In a recent article published inPLOS ONE, researchers designed five deoxyribonucleic acid (DNA) vaccine candidates based on different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. They evaluated the immunogenicity of each in mice.
Study:Evaluation of immunogenicity-induced DNA vaccines against different SARS-CoV-2 variants. Image Credit:M-Foto/Shutterstock.com
A safe and effective vaccination strategy is the key to combating SARS-CoV-2, the virus that caused the coronavirus disease 2019 (COVID-19) pandemic, which led to worldwide lockdowns, socioeconomic disruption, and an unprecedented threat to public health.
In the past, heterologous vaccination strategies have successfully combated many deadly diseases, such as malaria, influenza, and human papillomavirus.
Studies have shown that different vaccine platforms, such as DNA, adenoviral vectors, modified vaccinia Ankara viral vectors, and recombinant subunit vaccines, significantly increase humoral and cellular immunity.
In their previous study, researchers found DNA vaccine candidates safe, stable (at room temperature), and more convenient to store and ship than other vaccine platforms; thus, they seem apt for emergencies like the one induced by the COVID-19 pandemic.
DNA vaccines also elicit robust humoral and cellular immune responses. However, they often do not induce significant clinical benefits.
Given the proven benefits of homologous and heterologous vaccination against SARS-CoV-2, researchers tested the effectiveness of a prime-boost regimen of five DNA vaccines they developed against SARS-CoV-2 in a mouse model.
These newly developed vaccine candidates were based on the first genotype spike (S), which includes the Wuhan strain, the first ever SARS-CoV-2 strain isolated in Korea, and the Alpha, Beta, Gamma, and Delta variants, which are classified as SARS-CoV-2 variants of concern (VOCs) by the World Health Organization (WHO).
They intramuscularly (i.m) vaccinated mice with these DNA vaccine candidates to assess their immunogenicity based on elicited cellular and humoral immune responses.
For humoral immunogenicity evaluation, they drew the blood of vaccinated mice one week after the last vaccination dose. The sera of vaccinated test animals were analyzed for SARS-CoV-2 specific total immunoglobulin G (IgG) and its subtypes using enzyme-linked immunosorbent assay (ELISA).
Then, they calculated the total IgG titers as half maximal effective concentration (EC50) while determiningP-values using one-way ANOVA with Fishers LSD test. They also calculated the ratios of IgG2b and IgG2c to IgG1.
Additionally, they used a plaque reduction neutralization test (PRNT) to analyze neutralizing antibody (nAb) levels in the sera of the vaccinated animals; further, they foundP-values using a two-way analysis of variance (ANOVA) with Tukeys test.
A surrogate virus neutralization test (sVNT) helped test mice sera for their neutralization rate, wherep-values were determined using one-way ANOVA with Dunnetts test.
Furthermore, the researchers evaluated cell-mediated immune responses elicited in response to all five DNA vaccine candidates a week after the last vaccination.
To this end, they collected mice splenocytes and tested them using a spike glycoprotein peptide pool against unstimulated cells.
To evaluate cross-vaccination immunogenicity, the researchers autopsiedmice one week after the final vaccination; further, they isolated their splenocytes to measure the levels of secreted cytokines using ELISpot compared to the unstimulated group.
The authors noted that the mice vaccinated with DNA vaccine candidates based on the S genotype, Alpha, and Beta variants had higher nAb and total IgG levels than the others.
Exceptionally, the Alpha variant-based vaccine candidate elicited a strong and diverse cytokine response.
Additionally, splenocytes of all test mice showed high levels of cytokines, such as interleukin-6 (IL-6), IL-13, and interferon-gamma (IFN-), while the Alpha variant-based DNA vaccine also elicited more tumor necrosis factor- (TNF-) levels.
In mice vaccinated with homologous vaccination based on Alpha VOC, higher levels of IL-6 and IL-13 were associated with reduced angiotensin-converting enzyme-2 (ACE2) expression and increased SARS-CoV-2 entry via the nasal and bronchial epithelium. In addition, these mice displayed increased TNF- levels than the other groups.
