Wednesday, April 15, 2026

Obstetrics & Gyn: Recovery of Pregnancy-Related Death Ratios After the Coronavirus Disease 2019 (COVID-19) Pandemic


CDC MMWR Sept 2020


#19,119

While we've known that pregnant women and their unborn offspring are often among the hardest hit during influenza pandemics (see 2009's Pregnancy & Flu: A Bad Combination), COVID's impact on pregnancy remains less well understood. 

Early in the pandemic we looked at a number of studies that found increased risks for pregnant women, including:
  • ~3–4× higher risk of ICU admission
  • ~5× higher need for critical care
  • ~7–8× higher risk of maternal death (relative risk)
  • Much higher risk of mechanical ventilation and pneumonia

But today we've a analysis, published in Obstetrics & Gynecology, that quantifies the impact of pregnancy-related deaths during the COVID pandemic (up 60% in 2021), and the fact that those deaths - while lower now - still remain elevated for some sociodemographic subgroups

The full report is very much worth reading.  I'll have more after the break.
Original Research
Disparities by Age, Race and Ethnicity, and Geography
MacCallum-Bridges, Colleen L. PhD; Daw, Jamie R. PhD; Admon, Lindsay K. MD, MSc
Obstetrics & Gynecology ():10.1097/AOG.0000000000006255, April 2, 2026. | DOI: 10.1097/AOG.0000000000006255
 Abstract
 
OBJECTIVE: 

To describe trends in pregnancy-related death ratios from 2018 to 2024, assess the contribution of coronavirus disease 2019 (COVID-19) to these trends, and evaluate whether pregnancy-related death ratios have recovered to prepandemic levels.

METHODS: 

We conducted an observational study that used vital statistics data to calculate the annual pregnancy-related death ratio (the number of pregnancy-related deaths per 100,000 live births) for female individuals aged 15–49 years between 2018 and 2024. We compared the pregnancy-related death ratios across prepandemic (2018–2019) pandemic (2020–2022), and postpandemic (2023–2024) periods; to assess the contribution of COVID-19, we calculated the pregnancy-related death ratio including and excluding COVID-associated deaths (ie, those with ICD-10 U07.1 listed as a cause). Pregnancy-related deaths were identified using International Statistical Classification of Diseases, Tenth Revision codes (A34, O00–O99), and the total pregnancy-related death ratio was decomposed into the early pregnancy-related death ratio (deaths during pregnancy or within 42 days after pregnancy) and the late pregnancy-related death ratio (deaths 43–365 days postpartum). We conducted subgroup analyses by maternal age, race and ethnicity, or geographic region.

RESULTS: 

From 2018 to 2024, there were 8,298 pregnancy-related deaths (32.3/100,000 live births). From the prepandemic period to the pandemic period, the early pregnancy-related death ratio increased by 7.5 deaths per 100,000 live births (95% CI, 6.1–8.8) and the late pregnancy-related death ratio increased by 3.7 deaths per 100,000 live births (95% CI, 2.7–4.6). Most of this increase (76% for the early pregnancy-related death ratio, 50% for the late pregnancy-related death ratio) was COVID-associated deaths. 
By 2023–2024, the early pregnancy-related death ratio had returned to prepandemic levels, but the late pregnancy-related death ratio remained elevated (1.4 additional deaths/100,000 live births; 95% CI, 0.4–2.4). Most subgroups experienced an increase in early and late pregnancy-related death ratios during the pandemic, but recovery varied.
Notably, both early and late pregnancy-related death ratios remained substantially elevated among non-Hispanic Black mothers in 2023–2024 compared with the prepandemic period (early pregnancy-related deaths increased by 7.0/100,000 live births [95% CI, 1.3–12.8]; late pregnancy-related deaths increased by 5.4 /100,000 live births [95% CI, 1.3–9.5]).

CONCLUSION: 

Pregnancy-related death ratios increased dramatically during the COVID-19 pandemic, and by 2023–2024, recovery differed by the timing of death relative to pregnancy and across sociodemographic subgroups. Additional efforts are needed to identify drivers of differential recovery from the COVID-19 pandemic and inform clinical and policy initiatives to reduce pregnancy-related deaths, improve maternal health, and promote health equity.

       (SNIP)

Pregnancy-related deaths increased dramatically during the COVID-19 pandemic, peaking in 2021 with 32.7 early pregnancy-related deaths per 100,000 live births and 13.1 late pregnancy-related deaths per 100,000 live births. Pandemic era increases in pregnancy-related deaths were largely explained by COVID-associated deaths, but by 2023–2024, recovery from the COVID-19 pandemic differed across sociodemographic subgroups.
Although some groups had returned to prepandemic levels, pregnancy-related death ratios remained elevated for other groups, including non-Hispanic Black mothers, a demographic that already faced substantially higher rates of pregnancy-related deaths before the COVID-19 pandemic. Additional research is needed to identify drivers of differential recovery from the COVID-19 pandemic and inform clinical, public health, and public policy initiatives to reduce pregnancy-related deaths and promote maternal health and health equity.

