha 2,6 receptor cells most commonly found in the human respiratory system.

While it seems likely that it would require multiple concurrent mammalian adaptations to create a pandemic strain, the ability of avian flu viruses to bind to human α2-6 receptor cells is considered one of the biggest obstacles the virus must overcome in order to successfully spread in humans.

Complicating matters, as we've discussed previously (see here, here, and here), HPAI H5 viruses encompass a large and growing array of closely related - but genetically distinct subclades, subtypes, and genotypes - and a mutation that might impact one strain might not have the same effect on another. 

In December of 2024, a study in Science: A Single Mutation in Bovine Influenza H5N1 Hemagglutinin Switches Specificity to Human Receptors, suggested a single HA amino acid change (Q226L) could switch H5N1 B3.13 from binding preferentially to avian-type receptor cells to human-type receptor cells.

The authors wrote:

“Our experiments revealed that the Q226L mutation could significantly increase the virus’ ability to target and attach to human-type receptors,” explains Paulson. “This mutation gives the virus a foothold on human cells that it didn’t have before, which is why this finding is a red flag for possible adaptation to people.”

The shift alone, however, may not be enough to enable human-to-human transmission. Other genetic changes—such as mutations in polymerase basic 2 (E627K) that enhance viral replication and stability in human cells—would likely be necessary for the virus to spread efficiently among people.

The following month, in Preprint: The Q226L Mutation Can Convert a Highly Pathogenic H5 2.3.4.4e Virus to Bind Human-type Receptors, another study (later published in PNAS) found that adding Q226L to an older clade 2.3.4.4e H5N6 virus could switch receptor binding from avian to human-type receptors. 

While concerning, we've not seen any evidence of efficient or sustained spread of H5N1 in humans, suggesting there are additional enhancements required. 

Today we've a new study that offers an update on impact of the Q226L mutation in H5N1 B3.13, which finds that its impact varies between HPAI H5 strains. 

While Q226L did shift binding in laboratory tests towards human-type glycans, those glycans were not found on the human tracheal tissues tested, and the Q226L mutant failed to bind human trachea.

The addition of another HA mutation, N224K, increased human-tracheal binding, but only sparsely and mainly to goblet cells. All of which reinforces the notion that  receptor adaptation to humans in HPAI H5 is neither simple nor uniform.

Q226L appears to be decisive in some H5 strains, but the current bovine 2.3.4.4b H5N1 virus likely requires additional changes before it can efficiently bind to human receptors in the upper airway.  

I've only posted the link, abstract, and some excerpts from the study. Follow the link to read it in its entirety. 

Acquisition of specific human respiratory tract binding by 2.3.4.4b H5N1 hemagglutinins requires multiple mutations

Authors: María Ríos Carrasco, Mafalda F. Guerreiro Cabana, Eszter Kovács, Zoé Ducarne, Cindy G. J. Cleypool , Geert-Jan Boons, Robert P. de Vries  r.vries@uu.nlAuthors Info & Affiliations

https://doi.org/10.1128/jvi.01065-26

ABSTRACT

It has been suggested that the hemagglutinin of the human-infecting cattle-derived 2.3.4.4b virus A/Texas/34 H5N1 (H5TX) requires only one mutation, namely Q226L, to switch from binding avian-type to human-type receptor preference. In this study, we examined the binding of H5TX Q226L, along with other key mutations, to sections of human trachea. We conclude that, while H5TX Q226L can bind human-type receptors, more than a single mutation is required for this protein to bind to human respiratory tract tissue.

We also report changes in receptor-binding specificity of another 2.3.4.4b HA mutant, H5FR Q226L (from A/duck/France/161108/16 H5N8), associated with the presence of a multibasic cleavage site. This study offers insight into the determinants of evolution toward human-type receptor binding in currently circulating H5Nx viruses. It also emphasizes the importance of testing individual strains using additional methods, including tissue-based approaches, alongside synthetic glycans.

IMPORTANCE

Currently, H5N1 influenza A viruses are responsible for numerous zoonotic spillover events, from infecting birds to other mammals, including dairy cattle. Although no human-to-human transmission has been observed, several people have been infected. This host range expansion is typically linked to changes in one of the viral surface proteins, hemagglutinin, which can switch its preference from avian-type to human-type receptors. To better understand the potential of the currently circulating H5N1 virus to transmit among humans, we evaluated the effects of the Q226L mutation, in combination with other amino acid substitutions, on binding to the human trachea. We also studied the effect of the multibasic cleavage site, a specific motif present in highly pathogenic influenza strains, on receptor-binding properties. These findings provide insight into the role of receptor binding in influenza infections.

