Showing posts sorted by date for query pandemics and pregnancy. Sort by relevance Show all posts
Showing posts sorted by date for query pandemics and pregnancy. Sort by relevance Show all posts

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. 
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Wednesday, February 11, 2026

Viruses: Avian Influenza H5N1 Infection During Pregnancy: Preparing for the Next Flu Pandemic and Improving Perinatal Outcomes


Photo Credit – CDC

#19,050

During the 1918 pandemic an abnormally high number of pregnant women died from the influenza, and those that survived endured a very high miscarriage rate. Again, during the much milder 1957 Asian Flu, pregnant women reportedly suffered disproportionately higher mortality rates than non-pregnant women of the same age.
Historical reviews of both events are available in a Perspective, written by 3 CDC physicians (Sonja A. Rasmussen, Denise J. Jamieson, Joseph S. Bresee) and published in the CDC Journal of EID article, Pandemic Influenza and Pregnant Women in February of 2008.

A year after its publication, the arrival of the 2009 H1N1 pandemic saw similarly high rates of influenza complications among pregnant women, often with tragic results. 

  • During the 2009 H1N1 pandemic, pregnant women were six times more likely to be hospitalized than non-pregnant women (see Pregnancy & Flu: A Bad Combination).
  • And in 2011, in BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection we saw a study where pregnant women who were admitted to the hospital with an  H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.
In late 2024, in EID Journal: Systematic Review of Avian Influenza Virus Infection and Outcomes during Pregnancy - among 30 pregnant women diagnosed with avian flu (H5N1 n = 16, H7N9 n = 13, and H5N6 n = 1) - researchers reported high mortality rates for both mothers (90.0%, 27/30) and their babies (86.7%, 26/30).

Admittedly, this data is biased towards hospitalized cases with severe disease, and many other pregnant women with milder infections likely saw less dire outcomes. 
 
But we also continue to see evidence of the harm to the developing fetus from  maternal seasonal flu infection (see Nature: Severe Influenza in Pregnancy Linked to Neurodevelopmental Disorders in Offspring).

Despite these dangers, pregnant women and young children are often the last cohort to be approved to receive a novel flu (or CoV) vaccine, since most early clinical trials exclude them over safety concerns.

All of which brings us to a narrative review article published in Viruses that looks at the limited data we have on novel flu and pregnancy, and argues that H5N1 could be particularly dangerous to pregnant women and their offsprings if it should begin to spread in humans.

The authors propose a basic algorithm for initial clinical management of suspected H5N1 in pregnancy and lobby for prioritizing both antivirals and vaccines (when available) for high-risk patients, including those who may be pregnant. 

I've only posted the abstract and a few excerpts, so follow the link to read it in its entirety.  I'll have a bit more after the break. 


Avian Influenza H5N1 Infection During Pregnancy: Preparing for the Next Flu Pandemic and Improving Perinatal Outcomes
Matthew J. Zuber1,2,*, Callie L. Brown2,3 and Cara B. Janusz2,4
Viruses2026, 18(2), 212; https://doi.org/10.3390/v18020212

Abstract

Influenza (flu) is a common respiratory virus with seasonal global spread. Zoonotic viruses can occasionally cross species, leading to pandemic-level spread, and for flu viruses, this is considered an “antigenic shift”. The flu can be particularly severe during pregnancy due to immune system adaptations that occur during pregnancy, with prior global pandemics causing excess hospitalizations, deaths, and other complications in the mothers and the neonates.

We aim to review the current literature with respect to novel avian H5N1 and the potential impact of infection with flu during pregnancy. A systematic literature search was conducted.

Here we provide a rapid summary of epidemiology and understanding of viral spread, published risks of H5N1 in pregnancy, the unique physiologic, cellular, and molecular adaptations making H5N1 infection unique in pregnancy, implementation of an effective vaccine program in event of a pandemic specific to pregnant individuals, optimizing peripartum care for infected individuals, and direction for future research to direct vaccine strategy and mitigate risks in a future flu pandemic.

(SNIP)

Pregnancy has long been recognized as a risk factor for severe disease. Historically, pregnant persons have suffered increased rates of morbidity and mortality compared to their non-pregnant peers during the last several flu A pandemics of the past century, most recently during the 2009 H1N1 pandemic [2]. Similarly, pregnant persons had elevated morbidity and mortality during the recent COVID-19 pandemic [3]. Vaccine clinical trials continue to routinely exclude pregnant persons, creating substantial limitations in closing equitable care gaps for pregnancy and generating robust and early data during a pandemic to help support vaccine programs for pregnant persons at heightened risk for severe disease. 