       (Continue  . . . ) 

As the following CDC chart illustrates, pregnancy related mortality rose sharply in 2020, peaked in 2021, and began dropping significantly in 2022.

It is worth noting that while available, uptake of the COVID vaccine was quite limited among expectant mothers in 2021, with the CDC reporting:
Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) in 2021 indicate that approximately 97% of pregnant people hospitalized (either for illness or for labor and delivery) with confirmed SARS-CoV-2 infection were unvaccinated.
In late September 2021 the CDC Issued a HAN For Pregnant Women Urging COVID Vaccination, which helped to increase its uptake.  

It seems likely that the COVID vaccine, along with acquired immunity, better medical care options, and the arrival of less virulent Omicron variant in 2022, all contributed to this sharp decline. 

Today, according to the latest (March 2026) ACOG COVID-19 Vaccination Considerations for Obstetric–Gynecologic Care Practice Advisory update, only about 11% of pregnant women in 2026 have received a COVID-19 vaccine. 

However, vaccine uptake has waned, with a 25.7% year-to-date decrease in the 2025–2026 season compared with 2024–2025 (CDC 2025d). As of February 21, 2026, 11.1% of pregnant women overall have received a COVID-19 vaccine (CDC 2026). Clear, strong clinician recommendation remains one of the most influential factors in maternal vaccination acceptance and is essential to reducing preventable morbidity.
While many choose to view COVID as a non-threat today, it continues to cause significant morbidity and mortality (see WHO Statement: COVID-19 Still Causes Severe Disease & Renewed Vaccination Recommendations).

A few recent studies include:
Nature Comms: The Risk of Kidney Disease Increases Following SARS-CoV-2 Infection Compared to influenza
Unfortunately, our growing societal laissez-faire attitude towards this virus means that some people are only going to learn this the hard way. 
Posted by at

Tuesday, April 14, 2026

The Lancet Microbe: Characterisation of Immune Responses Targeting HPAI A(H5) Viruses in Health-care Workers in the Netherlands

 

Credit CDC Antigenic Characterization

#19,118


Until relatively recently it was assumed that most of the world's population had little to no immunity against HPAI H5 viruses. In June of 2024 (see CDC A(H5N1) Bird Flu Response Update: Population Immunity to A(H5N1) clade 2.3.3.4b Viruses) the CDC reported: 

Data from this study suggest that there is extremely low to no population immunity to clade 2.3.4.4b A(H5N1) viruses in the United States.  Antibody levels remained low regardless of whether or not the participants had gotten a seasonal flu vaccination, meaning that seasonal flu vaccination did not produce antibodies to A(H5N1) viruses.
This means that there is little to no pre-existing immunity to this virus and most of the population would be susceptible to infection from this virus if it were to start infecting people easily and spreading from person-to-person. This finding is not unexpected because A(H5N1) viruses have not spread widely in people and are very different from current and recently circulating human seasonal influenza A viruses.

Since then, however, we've seen a number of studies which have reported serological evidence of limited immunity - particularly in older cohorts - against some strains of H5N1.  

Probably not enough to prevent infection, but perhaps enough to reduce the severity of infection. 

A few recent examples include:


mBio: Low levels of influenza H5N1 HA and NA antibodies in the human population are boosted by seasonal H1N1 infection but not by H3N2 infection or influenza vaccination

Preprint: Cross-Reactive Human Antibody Responses to H5N1 Influenza Virus Neuraminidase are Shaped by Immune History

How much `real-world' protection any of this might offer is anyone's guess. But with a pandemic specific vaccine unlikely in the opening months of an outbreak, and growing concerns over our antiviral armamentarium, any immunological edge - no matter how small - would be welcome. 

While most of the studies we've seen to date have focused on the American Bovine B3.13 strain, today we've a study from the Netherlands which uses two European clade 2.3.4.4b H5N1 viruses along with an older Chinese (2005) clade 2.3.4 virus. 

The research summary reads:


Evidence before this study

We searched PubMed from Jan 1, 1997, to July 1, 2025 in English using combinations of “influenza”, “heterosubtypic”, “immunity”, “cross-immunity”, “baseline”, “population”, “humans”, “H5N1”, “avian influenza”, “clade 2.3.4.4b”, “humoral”, “antibodies”, “hemagglutinin”, “neuraminidase”, “cellular”, and “T-cells”. Previous reports on immunity to A(H5) influenza viruses on a population level are fragmented, because most examined binding or functional antibodies exclusively, and few examined T-cell responses.

