The bird flu outbreak in U.S. dairy cows is prompting development of new, next-generation mRNA vaccines akin to COVID-19 shots that are being tested in both animals and people.
Next month, the U.S. Agriculture Department is to begin testing a vaccine developed by University of Pennsylvania researchers by giving it to calves. The idea: If vaccinating cows protects dairy workers, that could mean fewer chances for the virus to jump into people and mutate in ways that could spur human-to-human spread.
Meanwhile. the U.S. Department of Health and Human Services has been talking to manufacturers about possible mRNA flu vaccines for people that, if needed, could supplement millions of bird flu vaccine doses already in government hands.
If there's a pandemic, there's going to be a huge demand for vaccine, said Richard Webby, a flu researcher at St. Jude Childrens Research Hospital in Memphis. The more different (vaccine manufacturing) platforms that can respond to that, the better."
The bird flu virus has been spreading among more animal species in scores of countries since 2020. It was detected in U.S. dairy herds in March, although investigators think it may have been in cows since December. This week, the USDA announced it had been found in alpacas for the first time.
At least three people all workers at farms with infected cows have been diagnosed with bird flu, although the illnesses were considered mild.
But earlier versions of the same H5N1 flu virus have been highly lethal to humans in other parts of the world. Officials are taking steps to be prepared if the virus mutates in a way to make it more deadly or enables it to spread more easily from person to person.
Traditionally, most flu vaccines are made via an egg-based manufacturing process that's been used for more than 70 years. It involves injecting a candidate virus into fertilized chicken eggs, which are incubated for several days to allow the viruses to grow. Fluid is harvested from the eggs and is used as the basis for vaccines, with killed or weakened virus priming the body's immune system.
Rather than eggs also vulnerable to bird flu-caused supply constraints some flu vaccine is made in giant vats of cells.
Officials say they already have two candidate vaccines for people that appear to be well-matched to the bird flu virus in U.S. dairy herds. The Centers for Disease Control and Prevention used the circulating bird flu virus as the seed strain for them.
The government has hundreds of thousands of vaccine doses in pre-filled syringes and vials that likely could go out in a matter of weeks, if needed, federal health officials say.
They also say they have bulk antigen that could generate nearly 10 million more doses that could be filled, finished and distributed in a matter of a few months. CSL Seqirus, which manufactures cell-based flu vaccine, this week announced that the government hired it to fill and finish about 4.8 million of those doses. The work could be done by late summer, U.S. health officials said this week.
But the production lines for flu vaccines are already working on this fall's seasonal shots work that would have to be interrupted to produce millions more doses of bird flu vaccine. So the government has been pursuing another, quicker approach: the mRNA technology used to produce the primary vaccines deployed against COVID-19.
These messenger RNA vaccines are made using a small section of genetic material from the virus. The genetic blueprint is designed to teach the body how to make a protein used to build immunity.
The pharmaceutical company Moderna already has a bird flu mRNA vaccine in very early-stage human testing. In a statement, Moderna confirmed that we are in discussions with the U.S. government on advancing our pandemic flu candidate."
Similar work has been going on at Pfizer. Company researchers in December gave human volunteers an mRNA vaccine against a bird flu strain that's similar to but not exactly the same as the one in cows. Since then, researchers have performed a lab experiment exposing blood samples from those volunteers to the strain seen in dairy farms, and saw a notable increases in antibody responses," Pfizer said in a statement.
As for the vaccine for cows, Penn immunologist Scott Hensley worked with mRNA pioneer and Nobel laureate Drew Weissman to produce the experimental doses. Hensley said that vaccine is similar to the Moderna one for people.
In first-step testing, mice and ferrets produced high levels of bird flu virus-fighting antibodies after vaccination.
In another experiment, researchers vaccinated one group of ferrets and deliberately infected them, and then compared what happened to ferrets that hadn't been vaccinated. All the vaccinated animals survived and the unvaccinated did not, Hensley said.
The vaccine was really successful, said Webby, whose lab did that work last year in collaboration with Hensley.
The cow study will be akin to the first-step testing initially done in smaller animals. The plan is for initially about 10 calves to be vaccinated, half with one dose and half with another. Then their blood will be drawn and examined to look for how much bird flu-fighting antibodies were produced.