Furthermore, mice vaccinated with S/S and S/Alpha showed markedly increased levels of T helper cells (Th1) and Th2-secreted cytokines, IFN-, and IL-6/13, suggesting that DNA vaccine candidates drive strong T cell responses by balancing cytokine levels.
Overall, the study results suggested that the efficacy of DNA vaccine candidates was variant-dependent, with vaccines based on the S and Alpha variants enhancing higher immune responses than the other vaccines.
The results, however, remained the same regardless of boosting with heterologous or homologous vaccines.
Thus, whether receiving a homo- or heterologous regimen, recipients of these vaccines require prolonging the elicited immune response (by booster vaccination) to achieve adequate protective efficacy against SARS-CoV-2.
Further research should identify which vaccination strategies are optimal for long-term immunity and which T resident memory cells contribute most to confer protection against SARS-CoV-2.
Brazzaville The quest to protect Africa from vaccine-preventable diseases has received a significant boost, with the commitment of Gavi, the Vaccine Alliance to invest US$ 1.8 billion to support African vaccine manufacturing, catching up missed children and pandemic preparedness.
The decision taken last week by the Gavi Board at its meeting in Accra, Ghana will help the continent to recover from the impact COVID-19 pandemic and be better prepared to respond to future public health emergencies.
This commitment comes at an opportune time when the sub-Saharan African region is witnessing stalled progress in immunization coverage, with the number of African children missing routine vaccinations rising from 6.2 million in 2019 to 7.8 million in 2022, translating into 2.8 million zero-dose children from 2019 to 2022 cumulatively.
Furthermore, the establishment of the African Vaccine Manufacturing Accelerator (AVMA), a financing instrument that will make up to US$1 billion, will strengthen ongoing efforts towards local vaccine manufacturing and address vaccine equity gaps identified during the COVID-19 pandemic.
The pandemic highlighted beyond any doubt the critical importance of vaccination as a public health tool. This decision by the Board of Gavi will contribute significantly to saving lives and livelihoods, says Dr Matshidiso Moeti, the WHO Regional Director for Africa.
At the 2023 WHO Africa Regional Immunization Technical Advisory Group (RITAG) and the Immunization Stakeholders meeting, experts shared their commitment to advance efforts toward the attainment of global immunization. Therefore, through WHOs coordination role, the African Vaccine Regulatory Forum (AVAREF), which facilitated the regulatory environment required for COVID-19 vaccine rollout and the RITAG have been positioned and ready to support these commitments by Gavi for a deepened outcome.
The WHO Regional Office for Africa also welcomes the decision by Gavi to translate lessons learned from the COVID-19 pandemic into concrete public health interventions, with a US$ 500 million investment to ensure the availability of funds for a future pandemic.
The lessons learned from decades of fighting and preventing diseases, including most recently, COVID-19 have led to the vision and strategies, articulated in WHO Africa Regional Offices Ending Disease in Africa: vision, strategies and Special Initiatives, 2023-2030, which will drive the work moving forward, including the vital acceleration of immunization uptake across the region. Anchored on this new strategy, WHO has supported countries in Africa in the development of innovative country plans to catch up with children who missed routine immunization.
This new strategy aligns with Gavis focus on protecting the next generation particularly zero-dose children through strengthening regional and country capacities on immunization and other diagnostics and therapeutics.
For us as WHO, serving about a billion people in 47 African countries, we welcome the opportunity to strengthen our ongoing collaboration with Gavi, Africa CDC and other partners to translate this latest commitment into action towards ending diseases in Africa, Dr Moeti said.
For more information on the fight against diseases in Africa, see related links. Ending diseases in Africa Status of Immunization in Africa The roll-out of COVID-19 vaccines in Africa Country Profiles on Immunization Coverage in the African Region
Joy Behar has successfully avoided the COVID-19 virus until now.
The View host, 81, will be absent from a few episodes of the daytime talk show after contracting the virus for the first time ever, her co-host Whoopi Goldberg revealed on Tuesdays show, according to Entertainment Weekly.
"Joy is out this week. You know why? She finally got COVID," Goldberg told the audience. "Three years, four years in, it finally got her."
