NWS Calling For `Catastrophic' Ice Accumulation Across Southern Tier of States

 

Credit: NWS Weather Prediction Center

#19,027

Five years ago (Feb 2021) 3 successive winter storms swept across Texas, Louisiana, and Oklahoma, causing the worst collapse of the Texas energy grid on record (see Texas: The Latest - But Not The Last - Grid Down Crisis).

At least 4.5 million homes were without power during a week of bitter winter temperatures, resulting in hundreds of deaths and tens of billions of dollars of damage (see City of Austin & Travis County 2021 WINTER STORM URI AFTER-ACTION REVIEW).

While it is too soon to know how this weekend's forecasted ice/snow storm will compare with that event, right now it is expected to impact a larger geographic region and millions more people.   

Although the exact path of the ice and storm is still subject to change, the most recent advisory from the National Weather Service (issued Jan 23rd, 3:45 am) calls for high impacts from Texas to New England.

In addition to the bitter cold, ice and snow, extended power outages, particularly in areas with large ice accumulations, are expected, and may last for days. 

Last November, in The NERC 2025-2026 Winter (Electrical Grid) Reliability Assessment we looked at their cautionary 56-page winter reliability assessment, which warned that:

Rising Demand, Evolving Resources Continue to Challenge Winter Grid Reliability
November 18, 2025

WASHINGTON, D.C.—NERC’s 2025–2026 Winter Reliability Assessment (WRA) finds that much of North America is again at an elevated risk of having insufficient energy supplies to meet demand in extreme operating conditions. Although resources are adequate for normal winter peak demand, any prolonged, wide-area cold snaps will be challenging. This is largely due to rising electricity demand, which has grown by 20 GW since last winter, significantly outpacing winter on-peak capacity. This, coupled with the changing resource mix, is affecting the winter outlook.

The growing vulnerability of our power grid is something we've discussed often over the past 15 years (see NIAC: Surviving A Catastrophic Power Outage), and has grown more acute in recent years due to the power demands of A.I. data centers. 

But ageing infrastructure, continually increasing power demands, cyber attacks (see DHS: NIAC Cyber Threat Report), solar flares and CMEs (see FEMA: Preparing the Nation for Space Weather Events), and natural disasters all take their toll. 

Last summer, the U.S. Department of Energy published a 73-page report that warned that if current schedules for retirement of reliable power generation (especially baseload) continue, without enough firm replacement, the risk of blackouts in 2030 could increase by 100× over current levels.

Number one on their Key Takeaways is:

Status Quo is Unsustainable. The status quo of more generation retirements and less dependable replacement generation is neither consistent with winning the AI race and ensuring affordable energy for all Americans, nor with continued grid reliability (ensuring “resource adequacy”). 

Absent intervention, it is impossible for the nation’s bulk power system to meet the AI growth requirements while maintaining a reliable power grid and keeping energy costs low for our citizens.

Their words, not mine.    

While there is admittedly not much you or I can do about the state of the power grid, we can all prepare for outages, particularly during times of severe weather. Ready.gov has a #WinterReady Preparedness page, with helpful advice on preparing for extreme cold. 

My `standard advice' is that everyone should strive to have the ability to withstand 7 to 10 days without power and water.

 Recommended preps include:

• A battery operated NWS Emergency Radio to find out what was going on, and to get vital instructions from emergency officials
• A decent first-aid kit, so that you can treat injuries
• Enough non-perishable food and water on hand to feed and hydrate your family (including pets) for the duration
• A way to provide light when the grid is down.
• A way to cook safely without electricity
• A way to purify or filter water
• A way to handle basic sanitation and waste disposal. 
• A way to stay cool (fans) or warm (alternate heat) when the power is out.
• A small supply of cash to use in case credit/debit machines are not working
• An emergency plan, including meeting places, emergency out-of-state contact numbers, a disaster buddy, and in case you must evacuate, a bug-out bag
• Spare supply of essential prescription medicines that you or your family may need
• A way to entertain yourself, or your kids, during a prolonged blackout

Some of my preparedness blogs on how to become better prepared in the event the lights go out include:

The Gift of Preparedness 2025

#NatlPrep: Prolonged Grid Down Preparedness

Wind Chill, Hypothermia & Other Cold Weather Hazards

Being prepared for prolonged power outages won't guarantee you and your loved ones will come through a major disaster unscathed.

But when things go pear-shaped, it can substantially improve your chances.