The USDA study first will have to determine the right dose for such a large animal, Hensley said, before testing if it protects them like it did smaller animals.
What scares me the most is the amount of interaction between cattle and humans, Hensley said.
Were not talking about an animal that lives on a mountain top," he said. "If this was a bobcat outbreak Id feel bad for the bobcats, but thats not a big human risk.
If a vaccine reduces the amount of virus in the cow, then ultimately we reduce the chance that a mutant virus that spreads in humans is going to emerge, he said.
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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institutes Science and Educational Media Group. The AP is solely responsible for all content.
The outbreak has been ongoing since February 2022
The H5N1 bird flu virus has spread to dairy cows in the United States, raising concerns about its spread to humans, reported Reuters.
Since 2022, bird flu in the US has infected over 90 million chickens, more than 9,000 wild birds, 67 dairy herds, oneperson who was exposed to poultry andthree people who werein close contact with an infected cattle.
The following is a timeline of the current outbreak in the country:
May 30
A third US dairy worker tested positive for bird flu in 2024 after exposure to infected cows, and was the first to suffer respiratory problems. The infection was the second human case in the state of Michigan.
May 22
Another human case of bird flu is confirmed in the US with the infection of a dairy worker in Michigan. It is the second case in humans this year after the virus was detected in cattle.
April 26
Colorado became the ninth US state to report an infected dairy herd.
April 25
Colombiarestricted the import of beef and beef products coming from US states due to bird flu in dairy cows.
April 24
The US government said it will require dairy cattle moving between states to be tested for bird flu.
April 23
The US Food and Drug administration said it had found bird flu virus particles in some samples of pasteurized milk, but said the commercial milk supply remains safe due to pasteurization.
April 11
South Dakota became the eighth US state to find avian influenza in a dairy herd, after the U.S. Department of Agriculture (USDA) reported infections in North Carolina, Texas, Kansas, Ohio, Michigan, Idaho and New Mexico.
April 4
Bird flu dairy cow outbreak widened to a dairy herd in Ohio.
April 2
Mexico's agriculture ministry said it was taking preventative measures to increase surveillance and reinforce inspections of US livestock imports after bird flu was found in dairy cattle there.
April 1
The second known human case of bird flu in the United States is reported in a person from Texas who had contact with dairy cows presumed to be infected with the virus.
The virus was detected in dairy cattle in New Mexico, Michigan and Idaho, along with Texas and Kansas.
March 25
The USDA said samples of milk collected from sick cattle in Kansas and Texas tested positive for avian flu, but the nation's milk supply was safe.
Dec. 12, 2023
Egg producer Cal-Maine Foods CALM.O said it had temporarilyceased production at a facility in Kansas after some of the flock tested positive for avian flu.
Nov. 3, 2023
Arkansas, a major US chicken producer, reported its first outbreakof lethal avian flu in a commercial poultry flock in a year.
Oct. 6, 2023
The United States detected its first case of avian flu on a commercial poultry farm since April, in a flock of 47,300 turkeys in Jerauld County, South Dakota.
April 14, 2023
The US government said it was testing four potential bird flu vaccines for poultry, after more than 58 million chickens, turkeys and other birds had died in the nation's worst outbreak ever.
March 20, 2023
Some of the world's leading makers of flu vaccines say they could make hundreds of millions of bird flu shots for humans within months if a new strain of avian influenza ever jumps across the species divide.
Oct. 7, 2022
Avian flu infected a commercial flock of breeding chickens in Arkansas, widening an outbreak of the disease in the southern region.
Nationwide, more than 47 million birds have been killed by avian flu or culled to control its spread this year in the nation's worst outbreak since a record 50 million birds were wiped out in 2015.
April 29, 2022
The first known human case of H5N1 bird flu in the United States appeared in a person in Colorado, who was involved in culling birds at a commercial poultry facility.
March 7, 2022
More than 22 million commercially raised US chickens and turkeys have been killed since February 2022 due to outbreaks of a highly lethal type of bird flu.
March 4, 2022
A bird flu outbreak is reported in a commercial flock of chickens being raised for meat in Stoddard County, Missouri, taking the spread of the virus to 10 commercial chicken and turkey farms in four states.