(SNIP)


 (SNIP)

7. Conclusions

While there is limited data on H5N1 or novel avian influenza viruses’ effects during pregnancy, the available data suggest we should prepare for and anticipate cases of severe disease in the perinatal setting in the event of a future global pandemic. We outlined here the current epidemiology, unique pathophysiology of the disease in the setting of pregnancy, suggested clinical approach during pregnancy and birth, and suggested future directions regarding vaccine research and policy approaches to vaccination strategy. As new viral strains evolve, so should the approach in pregnancy management and close surveillance that will help mitigate risk and improve perinatal outcomes.

       (Continue . . . ) 


While COVID hit the elderly the hardest (see CIDRAP Older adults made up 90% of US COVID deaths in 2023), there are reasons to believe that an H5Nx pandemic might severely impact a much younger cohort (see Preprint: Immune History Shapes Human Antibody Responses to H5N1 Influenza viruses).

As far back as 2007  - in A Predilection For The Young - we looked at the disturbing skewing of H5N1 cases (and deaths) among younger individuals (see WHO Chart below).

We've seen similar patterns in past pandemics, including in 1918 and again in 2009. Here is what the CDC had to say about the impact of the 2009 pandemic virus in 2012's First Global Estimates of 2009 H1N1 Pandemic Mortality Released by CDC-Led Collaboration.

2009 H1N1 Pandemic Hits the Young Especially Hard

This study estimated that 80% of 2009 H1N1 deaths were in people younger than 65 years of age which differs from typical seasonal influenza epidemics during which 80-90% of deaths are estimated to occur in people 65 years of age and older.

Complicating matters, vaccine hesitancy continues to grow, with nearly a 33% drop in uptake of influenza vaccine by pregnant women since 2019.


While an H5 pandemic is by no means assured, these are two (of many) reasons why HPAI H5 might have an even greater impact on society than COVID. 

Making it imperative that we consider the risks - and how we might handle them - now, while we still have the luxury of time. 
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Monday, January 12, 2026

JAMA: Maternal Vaccine Receipt and Infant Hospital and Emergency Visits for Influenza and Pertussis

 

#19,016

Over the past two decades we've looked at a number of studies which show that maternal vaccination  (Influenza or Tdap) - usually during the 3rd trimester - can provide valuable protection to the newborn child, who are too young for direct vaccination (usually 6 months for Influenza vaccine, 2 months for DTaP).

  • In 2010, in Study: Protecting Two With One Shot we saw a study in the Archives of Pediatric and Adolescent Medicine, that found that that babies born to mothers who received the flu vaccination experienced fewer infections and hospitalizations during their first six months than babies whose mothers did not.
  • The following year, in Pssst! Immunity . . . Pass it On, we saw a study in the American Journal of Obstetrics and Gynecology, that found that maternal receipt of the flu vaccine was linked to more than a 45% reduction in infant hospitalizations with laboratory confirmed flu.
Despite excellent safety profiles, uptake of these vaccines in pregnant women remains suboptimal.  As the following CDC chart illustrates, there has been nearly a 33% drop in uptake of influenza vaccine by pregnant women since 2019.


While the following Italian study published this week in JAMA probably won't change a lot of minds, it supports the benefits we've seen reported by previous studies on the benefits of maternal vaccination. 
In a nutshell, the authors report that offspring of pregnant women who received the Tdap or Influenza Vaccine were far less likely need hospital or ER care for those illness in the first 6 months of their lives.  Flu shots reduced infant risk by roughly 70% and Tdap cut whooping cough risk by nearly 90%. 

While these numbers are impressive, the confidence intervals (CIs) were very wide - likely due to the limited number of hospital/ER cases - making the absolute impact less certain.  

That said, these results are largely consistent with what we've seen in past studies.  

I've only posted the link and abstract below. Follow the link to read the full study, including the author's list of limitations. 
Maternal Vaccine Receipt and Infant Hospital and Emergency Visits for Influenza and Pertussis
Gabriella Morabito, MSc1,2; Giovanni Corrao, PhD3; Carlo Giaquinto, MD4 et al
 JAMA Netw Open
Published Online: January 8, 2026
2026;9;(1):e2553179. doi:10.1001/jamanetworkopen.2025.53179

Key Points

Question Are maternal influenza and Tdap vaccinations associated with influenza- and pertussis-related hospitalizations and emergency department (ED) visits in infants younger than 6 months?

