UKHSA Hepatitis Update: UK Reports 34 More Cases (n=145)

 #16,724

As is often the case with infectious disease outbreaks, the harder we look, the more cases we find.  And over the past 3 weeks we've seen a doubling of acute hepatitis cases of unknown etiology (mostly in children) double in the UK, now that clinicians have been alerted to the condition. 

While the UK leads the world in cases, we continue to see rising numbers reported from around the globe.  In yesterday's ECDC: Rapid Risk Assessment On Increase in Severe Acute Hepatitis Cases of Unknown Aetiology in Children, that health agency reported:

. . .  approximately 55 probable and confirmed cases have been reported from 12 EU/EEA countries. An additional 12 cases have been reported from the United States (US), 12 from Israel, and one from Japan.

These numbers are all likely undercounts, and will likely continue to rise.  

The leading theory right now centers around the possibility that a common adenovirus infection (possibly 41F)  is causing unusual liver damage in young children.  Whether this is due to a change in the virus, or to some other cofactor, isn't known. 

The following update from the UKHSA increases the number of confirmed cases in the UK from 111 reported last Monday, to 145 as of yesterday. 

News story
Increase in hepatitis (liver inflammation) cases in children under investigation

Regular UKHSA updates on the ongoing investigation into higher than usual rates of liver inflammation (hepatitis) in children across the UK.

From:UK Health Security Agency updated 29 April 2022  

Latest

The UK Health Security Agency (UKHSA), working with Public Health Scotland, Public Health Wales and the Public Health Agency, are continuing to investigate the cases of sudden onset hepatitis in children aged 10 and under that have been identified since January 2022.

The usual viruses that cause infectious hepatitis (hepatitis A to E) have not been detected. The cases are predominantly in children under 5 years old who showed initial symptoms of gastroenteritis illness (diarrhoea and nausea) followed by the onset of jaundice.

Active case finding investigations have identified a further 34 confirmed cases since the last update on 25 April, bringing the total number of cases to 145. Of the confirmed cases, 108 are resident in England, 17 are in Scotland, 11 are in Wales and 9 are in Northern Ireland.

Of these cases, 10 children have received a liver transplant. No children have died. As part of the investigation, a small number of children over the age of 10 are also being investigated.

Findings continue to suggest that the rise in sudden onset hepatitis in children may be linked to adenovirus infection, but other causes are still being actively investigated.

As it is not typical to see this pattern of symptoms from adenovirus, we are investigating other possible contributing factors, such as another infection – including coronavirus (COVID-19) – or an environmental cause.

We are also exploring whether increased susceptibility due to reduced exposure during the COVID-19 pandemic could be playing a role, or if there has been a change in the genome of the adenovirus.

UKHSA is working with scientists and clinicians across the country to answer these questions as quickly as possible.

Dr Meera Chand, Director of Clinical and Emerging Infections at UKHSA, said:

We know that this may be a concerning time for parents of young children. The likelihood of your child developing hepatitis is extremely low. However, we continue to remind parents to be alert to the signs of hepatitis – particularly jaundice, which is easiest to spot as a yellow tinge in the whites of the eyes – and contact your doctor if you are concerned.

Normal hygiene measures, including thorough handwashing and making sure children wash their hands properly, help to reduce the spread of many common infections.

As always, children experiencing symptoms such as vomiting and diarrhoea should stay at home and not return to school or nursery until 48 hours after the symptoms have stopped.

CDC HAN Advisory On Human H5 Infection In The United States

#16,723

On Thursday night the CDC announced the first U.S. Case of Human Avian Influenza A(H5) in a person who was involved in the culling (depopulating) of poultry with presumptive H5N1 bird flu. The patient - who was treated with oseltamivir - reported fatigue for several days, but has since recovered. 

It isn't entirely clear whether this person was actually infected, or whether this person's positive nasal swab picked up surface contamination, but for now this patient meets the CDC criteria for a presumptive case. 

The Eurasian H5N1 virus - which is currently spreading in wild birds and in poultry across the United States (and Europe) - is a far cry from Asian H5N1 virus that caused nearly 900 human infections - and hundreds of deaths - in Asia and the Middle East during the first two decades of the 21st century.  

But over the past couple of years we've seen subtle signs that Eurasian H5Nx (e.g. H5N1, H5N8, H5N6, etc.) viruses may be slowly evolving towards becoming a greater human threat.  

In early 2021 Russia announced 7 infections among poultry workers, which convinced the CDC To Add Zoonotic Avian A/H5N8 To Their IRAT List last May.  Last December the  ECDC/EFSA Raised the Zoonotic Risk Potential Of Avian H5Nx, following the detection of a human infection in the UK.

Over the past 18 months we've also seen an increasing number of reports of mammalian infections with the Eurasian H5Nx virus, resulting in severe illness and neurological manifestations (see here, here, and here).

While the CDC has repeatedly stated that the H5N1 Bird Flu Poses Low Risk to the Public they have also warned that ". . . sporadic human infections with current H5N1 bird flu viruses would not be surprising, especially among people with exposures who may not be taking recommended precautions (like wearing personal protective equipment, for example).

Now that a presumptive human case has been identified (and reportedly, 10 others have been offered antivirals and are being monitored), the CDC has released a HAN Health Advisory for clinicians and public health officials on identifying and investigating additional suspected cases. 

Because of its length, I've only include some excerpts from this HAN advisory. Follow the link to read it in its entirety.   I'll have a brief postscript when you return. 

Highly Pathogenic Avian Influenza A(H5N1) Virus: Recommendations for Human Health Investigations and Response

Distributed via the CDC Health Alert Network
Friday, April 29, 2022, 8:00 PM ET
CDCHAN-00464

Summary

A person has tested positive for avian influenza A(H5) virus (H5 bird flu) in the U.S., as confirmed by the Centers for Disease Control and Prevention (CDC) and reported by the Colorado Department of Public Health and Environment on April 28, 2022. This case occurred in a person who had direct exposure to poultry and who was involved in the culling (depopulating) of poultry with presumptive H5N1 bird flu.

Starting in January, the U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) detected highly pathogenic avian influenza (HPAI) A(H5N1) virus in wild birds in the United States followed by multiple detections in U.S. commercial poultry and backyard bird flocks [1,2]. Detection of A(H5) virus in one person who was involved in culling of poultry does not change the human health risk assessment, which remains low for the general public. People with work or recreational exposures to infected birds are at greater risk of infection and should follow recommended precautions.

The purpose of this HAN Health Advisory is to notify public health workers, clinicians, and the public of the potential for human infection with this virus and to describe the CDC’s recommendations for patient investigation and testing, infection control including the use of personal protective equipment, and antiviral treatment and prophylaxis.