Feb. 9 , 2022
The USDA reported an outbreak of highly pathogenic avian flu in an Indiana turkey flock, the nation's first case in a commercial poultry operation since 2020.
A third person in the United States has tested positive for avian influenza, aka bird flu, amid an ongoing outbreak affecting poultry and dairy cattle.
The case was detected in a farmworker in Michigan who was exposed to sick cows, the U.S. Centers for Disease Control and Prevention said on Thursday.
Since March, a highly contagious strain of avian influenza A (H5N1) has spread to over 60 dairy cattle herds in nine U.S. states. In addition to the three human cases in the U.S., a child in Australia was also recently infected with bird flu.
Bird flu is a disease caused by infection with avian influenza A viruses, which occur naturally among wild aquatic birds and circulate among poultry, TODAY.com previously reported.
Occasionally, bird flu viruses spread to mammals, and rarely, to humans. The highly pathogenic H5N1 strain causing the U.S. outbreak is severe and often fatal in birds, but appears to be mild in cows.
No known human-to-human spread has occurred with the current H5N1 strains, per theU.S. Centers for Disease Control and Prevention. The risk to the general public is low, but the outbreak has sounded the alarm among health officials in the U.S. and abroad, who are monitoring bird flu viruses closely.
The latest case marks the second farmworker in Michigan to test positive in one week and the third human case detected in the U.S. in the last two months. None of the three cases are connected and all occurred at different farms, the CDC said.
The first human case associated with the multi-state H5N1 outbreak among cows was reported in a dairy worker in Texas in March. It was the first time this strain of H5N1 referredto ashighly pathogenicavian influenza A (HPAI) had been detected in cows and the first instance of cow-to-human transmission, according to the CDC.
The current bird flu strain that were concerned with, H5N1, has been circulating around the world for quite some time, Dr. William Schaffner, professor of infectious diseases at Vanderbilt University Medical Center, previously told TODAY.com.
The Texas dairy worker and the first farmworker in Michigan to test positive both reported pink eye as their only symptoms. The third patient also had eye symptoms, as well as a cough and fever, officials said. The second patient in Michigan is the first to report upper respiratory symptoms associated with the bird flu infection.
"Based on the information available at this time, this case does not change CDCs current A(H5N1) bird flu human health risk assessment for the U.S. general public. The risk to members of the general public who do not have exposure to infected animals remains low," the CDC said.
Bird flu infections in humans can range in severity, experts note. Some people have no symptoms at all or only a mild flu-like illness, while others develop severe disease requiring hospitalization, according tothe CDC.
It can be a serious infection with a high mortality rate, said Schaffner.
According to the CDC, reported signs and symptoms of bird flu include:
Bird flu in humans may look similar to seasonal influenza flu or upper respiratory infection. In severe cases, bird flu can lead to pneumonia, respiratory failure and other complications, TODAY.com previously reported.
The recent case of H5N1 in the child in Australia was a severe infection, but the child fully recovered. Victorian health officials did not release additional details about the patient's symptoms.
The dairy worker in Texas who tested positive for H5N1 in March had a mild infection, with eye redness or conjunctivitis (pink eye) as the only symptom,the CDC said. The patient was treated with flu antivirals and recovered.
Similarly, the first farmworker in Michigan who tested positive for H5N1 only reported eye symptoms, per the CDC.
The third farmworker who tested positive reported eye symptoms, including discomfort and watery discharge, a cough, and a fever. They are being treated with antivirals and recovering, the CDC said.
The only other human case of H5N1 in the U.S., which was reported in Colorado in 2022, was a mild infection as well.
An infection with bird flu viruses cannot be diagnosed by signs or symptoms alone, the CDC says. Laboratory testing is required.
Transmission of bird flu viruses to humans is very rare. According to the WHO, since 2003, there have been 889 cases and 463 deaths caused by H5N1 in 23 countries.
Avian influenza can spread from infected birds to humans in a few ways, per the CDC:
Infected birds can shed the virus in their saliva, nasal secretions, mucus and feces, TODAY.com previously reported. People can become infected when the virus particles get into the mouth, nose, eyes or are inhaled, says Schaffner.