Fellow co-host Sara Haines added that Behar "can finally stop bragging now" that she never caught COVID-19 which is something she has mentioned on the show.
Yvette Nicole Brown took over the hosting duties from Behar on Tuesday, though it was unclear if she would stay in the seat for the rest of the week. Behar was also absent on Monday, though she typically takes that day off.
Lorenzo Bevilaqua/ABC via Getty
This isnt the first time that the daytime host has been absent due to the COVID-19. She previously took a few days off the show in 2020 at the height of the COVID-19 pandemic amid concerns of the virus spreading.
Im in a higher risk group because of my age, but Im perfectly healthy, Behar said of her decision to opt out of a few shows.
I dont look my age, but Im actually up there. The number makes me dizzy, added Behar, whose precautionary decision to stay home came at the urging of her daughter.
Several of The View hosts have previously tested positive for the virus or have had close calls in the past. Goldberg tested positive for the virus in January 2022 and then again a few months later in November 2022. The first time she tested positive, she noted that she had mild symptoms after being vaccinated and receiving the booster shot.
Sara Haines also was absent in January 2022 after having close contact with someone with the virus.
In 2021, Sunny Hostin and Ana Navarro were publicly pulled off The View stage after their COVID-19 test results showed up positive ahead of an appearance by Vice President Kamala Harris. Though their tests were later revealed to be false positives.
The View airs weekdays on ABC (check local listings).
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Planned Parenthood affiliates received $90 million in Paycheck Protection Program (PPP) loans meant for small businesses during the COVID-19 pandemic, according to a new report from the Government Accountability office (GAO) released Tuesday morning.
The PPP loans were designed to bail out small independent businesses with less than 500 employees. But pro-life advocates raised concerns with the Small Business Administration an independent government agency that supports entrepreneurs and argued that Planned Parenthood has more than 16,000 employees across the country, well above the cutoff to be considered a small business.
Sen. Marsha Blackburn, R-Tenn., one of the lawmakers who requested the report in January 2022, called the findings "appalling."
PLANNED PARENTHOOD ANNOUNCES RETURN OF ABORTION IN WISCONSIN AFTER KEY COURT RULING
Planned Parenthood signage is displayed outside of a health care clinic in Inglewood, California on May 16, 2023. (PATRICK T. FALLON/AFP via Getty Images)
"While small businesses struggled to make ends meet during the pandemic, Planned Parenthood illegally siphoned over $90 million from the Paycheck Protection Program, specifically designed to help our mom and pop shops keep their doors open," Blackburn said in a statement.
She added, "The American people want their tax dollars spent responsibly and in line with our nations values not on the Lefts abortion-on-demand agenda."
The report, also requested by New Jersey House Rep. Chris Smith, outlined federal funding received by several major pro-abortion organizations between 2019 and 2021 amounting to nearly $2 billion.
Smith said the PPP loans were "money that could have gone to struggling small businesses, many of which were forced to close."
"This money would have been better spent helping the businesses that were forced to close or providing comprehensive medical support for both women and children," Smith told Fox News Digital in a statement.
Aside from the PPP loans, government sources that funneled funds to the organization included Medicaid, Medicare, and Children's Health Insurance Program reimbursements, along with federal funding through grants and cooperative agreements amounting to $148.5 million.
Between 2019 and 2021, Planned Parenthood obtained $1.78 billion in government funding and executed one million abortion procedures, while International Planned Parenthood Federation received $2.03 million, MSI Reproductive Choices received $1.35 million, and four regional abortion providers got $107.74 million in funding.
PSAKI REPEATS CLAIM THAT DEMS DONT SUPPORT ABORTION UNTIL BIRTH: ENTIRELY MISLEADING
Sen. Marsha Blackburn, R-Tenn., questions Treasury Secretary Janet Yellen during a Senate Finance committee hearing about President Joe Biden's proposed budget request for the fiscal year 2024, Thursday, March 16, 2023, on Capitol Hill in Washington.