Findings In this cohort study of 84 348 mother-infant dyads in the influenza cohort and 171 141 mother-infant dyads in the Tdap cohort, a strong negative association between maternal influenza and Tdap vaccinations and influenza- and pertussis-related hospitalization or ED visits in infants younger than 6 months was found, with an estimated vaccine effectiveness of 69.7% and 88.6%, respectively. Additionally, our findings confirm the suboptimal vaccine uptake in Italy.

Meaning These findings suggest support for the current recommendations for administering the Tdap and influenza vaccines during pregnancy and underline the urgent need to implement strategies to improve their acceptance.
Abstract

Importance Influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccinations during pregnancy offer protection to infants from infections. However, evidence about their effectiveness against hospitalization and emergency department (ED) visits associated with influenza and pertussis remains limited.

Objective This study aimed to evaluate the association of maternal influenza and Tdap vaccinations with influenza- and pertussis-related hospitalizations and ED visits in infants younger than 6 months.

Design, Setting, and Participants This population-based cohort study used the health care utilization databases from the Lombardy region of Italy. Pregnant individuals who received the influenza and Tdap vaccine among all live-birth pregnancies in 2018 to 2022 were included. Each vaccinated mother was matched with a nonvaccinated counterpart based on month and year of delivery, gestational age at birth, and pregnancy multiplicity. Analyses were performed from April 2024 to February 2025.

Exposures Exposures of interest were influenza and Tdap vaccinations during pregnancy.

Main Outcomes and Measures The primary outcomes were infant hospitalizations or ED visits due to influenza and pertussis. Cox regression models were fitted to estimate the hazard ratio (HR) of each outcome associated with the corresponding maternal vaccine. Vaccine effectiveness (VE) was calculated as VE = (1 − HR) × 100%.

Results This study included 53 448 pregnant individuals who received the Tdap vaccine and 5347 who received influenza vaccine. The maternal vaccination coverage (ie, proportion of vaccinated pregnant individuals among those eligible) was 5359 (6.4%) for influenza and 70 119 (41.0%) for Tdap, respectively. Infants born to mothers who received the influenza and Tdap vaccine had a lower risk of hospitalization or ED visit for influenza (VE, 69.7%; 95% CI, 8.7%-90.0%) and pertussis (VE, 88.6%; 95% CI, 11.5%-98.5%), respectively.

Conclusions and Relevance This study found that maternal influenza and Tdap vaccinations were associated with reduced influenza- and pertussis-related hospitalization or ED visits in infants younger than 6 months. Given the low vaccination coverage, it is crucial to implement maternal vaccination campaigns to enhance infant health outcomes.
       (Continue . . .)


As we've discussed often, influenza or COVID infection during pregnancy carries significant risk for both the mother and the unborn child (see 2024's CIMB Review: Maternal Influenza and Offspring Neurodevelopment).
Historical accounts and studies following the 3 influenza pandemics (1918, 1957, and 1968) of the 20th century all showed distinct increases in maternal mortality, the number stillbirths, and evidence of impaired fetal development.
The best records come from the most recent, and mildest, of these flu pandemics (2009).
All of which only strengthens the case for pregnant women getting the recommended flu/COVID and Tdap vaccines. 


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Saturday, December 14, 2024

EID Journal: Systematic Review of Avian Influenza Virus Infection and Outcomes during Pregnancy

image

Photo Credit – CDC 

#18,486

We've known for quite some time that that novel influenza viruses often take a heavy toll among pregnant women and their unborn children (see 2009's Pregnancy & Flu: A Bad Combination)- and some novel viruses (like H5N1) - appear to attack younger individuals more robustly (see 2007's A Predilection For The Young). 

During the 1918 pandemic an abnormally high number of pregnant women died from the influenza, while during the much milder 1957 Asian Flu, pregnant women reportedly suffered disproportionately higher mortality rates than non-pregnant women of the same age.

In a Perspective, written by 3 CDC physicians (Sonja A. Rasmussen, Denise J. Jamieson, Joseph S. Bresee) and published in the EID journal article, Pandemic Influenza and Pregnant Women in 2008, we got this assessment of the historic impact of influenza on pregnant women.

Although appropriate nonpregnant control groups were generally not available, mortality rates among pregnant women in the pandemics of 1918 and 1957 appeared to be abnormally high (5,7). Among 1,350 reported cases of influenza among pregnant women during the pandemic of 1918, the proportion of deaths was reported to be 27% (5). 