EID Journal (Perspective): Emerging Respiratory Virus Threats from Influenza D and Canine Coronavirus HuPn-2018

 

#19,026

When I started this blog 20+ years ago, influenza A was widely regarded as the primary - and perhaps the only - respiratory virus capable of sparking a pandemic. SARS-CoV had briefly threatened in 2002-2003, but lacked the asymptomatic and presymptomatic transmission abilities of flu and was successfully contained. 

Influenza B had a very limited host range and lacked the ability to reassort, Influenza C was believed to be mild and relatively stable, and Influenza D had yet to be discovered. 

The discovery of other SARS-like viruses in wake of the first outbreak, and emergence of a more virulent MERS-CoV virus in 2012, helped change this  influenza A centric view. 

Which is why we've looked at scores of other plausible `pandemic contenders' over the past two decades - including Influenza D, Nipah/Hendra, orthopoxviruses, adenoviruses, and viral hemorrhagic fevers - even though most have a low probability of achieving viral infamy. 

In 2017 (and again in 2018) the WHO released a list (n=8) of priority diseases (see WHO List Of Blueprint Priority Diseases) - that in their estimation had the potential to spark a public health emergency and were in dire need of accelerated research:

• Crimean-Congo haemorrhagic fever (CCHF)
• Ebola virus disease and Marburg virus disease
• Lassa fever
• Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS)
• Nipah and henipaviral diseases
• Rift Valley fever (RVF)
• Zika
• Disease X

In 2024, the WHO unveiled an expanded 38-page Pathogens Prioritization report, increasing the number of priority pathogens to more than 30. Additions included 7 different influenza A subtypes (H1, H3, H3, H5, H6, H7, and H10), and 5 bacterial strains that cause cholera, plague, dysentery, diarrhea and pneumonia.

Last May, in OFID: Viral Families with Pandemic Potential, we looked at a perspective by two well known infectious disease experts (Amesh Adalja, MD FIDSA & Thomas Inglesby, MD) from Johns Hopkins Center for Health Security, that proposed - in addition to Influenza A and Coronaviruses - that 4 other viral families be considered as having significant pandemic potential.

• Picornaviridae     (e.g. rhinoviruses, EV-71, EV-D68, etc)
• Paramyxoviridae (e.g. HPIV, Nipah, measles, etc.)
• Adenoviridae        (e.g. Ad14, Ad7)
• Pneumoviridae     (e.g. Metapneumovirus, hRSV, etc.) 

The abrupt emergence of a new-and-improved SARS-CoV-2 in 2020 cemented the notion that influenza A was no longer the sole pandemic threat, and that the next crisis could emerge with little or no warning. 

All of which brings us to a perspective article, published today in the CDC's EID Journal, that focuses on two recently discovered viruses; Influenza D (see here, here, here, and here) and  Canine Coronavirus HuPn-2018 (see here and here) which seemingly have some pandemic potential. 

The authors also discuss the importance of monitoring other zoonotic pathogens, and lament the lack of robust proactive surveillance in the face of these threats. I've only posted the link, abstract and a small excerpt. 

Follow the link to read it in its entirety.  I'll have a brief postscript after the break.

Volume 32, Number 1—January 2026
Perspective
Emerging Respiratory Virus Threats from Influenza D and Canine Coronavirus HuPn-2018

Gregory C. Gray , Anastasia N. Vlasova, John A. Lednicky, Thang Nguyen-Tien, Ismaila Shittu, and Feng Li
 
Abstract

In 2009 and again in 2019, public health warnings were confirmed by the emergence, rapid widespread transmission, and lethality of novel influenza and coronaviruses. The world continues to suffer disease from these respiratory viruses. Two newly recognized emergent respiratory viruses, influenza D and canine coronavirus HuPn-2018, have been shown to have considerable potential for causing future human epidemics, but diagnostics and surveillance for the viruses are lacking. We reviewed data regarding influenza D virus and coronavirus canine coronavirus HuPn-2018. Those data strongly indicate that these viruses are major newly recognized threats. However, little is being done to respond to or prevent disease associated with these viruses, warranting the question of whether we will learn from previous pandemics.

Although science has developed effective countermeasures for most bacterial and vectorborne emerging pathogens, novel respiratory viruses continue to cause largescale human epidemics. Particularly problematic are pathogens that are of zoonotic origin. 

Viruses causing epidemics seem especially common among the Orthomyxoviridae and Coronaviridae viral families (1–6; link; link) (Table). Those epidemics have routinely caught medical professionals off-guard and caused largescale disease and death. Two recently discovered viruses, influenza D and canine coronavirus HuPn-2018 (CCoV-HuPn-2018), seem especially worthy of closer public health attention.