Background

(SNIP)

Influenza A viruses infect the respiratory and gastrointestinal tracts of birds causing birds to shed the virus in their saliva, mucous, and feces. Human infections with avian influenza A viruses can happen when enough virus gets into a person’s eyes, nose, or mouth or is inhaled. People with close or prolonged unprotected contact with infected birds or contaminated environments are at greater risk of infection. Illnesses in humans from avian influenza A virus infections have ranged from mild (e.g., eye infection, upper respiratory symptoms) to severe illness (e.g., pneumonia) resulting in death. The spread of avian influenza A viruses from one infected person to another has been reported in other countries, but is very rare, and when it has happened, it has not led to sustained spread among people.

At this time, CDC considers the human health risk to the U.S. public from these newly identified HPAI A(H5N1) viruses to be low; however, people with close or prolonged, unprotected contact with infected birds or contaminated environments are at greater risk of infection. While there is little information about the spectrum of illness that could result from human infections with current H5N1 bird flu viruses, currently, CDC considers this virus as having the potential to cause severe disease in humans and recommends the following:

Recommendations for Clinicians

Clinicians should consider the possibility of HPAI A(H5N1) virus infection in persons showing signs or symptoms of respiratory illness who have relevant exposure history. This includes persons who have had contact with potentially infected birds (e.g., handling, slaughtering, defeathering, butchering, culling, preparation for consumption); direct contact with water or surfaces contaminated with feces or parts (carcasses, internal organs, etc.) of potentially infected birds; and persons who have had prolonged exposure to potentially infected birds in a confined space. Clinicians should contact the state public health department to arrange testing for influenza A(H5N1) virus, collect respiratory specimens using personal protective equipment (PPE), consider starting empiric antiviral treatment (see below), and encourage the patient to isolate at home away from their household members and not go to work or school until it is determined they do not have avian influenza A virus infection. Testing for other potential causes of acute respiratory illness should also be considered depending upon the local epidemiology of circulating respiratory viruses, including SARS-CoV-2.

Recommendations for State Health Departments

State health departments should investigate potential human cases of HPAI A(H5N1) virus infection as described below and should notify CDC within 24 hours of identifying a case under investigation. Rapid detection and characterization of novel influenza A viruses in humans remain critical components of national efforts to prevent further cases, to allow for evaluation of clinical illness associated with them, and to assess the ability of these viruses to spread from human to human.

Recommendations for Surveillance and Testing

People exposed to HPAI A(H5N1)-infected birds (including people wearing recommended PPE) should be monitored for signs and symptoms of influenza beginning after their first exposure and for 10 days after their last exposure.

Patients who meet Epidemiologic criteria AND either Clinical OR Public Health Response criteria below should be tested for HPAI A(H5N1) virus infection by reverse-transcription polymerase chain reaction (RT-PCR) assay using H5-specific primers and probes at your state or local public health department.

(SNIP) 

Recommendations for the Public

People should avoid unprotected exposure to sick or dead birds, bird feces, litter, or materials contaminated by birds with suspected or confirmed HPAI A(H5N1) virus infection. Personal protective equipment (PPE) includes a properly fitted unvented or indirectly vented safety goggles, disposable gloves, boots or boot covers, a NIOSH-approved respirator (e.g., N95), disposable fluid-resistant coveralls, and disposable head cover or hair cover. PPE should be worn when in direct or close contact (within about six feet) with sick or dead poultry, poultry feces, litter, or materials potentially contaminated with HPAI A(H5N1) virus.

People exposed to HPAI A(H5N1)-virus infected birds (including people wearing recommended PPE) should monitor for signs and symptoms of influenza beginning after their first exposure and for 10 days after their last exposure. Influenza antiviral prophylaxis may be considered to prevent infection, particularly in those who had unprotected exposure to HPAI A(H5N1)-virus infected birds (see below). Persons who develop respiratory illness after exposure to HPAI A(H5N1) virus infected birds should seek prompt medical evaluation for influenza testing and antiviral treatment by their clinician or public health department. Symptomatic persons should isolate away from household members and others except for seeking medical evaluation.

          (Continue . . . )

When I began this blog more than 16 years ago, a far more dangerous ancestor of H5N1 was perceived as posing an imminent, and potentially devastating pandemic threat. Although H5N1 faltered - and eventually devolved into less dangerous variants - we have seen 2 unexpected pandemics emerge in the interim (H1N1 in 2009, and SARS-CoV-2 in 2020).

Today, there are arguably more credible pandemic threats on our radar than ever before.  

MERS-CoV, China's avian H5N6 virus, EA H1N1 `G4' swine flu, and the recently reported H3N8 virus in China all likely pose a greater public health threat than does H5N1, but the lesson of the past 20 years has been that we aren't very good at identifying the next pandemic threat. 

The one thing we can say with reasonable certainty is that another pandemic will occur, and it may even arrive before our current Coronavirus crisis has ended.

So we must treat every species jump seriously. 

ECDC: Rapid Risk Assessment On Increase in Severe Acute Hepatitis Cases of Unknown Aetiology in Children

#16,722

Three weeks ago, when word of the first cluster of cases had been announced by the UK (see UK HSA: Investigating An Unusual Increase In Hepatitis In Children), I opened my blog by saying "We've a bit of a medical mystery this morning."

While we know considerably more now than we did then - including the global nature of theses cases - the cause of these (nearly 200) cases of acute hepatitis is no less mysterious. 

The leading theory right now centers around the possibility that a common adenovirus infection (possibly 41F)  is causing unusual liver damage in young children.  Whether this is due to a change in the virus, or to some other cofactor, isn't known. 

We've seen a number of technical briefings and field reports (see here, here, here and here) on this outbreak, and today we have a Rapid Risk Assessment published by the ECDC. 

But as a practical matter, until a definitive cause can be established, it is impossible to reasonably quantify the risk. I've reproduced the Executive Summary below, but you'll want to follow the link to read the full 19-page report. 

Increase in severe acute hepatitis cases of unknown aetiology in children

Risk assessment

28 Apr 2022 

An increase in severe acute hepatitis cases of unknown aetiology among previously healthy children was first reported by the United Kingdom (UK) to the World Health Organization’s International Health Regulations (IHR) notification system on 5 April 2022 (testing had excluded viral hepatitis types A, B, C, D and E and other known causes of acute hepatitis). Following this alert, the United States and several European Union, European Economic Area (EU/EEA) and other countries have reported suspected cases.