Added value of this study

We profiled immune responses targeting A(H5) influenza viruses in a presumed unexposed cross-sectional cohort of health-care workers (n=107) by combining the measurement of antibody binding, haemagglutinin inhibition, antibody-dependent cellular cytotoxicity (ADCC), neuraminidase (NA) inhibition, and T-cell responses. A(H5) antibodies binding the haemagglutinin stalk, and NA inhibition-mediating and ADCC-mediating antibodies were common. Cross-reactive T cells targeting the haemagglutinin and NA of A(H5) influenza viruses were detected. Our rational selection of antigens from both seasonal and avian influenza viruses enabled a direct comparison of multiple effector mechanisms, establishing the first integrated baseline map of humoral and cellular responses against A(H5) influenza viruses.
 
Implications of all the available evidence

Our findings, in combination with existing research, show that partial immunity to A(H5) influenza viruses is widespread. Repeated exposure to seasonal influenza viruses likely led to the development of a cross-reactive antibody and T-cell repertoire recognising A(H5) influenza viruses. Although the protective value of cross-reactive immune responses remains speculative, evidence from animal model systems suggests that these responses might confer partial protection.

The full study, while fairly technical, is well worth reading. I've posted the abstract below.  I'll have a bit more after the break.


Mark A Power, MSca,∗ ∙ Willemijn F Rijnink, MSca,∗ ∙ Widia Soochit, PhDa ∙ Lennert Gommers, BSca ∙ Anne van der Linden, BSca ∙ Felicity Chandler, BSca ∙ Femke Volker, BSca ∙ Theo M Bestebroer, BSca ∙ Babs E Verstrepen, PhDa ∙ Alba Grifoni, PhDb ∙ Ngoc H Tan, MPharma ∙ Susanne Bogers, MSca ∙ Gijsbert P van Nierop, PhDa ∙ Prof Alessandro Sette, PhDb,c ∙ Prof Marion P G Koopmans, PhDa ∙ Corine H Geurts van Kessel, PhDa,† ∙ Reina S Sikkema, PhDa,† ∙ Mathilde Richard, PhDa,‡ ∙ Rory D de Vries, PhDa,‡ r.d.devries@erasmusmc.nl Show less
 
Published April 13, 2026
DOI: 10.1016/j.lanmic.2026.101367 External Link
 
Download PDF
 
Summary

Background

Highly pathogenic avian influenza A(H5) viruses pose a pandemic threat, with a history of mammalian adaptation and zoonotic spillovers into humans. We aimed to determine whether pre-existing cross-reactive immune responses to A(H5) clade 2.3.4.4b influenza viruses detected between 2020 and 2024 are present in the general population.

Methods

We conducted an observational, cross-sectional study within the prospective Surveillance of Respiratory Viruses in Healthcare and Animal Workers in the Netherlands (SENTINEL) cohort, in which we analysed a subset of health-care workers aged 18 years or older who provided blood samples at a periodic study visit in August or September, 2024. Blood samples were analysed for influenza A(H5)-specific antibody binding, haemagglutination inhibition, Fc-effector functions, neuraminidase (NA) inhibition, and T-cell responses.

Findings

We included 107 health-care workers. Participants’ median age was 50·0 years (IQR 40·0–58·0); 77 (72%) health-care workers were female, 29 (27%) were male, and one (1%) did not report their biological sex. Virus-specific antibodies were measured in 106 serum samples.
Low-level binding antibodies directed against the A(H5) haemagglutinin (HA) head were detected in up to 28 individuals (depending on the antigen), but without haemagglutination inhibition activity.
Nevertheless, we detected A(H5)-reactive antibodies with Fc-effector functions in all participants. Additionally, we observed high levels of antibodies with NA inhibition activity (geometric mean titre 208 [95% CI 153–284]) in up to 97% of the health-care workers against avian N1, and T-cell responses against HA and NA from A(H5) influenza viruses in 43–69% (46–74 of 107) health-care workers. A(H5)-specific responses correlated with immune responses targeting A(H1N1).

Interpretation

Together, our findings suggest that partial cross-reactive immunity to A(H5) influenza viruses exists in humans, likely induced by previous exposures to seasonal influenza viruses. This partial cross-reactive immunity might play an important role during future outbreaks, potentially by blunting disease severity. Characterising pre-existing baseline immunity is crucial for accurate pandemic risk assessment and preparedness planning.
While some of the headlines overnight in the European press (see Likely no deadly bird flu pandemic: Immunity against regular flu also works on H5N1) overstate these findings, any degree of immunity to H5N1 beats no immunity at all. 