Humans typically become infected with bird flu viruses through close, unprotected contact with an infected bird.
When it comes to the dairy workers with conjunctivitis, the CDC noted it's press release that "it's not known exactly how eye infections result from avian influenza exposures."
"It may be from contamination of the eye(s), potentially with a splash of contaminated fluid, or touching the eye(s) with something contaminated with A(H5N1) virus, such as a hand. High levels of A(H5N1) virus have been found in unpasteurized milk from H5N1-infected cows."
Human-to-human transmission of bird flu viruses is extremely rare. The few cases that have been documented have occurred primarily through prolonged, unprotected contact between a symptomatic person and a family member or caregiver, per the CDC.
"The virus doesnt have the (genetic) capacity to spread easily from person to person, says Schaffner.
However, in arecent press conference, the chief scientist of the World Health Organization called the risk of the bird flu spreading to humans an enormous concern, and warned about the potential for the virus to acquire the ability to spread more efficiently between people. Scientists are closely monitoring bird flu viruses for any changes.
There is no evidence that humans can get bird flu from chicken, eggs, or beef that's been properly prepared and cooked, and it is safe to drink pasteurized milk, experts say.
The risk of getting bird flu is low, but the CDC recommends people:
Caroline Kee is a health reporter at TODAY based in New York City.
By Michelle Jokisch Polo
Another dairy farm worker in Michigan is testing positive for bird flu, making it the third human case in the U.S. this year.
Michigan confirmed its first human case of bird flu last week amid a multi-state outbreak of the virus in poultry and dairy herds.
The countrys first case was reported in Texas in March.
State health officials say the most recent case occurred in a farmworker who had been working closely with an infected cow before developing symptoms.
This individual had respiratory symptoms and is recovering, which is a very positive sign. This individual did receive Tamiflu, Michigans Chief Medical Executive Dr. Natasha Bagdasarian told WKAR.
The Michigan Department of Health and Human Services has not confirmed the specific location of the states two infections but did say the farm workers were employed at two different facilities.
Bagdasarian said the states first case of bird flu resulted from a direct splash of milk from an infected cow directly into the eye. The farm worker subsequently displayed symptoms of an eye infection.
What we are seeing is that these are individuals who have direct, close contact with infected animals, said Bagdasarian. It really shows us that personal protective equipment is helpful in keeping individuals working on dairy and poultry farms safe.
Bagdasarian said the state health department is monitoring symptoms and testing workers at affected cattle and poultry farms.
According to the U.S. Agriculture Department, 66 dairy cattle herds in nine states have confirmed cases of the H5N1 virus responsible for bird flu.
In Michigan, nearly seven million livestock have been affected by the virus. State food and agricultural regulators say they are responding with a one-health approach.
"Proper use of personal protective equipment is the best tool we have to protect farm workers, said Michigan Department of Agriculture and Rural Development (MDARD) Director Tim Boring in a statement. MDARD is currently offering assistance to dairy farms in need of additional protective equipment. MDARD has and will continue to take bold actions to assist farms impacted by this disease."
Neither individual who tested positive for the bird flu in Michigan was wearing a mask before developing symptoms, according to state health officials.
Some migrant farmworkers in Michigan have voiced concerns to labor advocacy groups about the lack of personal protection equipment available at sites. Many worry that they will not be able to access paid sick leave if they are infected with bird flu.
Were hearing the need for these kinds of protections, anxiety over being able to take work off and lose pay if they are exposed to the bird flu and face health complications, said Diego Iiguez-Lpez, the government affairs director for the United Farmworkers Foundation.
A third person has tested positive for the H1N5 (bird flu) virus and is the first to suffer from respiratory problems, according to Reuters.
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The dairy worker was exposed to infected cows, the Centers for Disease Control and Prevention said, and was the second case of human infection in Michigan.
According to the CDC, the other two workers infected had only conjunctivitis pink eye not respiratory problems.
The person is isolating at home, the CDC said, and their symptoms are resolving. The persons contacts are also being monitored.
Since March, the avian flu in dairy cattle has affected 67 herds in nine states. The worker was employed at a different farm than the previous case in Michigan that was reported on May 22, the state said.