Similarly, among a small case series of 86 pregnant women hospitalized in Chicago for influenza in 1918, 45% died (6). Among pregnancy-associated deaths in Minnesota during the 1957 pandemic, influenza was the leading cause of death, accounting for nearly 20% of deaths associated with pregnancy during the pandemic period; half of women of reproductive age who died were pregnant

A year after the end of the 2009 H1N1 pandemic we looked at BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection, which found pregnant women who were admitted to the hospital with an H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.

Other studies over the years have linked maternal (usually severe) influenza infection with a variety of physical and developmental deficits in the unborn offspring (see Nature: Severe Influenza in Pregnancy Linked to Neurodevelopmental Disorders in Offspring).

Despite these dangers, pregnant women and young children are often the last cohort to be approved to receive a novel flu (or CoV) vaccine, since most early clinical trials exclude them over safety concerns. 

With the global H5N1 epizootic raising concerns, and the ever-present potential of another pandemic virus to emerge - we have a systematic review of outcomes on a (limited) number of H5N1 infected pregnant women over the past 2 decades.

This is a lengthy review, and I've only posted some excerpts, so follow the link to read it in its entirety.  I'll have a postscript after the break.

Synopsis
Systematic Review of Avian Influenza Virus Infection and Outcomes during Pregnancy

Rachael Purcell , Michelle L. Giles, Nigel W. Crawford, and Jim Buttery

Abstract

Human cases of avian influenza A(H5N2) and A(H5N1) viruses associated with outbreaks in birds and mammals are increasing globally, raising concerns about the possibility of a future avian influenza pandemic.
We conducted a systematic review examining 30 reported cases of avian influenza in pregnant women. We found high mortality rates for mothers (90.0%, 27/30) and their babies (86.7%, 26/30) when women were infected with avian influenza virus during pregnancy.
Despite being a high-risk population and having worse health outcomes across multiple pandemics, pregnant women are often excluded from vaccine trials.
However, as the risk for a new pandemic increases and human vaccines against avian influenza are developed, early inclusion of pregnant women in clinical trials can inform the risk–benefit analysis for both the mother and their newborn infant. Early inclusion of pregnant women in public health vaccination programs is vital for protecting this high-risk population.



During pandemics, special risk populations are often more vulnerable to severe disease and death. Pregnant women experienced higher mortality and critical illness rates during the 2009 influenza pandemic (1), the SARS-CoV-2 pandemic (2), and the 2014–2016 Ebola epidemic in Africa (3). Global efforts are needed to proactively recognize and mitigate risks to pregnant women before the onset of a pandemic, rather than as a reactive process after a pandemic has started.

Recent case reports of human infection with avian influenza A(H5N2) and A(H5N1) viruses have renewed concerns regarding the heightened risk for a pandemic. An increasing number of cases of human avian influenza virus infection have been reported since 2004, and increasing case numbers have been seen since 2023 (4), exceeding 1,400 cases across different subtypes (5). Avian influenza is commonly caused by influenza A virus subtypes H5, H7, and H9. Occurring naturally among wild water birds, a rising number of avian influenza infections have been reported in domestic poultry and in mammals, including domestic cats and dogs and humans (6).

(SNIP)

In previous influenza pandemics, pregnant women experienced worse health outcomes and higher mortality rates than the general population. In some studies, pregnant women accounted for up to 9% of intensive care unit (ICU) admissions and up to 10% of patients who died (1). The risk for severe disease or adverse outcomes among pregnant women was observed again during the COVID-19 pandemic (2), before the introduction of vaccination, when pregnant women were at an increased risk for critical illness requiring ICU admission, extracorporeal membrane oxygenation, or mechanical oxygenation compared with nonpregnant women of a similar age.

Despite the increased risks, in the past, pregnant women have been excluded from clinical prelicensure trials of vaccines and therapeutic agents aiming to address pandemics (15,16). Pregnant women also have been excluded or have had delayed entry into population-level public health vaccination programs (15). As avian influenza virus infections in humans increase (11,13,17), understanding which populations are likely to be most vulnerable will be critical to pandemic preparedness efforts. We conducted a systematic review of avian influenza virus infection during pregnancy to assess adverse effects among this population.

(SNIP)

Conclusions

We used PRISMA guidelines to conduct a systematic review of avian influenza virus during pregnancy to assess infection effects on pregnancy outcomes. We found limited reports of outcomes for pregnant women infected with avian influenza virus in the literature. Of those reports, mortality rates for infected women and their infants was >90%.