        (SNIP)

We conclude that more than a single mutation is required for the hemagglutinin of the currently circulating 2.3.4.4b viruses to bind human respiratory tissue. This aligns with previous work showing that multiple amino acid changes are required to switch from avian- to human-type receptors in H5 strains (3). One key takeaway from this study is the significance of glycan architecture. H5TX mutants, similarly to other HAs, distinguish not only between SIA linkage but are also selective according to glycan branch length and sialylation (31).

More research is needed on the presence of asymmetrical glycans in the human respiratory tract and their role in influenza A virus hemagglutinin attachment to cells. Moreover, we emphasize the importance of not underestimating the MBCS’s influence on hemagglutinin’s receptor-binding properties.

       (Continue . . . )

JAMA Peds: Effectiveness of Oseltamivir in Hospitalized Children With Laboratory-Confirmed Influenza, 2014-2023

 

#19,287

While the timing and severity of the next flu season is uncertain, we are already seeing reports of increased flu activity in Asia (see HK DH investigates case of severe paediatric influenza A infection), making the following JAMA Pediatrics  study on the effectiveness of Oseltamivir in hospitalized children both timely and reassuring.

One of the popular memes on the internet and in tabloid media has been that the influenza antiviral drug oseltamivir (Tamiflu ®) is either A) Ineffective or B) Ineffective and Dangerous.

A cherry picking of data, along with hyperbolic media reports – like the Daily Mail’s Ministers blew £650MILLION on useless anti-flu drugs - have helped to drive these beliefs. 

Admittedly, antivirals are not a panacea against influenza infection, but when administered early in an infection, they can significantly reduce the severity and duration of illness.

The addition of an FDA warning in 2008 - based on primarily on media reports from Japan - warning of rare `Neuropsychiatric events' (particularly among pediatric patients), further drove public opinion.  

A 2018 report, however (see Study Finds No Relationship Between Suicide & Oseltamivir In Pediatric Patients), strongly refuted those claims, but the stigma remains. 

As a result, oseltamivir is often underused, even though we've seen repeated studies showing their worth (see CID Journal: Under Utilization Of Antivirals For At Risk Flu Patients and  CDC Study: Early flu Antiviral Treatment Can Shorten Hospital Stays in Children With Flu).

   

CDC Influenza Antiviral Medications: Summary for Clinicians - Jan 2026

All of which brings us to a new investigative report, published yesterday in JAMA Pediatrics, which finds that oseltamivir treatment was associated with a 31% lower hazard of ICU admission and shortened hospital LOS (Length of stay) in hospitalized pediatric patients with lab confirmed influenza.

Due to its length, I've only reproduced the summary, abstract, and a few excerpts. Follow the link to read it in its entirety. 

Original Investigation

Effectiveness of Oseltamivir in Hospitalized Children With Laboratory-Confirmed Influenza, 2014-2023

Kacie Rytlewski, MD1; Angela Dunn, MS2; Alissa O’Halloran, MSPH3 et al
Published Online: August 10, 2026
doi: 10.1001/jamapediatrics.2026.3376

 Key Points

Question  Does oseltamivir treatment reduce risk of intensive care unit (ICU) admission and hospital length of stay among pediatric patients hospitalized with influenza?

Findings  Using a cohort study from a population-based surveillance network in 13 states across 8 influenza seasons, oseltamivir treatment was found to decrease both the likelihood of ICU admission and hospital length of stay among pediatric patients hospitalized with laboratory-confirmed influenza.

Meaning  These findings support the current national recommendations from the American Academy of Pediatrics, US Centers for Disease Control and Prevention, and Infectious Diseases Society of America that recommend antiviral treatment for children hospitalized with laboratory-confirmed influenza.

Abstract

Importance  National organizations recommend antiviral treatment for hospitalized children with influenza; however, use in this setting has recently declined. Studies of oseltamivir effectiveness in children are limited by misclassification bias, unknown symptom onset date, and incomplete capture of antiviral use prior to admission.

Objective  To assess the association between oseltamivir receipt and intensive care unit (ICU) admission and hospital length of stay (LOS) among pediatric influenza-associated hospitalizations.