Since this study utilized a convenience sample of healthcare workers, it did not include children or adolescents (< 20), or the elderly (> 70). 

But they did report:  In an age-stratified analysis, antibody levels against A(H5) influenza virus HA0 antigens appeared higher in health-care workers older than 60 years.

This increased immunity is likely the consequence of a lifetime of exposure to influenza viruses, but the majority (61%) of the test cohort also reported receipt of the seasonal flu vaccine over the past 4 years

Since we've seen other studies showing some limited protection against H5N1 (in ferrets) from the seasonal flu vaccine, it is possible that prior flu vaccination contributed to - or amplified - some of the preexisting immunity reported in this study.

While I find plenty of good reasons to get the flu shot each year, perhaps for some, that will provide an added incentive to get one this fall.  

At least, one can hope.

Posted by at

Monday, April 13, 2026

Front. Immunology: Thymidine phosphorylase promotes SARS-CoV-2 spike protein-driven lung tumor development

 

#19,117

While the world continues to treat COVID as if it is now a mild illness, over the past 6 years we've seen compelling evidence that repeated COVID infections can seriously affect one's health (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection), along with a long litany of post-COVID sequelae. 

A few (of many) recent studies include:


EID Journal: Thrombotic Events and Stroke in the Year After COVID-19 or Other Acute Respiratory Infection

European Society of Cardiology: Major Consensus Statement Released on Long-Term Cardiovascular Impact of COVID Infection 

Referral: JAMA - COVID-19 in Pregnancy Linked With Risk of Neurodevelopmental Disorders in Early Childhood



It may take years to fully parse out the long-term health impacts of COVID on society, but some researchers have expressed concerns over increased lung cancer risks due to SARS-CoV-2 infection (see 2022's SARS-CoV-2 and probable lung cancer risk). 

While it wasn't limited to COVID, last year in Nature: Respiratory Viral Infections Awaken Metastatic Breast Cancer Cells in Lungs, we saw a study in mice that demonstrate that common respiratory viruses may awaken dormant cancer cells.  The authors wrote:

Studies have shown that cancer metastasis can be triggered by inflammation. Infection by respiratory viruses, such as influenza and SARS-CoV-2, often causes inflammation. 

Last last year, Molecular Aspects of Medicine published The double-edged sword: How SARS-CoV-2 might fuel lung cancer, which suggested that Post-COVID-19 pulmonary fibrosis could be a precursor to lung cancer.

While we aren't at the point where we can say with any certainty that COVID infection causes cancer, researchers continue to find plausible reasons why it may create conditions that exacerbate the risks. 

Which brings us to a new study, which also suggests a potential link between COVID infection and an increased risk of lung cancer. First the Abstract, followed by some excerpts from a press release. 

Thymidine phosphorylase promotes SARS-CoV-2 spike protein-driven lung tumor development
Abstract

Background:

COVID-19 survivors exhibit increased interstitial lung fibrosis, a known risk factor for lung cancer. We investigated whether SARS-CoV-2 spike protein (SP)-induced lung injury and elevated thymidine phosphorylase (TYMP) promote lung tumorigenesis.

Methods:

A TriNetX retrospective cohort analysis was combined with mechanistic studies in K18-hACE2TG and K18-hACE2TG/Tymp–/– mice. Mice received intratracheal SP or control lysate followed by a urethane-induced lung cancer protocol. Lung injury, inflammation, thrombosis, fibrosis, STAT3 activation, cytokine profiles, and tumor burden were assessed. In vitro assays evaluated SP- and RBD-induced ACE2 processing.

Results:

Propensity score-matched TriNetX cohorts demonstrated an increased lung cancer risk after COVID-19, particularly among current smokers (n = 166,807; RR 1.22; HR 1.50; P<.001). In mice, SP induced acute lung injury, neutrophil infiltration, and microthrombi, which were reduced in TYMP-deficient mice. SP markedly increased lung tumor incidence and aggressiveness, whereas TYMP deficiency reduced tumor formation from 50% to 18% of lung lobes. SP-induced STAT3 upregulation and collagen deposition were significantly attenuated in K18-hACE2TG/Tymp–/– mice. Cytokine profiling revealed a tumor-promoting, myeloid-dominant inflammatory milieu in K18-hACE2TG mice, in contrast to a T cell-inflamed, anti-tumor profile in K18-hACE2TG/Tymp–/– mice. SP and RBD altered ACE2 processing, generating lower-molecular-weight fragments consistent with enhanced turnover.