As human cases of avian influenza A(H5N1) and A(H5N2) virus infection increase, awareness of the vulnerability of pregnant women to a new pandemic is needed. A paradigm shift is required to routinely include that population in pandemic preparedness programs and avoid preventable deaths. Inclusion could be achieved through using the capacity of existing surveillance systems, planning vaccine trials to include the complex needs of pregnancy, and scaling up signal detection systems to identify pregnancy outcomes.
 
About the Author

Dr. Purcell is a pediatric infectious diseases physician at Monash Health ad Department of Paediatrics, The University of Melbourne, Clayton, Victoria, Australia. Her research interests include perinatal infection and vaccination, and vaccination and infection in childhood.

Based on the evidence gathered over the past 20 years, an H5Nx pandemic would likely impact pregnant women, young children, and adolescents the hardest.  But even if we get lucky, and H5N1 fizzles, history suggests (see examples below) these same groups may suffer disproportionately in the next pandemic.

  • While the average (mean) age of a flu-related fatality in a `normal’ flu season here in the United States is about 76 years, the average during the (relatively mild) 2009 H1N1 pandemic was half that; at 37.4 years (see Study: Years Of Life Lost Due To 2009 Pandemic).
Given the likely delays in creating, manufacturing, and deploying the next novel flu vaccine (see Referral: SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1), anything that can be done to speed up approval for pregnant women and children could translate into many lives saved. 
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Wednesday, July 31, 2024

Nature: Severe Influenza in Pregnancy Linked to Neurodevelopmental Disorders in Offspring

image

Photo Credit – CDC 

#18,215

While most people tend to regard the flu as a nasty, but relatively trivial and self-limiting, respiratory infection, it is obvious that for some high risk groups - including children, the elderly, the immunocompromised, and those who are pregnant - influenza can have profound and lasting impacts. 

And we've seen evidence suggesting that repeated influenza infections may be linked to an increase risk of developing Parkinson's later in life (see 2017's Nature Comms: Revisiting The Influenza-Parkinson's Link). 

In early 2023, in Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks, we also looked at a study published in Cell Neuron which found a statistical linkage between viral illnesses and developing neurodegenerative diseases later in life.

Many studies have found links between maternal influenza infection and damage to the unborn child, as in last January's CIMB Review: Maternal Influenza and Offspring Neurodevelopment).

Historical accounts and studies following the last four influenza pandemics (1918, 1957, 1968, and 2009) all showed distinct increases in maternal mortality, the number stillbirths, and evidence of impaired fetal development. 

The best records come from the most recent, and mildest, of these flu pandemics (2009).  
We've also seen studies that have attempted to quantify the impact of influenza infection on both pregnant women and their offspring. While some of these studies are more compelling than others, we've seen a wide spectrum of sequelae linked to maternal flu infection, including:
Pregnancy, Influenza & Elevated Psychosis Risks In Adult Offspring
Molecular Psy.: Increased Autism Risk Linked To Prenatal Fever
JAMA Psych: Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero
Systematic Review & Meta-Analysis: First-Trimester Influenza Infection Increases the Odds of Non-Chromosomal Birth Defects

This week the Journal Nature has published another study, this time conducted using live mouse-adapted influenza virus and pregnant lab mice, which finds it is the mothers immune response to the virus that causes damage to the unborn offspring. 

This is a lengthy, and highly technical, report so I've just reproduced the link, and abstract, along with some excerpts from a press release from the University of Illinois.  Follow the links to read them in their entirety, I'll have a brief postscript after the break. 
Influenza A virus during pregnancy disrupts maternal intestinal immunity and fetal cortical development in a dose- and time-dependent manner
Ashley M. Otero, Meghan G. Connolly, Rafael J. Gonzalez-Ricon, Selena S. Wang, Jacob M. Allen & Adrienne M. Antonson 
Molecular Psychiatry (2024)Cite this article

Abstract

Epidemiological studies link exposure to viral infection during pregnancy, including influenza A virus (IAV) infection, with increased incidence of neurodevelopmental disorders (NDDs) in offspring.
Models of maternal immune activation (MIA) using viral mimetics demonstrate that activation of maternal intestinal T helper 17 (TH17) cells, which produce effector cytokine interleukin (IL)-17, leads to aberrant fetal brain development, such as neocortical malformations. Fetal microglia and border-associated macrophages (BAMs) also serve as potential cellular mediators of MIA-induced cortical abnormalities. However, neither the inflammation-induced TH17 cell pathway nor fetal brain-resident macrophages have been thoroughly examined in models of live viral infection during pregnancy. 