The U.S. government is collecting samples of ground beef at retail stores in states with outbreaks of bird flu in dairy cows, the U.S. Department of Agriculture said.
In addition, remnants of the virus were found in milk from some of those cows that was on grocery store shelves.
The U.S. Food and Drug Administration said on Friday that preliminary results of PCR (Polymerase chain reaction) tests showed pasteurization killed the bird flu virus in milk, though.
On April 16, the USDAs Animal and Plant Health Inspection Service microbiologists identified a shift in an H5N1 sample from a cow in Kansas that could indicate that the virus has an adaptation to mammals, according to a statement from the USDA.
The Centers for Disease Control and Prevention conducted further tests of the specimen sequence and said the overall risk factor of the virus infecting the general public had not changed.
The shift has been seen previously in other mammalian infections and it did not impact viral transmission, the agency said.
The lab, which tests animal samples from across the country, offers a peek at how scientists are racing to learn more about the virus, which experts are concerned may one day evolve to more easily infect people.
Its still very much an open question, scientifically: Whats going to happen as this virus continues to evolve and spread through animal populations? Runstadler said.
On Thursday, Michigan state officials confirmed the third human case of H5N1 in the US this year, in a farm worker exposed to infected cows. The worker had respiratory symptoms, a first for humans exposed to infected cattle, and is recovering.
Officials around the country are on high alert for new cases. Last month, the CDC asked state and local public health officials to keep flu monitoring efforts high throughout the summer to quickly detect any uptick in human illness. The agency also launched a dashboard that tracks Influenza A viruses H5N1 is part of that virus family in wastewater samples from across the country to pinpoint transmission hotspots.
Runstadlers work is an important piece of this broader monitoring effort. The lab tests a wide range of animals in hopes of catching H5N1 cases that might otherwise go undetected. One of their concerns is that the virus might make its way into an animal host that doesnt show any symptoms. There, the virus could develop more worrisome mutations, such as those that may promote adaptation to mammals.
Those are the places where viruses can evolve and circulate, because nobody had an eye on the ball, said Wendy Puryear, a virologist in Runstadlers lab.
Bird flu isnt new for Runstadler and his team. He formed his lab two decades ago to study flu viruses in animals. In 2013, the group began monitoring seals and, in the summer of 2022, became the first to identify and investigate the deaths of more than 180 gray and harbor seals from H5N1 off the coast of Maine.
The seal deaths concerned scientists because they were among the first signs that this strain of H5N1 could devastate mammals. Since then, the virus has killed tens of thousands of sea lions and seals in South America, and, more recently was detected in more than 60 dairy herds in nine states.
The lab is part of a network of Centers of Excellence for Influenza Research and Response, funded by the National Institutes of Health. Its one of less than a dozen network members that conduct wildlife surveillance and even fewer that conduct sampling as broad as Tufts, said Puryear.
The question that members of the Runstadler lab are now asking is whether any new wild birds and mammals are being infected along the East Coast and across the country. The team has tested around 10,000 bird and 2,500 mammal samples 1,000 of which are from marine mammals since the virus hit the United States in 2022.
The lab routinely finds positive H5N1 cases in birds, though they havent identified any mammals who have contracted the virus since the seal deaths in the summer of 2022. The USDA, however, has confirmed bird flu cases in over 200 mammals across the country including foxes, mountain lions, raccoons, and bears. The Runstadler lab has not tested any cattle, a process that is largely being handled by state and federal agencies, Puryear said.
In April, Runstadler traveled to a beach in Swampscott to swab a beached humpback whale. Though the large mammal tested negative for H5N1, whales have been shown to contract other types of influenza.
Bird samples are shipped to the lab from collaborators in New England and from as far south as Virginia. Samples from marine mammals come from Maine as well as Florida, California, Alaska, and even Hawaii. Lab members prepare care packages that include swabs, personal protective equipment, shipping materials, and instructions to help collaborators collect samples safely. Swabs arrive at the lab in small screw-cap tubes with a pink-colored liquid that helps preserve the samples. The tubes are placed inside Ziploc bags and packed in ice.