Executive summary

As of 20 April 2022, 111 cases had been reported from the UK, and as of 27 April 2022 approximately 55 probable and confirmed cases have been reported from 12 EU/EEA countries. An additional 12 cases have been reported from the United States (US), 12 from Israel, and one from Japan. The clinical picture is of severe acute hepatitis requiring hospitalisation with jaundice and markedly elevated liver transaminases. In most cases to date, the onset of jaundice was preceded by a gastrointestinal illness with vomiting, diarrhoea, and nausea. Information on the outcome of the cases is still being collected. So far, most patients for whom information is available have recovered, but a number have progressed to acute liver failure and required liver transplantation.

Detailed epidemiological and laboratory investigations of the cases are still ongoing to help determine the underlying aetiology. Cases have been tested for a range of different infectious causes, and the most common pathogens found were adenovirus and SARS-CoV-2. In England and Scotland, 75.5% and 50% of cases respectively tested positive for adenovirus. Subtyping of 11 cases from the UK investigation found that these were all type 41F, which is the same subtype identified among several of the cases reported from the US. Other adenoviruses were also found in some non-blood samples among the UK cases investigated. Information on testing in the EU/EEA is incomplete, but among cases reported 10 tested positive for adenovirus. Statistical exceedance compared to positive tests in previous years in the detection of many viruses in the community has been reported by the UK, including a marked recent exceedance in adenovirus detections in faecal samples among children aged 1-4 years.

Early epidemiological investigations of cases from the UK based on trawling questionnaires have failed to identify a common exposure of note (including food, medicines, or toxins). Toxicological analysis of specimens collected from cases as part of the UK investigation is ongoing. Although epidemiological links were reported from the Scottish investigation for two pairs of cases, no other clusters have been reported. Across all reporting countries, the majority of cases to date have not had significant past medical history.

Based on these investigations, the current leading hypothesis is that a cofactor affecting young children having an adenovirus infection, which would be mild in normal circumstances, triggers a more severe infection or immune-mediated liver damage. Other aetiologies (e.g. other infectious or toxic agents) are still under investigation and have not been excluded but are considered less plausible. The disease pathogenesis and routes of transmission are also still unknown. The disease is quite rare and evidence around human-to-human transmission remains unclear; cases in the EU/EEA are sporadic with an unclear trend. As a result, the risk for the European paediatric population cannot be accurately assessed. However, considering the reported cases with acute liver failure, with some cases requiring liver transplantation, the potential impact for the affected paediatric population is considered high. Access to highly specialised paediatric intensive care and transplantation services may further impact outcomes. Considering the unknown aetiology, the affected paediatric population, and the potential severe outcome, this currently constitutes a public health event of concern.

It is essential to establish surveillance at the national level for EU/EEA countries as soon as possible to collect detailed epidemiological, clinical, virological, and other information, including toxicological analyses, on cases. Additional information for hypothesis testing should be collected in the context of analytical studies looking at other factors and potential co-factors such as recent infections, personal and environmental determinants. Specific studies should be designed to identify risk factors for infection and for severe illness, to investigate routes of potential transmission, to describe the full clinical spectrum, and to ascertain whether the same aetiological agent causes different clinical presentations depending on age and other conditions. ECDC will provide guidance and coordination to EU/EEA countries planning to set up such studies.

Further investigations include an assessment of the underlying level of acute viral infections circulating in the community, in particular adenoviruses, by age, and whether this is above what would normally be expected.

Public health authorities should communicate with paediatricians, general practitioners and other medical specialists to inform about the need for active case finding and reporting of new cases.

Testing appropriate samples from symptomatic children for adenoviruses as well as for other viruses that can cause hepatitis should be performed early after symptom onset. ECDC recommends an extensive set of tests to help identify the causative agent or co-factors.

Cases fulfilling the case definition should be reported to The European Surveillance System (TESSy) as soon as possible. Case records can be updated as more test results become available.

As the aetiology remains unknown, effective control measures cannot be defined at this stage. Faecal-oral exposure to viruses such as adenoviruses is more likely for young children. We therefore recommend reinforcing general good hygienic practices (including careful hand hygiene, cleaning and disinfection of surfaces) in settings attended by young children.

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Increase in severe acute hepatitis cases of unknown aetiology in children - EN - [PDF-535.85 KB]

Colorado: BLM Reports an Outbreak of Equine H3N8 In WIld Horses

  

#16,721

Earlier this week in China: NHC Confirms Human Avian H3N8 Infection In Henan Province we saw the first confirmed human infection with avian H3N8, but this influenza subtype can also be found in Canines (CIV) and Equines (EIV).  

There are subtle, genetic differences between the AIV, CIV, and EIV versions of this subtype, and each pretty much stays in its own lane, infecting only birds, dogs, or horses.  But all three lineages continue to evolve, and that increases their potential to jump species. 

Originally, Canine H3N8 evolved directly from Equine H3N8, when it abruptly mutated enough to adapt to a canine host, and rapidly began to spread among greyhounds at a Florida race track in 2004 (see EID Journal article Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida). 

While equine H3N8 isn't considered to be a zoonotic disease, it has jumped species (to dogs in 2004), and has been shown experimentally capable of infecting both pigs (see J.Virol.: Experimental Infectivity Of H3N8 In Swine) and cats (see Equine influenza A(H3N8) virus infection in cats).

In 2019, an EID Journal Historical Review of Equine H3N8 warned:

Volume 25, Number 6—June 2019
Historical Review
Equine Influenza Virus—A Neglected, Reemergent Disease Threat 

Alexandra Sack, Ann Cullinane, Ulziimaa Daramragchaa, Maitsetseg Chuluunbaatar, Battsetseg Gonchigoo, and Gregory C. Gray
.C. Gray)

Abstract

Equine influenza virus (EIV) is a common, highly contagious equid respiratory disease. Historically, EIV outbreaks have caused high levels of equine illness and economic damage. Outbreaks have occurred worldwide in the past decade. The risk for EIV infection is not limited to equids; dogs, cats, and humans are susceptible.

This is a topic we also looked at in 2018, in Equine H3N8: Looking At A long-shot In The Pandemic Sweepstakes and before that, in 2014's Study: Dogs As Potential `Mixing Vessels’ For Influenza.  

So, while the risks of human infection are believed to be very low - when we see outbreaks of H3N8 - we tend to pay attention. 

Earlier this week the Bureau of Land Management (BLM) announced the deaths of scores of wild horses at a facility in Colorado (see FluTrackers thread CO: Mystery illness kills 95 horses at a federal cañon city holding facility, facility on quarantine). 

Overnight, the BLM announced a viral (Equine H3N8 influenza) cause has been identified. 