The report noted that in 2019, Planned Parenthood, under the Trump Administration's Protect Life Rule, declined Title X funding a federal grant program that provides funding for family planning and reproductive health services due to the rule's stipulation against abortion referrals and demanded financial separation from abortion providers.
The GAO found that Planned Parenthoods refusal to comply and forfeit its Title X funding "led almost all affiliates to discontinue using family planning grants under Title X" during 2020 and 2021.
From 2019 to 2021, Planned Parenthood conducted 1.11 million abortions while obtaining around $1.78 billion in federal funding, equating to an average of $592 million annually, according to the report.
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Planned Parenthood operates over 600 health centers across the United States.
Fox News Digital reached out to Planned Parenthood for comment.
Health
By Marc Lallanilla
Published Dec. 12, 2023, 12:19 p.m. ET
In the rush of holiday activities, you may have forgotten about COVID-19 but it hasnt forgotten about us.
New data from the Centers for Disease Control and Prevention reveal that as of November 25, there were almost 20,000 weekly hospitalizations due to the coronavirus, a jump of nearly 30% in just four weeks.
The rates of hospitalization typically a sign of severe, life-threatening infection have been highest among seniors ages 65 and older. Adults ages 50 to 64 were also hospitalized at rising rates, as were infants and children younger than four years old.
COVID has not disappeared, although it may have gone from many peoples minds, Dr. William Schaffner, professor at Vanderbilt University Medical Center, told ABC News. Im afraid the COVID virus is still very much with us.
One reason hospitalizations have jumped in recent weeks is because fewer people are getting vaccinated this year compared to earlier in the pandemic.
Over 94% of adults aged 65 and older have completed a primary series of the original vaccine, but just 33% of those seniors have received the updated vaccine, according to the CDC. And earlier vaccines have limited strength against newer variants of the coronavirus.
Many people, although they have been vaccinated in the past, have not taken advantage of this updated vaccine, Schaffner said. And the protection afforded by the previous vaccinations is now slowly declining. And so, we have a highly vulnerable population whose protection is slowly waning.
Moreover, people above the age of 50 are likely to have underlying health conditions and chronic diseases that leave them vulnerable to severe disease and hospitalization.
Infants and young children under age 4 have the third-highest rate of hospitalizations, according to the CDC, at 1.6% per 100,000 for the week ending December 2.
And young children have very low rates of vaccination, according to CDC data: Less than 7% of children ages six months to 17 years have received the updated vaccine as of November 25.
Experts believe that many people assume healthy children are immune to severe COVID-19 infection.
Everyone knows that children are less apt to be seriously affected by COVID infections than older adults, said Schaffner. The alternate concept that is hard for parents to grasp is that nonetheless, young children account for the third most common age group with hospitalizations.
Healthcare providers are concerned that as the holiday season continues, infections of COVID-19 and other respiratory illnesses will also continue to climb.
Past trends show that increases in severe illnesses and hospitalizations have occurred during the colder months when people stay indoors, close their windows and gather to celebrate the holidays, creating ideal conditions for respiratory viruses to spread, Dr. John Brownstein of Boston Childrens Hospital told ABC News.
As people gather for the holidays, its crucial to remain vigilant about COVID-19, especially in protecting vulnerable populations like the elderly and infants, Brownstein said.
Practicing good hygiene, such as regular hand washing, and staying home if feeling unwell are key. Additionally, ensuring proper ventilation in indoor spaces and considering wearing masks in crowded settings can significantly reduce the risk of transmission.
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New data shows that Americans living in four key states are suffering the highest prevalence of COVID-19 infections in the country, according to the Centers for Disease Control and Prevention (CDC).
Each week, the CDC produces a map of the U.S. showing the rates of people testing positive for COVID-19 after taking a test. The percentage of positive cases are subsequently calculated and shown on a map. Results are no longer provided for individual states, but are instead recorded as an average across various administrative regions.
The results come as winter tightens its grip across the country. Colder weather tends to lead to an increased spread in viruses and other infections, as immunity is lower. One 2020 study found the COVID-19 virus itself could remain active for longer in cold, dry conditions.