Conclusions:

SARS-CoV-2 SP drives lung injury, fibrosis, and tumorigenesis through a TYMP-dependent mechanism involving STAT3 signaling and inflammatory microenvironment remodeling. COVID-19 significantly increases lung cancer risk, especially in current smokers. TYMP represents a potential therapeutic target to mitigate long-term pulmonary consequences of COVID-19.

       (Continue . . . )

 

Researchers explore potential link between COVID-19 and lung cancer risk 

Marshall University Joan C. Edwards School of Medicine

New findings from researchers at the Marshall University Joan C. Edwards School of Medicine and The Hebrew University of Jerusalem have identified a potential association between COVID-19 and increased lung cancer risk, driven by underlying biological mechanisms in the lung.

The study, published in Frontiers in Immunology, integrates human clinical data with mechanistic research in animal and cellular models to better understand how SARS-CoV-2, the virus that causes COVID-19, may contribute to long-term lung disease.

“Our findings suggest that COVID-19 may do more than cause acute illness—it may also create biological conditions in the lung that could contribute to increased cancer risk over time,” said Wei Li, Ph.D., professor of biomedical sciences at the Joan C. Edwards School of Medicine and co-corresponding author on the study. “Understanding these pathways is critical as we continue to study the long-term health impacts of the virus.”

The study identified a key role for thymidine phosphorylase (TYMP), a protein that may interact with the SARS-CoV-2 spike protein to promote inflammation, fibrosis and tumor-related pathways in the lung. Researchers found that this interaction may activate processes associated with cancer growth and alter the lung’s immune environment in ways that could support tumor formation.


While there is growing circumstantial evidence that COVID may promote tumor-promoting environments, we still lack causal proof. That may come in time, but even without it, we've pretty good evidence that repeated COVID infections are best avoided if at all possible. 
Posted by at

WHO Burundi: Investigation into a `Mystery' Disease in Mpanda

 

#19,116

Caveat : Reports of `mystery' diseases are fairly common around the globe, and while these reports usually turn out to be something already known, on rare occasions they can alert us to a new, or re-emerging threat.

Yesterday on FluTrackers, Pathfinder posted two reports on a `mystery' illness affecting several households in Burundi, in east Africa.  Since late March, at least 5 deaths, and roughly 3 dozen illnesses have been reported, `. . . primarily among members of the same household and close contacts.'

According to the WHO: `Symptoms include fever, vomiting, diarrhoea, blood in urine, fatigue and abdominal pain. Some severe cases have also presented with jaundice and anaemia.'

So far, tests have ruled out many of the `usual suspects'; Ebola virus disease, Marburg virus, yellow fever, Rift Valley fever, and Crimean-Congo hemorrhagic fever.  Further testing is underway. 

While this could be something new, there are still a number of diagnoses that must be ruled out including infectious diseases like Severe Malaria, Leptospirosis, Enteric Fever, etc., environmental contaminants (heavy metals or pesticides), or food or alcohol poisoning. 

The CIA Factbook describes Burundi as:

Burundi is a landlocked, resource-poor country with an underdeveloped manufacturing sector. The economy is predominantly agricultural with roughly 90% of the population dependent on subsistence agriculture.

According to the WHO:

In Burundi, life expectancy at birth (years) has improved by ▲ 19.6 years from 44.4 [43.5 - 45.4] years in 2000 to 64 [63.3 - 65] years in 2021.

But this still puts it in the bottom 20% among african nations. The WHO AFRO statement follows:

Burundi investigates illness that has caused five deaths
11 April 2026

Bujumbura—The health authorities in Burundi, with support from the World Health Organization (WHO) and partners, are deepening investigations to determine the cause of an illness that has led to five deaths and sickened 35 people in Mpanda district in the north of the country.

Laboratory analysis has turned negative for Ebola and Marburg virus diseases, Rift Valley fever, yellow fever and Crimean-Congo haemorrhagic fever. An alert about the undiagnosed illness was received on 31 March 2026, primarily among members of the same household and close contacts. Symptoms include fever, vomiting, diarrhoea, blood in urine, fatigue and abdominal pain. Some severe cases have also presented with jaundice and anaemia.

“While it’s reassuring that preliminary analysis is negative for these serious infections, further investigations are ongoing to determine the cause of the disease,” said Dr Lydwine Badarahana, Burundi’s Minister of Health. “All the necessary measures are being taken to safeguard public health and prevent potential spread of infection.”

A joint team of experts from the country’s public health emergency operations centre and the national reference laboratory has been deployed to the field to support ongoing investigations.