A VIRUS HAS BEEN IDENTIFIED AS THE PRINCIPAL CAUSE OF THE OUTBREAK AND MORTALITY AT BLM’S WILD HORSE AND BURRO FACILITY

CAÑON CITY, Colo. – An equine influenza virus that is not uncommon among both wild and domestic horses has been identified as the likely cause of the respiratory disease outbreak and associated mortality that is occurring at the BLM’s Wild Horse and Burro Corrals located on the Colorado Department of Corrections (CDOC) East Canon Complex in Canon City, CO. Positive polymerase chain reaction (PCR) laboratory test results from two leading veterinary diagnostic laboratories in the United States identified the virus in nasal swabs and lung tissue from several horses.

This strain of equine influenza (subtype H3N8) is not related to the current outbreak of highly pathogenic avian influenza (subtype H5N1) that is currently impacting wild birds and poultry across the United States.

The PCR testing has also identified two equine herpes viruses (EHV-2 and EHV-5) but these commonly occur in normal, healthy horses, and it is unclear to what extent these may also be contributing to the severity of the clinical signs observed in the more severely affected group of horses at the facility.

More typical mild clinical signs of influenza are also being observed in approximately 10-20 percent of the other 2,184 horses at the facility that are not from West Douglas. No mortality has occurred in the larger groups of horses. The West Douglas horses were gathered in an emergency operation in 2021 following a wildfire that impacted their habitat. As of today, April 28, 95 horses have died at the facility since April 23.

“The Bureau of Land Management will review operations at the Canon City facility to prevent future outbreaks like this from occurring,” said BLM Colorado Acting Associate State Director Ben Gruber. “This tragic outcome was influenced by a population of horses that may have been particularly vulnerable given their time in the West Douglas area and their exposure to last year’s wildfire that prompted their emergency gather.”

“This unfortunate event is being taken very seriously by the Department of Corrections and the BLM,” said CDOC Executive Director Dean Williams. “We are working in coordination to mitigate the spread of the virus and identify and prevent any potential risk which could lead to future similar events.”

BLM continues to work with the attending veterinarians on scene as well as the diagnostic laboratories, veterinarians and epidemiologists from the US Department of Agriculture and the Colorado State Veterinarian’s Office to investigate and mitigate the factors that may be contributing to the most severe cases and prevent further spread of the disease. The facility remains under a voluntary quarantine with no horses allowed to leave the premises at this time and for the foreseeable future until it has been determined that the animals are again healthy and pose no risk to the domestic equine population in the community.

The veterinarian report and additional information can be found online at https://www.blm.gov/programs/wild-horse-and-burro/herd-management/herd-management-areas/colorado

-BLM-

Over the past decade we've seen a resurgence of Equine H3N8 around the world (see here, here, and here), which Merck Animal Health - a manufacturer of vaccines - attributes to:

• Equine influenza virus (EIV) strains are undergoing significant antigenic drift (evolutionary changes or mutations that lead to new virus strains the immune system doesn’t recognize), and this antigenic drift is the most probable cause for the increased incidence of influenza vaccine failure in the U.S.;3
• Ongoing sequencing of real-world influenza isolates infecting U.S. horses demonstrates significant antigenic differences in field isolates and isolates contained within most vaccine strains, thus inhibiting their ability to offer adequate protection against current circulating strains of equine influenza;

In 2016, in Epizootics, Host Ranges, and Conventional Wisdom we looked at the history of equine epizootics - including the panzootic of 1872 - and at a study (see A Review of Evidence that Equine Influenza Viruses Are Zoonotic) that argued that human EIV infections occasionally occur. 

While H3N8 is currently pretty far down our worry list, there is evidence to suggest it may have sparked one or more human influenza pandemics prior to 1918, and so we continue to watch its evolution (and any species jumps) with considerable interest.  

Colorado Investigating 1st Human HPAI H5 Infection In the United States

#16,720

For the past 3 months the United States (and Canada) have been dealing with an H5N1 epizootic in poultry and wild birds, and while this virus has been primarily a disease of birds, the CDC has warned: 

Given past human infections with bird flu viruses resulting from close contact with infected birds/poultry, sporadic human infections with current H5N1 bird flu viruses would not be surprising, especially among people with exposures who may not be taking recommended precautions (like wearing personal protective equipment, for example).

Overnight the state of Colorado (and the CDC via Email) have verified that 1 person with direct contact with poultry has been diagnosed with a probable - and apparently mild - H5N1 infection.   This comes roughly 4 months after a similar case was reported from the UK (see UKHSA Statement On Human H5 Infection In England).

It should be noted that while it bears the same name (H5N1) as its far-more pathogenic Asian counterpart, the European lineage which is impacting Europe and North America has never been linked to severe human infection. 

But since 2016 we've seen increasing avian mortality and increased host range in HPAI H5Nx viruses circulating in Europe, including serious infection of several mammalian species (see CDC EID Journal: Encephalitis and Death in Wild Mammals at An Animal Rehab Center From HPAI H5N8 - UK).

In early 2021 Russia announced 7 mild cases of H5Nx infection, and in late December  the ECDC/EFSA Raised the Zoonotic Risk Potential Of Avian H5Nx.  

 

All of which brings us to the statement (below) by the State of Colorado DOH on the first U.S. infection with this H5N1 virus. 

State health officials investigate a detection of H5 influenza virus in a human in Colorado

Person had direct contact with infected poultry; public health experts say the risk to the public is low.

April 28, 2022—The Colorado Department of Public Health and Environment has been monitoring and testing people exposed to poultry and wild birds infected with avian flu (Highly Pathogenic Avian Influenza, HPAI), also known as H5N1 flu. Earlier this week, a test revealed the presence of the influenza A (H5) virus in a single nasal specimen from a person who was working on a farm with infected poultry. CDC confirmed the result on April 27, 2022. Repeat testing on the person was negative for influenza. Because the person was in close contact with infected poultry, the virus may have been present in the person’s nose without causing infection.

The adult male, who is younger than 40, is largely asymptomatic, reporting only fatigue. He is now isolating and receiving the influenza antiviral drug oseltamivir (tamiflu) per CDC guidance. Scientists believe that the risk to people is low as H5 flu viruses spread among wild birds and poultry. They do not normally infect humans nor spread from person to person. There are currently no known cases of this H5 flu virus spreading among people. There are no other confirmed human cases in Colorado or the United States at this time.