When a sample tests positive for H5N1, Puryear and her colleagues notify the submitter to warn them about potential contact with infected animals. They then send the sample to a USDA lab for confirmation. Either the Runstadler lab or a lab at the Icahn School of Medicine at Mount Sinai in New York City then sequences the RNA, or genetic information, of the virus to see if there are any changes in its code. A computer identifies abnormalities like an A in the genetic code changing to a C and the string of letters is uploaded to an online database. There, scientists across the world can access the sequences to pin down if and how the virus might be evolving.
One concerning mutation, which makes the H5N1 virus better at copying itself inside of mammal cells, was detected in a seal the Runstadler lab tested in the summer of 2022. The mutation, called PB2 E627K, has also emerged in multiple mammals who contracted H5N1 in recent years and, in a paper published in the New England Journal of Medicine earlier in May, scientists reported the human who contracted H5N1 in Texas had also acquired the PB2 E627K mutation.
While that mutation is on scientists radars, they stress the virus would need additional genetic changes to promote spread between humans. In early April, the CDC said the presence of the mutation in the Texas farm worker did not change their assessment that the current risk of H5N1 to human health is low.
I think one of the things thats very valuable about their work is that its been continuous over time, said Ana Silvia Gonzalez-Reiche, a virologist at Mount Sinai who collaborates with the Runstadler lab. Throughout the years, they have accumulated a lot of data, and the value of that is that you can start seeing patterns and learning.
Puryear and her colleagues dont always know what samples theyre going to get in the mail on any given day. Around 11 a.m. on a recent Wednesday, a delivery man entered with the days packages. Puryear grabbed one a cardboard box branded with a pet food logo that had been repurposed to transport animal samples and placed it on the fridges bottom shelf.
The next day, the team tested the boxs contents. One of the samples, belonging to a crow from Cape Cod, came back positive for H5N1.
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Posted: May 30, 2024
Another Michigan dairy worker has been diagnosed with bird flu, the third human case associated with an outbreak in U.S. dairy cows, health officials said Thursday.
The patient reported a cough and eye discomfort, unlike the other two workers, who had only eye symptoms, health officials said. The farmworker was quickly provided antivirals and is recovering from respiratory symptoms, Michigan health officials said.
The risk to the public remains low, although farmworkers exposed to infected animals are at higher risk, health officials said. The Michigan cases occurred on different farms and there are no signs of spread among people, officials said.
"Risk depends on exposure, and in this case, the relevant exposure is to infected animals," the U.S. Centers for Disease Control and Prevention said in a statement.
In late March, a farmworker in Texas was diagnosed in what officials called the first known instance globally of a person catching this version of bird flu from a mammal.
Last week, Michigan officials announced the first case there. That worker developed eye symptoms after "a direct splash of infected milk to the eye," Michigan health officials said in a statement.
Neither of the Michigan workers was wearing face shield or other personal protective equipment, which "tells us that direct exposure to infected livestock poses a risk to humans, and that PPE is an important tool in preventing spread among individuals who work on dairy and poultry farms," Dr. Natasha Bagdasarian, the chief medical executive of Michigan's health department, said in a statement.
Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization (VIDO) at the University of Saskatchewan, studies H5N1 bird flu.
"H5N1 is a clear occupational risk to dairy workers and this highlights the importance of detecting new cases as early as possible, so we can understand how to reduce risks to both cows and the people who are working with them," Rasmussen said.
"In Canada, it's important we remain vigilant for introduction to cattle here, for the safety of cows and the milk supply, as well as the safety of workers and producers."
There is no evidence that the risk to the general population has increased in Canada, Rasmussen added.
Health Minister Mark Holland told reporters on Thursday that Canada has no cases of H5N1 in cows and none has been found in the commercial milk supply.
Since 2020, a bird flu virus has been spreading among more animal species including dogs, cats, skunks, bears and even seals and porpoises in scores of countries.
As of Thursday, H5N1 has been confirmed in 66 dairy herds in nine states, according to the U.S. Agriculture Department.
Michigan will soon begin testing dairy farmworkers for signs of prior infection with bird flu, a countyhealth official told Reuters.
The new case marks the fourth time a person in the United States has been diagnosed with what's known as Type A H5N1 virus.
In 2022, a prison inmate in a work program picked it up while killing infected birds at a poultry farm in Montrose County, Colo. His only symptom was fatigue, and he recovered. That predated the virus's appearance in cows.