        (SNIP)

Other Viruses

Of course, in addition to IDV and CCoV-HuPn-2018, public health professionals should seek to detect other animal respiratory viruses as they spill over to infect humans. When possible, such surveillance should be strategically focused at the human–animal nexus where we recognize the risk is high (31). For instance, the risk for novel swine viruses spilling over from swine to infect swine workers is exceedingly high compared with the similar risk for avian influenza viruses spilling over from poultry to infect poultry workers (32–37). Similarly, we are aware of the zoonotic threat of other animal coronaviruses infecting persons directly or indirectly exposed to their animal hosts (38,39).

 In addition, we posit that evidence of animal adenoviruses spilling over to infect humans is mounting (40). In recent years, molecular evidence has shown that a vampire bat–like adenovirus in Malaysia (41) and a bovine adenovirus in Pakistan (J.R.E. Ansari et al., unpub. data, link) were associated with human respiratory disease.

Because of those and other observations, we argue that periodic surveillance with targeted and panspecies diagnostics would be prudent when addressing emerging respiratory virus threats for viruses in 6 viral families (Adenoviridae, Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Picornaviridae, and Pneumoviridae) (42). 

Conducting such surveillance in concert with occasional agnostic next-generation sequencing of specimens associated with unusual illnesses can help us better prepare for future pandemic threats at more sustainable costs than previous strategies that sought to detect novel pathogens in many wildlife hosts (43).

(Continue . . . )

   

A little over a years ago, and for the umteenth time, we looked at the dismantling of our global disease surveillance, testing, and reporting systems in The Wrong Pandemic Lessons Learned.   

If anything, things are even worse now. 

The vacuum left behind by these shutdowns is now being filled with reams of  disingenuous A.I. generated slop, and incessant clickbait headlines, making it almost impossible to detect early signs of genuine outbreaks around the world. 

With the current signal to noise ratio, we could be in the next pandemic for days or even weeks before we know it. 

Which is why I continue to recommend that people consider (see #Natlprep 2025: Personal Pandemic Preparedness) what they will need if another pandemic virus should emerge, and plan accordingly. 

J.I.D.: Cross-reactive H5N1 Neuraminidase Antibodies by Age and Influenza A Imprinting Cohorts of the Past Century:Population-Based Serosurvey, British Columbia, Canada

 

#19,025

While H5 viruses have never circulated widely (in modern times, anyway), the $64 question surrounding any potential HPAI H5N1 pandemic is whether there is any preexisting `immunity' in the general population against the virus, and what community cohorts might have greater or lesser degrees of protection.

The CDC original assessment (see July 14th, 2024 H5N1 Update) that `. . . that there is extremely low to no population immunity to clade 2.3.4.4b A(H5N1) viruses in the United States', has been challenged by a few studies suggesting there may be some limited immunity; particularly in those born before 1968.

Initially, the focus was on HA immune imprinting (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression), where the HA group (1 or 2) you are first exposed to (see chart above) can provide some degree of protection against other HAs in that group. 

How much real-world protection early or past H1/H2 exposure might offer against H5Nx - or how long it might last - are unknown, but it has been suggested it might provide an `edge' against severe disease.

More recently, we've seen attempts to quantify the impact of the first NA (Neuraminidase) one is exposed to (see last December's Nature Comms: Pre-existing Cross-reactive Immunity to HPAI 2.3.4.4b A(H5N1) Virus in the United States).

This study found`very low levels of pre-existing binding antibodies to the HA head of the HPAI A(H5N1) 2.3.4.4b virus', but slightly more encouragingly, `. . . substantial cross-reactive binding antibodies to N1 neuraminidase (NA) of 2.3.4.4b A(H5N1).

 

The `very low levels' of HA binding antibodies were highest in those over 70 years of age, which correlates with early childhood exposures to HA Group 1 viruses (H2N2 and H1N1) in the 1950's and 1960s. 

Regarding the the value of cross-reactive antibodies to the N1 Neuraminidase, the authors wrote:

Neuraminidase antibodies have been considered as an independent correlate to protect against influenza 20. Although they cannot prevent infection, neuraminidase antibodies can prevent virus egress, reduce viral shedding, and thus could attenuate disease and lessen disease severity 21,22,23.