WHO is supporting the Ministry of Health to strengthen disease surveillance, field investigation, clinical care, laboratory diagnosis and infection prevention and control, while also providing logistical support to sustain key operations. The Organization has also facilitated the shipment of samples to the National Institute of Biomedical Research in neighbouring Democratic Republic of the Congo for further analysis.

The Ministry of Health is leading the response, working with partner organizations to coordinate joint efforts. 
The old medical adage that; if you're in Central Park and hear hoofbeats, think `horses' not `zebras' still applies. But of course, Burundi is a long way from Central Park, so this is an outbreak worth keeping our eye on. 
Posted by at

Sunday, April 12, 2026

CHEST Review: Examining the Threat of H5N1 Highly Pathogenic Avian Influenza to Human Health

#19,115

This morning we've an open access review published in CHEST® - the monthly clinical research journal of the American College of Chest Physicians - which looks at the continued evolution of HPAI H5N1's threat to human health.
 
At a time when many government agencies appear to have reduced their coverage of HPAI (the CDC's last Avian Flu News & Spotlights update was Sept 8th, 2025), this review for clinicians is particularly timely. 

This article covers a lot of ground, starting with a a literature search and evidence review which documents HPAI's shift from being primarily a disease of birds to increased mammalian adaptation. 


While focusing primarily on H5N1 clade 2.3.4.4b, this review also briefly discusses the Cambodian 2.3.2.1e clade.  While H5N5 is mentioned, this article went to press prior to last year's announced human infection in Washington state.

Much of this review is focused on practical concerns for clinicians, including testing, treatment, and isolation of cases.  A few `pearls' from the narrative include:
  • Exposure to cattle or commercial poultry operations thus may be indicative of potential clade 2.3.4.4b A(H5N1) infection; however, lack of exposure cannot rule out potential infection, as observed in 5 patients with unknown exposure or exposure to other animals.39,41
  • Timely identification and isolation of infected patients is essential and is enabled by a low threshold of suspicion for patients with consistent clinical presentations and epidemiologic factors, including exposure to sick birds or cattle within 10 days of symptom onset.
  • Patients with positive findings may go undetected if they do not seek diagnosis or treatment in the absence of access to health care or because they experience only mild symptoms.
 While this review acknowledges the `low' risk today, it warns that could change:
Future Directions

At this time, the risk posed to the general public from AIV is considered low.29 However, that reality could change at any time given the rapidly evolving situation involving infection in mammals and substantial knowledge gaps surrounding clade 2.3.4.4b A(H5N1) and human infections.

This is an excellent review for clinicians, and makes for a good Sunday morning read for anyone interested in the topic. 

Highly recommended. 

Open access

Examining the Threat of H5N1 Highly Pathogenic Avian Influenza to Human Health

Juliette Blais-Savoie, Emily Halajian, Kuganya Nirmalarajah, Andra Banete, Juan C. Corredor, Jonathon D. Kotwa,Yaejin Lee, Sugandha Raj, Shayan Sharif ,Nicole Mideo, Samira Mubareka

Publication: CHEST
Publisher: Elsevier
Date: April 2026

Abstract

Topic Importance
The clade 2.3.4.4b highly pathogenic avian influenza (HPAI) virus H5N1 is the etiologic agent for an ongoing panzootic with a rapidly increasing number of human infections. Although morbidity and mortality in humans with this clade seems to be limited to date, previous HPAI H5N1 viruses have been associated with mortality rates of approximately 50% in humans. Not all cases of clade 2.3.4.4b influenza A(H5N1) HPAI in humans have been associated with known exposure to infected animals. Therefore, clinicians must be aware of the changing viral ecology, human risk factors, and clinical presentations associated with H5N1 viruses to facilitate early case recognition and management of clade 2.3.4.4b A(H5N1) HPAI infection in humans.
Review Findings
Historic H5N1 presentations have involved multiorgan systemic disease, notably including severe neurological disease. Common symptoms associated with clade 2.3.4.4b A(H5N1) HPAI include conjunctivitis, fever, and upper respiratory tract infection. Exposure to infected dairy cattle is a novel risk factor.
Summary
The rapid global spread of clade 2.3.4.4b A(H5N1) viruses has been associated with severe disease and high mortality in many farmed animal species and wildlife. The composite picture of emerging risk to human health comprises an unprecedented number of mammalian infections, viral adaptations to mammalian hosts, severe neuroinvasive disease in naturally infected mammals, and spillover into novel species such as dairy cows with forward transmission to humans. Preparedness measures are crucial to mitigating significant human health impacts from this virus and must include a Canadian One Health Training Program in Emerging Zoonoses approach that promotes both animal and human health

      (Continue . . . .)