Design, Setting, and Participants  This cohort study used data that were obtained from the Influenza Hospitalization Surveillance Network (FluSurv-NET), which conducts US population-based surveillance for laboratory-confirmed influenza hospitalizations for all ages across 13 states. The study data include seasons 2014 to 2015 through 2022 to 2023, excluding 2020 to 2021. Participants included children aged younger than 18 years who were hospitalized with laboratory-confirmed influenza and for whom a respiratory symptom onset date was available. These data were analyzed from October 2024 through May 2026.

Exposures  Oseltamivir receipt as a time-dependent exposure.

Main Outcome(s) and Measure(s)  The primary outcome was time from symptom onset to ICU admission. Secondary outcome was time from admission to discharge (LOS). Adjusted Cox proportional hazard models (aHR) with oseltamivir receipt as a time-dependent exposure were used.

Results  After exclusions, 6044 influenza cases were included in the primary ICU analysis, of whom 4240 (70.2%) received oseltamivir, and 7103 cases were included in the secondary LOS analysis, of whom 5746 (80.9%) received oseltamivir. In the ICU analysis, the median (IQR) age was 3 (1-7) years, 3382 (56%) were male and 3721 (44%) were female, and 2937 (49%) had 1 or more medical comorbidity—the most common of which was asthma in 1547 children (26%). In adjusted models, compared with untreated children, oseltamivir treatment reduced the hazard of ICU admission (aHR, 0.69; 95% CI, 0.60-0.80) and shortened LOS (analyzed as hazard of hospital discharge; aHR, 1.13; 95% CI, 1.06-1.21).

Conclusions and Relevance  In this cohort of children hospitalized with influenza, oseltamivir treatment was significantly associated with a reduced risk of ICU admission by 31% and decreased hospital LOS. These findings demonstrate the benefits of oseltamivir receipt and support current national recommendations for oseltamivir treatment as soon as possible in children hospitalized with suspected or laboratory-confirmed influenza.

        (SNIP)

Our main finding was a significant decrease in ICU admission risk among hospitalized children with laboratory-confirmed influenza treated with oseltamivir compared with those not treated. The association persisted after excluding patients who received oseltamivir prior to admission. The association of oseltamivir with decreased odds of ICU admission has been shown in prior retrospective cohort studies in children.7 Importantly, our additional analyses of age, underlying medical comorbidity, and timing of oseltamivir initiation from symptom onset showed consistent benefit for all hospitalized pediatric patients with influenza.

Our analyses also demonstrated a significant decrease in the hospital LOS among those receiving oseltamivir, reflected as an increased hazard of discharge; this is notable particularly given that cases had a relatively short LOS (median, 3 days). This finding persisted in our sensitivity analyses. There was no evidence of effect modification by age or medical comorbidity. We observed the reduction in LOS most prominently with early treatment, which has been observed previously.5,7 Our findings suggest that health care professionals should encourage caregivers of children to seek care early in the course of influenza-like illness and also urgently consider oseltamivir treatment for all children and adolescents hospitalized with suspected or confirmed influenza.

       (Continue . . . )

 

A Summer Snapshot Of U.S. Wild & Captive Mammals With Confirmed HPAI H5

 

#19,286

The USDA maintains a public database of wild and captive mammals (excludes livestock) infected with HPAI H5 across the country since its arrival in 2022; one which is highly dependent upon investigations and submissions by individual states and/or veterinarians. 

Last December, in Declining Mammalian Spillover Submissions To USDA Over Past 8 Months, we looked at a 90% drop in reported infections of HPAI H5 to mammalian wildlife during the 2nd half of 2025, despite increased detections in wild birds.

What the above chart did not reflect was the existing backlog, and gaps (between collection and confirmation dates) and/or delays in reporting cases (see chart below). Delays of 2 to 3 months are common (see graph below), and delays of 6 to 8 months are not unheard of. 

Graph created by Gemini using USDA data

Since April of this year, only 3 cases (2 skunks and 1 domestic cat from Utah) have been confirmed by the USDA.  While there may be as-yet unpublished data in the pipeline, the decline in case reports appears to be ongoing. 

Graph created by Gemini using USDA data

Reporting varies considerably by state (see chart below), with New Mexico reporting the highest total.

Graph created by Gemini using USDA data

But after 4 years, there are still 8 states which have yet to report a single detection.

• Alabama
• Arkansas
• Hawaii
• Maryland
• Mississippi
• New Hampshire
• South Carolina
• West Virginia

These disparities may come down to differences in climate and terrain (swamps vs. forests vs. deserts), varying activity by migratory flyways, and the fact that infected wildlife quite often die in remote, difficult to access places where their carcasses are quickly scavenged by other animals, making them unlikely to be discovered or tested.