Last summer, in Preprint: Neuraminidase Imprinting and the Age-related Risk of Zoonotic Influenza, we looked at a hypothesis by the authors of today's study, which proposed:

Here we review the complex immuno-epidemiological interactions underpinning influenza risk assessment and extend the imprinting hypothesis to include a potential role for cross-protective neuraminidase (NA) imprinting.

We compare H5N1 distributions and case fatality ratios by age and birth cohort (as proxy for HA2 and/or NA imprinting epoch) not only to H7N9 but also H5N6 and H9N2 avian influenza, representing more varied conditions of zoonotic influenza relatedness to human subtypes of the past century.

We show homosubtypic NA imprinting likely further modulates the age-related risk of zoonotic H5N1 and H9N2, with implications for pandemic risk assessment and response.

Taking this idea one step further, these authors gathered convenience blood samples collected from 575 people (ages 1 to 80) in British Columbia in 2024 and  tested them for antibodies against the (N1) neuraminidase from 2.3.4.4b H5N1 avian strain, A/RT-Hawk/ON/FAV-0473-4/2022.

They found roughly 70% of the population had detectable anti-N1 titres (>10), and around half had titres (>40) that might offer some (unknown) degree of protection. 

Specifically, the authors report:

• Anti-N1 titres were highest among young adults born 1997-2003 who were school-aged children during the 2009 H1N1 pandemic.

• Anti-N1 titres were lowest among the `youngest and least influenza-experienced pediatric cohorts'; those born after 2015 and in middle-aged adults born during the 1957-1967 H2N2 era 

How much practical impact higher anti-N1 titres would have on the duration, severity, and outcome of an H5N1 infection isn't known, although there are reasons to believe it might lessen its severity. 

Of course, if H5N5, or some other NA type (H5N6, H5N8, H5N9) should emerge as a pandemic threat, then all bets are off. 

I've posted the link, abstract, and a brief excerpt from the study. Follow the link to read it in its entirety. 

Cross-reactive H5N1 neuraminidase antibodies by age and influenza A imprinting cohorts of the past century: population-based serosurvey, British Columbia, Canada

Open Access
Danuta M Skowronski, MD , Charlene Ranadheera, PhD , Samantha E Kaweski, MSc , Suzana Sabaiduc, BSc , Lea Separovic, MSc , Gaby Makowski, BSc , Johnny Ung, BSc , Romina C Reyes, MD , Bonnie Henry, MD , Arianne Albert, PhD ... Show more
The Journal of Infectious Diseases, jiag030, https://doi.org/10.1093/infdis/jiag030
Published:
16 January 2026 Article history

PDF

Abstract

Background
Pre-existing immunity to emerging influenza viruses informs pandemic risk assessment. We compared cross-reactive neuraminidase (NA) antibody levels against avian influenza A(H5N1) by age and birth (imprinting) cohorts defined by periods of human influenza A subtype (H1N1, H2N2 or H3N2) circulation over the past century.

Methods

We used anonymized, residual sera collected from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey conducted in British Columbia, Canada. We assessed NA inhibition antibody titres by enzyme-linked lectin assay against clade 2.3.4.4b H5N1, and 2009 H1N1pdm09 and 1968 H3N2 pandemic strains

Results

Among 575 participants with median age 32 (IQR: 15-62) years, 404 (70%) had detectable anti-N1 titres >10 against H5N1, with 260 (45%), 182 (32%) and 98 (17%) having titres >40, >80 and >160, respectively. Anti-N1 titres against 2009 H1N1pdm09 and H5N1 were strongly correlated (r=0.86; 95%CI: 0.82-0.89), with both highest among young adults born 1997-2003 who were school-aged children during the 2009 H1N1 pandemic (427.9, 100.8), lowest among the youngest and least influenza-experienced pediatric cohorts born 2015-2023 (20.7, 6.8) and middle-aged adults born during the 1957-1967 H2N2 era (25.1, 10.7), thereafter increasing toward a similar secondary peak among the oldest cohorts born during the pre-1947 H1N1 era (387.3, 81.0).

Conclusions

A substantial proportion of the population has pre-existing anti-N1 against H5N1, with age-related variation reflecting H1N1 imprinting and exposure opportunities. Through heightened attack rates and shifts in immunological hierarchies, historic pandemics shape and expand the immune repertoire with implications for pre-immunity to emerging zoonotic threats.