While HPAI H5Nx remains our biggest concern, recents human infections with other subtypes (see Taiwan CDC Update: Novel H7 Infection Identified as H7N7 and WHO DON: Avian Influenza A(H9N2) - Italy (Ex Senegal)) remind us that Nature's laboratory is open 24/7, and we could easily be blindsided by something unexpected coming out of left field.

Posted by at

Saturday, April 11, 2026

WHO DON: Avian Influenza A(H9N2) - Italy (Ex Senegal)

 
Senegal - Base Map Credit Wikipedia

#19,114

In late March we learned of the first (imported) human infection with H9N2 in Europe when Italy's MOH announced a hospitalized case (see Italy: MOH Statement on First LPAI H9N2 Human Case in Europe (imported)). 

At that time, few details were made available, including the country of origin. 

Yesterday the WHO released a detailed DON (Disease Outbreak News) report, where we learn that the infected individual was a man who had traveled to Italy after staying in Senegal for more than 6 months - who presented at a local hospital with fever and persistent cough - and who tested positive for both Mycobacterium tuberculosis and LPAI H9N2. 

Unlike most H9N2 infections we've seen in Asia and (less often) in Africa, this patient denied having contact with poultry, birds, wildlife, or a rural environment. The source of his infection remains unknown.

This is the second human case to be reported from Senegal. 

The first occurred during the opening wave of COVID (January 2020); no WHO DON was generated, and most of what we know about it comes from a report (Genetic characterization of the first detected human case of low pathogenic avian influenza A/H9N2 in sub-Saharan Africa, Senegal) published several months later.

The first case - involving a 16 month-old child - occurred before H9N2 had been identified in Senegal's poultry. While details on this 2020 case are scant, I can find no indication of a likely exposure. 

In 2023's Influenza A Virus in Pigs in Senegal & Risk Assessment of AIV Emergence and Transmission to Humans, we saw a study that found evidence of A/H9N2, A/H5N1, A/H7N7 and A/H5N2 in local pigs, with H9N2 and H7N7 antibodies detected in > 50% of samples tested. 

The authors wrote:

Serological analyses revealed that 83.5% (95%CI = 81.6–85.3) of the 1636 sera tested were positive for the presence of antibodies against either H9N2, H5N1, H7N7 or H5N2. Influenza H7N7 (54.3%) and H9N2 (53.6%) were the dominant avian subtypes detected in Senegalese pigs.
Given the co-circulation of multiple subtypes of influenza viruses among Senegalese pigs, the potential exists for the emergence of new hybrid viruses of unpredictable zoonotic and pandemic potential in the future.

In 2024, Ghana (also in West Africa) reported a human case; that of a 5 y.o. (see WHO DON: Avian Influenza A(H9N2) - Ghana), who once again, reportedly had `. . . no known history of exposure to poultry or any sick person with similar symptoms prior to onset of symptoms.'

Yesterday's WHO DON report follows, after which I'll have a bit more.
Avian Influenza A(H9N2) - Italy
10 April 2026
Situation at a glance
On 21 March 2026, the National International Health Regulations (IHR) Focal Point for Italy notified the World Health Organization (WHO) of the identification of a human case of avian influenza A(H9) in an adult male returning from Senegal. Next generation sequencing confirmed Influenza A(H9N2). According to epidemiological investigations, the patient had no known history of exposure to poultry or any person with similar symptoms prior to the onset of symptoms.
Authorities in Italy have implemented a series of measures aimed at monitoring, preventing and controlling the situation. According to the IHR (2005), a human infection caused by a novel influenza A virus subtype is an event that has the potential for high public health impact and must be notified to the WHO. This is the first imported human case of avian Influenza A(H9N2) reported in the European Region. Based on currently available information, WHO assesses the current risk to the general population posed by A(H9N2) viruses as low but continues to monitor these viruses and the situation globally.
Description of the situation

On 21 March 2026, the National IHR Focal Point for Italy notified WHO of the identification of a human case of avian influenza A(H9) in an adult male.

The patient had been in Senegal for more than six months and traveled to Italy in mid-March. Upon arrival, he visited the emergency department with a fever and a persistent cough.
On 16 March, a bronchoalveolar lavage specimen was collected, which showed a positive Mycobacterium tuberculosis result, as well as detection of un-subtypeable influenza A virus. The patient was placed in a negative-pressure isolation room with airborne precautions. He was treated with antitubercular medication and antiviral oseltamivir. By 9 April, his condition was stable and improving.