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute's Science and Educational Media Group. The AP is solely responsible for all content.
Study design and participants
This cross-sectional study was conducted on COPD inpatients infected by SARS-CoV-2 at Afzalipour Hospital, Kerman, Iran, from January to July 2022. According to reference [14], in people with COVID-19, the frequency of eosinopenia was 53%, with an error of d=0.3, p=0.05 and =0.05, the sample size was equal to 50 people using the sample size formula for a population. In order to improve the results, increase the statistical power of the test and the possibility of dropping samples, 100 people were examined. Then six patients declined to participate in study and four patients had left the hospital with satisfaction. After that, 49 and 41 people were allocated to non-eosinophilia and eosinophilia group. 11 people in non-eosinophilia group and 6 people in eosinophilia group were lost to follow-up. Finally, 73 people remained in the study (38 in non-eosinophilia and 35 in eosinophilia group) (Fig. 1).
The patients were selected by random sampling. The inclusion criteria were age 40 years and older, positive throat and nose reverse transcriptase polymerase chain reaction (RT-PCR) test for COVID-19, history of COPD, and informed consent to enter the study. Also patients with clinical signs of pneumonia (i.e., fever, cough, and dyspnea) and SPO2 90% on room air were classified as non-severe cases and patients with clinical signs of pneumonia (i.e., fever, cough, and dyspnea) and at least one of the following signs were classified as severe cases: respiratory rate> 30 breaths/minute, severe respiratory distress, SpO2 < 90% on room air, shock, or other organ failures included in study. The exclusion criteria were known immunodeficiency (patients who used immunosuppressive drugs before the diagnosis of COVID-19), previous diagnosis or clinical symptoms consistent with asthma, cancer, oral corticosteroid use before hospitalization, and lack of cooperation or consent to participate in the study.
Immediately after positive PCR test, a 7-cc peripheral blood sample was taken from each hospitalized COPD patient infected by COVID-19 to test hematological parameters, including erythrocyte sedimentation rate (ESR), white blood cells (WBC), lactate dehydrogenase(LDH), D-dimer, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), platelets (PLT), neutrophils (NEUT%) and lymphocytes (LYMPH%). Peripheral blood slides were stained using Giemsa staining to determine the eosinophil percentage. Oxygen saturation on admission and discharge days (SPO21 and SPO22, respectively) was measured by pulse oximetry when the patient did not receive oxygen therapy.
The patients demographic information, including age, gender, history of smoking and inhaling opium, past medical history, oxygen therapy methods, CT scan information, and treatment outcomes, was extracted from patients records.
Chest CT was performed using a Philips Diamond Select Brilliance CT scanner (made in the USA). The radiologists reported the CT scans, then an expert pulmonologist who was blinded to the patients laboratory results, read and reported all the CT scans based on the scoring of reference [19].
The severity of pulmonary involvement was determined based on chest CT severity score (CT-SS) (based on the degree of involvement of the lung lobes, 0%: 0 points, 125%: 1 point, 2650%: 2 points, 5175%: 3 points, and 76100%: 4 points). The CT-SS was the sum of the scores of the five lobes (range 020) [19].
According to the WHO disease severity classification, patients were divided into severe and non-severe COVID-19 groups. Patients with clinical signs of pneumonia (i.e., fever, cough, and dyspnea) and SPO2 90% on room air were classified as non-severe cases and patients with clinical signs of pneumonia (i.e., fever, cough, and dyspnea) and at least one of the following signs were classified as severe cases: respiratory rate> 30 breaths/minute, severe respiratory distress, SpO2 < 90% on room air, shock, or other organ failures [20].
Eosinophilia was defined as eosinophil levels 2% and non-eosinophilia as eosinophil levels< 2%.
This study has been approved by the ethics committee of Kerman University of Medical Sciences (Code: IR.KMU.AH.REC.1400.254). Written informed consent was obtained from each participant.
Descriptive statistics (frequency, relative frequency, mean, and standard deviation), analytical statistics (chi-square test and independent t-test), and SPSS software version 20 were used to analyze the data. The significance level considered was P 0.05.