       (SNIP)

DISCUSSION

 With H5N1 expansion but without endemicity in humans, we report cross-reactive anti-N1 antibodies to this emerging zoonosis in more than two-thirds of population-based serosurvey participants ranging one to >80 years of age, including half with titres >40, one-third >80 and nearly 20% >160. Anti-N1 titres to H1N1pdm09 and H5N1 were strongly correlated, with both varying by age and birth cohort, highest among young adults born 1997-2003, declining to lows among the youngest children born 2015-2023 and middle-aged adults born 1957-1967, thereafter increasing to a similar secondary peak among the oldest adults born pre-1947. We interpret this variation within a unifying hypothesis incorporating both age and imprinting effects, emphasizing the role of historic influenza pandemics in expanding and refining the immune repertoire through heightened attack rates and shifts in immunological hierarchies. 

(Continue . . . )

 

WHO WPRO: China Reports 3 More H9N2 Cases On The Mainland

 

#19,024

Although there is no mention of it in today's CHP Weekly Avian flu report, the WHO's WPRO (Western Pacific Region Office) latest avian flu report contains a brief description of 3 new H9N2 cases reported by China. 

Human infection with avian influenza A(H9N2) virus

From 9 to 15 January 2026, three new cases of human infection with avian influenza A(H9N2) virus were reported to WHO in the Western Pacific Region. All three cases were reported from China: The first case is a five-year-old male from Hubei Province, with an onset of symptoms on 30 November 2025; the second case is an eight-year-old female from Jiangsu Province, with an onset date on 4 December 2025; the third case is a one-year-old male from Guangxi Province, with an onset date on 7 December 2025.

The first case had exposure to backyard poultry whereas the other two cases reported no known exposure to live poultry.The parents of the second case visited a store selling freshly slaughtered poultry, and the third case also had indirect exposure to freshly slaughtered poultry. All three cases have now recovered.

Since December 2015, a total of 155 cases of human infection with avian influenza A(H9N2), including two deaths (both with underlying conditions), have been reported to WHO in the Western Pacific Region. Of these, 152 were reported from China, two were from Cambodia, and one was from Viet Nam.

This comes on the heels of 7 cases reported by WHO in the 3rd week of December.  The ECDC summarized those cases as:

The cases were reported in Guangdong (1), Guangxi (3), Henan (1) and Hubei (2) provinces with onset of symptoms in September, October and November 2025. Five patients were children and two were adults. Five of the seven individuals had mild disease, two elderly individuals were hospitalised, of whom one with underlying conditions was hospitalised with severe pneumonia. All but one had exposure to birds either in backyard poultry (4) or live poultry market (2). Investigations are ongoing for one case to determine the source of infection.

As we discussed last month, in HK CHP: Another Cryptic Announcement of H9N2 Cases From the Chinese Mainland, reports out of China are often belated, and many lack critical details. 

And of course, the expectation is that most cases are never detected by surveillance, since most are believed mild, and testing (particularly of adults) in China usually only occurs in hospitalized patients. 

While HPAI H5N1 remains firmly atop our pandemic concerns list - primarily due to its potential severity - the CDC's IRAT List contains 25 influenza A strains across 12 different subtypes (H1N1, H1N2, H3N2, H5N1, H5N2, H5N6, H5N8, H7N7, H7N8, H7N9, H9N2, H10N8).

Arguably, there are several more which could be added to this list, including H3N8, H6N1, and H10N3. Even among this narrow field of influenza A viruses, H5N1 ranks fairly far down the CDC's list (#7).

In terms of likelihood of emergence, the CDC currently ranks a Chinese EA H1N1 `G4' swine virus at the very top of their list of zoonotic influenza A viruses with pandemic potential, with 3 other North American swine variant viruses and H9N2 scoring above H5N1.

While H9N2 has a reputation of being a relatively mild viral infection - primarily reported in children - we've seen changes in its epidemiology of late; including more adult infections (some seriously ill) reported out of China.

H9N2 also easily reassorts with, and often enhances, other novel influenza viruses (including H7N9, H5N1, and H5N6), making it an important viral co-conspirator (see Vet. Sci.: The Multifaceted Zoonotic Risk of H9N2 Avian Influenza).

But, despite all of this,, LPAI H9N2 doesn't get a lot of respect. 

Since it is a low-path virus in poultry, it is not considered `reportable' to WOAH, so surveillance is suboptimal. Some countries vaccinate poultry against it, but existing vaccines have not been very effective (see J. Virus Erad.: Ineffective Control Of LPAI H9N2 By Inactivated Poultry Vaccines - China), and that may have even helped drive its evolution. 