But it is also possible that some states are simply more proactive in investigating, and reporting suspected cases, than others.

As far as host range is concerned, there are 54 different species listed in the USDA database, with the top 3; Domestic cat (155), Red fox (126), and House mouse (111) make up nearly half (48.0%) of all reported mammal submissions.

• There are, altogether, 16 different feline species (wild/captive/domestic) - which combined account for 238 submissions or (29.2%) of confirmed cases.

• Marine mammals make up another large chunk of the data accounting for 13.7% of all submissions (n=112), led by Northern Elephant Seal (57), Harbor seal (27), and Bottlenose dolphins (11)

(Excludes 22 one-off single detections)

Graph created by Gemini using USDA data

All of these numbers are presumed to represent a small fraction of the actual number of infections, as limited seroprevalence studies have found antibodies in a large array of wildlife species (see Virology: Susceptibilities & Viral Shedding of Peridomestic Wildlife Infected with Clade 2.3.4.4b HPAI Virus (H5N1).

Meanwhile, the public remains largely oblivious to the threat of HPAI (see Two Surveys (UK & U.S.) Illustrating The Public's Lack of Concern Over Avian Flu), while some state and local governments appear not to have prioritized surveillance, testing, and reporting. 

Although the decline in reported wildlife infections to the USDA may turn out to be a good sign, a lack of evidence is not evidence of lack.

WHO: Risk assessment of the introduction, spread, and zoonotic spillover of MERS-CoV Clade B in camel populations of the Nile Basin and Across Africa

 

#19,285

While the number of human MERS-CoV cases reported over the past six years has fallen dramatically, this high morbidity/mortality coronavirus continues to pose a significant public health threat ((Referral) Nature: Human MERS-CoV cases are falling but pose an ongoing pandemic threat) as it spreads and evolves in camels in the Middle East and Africa.

Some of this decline may be due to difficulties in identifying cases, while some Middle Eastern countries have shown past reluctance to report cases. It also seems likely that cases are being missed in North and Central Africa as well (see EID Journal: Geographic Distribution of MERS-CoV among Dromedary Camels, Africa). 

As of 11 June 2026, the WHO had reported a total of 2,637 laboratory-confirmed human cases have been reported - mostly from countries in the Arabian Peninsula - with an estimated case fatality ratio (CFR) of approximately 37%.   

But both the  EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016 and Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study by Drosten & Memish et al., suggest that far more MERS-CoV cases have occurred than have been reported.

  

MERS-CoV clade B is most common on the Arabian peninsula, while Africa is dominated by clade C, which is thought to be less well adapted to human physiology.  Clade A hasn't been reported in humans or camels since 2015, and is now considered extinct. 

But over the past year at least two studies have reported evidence that clade B-like viruses (or clade B/C recombinants) may be circulating in Africa. Today's risk assessment cites:

• In Egypt, phylogenetic analyses of a camel-derived sample identified genome fragments clustering with clade B viruses from the Arabian Peninsula, circulating alongside endemic African clade C viruses (Gomaa, Edwards, Wang, Taweel, et al., 2025).

• In a separate study (Hassan et al., 2025), metagenomic sequencing of nasal swabs from camels imported from Sudan also detected MERS-CoV genome fragments clustering with clade B human and camel strains

In both cases, the available sequences were limited and less than 100% complete, and so they must be regarded as preliminary, and will require full-genome confirmation.

The 24-page  FAO–WHO–WOAH GLEWS+ assessment (below) reached three primary conclusions; the first two question only deal with the impact on dromedaries, while the third deals with the public health risk.

Confidence in the two camel specific answers is low, while the confidence in the public health question is moderate. 

The section discussing question 3, provides the following rationale (excerpt):

Once introduced into camels in the Nile Basin countries, the likelihood of MERS-CoV clade B spillover to occupationally exposed humans is assessed as very likely, reflecting the intensity of human-camel contact, weak and uneven implementation of biosecurity and hygiene measures and constraints in surveillance and early detection systems.

The consequences are assessed as moderate. MERS-CoV Clade B can cause severe disease in humans and is associated with a high case fatality ratio, particularly among those with underlying medical conditions, and immunocompromised individuals. 

In the absence of licensed vaccines for the general population or widely available specific treatments, spillover events have the potential to result in severe clinical outcomes, especially in settings with limited access to advanced healthcare. Healthcare-associated outbreaks also remain a concern where infection prevention and control measures are insufficient. However, despite its high replication competence, a substantial proportion of MERS-CoV infections are asymptomatic or mild.