On 20 March, a regional reference laboratory identified the A(H9) subtype, and on 21 March, next-generation sequencing confirmed influenza A(H9N2). Initial genetic findings suggest the infection was likely acquired from an avian source linked to Senegal. Additional samples have been sent to Italy’s National Influenza Center, where further characterization confirmed virus subtype Influenza A(H9N2), with close genetic similarity to strains previously identified in poultry in Senegal.

No direct exposure to animals, wildlife or rural environments was identified. There was also no reported contact with symptomatic or confirmed human cases. Further epidemiological investigations on the source of exposure are ongoing.

Contacts identified in Senegal were asymptomatic. All identified and traced contacts in Italy have tested negative for influenza and completed the period of active monitoring for the onset of symptoms and the quarantine required by national guidelines. They also received oseltamivir as a preventive measure.
Epidemiology
Animal influenza viruses normally circulate in animals but can also infect people. Infections in humans have primarily been acquired through direct contact with infected animals or through indirect contact with contaminated environments. Depending on the original host, influenza A viruses can be classified as avian influenza, swine influenza, or other types of animal influenza viruses.

Avian influenza virus infections in humans may cause diseases ranging from mild upper respiratory tract infection to more severe diseases and can be fatal. Conjunctivitis, gastrointestinal symptoms, encephalitis and encephalopathy have also been reported.

Laboratory tests are required to diagnose human infection with influenza. WHO periodically updates technical guidance protocols for the detection of zoonotic influenza using molecular methods.

Human infections with influenza A(H9) viruses have been reported from countries in Africa and Asia, where these viruses are also detected in poultry. The majority of cases of human avian influenza A(H9N2) infection have been reported from China. This is the first imported human case of avian Influenza A(H9N2) virus infection reported in the European Region.

Public health response

Contact tracing procedures have been initiated, and relevant authorities in Italy, as well as internationally (National IHR Focal Point for Senegal, WHO, and European Centre for Disease Prevention and Control (ECDC)) have been informed through IHR channels. Once avian influenza was suspected, the response moved quickly from hospital-level management to regional laboratory confirmation and national coordination. Additionally, the regional surveillance system was notified, integrated within the One Health avian influenza reporting framework.
WHO risk assessment

Most reported human cases of A(H9N2) virus infection have been linked to exposure to infected poultry or contaminated environments, with the majority of cases experiencing mild clinical illness. Sporadic human cases following exposure to infected birds or contaminated environments can be expected since the virus remains enzootic in poultry populations. 
Avian influenza A(H9N2) viruses have been detected in poultry and environmental samples collected at live bird markets in Senegal and authorities in the country reported a human case of infection with an A(H9N2) virus in 2020.

Current epidemiological and virological evidence indicates that none of the characterized influenza A(H9N2) viruses thus far have acquired the ability for sustained transmission among humans. Thus, the likelihood of sustained human-to-human spread is low at this time. Infected individuals traveling internationally from affected areas may be identified in another country during or after arrival. However, if this were to occur, further community-level spread is considered unlikely. The risk assessment would be revisited if and when further epidemiological and virological information becomes available.

WHO advice

This case does not change the current WHO recommendations on public health measures and surveillance of influenza.

The public should avoid contact with high-risk environments such as live animal markets/farms or surfaces that might be contaminated by poultry feces. Respiratory protection is highly recommended for those handling live or dead (including slaughtering) poultry in occupational or backyard-farming settings. Good hand hygiene, i.e. frequent washing of hands or the use of alcohol-based hand sanitizer is recommended. WHO does not recommend any specific additional measures for travelers.

Under Article 6 of the IHR, all human infections caused by a new subtype of influenza virus are notifiable. The case definition for notification of human influenza infection caused by a new subtype under the IHR is provided here. State Parties to the IHR are required to immediately notify WHO of any laboratory-confirmed case of a human infection caused by such an influenza A virus.

WHO advises against the application of any travel or trade restrictions based on the current information available on this event.

As we've discussed often, our ability to detect novel flu in the community is limited, and is often heavily dependent on luck. Most people with mild or moderate flu never consult a doctor - and even of those that do - few will be tested for a novel subtype. 

In 2024 the ECDC issued guidance for member nations on Enhanced Influenza Surveillance to Detect Avian Influenza Virus Infections in the EU/EEA During the Inter-Seasonal Period., which cautioned:

Sentinel surveillance systems are important for the monitoring of respiratory viruses in the EU/EEA, but these systems are not designed and are not sufficiently sensitive to identify a newly emerging virus such as avian influenza in the general population early enough for the purpose of implementing control measures in a timely way.

It is fair to assume that novel flu detection is even less likely in medically underserved communities. Which means there could easily be more community cases in West Africa than have been reported.  

Posted by at
Subscribe to: Comments (Atom)