Last October, in China CDC Weekly: Epidemiological and Genetic Characterization of Three H9N2 Viruses Causing Human Infections, we looked at a local CDC investigation into 3 pediatric cases which were reported last April from Changsha City, Hunan Province, China.

Their report found a number of indicators of increased mammalian adaptation within the virus, including an enhanced ability to infect upper respiratory (α2,6-sialic acid) tract receptors, and a number of HA protein mutations, including; H191N, A198V, Q226L, and Q234L.

Last November, in EM&I: Enhanced Replication of a Contemporary Avian Influenza A H9N2 Virus in Human Respiratory Organoids, we looked at a study which compared two H9N2 isolates (from 2024 and 1999) across several organoid models, and found today's virus to be far better adapted to human hosts.

 

The authors wrote:

In summary, we demonstrated that a recent H9N2 virus is more adapted to humans, and is able to replicate to high titres in both upper and lower human respiratory tract which may confer higher person-to-person transmissibility and virulence. Our study underscores the importance of human organoid-based phenotypic monitoring and inter/intrahost genotypic monitoring for assessing the zoonotic risk of avian influenza viruses.

These, and other recent studies (see here, here, and here) have elevated concerns over the trajectory of LPAI H9N2 viruses. While trying to predict the source of the next pandemic is a mug's game, H9N2 certainly deserves our attention. 

The Lancet: Prenatal Paracetamol Exposure and Child Neurodevelopment: A Systematic Review and Meta-Analysis

Photo Credit – Wikipedia

#19,023

Last September the WHO & Other Major Medical Stakeholders Pushed Back On A Suggested Acetaminophen/Autism Link after the White House issued an announcement suggesting that such a link existed. 

Acetaminophen/Paracetamol have long been considered the safest analgesic & antipyretic drugs for pregnant women and their unborn child, with few safe alternatives currently available.  

While a few studies have claimed a statistical link between acetaminophen use during pregnancy and autism (Link), none have found a causal link, and one of the most robust recent (2024) studies (see Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability) found:

Conclusions and Relevance  Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.

We've previously looked at potential drivers of increased autism, and after genetics, environmental exposures, and increased recognition of those on the spectrum, fevers during pregnancy are frequently cited (see Molecular Psy.: Increased Autism Risk Linked To Prenatal Fever).

The concern is that discouraging the use of the only `presumed safe' option to reduce fevers could actually end up increasing the incidence of autism, instead of decreasing it.

Admittedly, no medication is 100% safe for 100% of the population 100% of the time. As with everything in life, there there is always a risk-reward calculation involved: Is the risk (no matter how slight) worth the benefit? 

While absolute statements on the absolute safety of any drug are impossible to make, over the weekend The Lancet has published a Systematic Review and Meta Analysis on Paracetamol/Acetaminophen exposure and child neurodevelopment.  

This review incorporated 43 studies (17 of which were combined in the meta-analysis), and they report:

Current evidence does not indicate a clinically important increase in the likelihood of autism spectrum disorder, ADHD, or intellectual disability in children of pregnant individuals who use paracetamol as directed, supporting existing recommendations on its safety.

While additional research is still needed to better understand heavy or prolonged usage, these findings should be reassuring to anyone who chooses to use these drugs during pregnancy. 

Under Implications of all the available evidence, the authors write:

Taken together with large-scale sibling-controlled studies from Sweden and Japan published in 2024 and 2025, our findings support the safety of paracetamol when used appropriately during pregnancy. They reinforce the guidance of major professional and regulatory bodies, including the American College of Obstetricians and Gynecologists, the Royal College of Obstetricians and Gynaecologists, and the European Medicines Agency, which continue to recommend paracetamol as the first-line analgesic and antipyretic in pregnancy.

Avoiding paracetamol based on inconclusive or biased evidence might increase the risk of maternal fever or untreated pain, both of which can harm pregnancy outcomes. Future research should focus on improving exposure measurement, standardising outcome definitions, and integrating mechanistic and family-based designs to clarify any residual uncertainties.

I've posted the link and the abstract from the open-access meta-analysis below.

Prenatal paracetamol exposure and child neurodevelopment: a systematic review and meta-analysis
Francesco D'Antonio, PhDa,† ∙ Maria Elena Flacco, PhDb,† ∙ Lorenza Della Valle, MBBSc ∙ Smriti Prasad, MRCOGd ∙ Lamberto Manzoli, PhDf ∙ Athina Samara, PhDg,h,i ∙ et al.  