Furthermore, sustained human-to-human transmission is generally limited and typically requires close and prolonged contact. Consequently, widespread community transmission is not expected. Overall, the public health risk of MERS-CoV clade B spillover from camel populations to humans exposed to camels or their products in the Nile Basin countries is assessed as high.

The level of confidence in the assessment is considered moderate, reflecting evidence of frequent human–camel contact and known zoonotic potential of MERS-CoV clade B, but also important uncertainties regarding the frequency of spillover events, the role of specific exposure pathways, and gaps in surveillance and epidemiological data from the Nile Basin region.

The full risk assessment is well worth reading in its entirety. 

Australia: Bird Flu Detection in Wild Birds Doubles in Less Than 4 Days

 

#19,284

On August 4th, the official count of H5 positive birds in Australia broke 100 (n=102), today that number stands at 215, with the backlog of uninvestigated bird deaths continuing to rise.         

Detection of H5 bird flu 

As of 3.00pm AEST, 8 August 2026, Australia has 215 confirmed detections of H5 bird flu in wild birds.

• 10 in Western Australia (WA)
• 147 in South Australia (SA) 
• 4 in New South Wales (NSW)
• 1 in Queensland (QLD)
• 53 in Victoria (VIC).

We've two brief updates from DAFF:

8 August 2026

Attributable to Australian Chief Veterinary Officer, Dr Beth Cookson:

Testing at CSIRO’s Australian Centre for Disease Preparedness (ACDP) has confirmed a further 2 positive detections in New South Wales, one greater crested tern near Narooma and one greater crested tern near Wentworth.

An additional 10 positive detections have also been confirmed in Victoria. These were all from greater crested terns in south-west Victoria and Clyde in south-east Melbourne.

There have now been 215 confirmed or presumed positive detections of H5 bird flu in Australia, based on samples tested.

There remain no detections in poultry or in our agricultural production system.

The risk to human health remains low.

8 August 2026

Attributable to Australian Chief Veterinary Officer, Dr Beth Cookson:

Testing at CSIRO’s Australian Centre for Disease Preparedness (ACDP) has confirmed a further 28 positive detections in South Australia.

The new confirmed cases are all in wild seabirds, including 15 greater crested terns from the Limestone Coast (5 at Robe, 4 at Port MacDonnell, 2 at Beachport, 1 at Southend, 1 at Pelican Point, 1 at Cape Douglas, and 1 at Eight Mile Creek); 11 greater crested terns on Kangaroo Island (3 at Haines, 6 at Seal Bay, 1 at Penneshaw, and 1 at Vivonne Bay); and 2 silver gulls on the Limestone Coast (Port MacDonnell and Robe).

There have now been 203 confirmed or presumed positive detections of H5 bird flu in Australia.

There remain no detections in poultry or in our agricultural production system.

The risk to human health remains low.

Thus far, no poultry, livestock, or marine mammals have been detected with the virus on the Australian mainland. 

Referral: Two Related Papers (PNAS & The Lancet) on Preparing for The Next Pandemic

 

Credit Mechanics of pandemics

#19,283

In January of 2020 - 6 weeks before the WHO declared COVID-19 a pandemic - we revisited the WHO's recently published 91-page NPI Guidance document and discussed some of the practical limitations of current pandemic planning (see No Pandemic Plan Survives Contact With A Novel Virus).

What emerged in China, and around the world with COVID, were emergency responses that ranged from draconian to laissez faire, sometimes alternating wildly between the two extremes.

 

We saw mixed, and often egregious, messaging from governments. 

And early on, overly optimistic messaging was that COVID wasn't `airborne', it wasn't likely transmitted asymptomatically, that infection produced durable immunity, that public masking was unnecessary, and that `herd immunity' would end the pandemic in a matter of months. 

Many of these ideas were promoted long after scientific evidence emerged to the contrary. And it seemed, every country and every state was working from a different script. 

Today, despite more than 15 million estimated deaths in the first 2 years, much of the world is in denial over the severity of the COVID pandemic, and believe they were somehow duped by their governments.  

Sadly, the failures and mixed messaging from the last pandemic - along with the anti-science vitriol permeating social media - have only further eroded the ability of governments to deal with the next global health threat. 

Some of this is obviously a self-inflicted wound. While some of it comes down the lack of any good options when dealing with any fast-moving, novel pathogen, which we'd never dealt with before. 