Here, we inoculated pregnant mice with two infectious doses of IAV and evaluated peak innate and adaptive immune responses in the dam and fetus. While respiratory IAV infection led to dose-dependent maternal colonic shortening and microbial dysregulation, there was no elevation in intestinal TH17 cells nor IL-17. Systemically, IAV resulted in consistent dose- and time-dependent increases in IL-6 and IFN-γ. Fetal cortical abnormalities and global changes in fetal brain transcripts were observable in the high-but not the moderate-dose IAV group. Profiling of fetal microglia and BAMs revealed dose- and time-dependent differences in the numbers of meningeal but not choroid plexus BAMs, while microglial numbers and proliferative capacity of Iba1+ cells remained constant. Fetal brain-resident macrophages increased phagocytic CD68 expression, also in a dose- and time-dependent fashion. 

Taken together, our findings indicate that certain features of MIA are conserved between mimetic and live virus models, while others are not. Overall, we provide consistent evidence of an infection severity threshold for downstream maternal inflammation and fetal cortical abnormalities, which recapitulates a key feature of the epidemiological data and further underscores the importance of using live pathogens in NDD modeling to better evaluate the complete immune response and to improve translation to the clinic.

 

Fetal brain impacted when mom fights severe flu: New mouse study explains how

Peer-Reviewed Publication

UNIVERSITY OF ILLINOIS COLLEGE OF AGRICULTURAL, CONSUMER AND ENVIRONMENTAL SCIENCES

URBANA, Ill. -- A bad case of the flu during pregnancy can increase the risk for fetal neurodevelopmental disorders such as schizophrenia and autism spectrum disorder. But it’s not the virus itself doing the damage; it’s the mother’s immune response.

New University of Illinois Urbana-Champaign research using live mouse-adapted influenza virus improves upon previous mouse experiments to explain the process on a cellular and molecular level. It also indicates fetal brain changes are more likely once the severity of the mother’s infection meets a specific threshold.

“Our data provide really compelling evidence for an infection severity threshold, which mimics what we see in humans. There are only a subset of maternal infections that are going to be severe enough to cause concerns like this. That said, pregnant people should definitely get the flu vaccine to reduce their risk,” said senior study author Adrienne Antonson, assistant professor in the Department of Animal Sciences, part of the College of Agricultural, Consumer and Environmental Sciences at Illinois.

The study is one of only a handful to investigate maternal infection in mice using live influenza virus at doses that replicate seasonal flu outbreaks in humans. “That means our results are more relevant to human pathological infection,” said lead study author Ashley Otero, a doctoral student in the Neuroscience Program at Illinois.

Antonson’s team infected pregnant mice with live influenza A virus, rather than a viral mimic — an inert molecule that mimics viral behavior — used by most research groups in recent decades. The viral mimic elicits the innate immune response, broadly categorized as non-specific inflammation, that occurs within 24 to 48 hours of infection.

These studies have provided important clues about which inflammatory proteins are made by the mother and how they interact with the fetal brain. But Otero says viral mimics may prompt slightly different immune responses than the live virus in both mother and fetus, and they fail to capture what happens during the mother’s adaptive immune response, which occurs later and helps an animal “remember” past infections.

To address these issues, the team subjected the mice to one of two doses of the virus — representing a moderate or severe infection — at the moment in gestation closest to the end of the first trimester in humans. Then, at two and seven days post-infection, they tracked how the infection progressed in the lungs and intestines of the mother, as well as how products from the mother’s immune response interacted with the fetal brain. They also measured the physical properties of fetal brains, including the thickness of the cortex, which has been linked to neurodevelopmental disorders in humans.

(SNIP)

Antonson emphasizes that maternal infection is only one of many risk factors for neurodevelopmental disorders.

“These disorders are caused by a multitude of elements, including environmental factors, genetics, pharmacological exposures, and more. We're focusing on just this in-utero period, but the early postnatal period is important, and adolescence is important. It’s just one slice of a very complicated pie.”

The study, “Influenza A virus during pregnancy disrupts maternal intestinal immunity and fetal cortical development in a dose- and time-dependent manner,” is published in Molecular Psychiatry [DOI: 10.1038/s41380-024-02648-9]. The research was supported by the Roy J. Carver Charitable Trust (grant #23-5683), USDA NIFA Research Capacity Fund (Hatch project #ILLU-538-940), the Department of Animal Sciences, and the College of ACES.

Antonson is also affiliated with the Beckman Institute, the Microbial Systems Initiative, and the Carl R. Woese Institute for Genomic Biology at Illinois.