This positive result is due to direct exposure to infected poultry at a commercial farm in Montrose County. The person, who is an inmate at a state correctional facility in Delta County, was working with poultry as part of a pre-release employment program where participants have the opportunity to work for private employers and be paid a prevailing wage. The affected flock has been euthanized and disposed of under the guidance of the USDA and CDA. All members of the response team, including other inmate workers, were provided personal protective equipment while working on the farm.

“We want to reassure Coloradans that the risk to them is low,” said Dr. Rachel Herlihy, state epidemiologist, Colorado Department of Public Health and Environment. “I am grateful for the seamless collaboration between CDC, Department of Corrections, Department of Agriculture, and CDPHE, as we continue to monitor this virus and protect all Coloradans.”

While human infections of the H5 viruses are rare, direct exposure to infected birds increases that risk. Infected birds shed flu viruses in their saliva, mucous, and feces. Public health officials in the United Kingdom confirmed H5N1 virus in January 2022 in a person who was asymptomatic and had direct contact with infected birds.

People should avoid contact with poultry that appear ill or are dead, and avoid contact with surfaces that appear to be contaminated with feces from wild or domestic birds. If you must handle sick or dead poultry, wear gloves and wash your hands with soap and water afterwards. If possible, wear respiratory protection such as a medical facemask and eye protection such as goggles. CDC also has guidance for specific groups of people with exposure to poultry, including poultry workers and people responding to poultry outbreaks. CDC will continue to provide further updates to the situation and update guidance as needed.

It is safe to eat properly handled and cooked poultry and poultry products in the United States. The proper handling and cooking of poultry and eggs to an internal temperature of 165˚F kills bacteria and viruses, including H5N1 viruses.

What flock owners can do
HPAI is a highly contagious and deadly foreign animal disease in domestic poultry. Wild birds serve as a reservoir for influenza viruses and can spread these viruses to poultry. Certain strains of avian influenza are also zoonotic. USDA has published all detections of HPAI in poultry and wild birds on the APHIS website. Learn more about avian influenza and how to report unusual bird deaths on the CDA website at ag.colorado.gov/hpai.

INCREASE BIOSECURITY: It is extremely important for poultry owners to increase biosecurity measures to protect their birds. The USDA Defend the Flock website has helpful resources for keeping poultry healthy in any operation. Commercial poultry producers can use this toolkit to assess their biosecurity practices and preparedness.

MONITOR FLOCKS: Monitor your flock for clinical signs of H5N1, including monitoring production parameters (feed and water consumption, egg production) and increased morbidity and mortality. Any changes in production parameters that could indicate H5N1 should be reported.

REPORT DISEASE: It is important for veterinarians and producers to report any suspicious disease events in poultry flocks to the State Veterinarian’s office at 303-869-9130. If it is after hours, the voicemail message will indicate which veterinarian is on call.

If you have sick birds or birds that have died from unknown causes, help is available at the Colorado Avian Health Call Line at Colorado State University Their number is 970-297-4008.

SECURE FOOD SUPPLY: The Colorado Department of Agriculture strongly encourages poultry producers to enroll as a Secure Food Supply participant through their office. The most important component of ensuring your continuity of business in an outbreak is to enroll in Secure Food Supply and have a biosecurity plan in place. If you would like more information, contact dave.dice@state.co.us or 303-263-2407.

Although the CDC has not yet posted a notice on their website, or updated their HPAI H5 status page (below), they did send out an emailed statement overnight, which you can view on FluTrackers.  I've excerpted the following snippet:

This one H5-positive human case does not change the human health risk assessment. CDC will continue to watch this situation closely for signs that the risk to human health has changed. Signals that could raise the public health risk might include multiple reports of H5N1 virus infections in people from exposure to birds, or identification of spread from one infected person to a close contact. CDC also is monitoring H5N1 viruses for genetic changes that have been associated with adaptation to mammals, which could indicate the virus is adapting to spread more readily from birds to people. CDC is taking routine preparedness and prevention measures, which includes an existing candidate vaccine virus that could be used to make vaccine for people if one were needed.

While this story is likely to get a lot of attention today, and over the weekend, this case is not unexpected, and we will likely see more in the future. In its current incarnation, H5N1 is unlikely to pose much of a threat to public health. 

But H5Nx continues to mutate, and what we can say about its threat today may not hold true tomorrow. 

In May of 2021,  in  Science: Emerging H5N8 Avian Influenza Viruses, we looked at a review by two well-respected Chinese scientists (Weifeng Shi and George F. Gao)  on the evolution, and growing zoonotic threat, of avian H5N8, stating:

•  the  ". . . global spread of AIVs, particularly the H5N8 subtype, has become a major concern to poultry farming and wildlife security but, critically, also to global public health."
• And due to the ". . . long-distance migration of wild birds, the innate capacity for reassortment of AIVs, the increased human-type receptor binding capability, and the constant antigenic variation of HPAIVs  the authors warned that it was imperative that " . . . the global spread and potential risk of H5N8 AIVs to poultry farming, avian wildlife, and global public health are not ignored."

And in June 2021, in V. Evolution: Genomic Evolution, Transmission Dynamics, and Pathogenicity of Avian H5N8 Viruses Emerging in China, 2020, we saw Chinese researchers describe the rapid rise in 2020 of an antigenically distinct H5N8 virus that is lethal to chickens and mice, that is similar to the Russian Zoonotic strain, and has shown signs of mammalian adaptation.

For now, the zoonotic potential of these European H5Nx viruses remains quite limited, but they need to be monitored closely for any signs that might be changing.  

EID Journal: Epidemiologic, Clinical, and Genetic Characteristics of Human Infections with Influenza A(H5N6) Viruses, China

 

#16,719

China's avian H5N6 virus, which has been on our radar since the spring of 2014 when it infected a man in Sichuan Province, caused just over 2 dozen known human infections during its first six years of circulation (average of 4 per year).  

Since the fall of 2020, however, we've seen a marked increase in cases, with more than 50 reported over the past 18 months (see map above).  This number, however, is likely an undercount. 

As with all influenza subtypes, when we talk about H5N6, we're aren't talking about a single viral threat, but rather an expanding array of related viruses sharing similar HA and NA genes. Viruses which can vary considerably in their behavior and the threat they pose (see Differences In Virulence Between Closely Related H5N1 Strains).

And over the past 8 years H5N6 has been busy reinventing itself via antigenic drift and antigenic shift (reassortment), so that now there are numerous `flavors' of H5N6 co-circulating in China and Southeast Asia. Some are more pathogenic than others, but all continue to evolve. 

Although categorized by their two surface proteins (HA & NA) Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2).

Shift, or reassortment, happens when two different influenza viruses co-infect the same host swap genetic material.  New hybrid viruses may be the result of multiple reassortments, with gene contributions coming from several parental viruses.