Since another pandemic is considered inevitable, there is understandably considerable interest in developing better, more flexible, frameworks to deal with the next global health threat. 

To that end we have two overlapping pandemic-preparedness papers from Max Planck which look at the same problem from different perspectives. Both are long reads, and so I'll just briefly summarize them and provide links. 

The first, Mechanics of pandemics (published in eClinicalMedicine, a Lancet journal), is a broad guide to the spread and containment of a pandemic virus. 

Mechanics of pandemics

Seba Contrerasa,b,w Send email to seba.contreras@ds.mpg.de ∙ Philipp Döngesa,b,w ∙ Laura Müllera,b,w ∙ Piklu Mallicka,b,w ∙ Sydney Paltrac ∙ Ulrik Hvidd,e,a ∙ et al. Show more

 

Summary

COVID-19 and previous pandemics have shown how diseases can disrupt, threaten, and transform daily life. Since pathogens and societies are continuously evolving, every pandemic is different. However, certain fundamental principles of disease transmission appear to hold true across different outbreaks. These “mechanisms” are grounded in natural laws or the very structure of our biology and societies.

This paper compiles ten fundamental mechanisms, curated by a multidisciplinary team with backgrounds spanning public health, medicine, epidemiology, political science, mathematics, physics, and psychology.

These mechanisms, although perhaps underappreciated, substantially shape how pandemics unfold and are controlled. The better we succeed in understanding these mechanisms and establishing this knowledge in our societies, the better we will be able to prepare for future pandemics and respond appropriately when they occur.

You'll find a brief summary provided in the following press release from Max Planck:

Beyond COVID-19: Fundamental principles that shape pandemics

Scientists have compiled ten fundamental mechanisms governing the course of pandemics from various disciplines 

Max-Planck-Gesellschaft

The second paper -  Optimizing infectious disease mitigation under dynamic conditions - published in PNAS, uses mathematical models to weigh the estimated direct and indirect costs of infections against the assumed social, economic, and psychological costs of reducing transmission through NPIs.

Optimizing infectious disease mitigation under dynamic conditions

Laura Müller, Fabio Sartori, Jonas Dehning, +1 , and Viola Priesemann viola.priesemann@ds.mpg.deAuthors Info & Affiliations
Edited by Nils Chr. Stenseth, University of Oslo, Oslo, Norway; received October 9, 2025; accepted June 26, 2026

August 3, 2026

123 (32) e2527395123
https://doi.org/10.1073/pnas.2527395123

Significance

Managing a pandemic requires balancing competing costs: interventions such as mask mandates and lockdowns reduce infections but disrupt economies and social life, while uncontrolled spread imposes treatment costs and loss of productivity and well-being. We present a general framework for identifying optimal strategies that balance these trade-offs under realistic conditions, including seasonality and vaccination.

We uncover three key principles: i) interventions are best applied either very strictly or not at all, depending on disease severity; ii) anticipating seasonal changes shifts large outbreaks away from winter, reducing their impact; and iii) even with optimal mitigation, small infection waves can arise during vaccination. By providing both insights and practical tools, our approach offers a foundation for designing responses to future epidemics.

Abstract

Mitigation measures are essential for controlling the spread of infectious diseases during pandemics and epidemics, but they impose considerable societal, individual, and economic costs. We developed a general framework that combines simulation of disease dynamics with optimal control to determine mitigation strategies that balance infection and mitigation costs.

Optimizing this trade-off, we identified three surprising effects: first, assuming a constant reproduction number , the optimal response is typically “all-or-nothing”: depending on disease severity, either strict mitigation or none at all is optimal, with intermediate levels emerging only in restricted regimes that we characterize analytically. Second, under seasonal variations, optimal mitigation is stricter during winter. Interestingly, a single wave of infections still arises in spring, replacing the autumn/winter waves known for classical influenza. Third, during steady vaccination campaigns, even optimal mitigation can result in transient infection waves.

Finally, we quantify the cost of delayed mitigation onset and show that even short delays can substantially increase total costs—if the disease is severe. Overall, our framework is easily applicable to general and complex settings and thereby presents a versatile tool to explore optimal mitigation strategies for endemic and pandemic infectious disease.

Once again, you'll find a press release available at: 

Taking appropriate protective measures during pandemics

Optimal containment measures exhibit a clear threshold depending on the severity of the disease 

While I confess to being less than optimistic about our global response to the next severe pandemic, I'm glad that some people are still working to improve our odds.