Region Sevenan administrative area consisting of Iowa, Missouri, Kansas, and Nebraskais once again at the top of this chart as it has the highest proportion of COVID-19 diagnoses following testing. That region saw the most cases out of the entire U.S. in last week's figures, too.
Published on Monday, but relating to the week through December 2, the latest results show that 16.7 percent of tests proved positive, out of 6,541 tests taken. Those figures are up 0.3 percent on the previous week's.
Last week, administrative area 5 (Ohio, Indiana, Illinois, Michigan, Wisconsin, Minnesota) and 8 (the Dakotas, Montana, Wyoming, Utah, Colorado) all saw COVID-19 diagnoses in between 10 percent and 14.9 percent of tests. Those regions saw similar figures this week.
However, the two areas have now been joined by another pair of administrative regions recording that percentage range of positive tests. That means yet more states that are experiencing higher COVID-19 results have been added to the map.
Administrative area 1 (Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, Vermont) and 3 (Delaware, District of Columbia, Maryland, Pennsylvania, Virginia, West Virginia) are now also recording percentages of between 10 percent and 14.9 percent of tests confirming COVID-19 cases. In the previous week's figures, all those states had between a 5 percent and 9.9 percent positive-test result rating.
A CDC spokesperson previously told Newsweek that fall marks the "typical start of the respiratory virus season" and said hospitalization rates "could increase" heading into the winter months.
Localized rises of COVID-19 cases through the summer prompted some private institutions, hospital operators and colleges in the U.S. to reintroduce the requirements for staff or visitors to wear masks while at their sites. Many of the institutions have since relaxed their mask mandates, although some hospitals in New Jersey later brought them back in response to infection rates.
Newsweek is committed to challenging conventional wisdom and finding connections in the search for common ground.
Newsweek is committed to challenging conventional wisdom and finding connections in the search for common ground.
Australia's eighth COVID-19 wave may be peaking, but people are being warned to be wary of the virus as the festive season ramps up.
But now that there are no hard and fast rules regarding isolation, what should you do if you get COVID-19?
Here's a quick refresh.
Australia's Chief Medical Officer Paul Kelly said the latest COVID wave has been less severe in terms of hospitalisation, but warned cases may rise.
"My sense is that we have probably peaked and will start to decrease [in cases]," Professor Kelly told ABC News Breakfast last week.
"[However] we are in the festive season and there are lots of parties and so forth so the possibility that transmission will happen is certainly there."
The amount of time someone remains infectious with COVID can be hard to pinpoint.
However, Adelaide epidemiologist Adrian Esterman says there is evidence that suggests people can shed virus particles between day seven and 10 from diagnosis.
"However, if symptoms have resolved [no coughing or sneezing], they would be less likely to infect others," Professor Esterman said.
Here's what a spokesperson from the federal Department of Health had to say:
"The infectious period is dependent on individual factors such as age, severity of illness, vaccination status, including time since last vaccination against COVID-19, and whether someone is immunocompromised.
"Some people can have a prolonged infectious period, however most people with mild-moderate illness are unlikely to be infectious for more than 10 days after symptom onset.
"Recent evidence suggests most children are likely no longer infectious by five days following a positive COVID-19 test."
Yes. They haven't changed since the start of the pandemic.
According to the department you can experience:
You're not required by law to isolate if you have COVID-19 symptoms, but it is strongly encouraged you stay at home.
Here's what the federal health website says to do if you test positive for COVID-19:
You should not visit high-risk settings like hospitals and aged and disability care settings:
To help protect those around you, we recommend:
If you do need to leave your home during the infectious period, Professor Esterman recommends wearing a P2/N95 mask to protect others.
A new vaccine targeting the Omicron subvariant XBB 1.5 is now available in pharmacies and GPs across Australia.
Three versions of XBB 1.5 is available:
Australian Medical Association vice-president Danielle McMullan said vaccines do take 7-14 days to reach full effectiveness so if you're due for a booster, now is the time.
"The new XBB vaccines recently approved by ATAGI are better targeted to the strains currently circulating in Australia and provide a modest improvement in immunity compared to previous vaccines," Dr McMullan said.