In addition to seeing a marked increase in human H5N6 infections over the past 18 months, we've also seen a number of studies coming out of China describing evolutionary changes - and potential signs of mammalian adaptation - in the virus.

China CCDC Weekly: Genetic Characterization of Two Human A (H5N6) Viruses — Guangxi , China, 2021

CCDC Weekly: Outbreak Report - Five Independent Cases of Human Infection With HPAI H5N6 — Sichuan Province

Six months ago the CDC Added A New H5N6 Avian Flu Virus To Their IRAT List of zoonotic influenza viruses with pandemic potential.  While this particularly HPAI H5 virus has only been reported in China, and parts of Southeast Asia, the concern is that it could eventually expand its geographic horizons the way that H5N1 and H5N8 have previously. 

For now, H5N6 has shown no ability to spread efficiently from human-to-human.  And as long as that status quo remains, the virus is primarily a threat to those who have close contact with poultry in China.

But evolution never stops, and with an increasing number of variations on an H5N6 theme spreading across China, the risk of seeing a more dangerous version emerge cannot be ignored. 

The following research article, published yesterday in the EID Journal, reports on 13 types of reassortant H5N6 viruses that have infected humans in China - 4 of them added since 2021 - and on the detection of several mammalian-adapted mutations. 

I've only posted some excerpts, so follow the link to read it in its entirety.  I'll have a brief postscript when you return. 

Research

Epidemiologic, Clinical, and Genetic Characteristics of Human Infections with Influenza A(H5N6) Viruses, China

Wenfei Zhu1, Xiyan Li1, Jie Dong1, Hong Bo, Jia Liu, Jiaying Yang, Ye Zhang, Hejiang Wei, Weijuan Huang, Xiang Zhao, Tao Chen, Jing Yang, Zi Li, Xiaoxu Zeng, Chao Li, Jing Tang, Li Xin, Rongbao Gao, Liqi Liu, Min Tan, Yuelong Shu, Lei Yang , and Dayan Wang

Abstract

The recent rise in the frequency of influenza A(H5N6) infections in China has raised serious concerns about whether the risk for human infection has increased. We surveyed epidemiologic, clinical, and genetic data of human infections with A(H5N6) viruses. Severe disease occurred in 93.8% of cases, and the fatality rate was 55.4%. Median patient age was 51 years.

Most H5N6 hemagglutinin (HA) genes in human isolates in 2021 originated from subclade 2.3.4.4b; we estimated the time to most recent common ancestor as June 16, 2020. A total of 13 genotypes with HA genes from multiple subclades in clade 2.3.4.4 were identified in human isolates. Of note, 4 new genotypes detected in 2021 were the major causes of increased H5N6 virus infections. Mammalian-adapted mutations were found in HA and internal genes.

 

Although we found no evidence of human-to-human transmission, continuous evolution of H5N6 viruses may increase the risk for human infections.

(SNIP)

Discussion

Among AIVs, viruses of subtypes H5 and H7 have been of particular concern because of their high rates of death. The hospitalization fatality risk for H5N6 infections (59.0%) was slightly lower than that for H5N1 infections (70.0%) but higher than that for H7N9 (35.0%) (44). In addition, the median age of patients with H5N6 virus (51 years) was older than the median age for patients with H5N1 virus (26 years) but younger than the age for patients with H7N9 virus (62 years) (44).

On the basis of epidemiologic investigations, 93.8% of influenza H5N6 case-patients were confirmed to have poultry exposure history. The contamination of live poultry markets and backyard birds, as well as the practice of processing poultry without personal protection, could be ongoing exposure sources for influenza A(H5N6) virus. While H5N6 viruses continue to circulate in poultry, human infections will undoubtedly continue.

WHO has recommended early antiviral therapy, ideally within 48 hours of symptom onset, for suspected or confirmed influenza patients (45). Our study found that early initiation of antiviral treatments could reduce the fatality rate in H5N6 patients to some extent. However, symptoms at the onset of influenza H5N6 infections were clinically similar to those of other respiratory pathogen infections. Thus, increased sensitivity of diagnostic systems is needed to improve case identification and initiate timely antiviral treatment.

During the COVID-19 pandemic, diagnostic capacity for respiratory illnesses among human health systems in China, including hospitals, Centers for Disease Control and Prevention at different levels, and third-party agencies, was increased. In our study, clinical samples from 15 H5N6 cases during the COVID-19 pandemic (2 in 2020 and 13 in 2021) were first identified by third party agencies. This additional diagnostic capacity contributed to the detection of H5N6 cases reported in 2021.

Genetic analysis in our study detected at least 13 types of reassortant H5N6 viruses in infected humans in China (Figure 6). Origins of internal genes were dramatically diversified, indicating the advanced genetic compatibility of H5N6 viruses with other AIVs. In 2021, a total of 4 new H5N6 genotype viruses emerged and accounted for almost all of the H5N6 human viruses based on the available full genome. Of note, different from previously isolated viruses, the HA gene of almost all H5N6 human viruses in 2021 belonged to genetic clade 2.3.4.4b and was closely related to that of the first H5N8 isolate, which caused infection in a patient in Russia (46). Additional mammal-adapted mutations, including Q226L and T192I in the HA protein, which could increase the viral affinity for human cells, were also detected (Appendix Table 3), indicating the viral adaptation process from birds to humans.

In summary, although we observed a rise in the number of influenza A(H5N6) infections in 2021, the disease course and CFR were comparable to previously detected H5N6 cases. Antiviral drugs remain effective if used early. However, new genotype viruses and mammal-adapted substitutions emerged. Moreover, reports from OFFLU (https://www.offlu.org ) and WHO have documented that clade 2.3.4.4h and 2.3.4.4b H5N6 viruses and clade 2.3.4.4b H5N8 viruses have been detected in poultry and wild birds in China.

Considering the continuous viral circulation in birds and incidence of human infection, more H5N6 variants and genotypes with further advantages in humans might emerge. Increased attention to such emerging viruses is vital for public health and pandemic preparedness.

Dr. Zhu works in the Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention. Her research interests include evolutionary analysis and pathogenicity mechanism of influenza viruses.

With an estimated mortality rate of > 50%, we watch avian viruses like H5N6  very carefully, but since the only human influenza pandemics we know of have been caused by H1, H2, or H3 viruses, we really don't know if H5 or H7 viruses are capable of sparking a human pandemic (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?). 

Of course, until quite recently, we didn't have proof that a novel coronavirus could spark a human pandemic either. 