Download PDF
 
Summary

Background

Concerns have emerged about the impact of paracetamol use in pregnancy on child neurodevelopment, particularly in relation to autism spectrum disorder. We aimed to synthesise available evidence to investigate associations between prenatal paracetamol exposure and autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), and intellectual disability.

Methods

For this systematic review and meta-analysis, we searched MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Library from inception to Sept 30, 2025, for cohort studies reporting adjusted estimates of the risk of autism spectrum disorder, ADHD, and intellectual disability. Eligible studies used validated questionnaires or medical records to define outcomes, reported maternal comorbidities and treatments, and compared pregnancies with and without paracetamol exposure, whereas unadjusted studies were excluded. Quality assessment of the included studies was conducted using the Quality In Prognosis Studies (QUIPS) tool. The primary outcomes were the associations between prenatal paracetamol exposure and the likelihood of autism spectrum disorder, ADHD, and intellectual disability. Analyses were restricted to sibling-comparison studies with adjusted estimates, and odds ratios (OR) were calculated. Random-effects meta-analyses used the generic inverse variance method. Subgroup analyses were performed when possible (trimester, duration of use, offspring sex, and follow-up length). This study was registered with PROSPERO, CRD420251156690.

Findings

43 studies were included in the systematic review, and 17 studies in the meta-analysis. When considering sibling comparison studies, paracetamol exposure during pregnancy was not associated with the risk of autism spectrum disorder (OR 0·98, 95% CI 0·93–1·03; p=0·45), ADHD (0·95, 0·86–1·05; p=0·31), or intellectual disability (0·93, 0·69–1·24; p=0·63).

There was also no association between paracetamol intake during pregnancy and autism spectrum disorder (OR 1·03, 95% CI 0·86–1·23; p=0·78), ADHD (0·97, 0·89–1·05; p=0·49), or intellectual disability (1·11, 0·92–1·34; p=0·28) when considering only studies at low risk of bias according to QUIPS. This absence of association persisted when considering all studies with adjusted estimates and those with more than 5 years of follow-up.

Interpretation

Current evidence does not indicate a clinically important increase in the likelihood of autism spectrum disorder, ADHD, or intellectual disability in children of pregnant individuals who use paracetamol as directed, supporting existing recommendations on its safety.

Preprint: Bovine-derived Influenza A virus (H5N1) Shows Efficient Replication in Well-differentiated Human Nasal Epithelial Cells Without Requiring Genetic Adaptation

Flu Virus binding to Receptor Cells – Credit CDC

#19,022

Based on limited surveillance and reporting systems (see NAS : Diagnostic Tools, Gaps, and Collaborative Pathways in Human H5N1 Detection (Rapid Expert Consultation), the available evidence suggests that HPAI H5N1 viruses are not currently transmitting efficiently (or often) among humans. 

While somewhat reassuring, we've also seen evidence to suggest that mild, or asymptomatic cases are likely being missed (see MMWR: Serologic Evidence of Recent Infection with HPAI A(H5) Virus Among Dairy Workers and JAMA Open: Asymptomatic Human Infections With Avian Influenza A(H5N1) Virus Confirmed by Molecular and Serologic Testing).

While the WHO, PAHO, and the ECDC (see ECDC Pre-pandemic Guidance: Strategies to Fight Avian and Swine flu in Humans) have all called for increased vigilance, there appears to be some reluctance among many member countries - and their agricultural interests - to comply.   

Meanwhile, we continue to see studies and preprints that suggest that HPAI H5Nx viruses are continuing to accrue mammalian adaptations (see here, here, here, here, and here).

To this rapidly expanding list we can add a new preprint from researchers in Switzerland who conducted experiments to test the replication of the bovine (B3.13) H5N1 virus in human nasal epithelial cells - and found they replicated remarkably well - even at low temperatures. 

That said, after 24-hours, the human innate immune system was able to substantially reduce replication via IFN-λ (`lambda interferons'), which may explain its relatively mild presentation.

While lengthy, and somewhat technical, this is a fascinating report and many will want to read it in its entirety.  I've reproduced the abstract and some highlights below. 

I'll return with a bit more after the break. 

Bovine-derived influenza A virus (H5N1) shows efficient replication in well-differentiated human nasal epithelial cells without requiring genetic adaptation
Etori A. Moreira,Samuel Constant, Charlene Constant, Lisa Butticaz, Michele Wyler, Teodora David, Peter M. Grin, Charaf Benarafa, Volker Thiel,Marco P Alves, Gert Zimmer
doi: https://doi.org/10.64898/2026.01.16.699876
This article is a preprint and has not been certified by peer review 

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Abstract

Highly pathogenic avian influenza H5N1 viruses of clade 2.3.4.4b have caused widespread avian mortality and sporadic mammalian infections, raising concerns about their potential for efficient replication in the human population. Efficient replication in the human upper respiratory tract is considered a key barrier to transmission.