This study adds to the growing list of evidence that influenza (and other viral infections) can sometimes have a profound, and long-term, impact on the host. 

At the same time we've seen many studies confirming the safety and benefits of flu vaccination and the early use of antivirals in protecting the lives of pregnant women and their unborn child, including:

Pediatrics: Maternal Flu Vaccination Extends Protection To Infants

Clinical Infectious Diseases: Flu Vaccine May Reduce Incidence of Stillbirth

JID: Benefits Of Early Use of Influenza Antivirals In Pregnancy

While seasonal flu vaccines only provide moderate protection against infection, they do a much better job at reducing the severity of the illness (see CDC MMWR: Interim 2023-2024 Flu Vaccine Effectiveness Estimates).  

And as this study points out, the risks to the unborn child go up with the severity of the maternal infection. If you can reduce the severity, you should also reduce the chances of neurodevelopmental disorders.

While there is no doubt we need better seasonal flu vaccines, even a little protection can make the difference between a mild, self-limiting illness, and something much worse. 


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Thursday, July 04, 2024

CDC NCIRD: COVID-19 Can Surge Throughout the year


#18,165

The `conventional wisdom' about pandemics - and in 2020, about COVID - was that a pandemic might last between 12-18 months, during which time the community would (through exposure or vaccines) develop increasing `herd' immunity.   

While not everyone agreed  (see Apr 2020's From Here to Immunity), starting only months into the pandemic, many governments were predicting an early end to the COVID pandemic once a `magic number' of infected was reached (see GAO: A Herd Immunity For COVID-19 Primer). 


There were problems - evident from quite early in the pandemic - to that cheery scenario. First, COVID infection tended to leave behind only temporary immunity.  Some of the studies that emerged in the summer and fall of 2020 included:

CDC Clarifies: Recovered COVID-19 Cases Are Not Necessarily Immune To Reinfection

Kings College: Longitudinal Evaluation & Decline of Antibody Responses in SARS-CoV-2 infection

EID Journal: Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection

Second, while the COVID virus had remained relatively stable during the first year, it began to mutate rapidly starting in 2021. Fast forward to 20 months into the pandemic - after the emergence of both the Alpha & Delta waves - and once again we began to see predictions that  `immunity was just around the corner'. 

Some headlines from October, 2021 included:

OHSU analysts predict herd immunity impacts by end of year

Hawaii is at the ‘beginning of the end of the pandemic’ with herd immunity on the horizon; Officials warn not to let guard down

Florida could reach herd immunity by Nov. 10

But of course, the emergence of a radically different Omicron variant the following month derailed those hopes, and we saw the biggest wave of the pandemic in the winter of 2022. 

While a `political' decision was made to end the pandemic in 2023 - and greatly reduce surveillance and reporting - the virus is very still with us.  

Despite continued expectations that the virus would attenuate and become another in the panoply of `seasonal respiratory viruses', it continues to produce significant and unpredictable waves throughout the year.


We are now 54 months since the emergence of COVID in late 2019, and we are facing another summer wave of the virus. Yesterday the CDC's NCIRD (National Center for Immunization and Respiratory Diseases) published an overview of the COVID virus, stressing that:

`Because the evolution of new variants remains unpredictable, SARS-CoV-2 is not a typical “winter” respiratory virus.'

They go on to stress the importance of staying current with COVID vaccinations, staying home if sick, and using NPIs.  Some excerpts from their report follow, after which I'll have a brief postscript.

COVID-19 can surge throughout the year

AT A GLANCE

Many respiratory virus illnesses peak during the winter due to environmental conditions and human behaviors. COVID-19 has peaks in the winter and also at other times of the year, including the summer, driven by new variants and decreasing immunity from previous infections and vaccinations. You can protect yourself from serious illness by staying up to date with vaccinations, getting treated if you have medical conditions that make you more likely to get very sick from COVID-19, and using other strategies outlined in CDC's respiratory virus guidance.

Summary

What CDC knows

In the United States, respiratory virus illnesses typically peak during the fall and winter. These peaks are due to several factors, including human behaviors and environmental conditions that can affect the ability of viruses to survive and spread.

Since the start of the COVID-19 pandemic, infections with SARS-CoV-2, the virus that causes COVID-19, have peaked during the winter and also surged at other times of the year. These periodic surges are due in part to the emergence of new variants and decreasing immunity from previous infections and vaccinations. Because the evolution of new variants remains unpredictable, SARS-CoV-2 is not a typical “winter” respiratory virus.