It is probably more likely that the next influenza pandemic will emerge from an avian or swine H1, H3, or H3 virus that carries a much lower case fatality rate. The CDC currently ranks a Chinese Swine-variant EA H1N1 `G4' as having the highest pandemic potential of any flu virus on their list.

But another pandemic is inevitable, and like it or not, long-shots sometimes do come in.  

ECDC: Transitioning Beyond the Acute Phase of the COVID-19 Pandemic

 

#16,718

Although I strongly suspect COVID has a few more cards to play, nations around the world are looking for an `exit strategy' from the acute phase of the pandemic; one that would help reinvigorate their economies and return life to a more `normal' existence. 

Whether, and for how long, the SARS-CoV-2 virus cooperates remains to be seen.  But for most countries outside of Asia, COVID activity has slowed markedly - and in the Northern Hemisphere - there are hopes for seeing a prolonged respite over the summer. 

Many countries have already relaxed or dropped social distancing and public face mask requirements, testing recommendations, and the daily reporting of cases has been gradually `de-emphasized'.  

As a result, the visceral impact of pandemic is slowly receding from headlines. But that doesn't mean the pandemic virus has gone away. 

Today the ECDC published a 9-page technical document discussing how 8 European nations are approaching their transition beyond the Acute Phase of COVID-19.  Although they are all following  different approaches and are moving at different speeds, they are all looking for a path towards a more sustainable COVID policy. 

Transitioning beyond the acute phase of the COVID-19 pandemic: Approaches and tools used by a sample of EU countries in the transition and de-escalation phase – interim report

Technical report
27 Apr 2022 

While the COVID-19 pandemic is not yet over, European Union (EU)/European Economic Area (EEA) countries are transitioning beyond the acute phase of the pandemic and towards a more sustainable and integrated approach to COVID-19 response in the longer term.

In February and March 2022, ECDC carried out a series of dialogues with selected EU countries to discuss their approaches to transitioning into the post-acute phase of the pandemic and/or de-escalating measures, including their plans regarding specific key areas. The synthesis and sharing of the experiences and approaches by the selected EU countries that participated in the dialogue are presented in this document and linked with tools ECDC has developed during the pandemic that can be used in support of this process.

Executive summary

Key messages

• Although globally the COVID-19 pandemic is not yet over, European Union (EU)/European Economic Area (EEA) countries are transitioning beyond the acute phase of the pandemic and towards a more sustainable and integrated approach to COVID-19 response, thanks to the high level of vaccination coverage achieved and the confidence in their strengthened healthcare systems. In February and March 2022, eight EU countries participated in a dialogue with ECDC on their approaches for transitioning into the post-acute phase and/or de-escalating measures, in order to identify common approaches and useful tools that can be used by other countries.
• The results of this analysis indicate that the consulted countries have shifted from an acute emergency phase approach, where efforts were invested in reducing transmission and protecting the healthcare system, towards a post-acute phase, which aims to ensure ongoing support and management of severe outcomes and the protection of vulnerable populations.
• In transitioning to this post-acute phase, all the consulted countries are de-escalating their response measures, including non-pharmaceutical interventions (NPIs). The countries will continue monitoring pandemic trends and key indicators but are moving away from widespread screening and towards approaches focused on testing for diagnostic purposes as well as targeted and representative sentinel surveillance, to enable continued monitoring while making a more sustainable use of resources.
• The consulted countries reported the continued importance of maintaining sequencing capacity in order to ensure the ongoing ability to detect new COVID-19 variants as well as supporting the wider ability to detect and characterise other new and emerging pathogens.
• The responding countries highlighted the continued importance of risk communication and community engagement and emphasised research readiness as a priority but reported that challenges surrounding funding and coordination remain.
• Several countries reported an increased focus on the recovery of their healthcare systems and the need to assess and address the wider health impacts of the pandemic, including delays or disruptions of childhood vaccination programmes, health screening programmes, and other medical interventions.
• While the consulted countries reported a number of efforts to review their pandemic response to date, many of them had not yet conducted formal evaluations or after-action reviews.
• ECDC has developed a number of reports and technical guidance that can support countries’ transition to the post-acute phase, including those related to surveillance, testing strategies, genomic sequencing, behavioural insights, and conducting after-action reviews.

Transitioning beyond the acute phase of the COVID-19 pandemic: Approaches and tools used by a sample of EU countries in the transition and de-escalation phase – interim report - EN - [PDF-420.97 KB]

 

As a blogger, I obviously want every scrap of information I can get my hands on.  And I worry that the recent rolling back of testing and reporting could backfire, and even allow new variants to get a foothold (as we just saw with BA.2.12.1) while flying under the radar. 

But I also understand that we can't remain in a heightened state of alert forever.  

My hope is that in scaling back our pandemic response, we remain nimble enough to pivot should another serious pandemic wave threaten. That we don't get locked into a self-defeating `we declared victory, and we aren't going back' mentality. 

I also plan to get my second booster, and will continue to wear face masks in crowded, or indoor venues, throughout the summer.  But beyond that, I'm living my life as `normally' as possible. 

That said, I still wouldn't put any money on COVID going quietly into the night. 

MMWR: Seroprevalence of Infection-Induced SARS-CoV-2 Antibodies - U.S.

GAO: A Herd Immunity For COVID-19 Primer 

#16,717

Two years ago - in the opening months of our Coronavirus pandemic - many hopes for a quick resolution to this crisis were pinned on society achieving `Herd Immunity', either through natural infection, or eventually from a vaccine.

Many governments, eager to reassure a worried public, touted the notion that once 65%-75% of the public had been exposed to the virus the `pandemic phase' would end. And some even hinted  that might only be a few months months away.

The flaw in this ointment - which we discussed at length in COVID-19: From Here To Immunity - was that this assumed that there we're a large number of moderate, mild, or asymptomatic infections that we didn't see, and that once you were infected - even asymptomatically - you acquired long-lasting immunity.

But in 2016  a study (see EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors) that tested 9 Health care workers who were infected with MERS during the 2014 Jeddah outbreak (2 severe pneumonia, 3 milder pneumonia, 1 URTI, and 3 asymptomatic),found only those with severe pneumonia still carried detectable levels of antibodies 18 months later.

Similarly, in Fenner and White's Medical Virology (Fifth Edition - 2017), the authors describe the clinical features of seasonal human coronaviruses (hCoVs) in Chapter 31:

The typical coronavirus “common cold” is mild and the virus remains localized to the epithelium of the upper respiratory tract and elicits a poor immune response, hence the high rate of reinfection. There is no cross-immunity between human coronavirus-229E and human coronavirus-OC43, and it is likely that new strains are continually arising by mutation selection.