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Research strands involving decades of work on a wide assortment of diseases collidedsuccessfullyrecently when news came out that an old vaccine against tuberculosis (TB) being tested for its potential utility in treating type 1 diabetes (T1D), was also effective in warding off COVID-19 infection. Authors reported their findings in iScience.1
The Bacillus Calmette-Gurin (BCG) vaccine has been given for about a century in most non-Western nations to children to prevent TB. For just about as long, scientists suspected that BCG could offer wider anti-infection protection, and as the years progressed, these off-target benefits began being considered more carefully and then more formally researched.2 For instance, in the 1980s, patients with bladder cancer began receiving BCG to boost their immune systems.
One research team began focusing on potential benefits to individuals with T1D. In 2012, the results of a proof-of-concept trial showing that BCG could help treat T1D were published.3
After the COVID-19 pandemic began, the same team decided to launch randomized double-blinded placebo-controlled trials to test the ability of BCG to ward off COVID-19 infection in their study participants with T1D. Results of their phase 2 trial showedalmost full protection against COVID-19 in the BCG group (92% vs placebo; P = .0036)
The phase 3 trial had 2 coprimary outcomes: to see if at-risk US adults with T1D were protected against COVID-19 and other viral, bacterial, and fungal diseases by taking multiple (5 or 6 over a 2-year period) doses of powerful Tokyo-strain BCG. The results, just published, show that those outcomes were both met, with significantly high levels of protection against COVID-19 (P = .023) and all infectious diseases (P < .0001).
Whats more, in this population, particularly vulnerable to infectious disease, it had been shown that no standard COVID-19 mRNA vaccine alone provided sufficient protection from COVID-19 (P = .43). Those vaccines also neither helped nor hindered the COVID-19 protection offered by BCG.
The time element. If BCG is so effective against COVID-19, why was it not heralded as a pandemic hero? When administered intradermally to adults who have never taken BCG before, it takes at least 2 years to achieve full protection for many off-target effects. The patients in the trials had already been taking BCG (or placebo) experimentally when the pandemic, and the COVID-19focused research, began.
Denise Faustman, MD, PhD | Image Credit: Mass General Research Institute
Given mRNA vaccinations lack of efficacy for those with T1D, an unmet need remains, especially as it relates to new and emerging SARS CoV-2 variants, the authors stated. As the pandemic continues to evolve, it will be interesting to see if we can work with the FDA to allow access to BCG vaccine for [patients with] T1D who appear to be particularly at risk for all infectious diseases, said senior author Denise Faustman, MD, PhD, in a statement.The BCG vaccine offers the prospect of near-lifelong protection against every variant of COVID-19, the flu, respiratory syncytial virus, and other infectious diseases.4
The authors pointed out that BCG is heralded as the safest vaccine in continuous use globally[and] is designated an essential medicine by the World Health Organization. Its a live but weakened version ofMycobacterium bovis, a bacterium related to M tuberculosis, which causes TB. The off-target effects in adults of BCG vaccination, explained the authors, are caused by changes in DNA methylation of genes of the innate and adaptive immune system and of metabolism pathways. Signaling pathways become rewired in a time frame that correlates with the slow but durable clinical improvements.
References
1. Khtreiber WM, Hostetter ER, Wolfe GE, et al. Late in the US pandemic, multi-dose BCG vaccines protect against COVID-19 and infectious diseases. iScience. Published online May 22, 2024. doi:10.1016/j.isci.2024.109881
2. Keener AB. A repurposed TB vaccine shows early promise against diseases like diabetes and MS. Science News. June 2, 2021. Accessed May 29, 2024. https://www.sciencenews.org/article/bcg-tb-vaccine-diseases-diabetes-multiple-sclerosis
3. Faustman DL, Wang L, Okubo Y, et al. Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes. PLosOne. 2012;7(8):e41756. doi:10.1371/journal.pone.0041756
4. Brown N. Century-old vaccine protects type 1 diabetics from infectious diseases. News release. Massachusetts General Hospital. May 23, 2024. Accessed May 29, 2024. https://www.massgeneral.org/news/press-release/century-old-vaccine-protects-type-1-diabetics#:~:text=BOSTONIn%20new%20research%20investigators,disease%20and%20other%20infectious%20diseases