Here, we demonstrate that an H5N1 virus isolated from bovine milk in Texas in 2024 (H5N1Tex/24) replicates as efficiently as the 2009 pandemic H1N1 virus (H1N1HH4/09) in well-differentiated human nasal epithelial cells.

These cells express both avian- and human-type influenza receptors, indicating receptor adaptation is unnecessary for entry. H5N1Tex/24 replicates effectively at 33 degrees Celsius, reflecting nasal cavity temperature, whereas earlier avian H5N1 strains require 37 degrees Celsius, suggesting that H5N1Tex/24 has acquired another key adaptive feature to the human upper respiratory tract.

H5N1Tex/24 remains sensitive to interferon-λ (IFN-λ) despite inducing low cytokine levels. Notably, no known mammalian-adaptive mutations such as PB2-E627K were detected. These findings suggest that H5N1Tex/24 possesses intrinsic traits enabling efficient replication in the human upper airways, a critical step toward potential airborne transmission, underscoring the need for vigilant surveillance.

       (SNIP)

Overall, our results show that bovine-derived H5N1Tex/24 replicates at high titers in primary human nasal epithelial cells even though it lacks many canonical markers of adaptation to mammals. This observation contrasts with the currently low number of confirmed human infections. There are several possible explanations for this discrepancy. 

• First, the sensitivity of H5N1Tex/24 to the antiviral effects of MxA may limit virus dissemination to the lower respiratory tract and thus disease severity. 
• Second, human infections may go undetected because they are completely asymptomatic or because they are associated with only mild symptoms.
• Third, efficient airborne transmission of H5N1 requires that HA induces membrane fusion at pH values significantly lower than pH 6.076,77. However, the HA protein of bovine H5N1 retains typical avian characteristics, with fusion triggered at approximately pH 6.046,78. 
• Finally, pre-existing immunity to influenza viruses may provide some partial protection against bovine H5N1. Cross-reactive antibodies against the NA protein of human H1N1 viruses can particularly inhibit avian N1 sialidase activity, thereby potentially limiting replication of clade-2.3.4.4b viruses. 

The recent fatal human case caused by a H5N5 HPAI virus in the United States is alarming, as there is probably no pre-existing immunity to the N5 antigen in the human population.

Overall, our results show that H5N1Tex/24 has a remarkable ability to replicate in primary human nasal epithelial cells. Since well-differentiated nasal epithelial cells represent a relevant model for the human upper respiratory tract, it is not unlikely that the virus can also replicate efficiently in vivo in humans

       (Continue . . . )

This study confines itself primarily to the milder B3.13 `bovine' H5N1 virus (with a brief mention of HPAI H5N5), but there are also concerns over other genotypes (and subclades) including the D1.1 genotype, which burst onto the scene in the fall of 2024, and has caused more severe (and 2 fatal) infections in humans. 

The exact number of human infections with the D1.1 genotype is unknown, since not all of the (now, roughly 6 dozen) North American human cases have been fully characterized.  

A study, published 2 months ago (see J.I.D.: Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13) described this ambiguity:

A total of 53 strains were identified, of which 6 strains had 2 sequences deposited. These 53 strains were collected from patients between March 28, 2024 and February 12, 2025 (Supplementary Table S3). Of these 53 strains, 22 (41.5%) were assigned to genotype B3.13, 8 (15.1%) were assigned to D1.1, 1 (1.9%) was assigned to D1.3, and 22 (41.5%) could not be assigned to any genotypes according to GenoFLU version 1.06 (https://github.com/USDA-VS/GenoFLU). 

Based on those numbers, it appears that Bovine B3.13 human infections have likely outnumbered D1.1 infections by a factor of 2:1, making the difference in virulence even more striking.

That study attributed D1.1's increased severity to their findings that the D1.1 genotype replicates better in lab-grown nasal and lung tissues than the bovine B3.13 strain, and it binds more tightly to human‑type (α2,6-linked SA) receptors.

While direct comparisons between these studies are difficult due to differences in methods and materials, both show that - compared to older H5Nx strains - both the B3.13 and D1.1 genotypes have become much better adapted to the human nasal passage.  

And that's a trend we really shouldn't sneeze at.