By late summer of 2020 we were beginning to see evidence of reinfections - long before the first of the new variants (Alpha, Delta, Omicron, etc.) began to appear - leading to the following statement (see
CDC Clarifies: Recovered COVID-19 Cases Are Not Necessarily Immune To Reinfection).

The initial high degree of protection offered by COVID vaccines provided a badly needed boost to the idea of achieving `herd immunity',  but within a year the arrival of 3 distinct classes of variants (Alpha, Delta, and Omicron) had severely eroded the vaccine's effectiveness. 

While vaccines still provide significant reductions in severe illness, hospitalizations, and deaths from COVID, they provide only limited protection against reinfection.  Similarly, protection offered by previous COVID infection wanes over time, and is further eroded when new variants are introduced. 

Which is why - even though Omicron has spread widely across the nation over the past 5 months and  increased the number of people with SARS-CoV-2 antibodies to an estimated 58% - we can't assume that most of us are now `immune' to the virus. 

Particularly with new variants constantly emerging. 

The development of more cross-protective, and longer lasting COVID vaccines - or the emergence of a more `stable' SARS-CoV-2 virus - could someday still lead us to something approaching herd immunity.  

But for the foreseeable future, getting the COVID vaccine - and staying current with your`booster' shots - likely provides the best available protection.  

Seroprevalence of Infection-Induced SARS-CoV-2 Antibodies — United States, September 2021–February 2022

Weekly / April 26, 2022 / 71(17) 

Kristie E.N. Clarke, MD1; Jefferson M. Jones, MD1; Yangyang Deng, MS2; Elise Nycz, MHS1; Adam Lee, MS2; Ronaldo Iachan, PhD2; Adi V. Gundlapalli, MD, PhD1; Aron J. Hall, DVM1; Adam MacNeil, PhD1  

In December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, became predominant in the United States. Subsequently, national COVID-19 case rates peaked at their highest recorded levels.* Traditional methods of disease surveillance do not capture all COVID-19 cases because some are asymptomatic, not diagnosed, or not reported; therefore, the proportion of the population with SARS-CoV-2 antibodies (i.e., seroprevalence) can improve understanding of population-level incidence of COVID-19. This report uses data from CDC’s national commercial laboratory seroprevalence study and the 2018 American Community Survey to examine U.S. trends in infection-induced SARS-CoV-2 seroprevalence during September 2021–February 2022, by age group.

The national commercial laboratory seroprevalence study is a repeated, cross-sectional, national survey that estimates the proportion of the population in 50 U.S. states, the District of Columbia, and Puerto Rico that has infection-induced antibodies to SARS-CoV-2.† Sera are tested for anti-nucleocapsid (anti-N) antibodies, which are produced in response to infection but are not produced in response to COVID-19 vaccines currently authorized for emergency use or approved by the Food and Drug Administration in the United States.§

During September 2021–February 2022, a convenience sample of blood specimens submitted for clinical testing was analyzed every 4 weeks for anti-N antibodies; in February 2022, the sampling period was <2 weeks in 18 of the 52 jurisdictions, and specimens were unavailable from two jurisdictions. Specimens for which SARS-CoV-2 antibody testing was ordered by the clinician were excluded to reduce selection bias. During September 2021–January 2022, the median sample size per 4-week period was 73,869 (range = 64,969–81,468); the sample size for February 2022 was 45,810. Seroprevalence estimates were assessed by 4-week periods overall and by age group (0–11, 12–17, 18–49, 50–64, and ≥65 years). To produce estimates, investigators weighted jurisdiction-level results to population using raking across age, sex, and metropolitan status dimensions from 2018 American Community Survey data¶ (1). CIs were calculated using bootstrap resampling (2); statistical differences were assessed by nonoverlapping CIs. All specimens were tested by the Roche Elecsys Anti-SARS-CoV-2 pan-immunoglobulin immunoassay.** All statistical analyses were conducted using R statistical software (version 4.0.3; The R Foundation). This activity was reviewed by CDC, approved by respective institutional review boards, and conducted consistent with applicable federal law and CDC policy.††

During September–December 2021, overall seroprevalence increased by 0.9–1.9 percentage points per 4-week period. During December 2021–February 2022, overall U.S. seroprevalence increased from 33.5% (95% CI = 33.1–34.0) to 57.7% (95% CI = 57.1–58.3). Over the same period, seroprevalence increased from 44.2% (95% CI = 42.8–45.8) to 75.2% (95% CI = 73.6–76.8) among children aged 0–11 years and from 45.6% (95% CI = 44.4–46.9) to 74.2% (95% CI = 72.8–75.5) among persons aged 12–17 years (Figure). Seroprevalence increased from 36.5% (95% CI = 35.7–37.4) to 63.7% (95% CI = 62.5–64.8) among adults aged 18–49 years, 28.8% (95% CI = 27.9–29.8) to 49.8% (95% CI = 48.5–51.3) among those aged 50–64 years, and from 19.1% (95% CI = 18.4–19.8) to 33.2% (95% CI = 32.2–34.3) among those aged ≥65 years.

The findings in this report are subject to at least four limitations. First, convenience sampling might limit generalizability. Second, lack of race and ethnicity data precluded weighting for these variables. Third, all samples were obtained for clinical testing and might overrepresent persons with greater health care access or who more frequently seek care. Finally, these findings might underestimate the cumulative number of SARS-CoV-2 infections because infections after vaccination might result in lower anti-N titers,§§,¶¶ and anti-N seroprevalence cannot account for reinfections.

As of February 2022, approximately 75% of children and adolescents had serologic evidence of previous infection with SARS-CoV-2, with approximately one third becoming newly seropositive since December 2021. The greatest increases in seroprevalence during September 2021–February 2022, occurred in the age groups with the lowest vaccination coverage; the proportion of the U.S. population fully vaccinated by April 2022 increased with age (5–11, 28%; 12–17, 59%; 18–49, 69%; 50–64, 80%; and ≥65 years, 90%).*** Lower seroprevalence among adults aged ≥65 years, who are at greater risk for severe illness from COVID-19, might also be related to the increased use of additional precautions with increasing age (3).

These findings illustrate a high infection rate for the Omicron variant, especially among children. Seropositivity for anti-N antibodies should not be interpreted as protection from future infection. Vaccination remains the safest strategy for preventing complications from SARS-CoV-2 infection, including hospitalization among children and adults (4,5). COVID-19 vaccination following infection provides additional protection against severe disease and hospitalization (6). Staying up to date††† with vaccination is recommended for all eligible persons, including those with previous SARS-CoV-2 infection.