What CDC is doing

CDC continues to monitor seasonal trends of COVID-19 and the factors driving these trends, including the emergence of new variants, and to collaborate with state and local health departments, commercial laboratories, and global partners. On June 27, the Advisory Committee on Immunization Practices (ACIP), an independent advisory group to CDC, recommended that persons ≥6 months of age receive the 2024–2025 COVID-19 vaccines when they become available this fall.
Why do many respiratory viruses spread more in the winter?

Many respiratory viruses have increased circulation during the winter. Factors that drive these seasonal patterns fall into a few broad categories:
  • Environmental conditions: Temperature and humidity can affect the ability of viruses to survive and spread. Dry conditions, which are particularly common in winter, can cause water to evaporate more quickly from respiratory droplets produced by coughing or sneezing, resulting in smaller particles that last longer in the air and travel longer distances. SARS-CoV-2, the virus that causes COVID-19, survives longer in colder temperatures, and increased spread has been associated with lower fall/winter temperatures.
  • Immune susceptibility: Dry and cold air interfere with the ability of the body to sweep viruses out of the upper respiratory tract, which is the first line of the immune system's defense. At the population level, protection from prior infection and vaccination wanes over time. This results in more people being susceptible in the winter when respiratory viruses are spreading the most.
Behavioral patterns: Spending more time indoors with less ventilation during the colder months, as well as holiday gatherings and travel, can increase spread. That's because viruses spread between people more easily indoors than outdoors in part because the concentration of these particles is often higher indoors. Similar conditions can also happen in summer when people spend more time indoors, keep windows closed while using air conditioning, and travel for summer vacations.

COVID-19 seasonality
COVID-19 activity tends to fluctuate with the seasons, meaning it has some seasonal patterns. Data from four years of COVID-19 cases, hospitalizations, and deaths show that COVID-19 has winter peaks (most recently in late December 2023 and early January 2024), but also summer peaks (most recently in July and August of 2023).
There is no distinct COVID-19 season like there is for influenza (flu) and respiratory syncytial virus (RSV). While flu and RSV have a generally defined fall/winter seasonality and circulate at low levels in most parts of the United States in the summer, meaningful COVID-19 activity occurs at other times of the year.

Understanding when COVID-19 tends to peak helps to better tailor public health prevention strategies and recommendations, prepare our healthcare system, and allocate resources. That's especially important because the winter peak tends to overlap with those for flu, RSV, and many other viruses. Getting an updated COVID-19 vaccine in the fall can help better protect you through the winter peak. People who might benefit from additional doses of COVID-19 vaccine this summer include those who are:
  • 65 years of age and older,
  • Moderately or severely immunocompromised or with underlying medical conditions,
  • Living in long-term care facilities,
  • Of any age and have never received COVID-19 vaccine, and
  • Pregnant, especially in late pregnancy.
CDC's Advisory Committee on Immunization Practices (ACIP) met on June 27 and recommended that persons ≥6 months of age receive the 2024–2025 COVID-19 vaccines when they become available this fall. The U.S. Foospringd and Drug Administration recently selected strains for the vaccine based on currently circulating variants.
New variants affect patterns of COVID-19 activity

The emergence of new SARS-CoV-2 variants has been associated with COVID-19 surges, including an increase in the magnitude of winter peaks and additional peaks at other times of the year. Peaks in COVID-19 activity often, but not exclusively, occur in winter (blue bar in chart, below) and in summer (pink bar in chart). New variants, such as Delta and Omicron, contributed to several peaks.

Although the future pace of SARS-CoV-2 evolution is unpredictable, surges outside the winter season will likely continue as long as new variants emerge and immunity from previous infections and vaccinations decreases over time.

CDC continues to track the emergence of new variants through genomic sequencing, in collaboration with state and local health departments, commercial laboratories, and global partners. CDC also continues to monitor trends in COVID-19 to inform vaccine recommendations, and to publish weekly data so that the public can make informed decisions regarding their individual risk throughout the year.

          (Continue . . . )

 
During the spring, with COVID activity waning, I discontinued my routine of wearing a KN95 mask when in crowded indoor conditions, but over the past month I've resumed the practice.  I go through a fair amount of alcohol hand sanitizer, and I'll be getting both updated flu and COVID shots in the fall. 

While COVID infection isn't as deadly as it once was, it still claims thousands of lives every month, and we continue to see studies that validate early concerns over the damage from `Long COVID' (see CIDRAP New definition of long COVID aims to offer clarity, direction).

All of which makes me believe the extra effort required to protect myself against COVID is still worth doing. 

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