Eligibility varies based on age, other health conditions, how many vaccines you've already had and when, and whether you've recently had a COVID infection. The vaccine advisory group ATAGI explains in more detail on its website.
The federal government now reports COVID-19 case numbers via the National Notifiable Disease Surveillance System.
Between November 1 and November 30, 43,899 cases were reported across the country.
This is compared to 27,903 cases reported for the month of October.
One thing to keep in mind is the figures for November may lag due to backlogs in notifications from the states and territories.
The ABC has been monitoring the figures for November and they're still changing every day.
Here's the state by state breakdown of laboratory case numbers for November as of Tuesday, December 12:
Meanwhile, the latest national data on hospital admissions shows there were 118 people with COVID-19 admitted to hospitals in the seven days to December 4, with 54 of those cases in ICU.
Nothing puts a damper on your holiday plans like a positive
But what if that line is, like, super faint? Do you still have COVIDor can you go ahead and attend your office party like you planned?
Well, unfortunately, infectious disease experts stress that a faint line is definitely worth paying attention toalthough a re-test may be in your future.
Here's what you need to know.
Its probably not what youre hoping to hear, but a faint line on a COVID test means you have COVID-19. A faint line is a positive test result, says infectious disease expert Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security.
Thomas Russo, MD, a professor and chief of infectious diseases at the University at Buffalo in New York, agrees. A faint line means youre almost certainly positive, he says.
Kind of. If you test positivefaint or notit means that you have infectious COVID-19 particles in your body, Dr. Russo says.
But how dark the line is does give you a little insight into whats going on, Dr. Adalja says. The less dark, the line is, the less viral material that is present, he says. This could reflect diminishing contagiousness, or the start of it.
Meaning, you could be becoming more contagious or less contagious at that point, but a lot depends on the context. If youve been sick for a while and get a faint test result, it might mean youre getting better and are less likely to make others sick. If you just started feeling sick and you got a faint line, you likely only recently became infectious.
Remember, though, the CDC still advises staying home for five days after testing positiveor until you test negative.
It's also entirely possible that you just didnt get a great sample, which could lead to a faint line, Dr. Russo says.
Yes, it does. (Sorry.) Since home tests are not as sensitive as PCR testswhich are considered the gold standard of COVID-19 testinggetting a positive result still means that you have a fair amount of virus in your body, Dr. Russo says. A faint line means youre positive and infectious.
Lots of new COVID variants have emerged since home tests were created. And, FWIW, the most common variants in the U.S. right now include HV.1, JN.1, and EG.5, according to data from the Centers for Disease Control and Prevention (CDC). But doctors stress that home tests should still detect any new variant.
Why? A lot of changes in new variants have been on the spike protein, which SARS-CoV-2 (the virus that causes COVID-19) uses to latch onto your cells and infect you. The home tests are not based on the spike protein, Dr. Russo says. They detect nucleocapsid protein. The home tests should work for these new variants as well.
Dr. Russo also stresses this point: If you have symptoms of COVID-19 and test negative, it doesnt necessarily mean you dont have COVID. The sensitivity of these tests is 80 percent at best, he says. If the test is positive, you know you have COVID. If the result is negative, it doesnt necessarily mean you dont have COVID. (Usually for reasons like the sample you took wasn't the best or the amount of virus in your body isn't high enough yet.)
If you have symptoms and test negative, he suggests testing yourself again in 24 hours and seeing what you get. If youre still negative but feel sick, call your doctor. Its entirely possible that you have the flu, RSV, or something else.
Korin Miller is a freelance writer specializing in general wellness, sexual health and relationships, and lifestyle trends, with work appearing in Mens Health, Womens Health, Self, Glamour, and more. She has a masters degree from American University, lives by the beach, and hopes to own a teacup pig and taco truck one day.
By A.J. Hostetler
A simple, widely used test developed by a Virginia Commonwealth University researcher to predict advanced liver disease can also predict which COVID-19 patients might need a respirator, with patients higher on the scale almost twice as likely to need help to breathe.
In the Journal of Clinical and Translational Science, VCU researchers report their analysis of more than 232,000 hospitalized adults across the country who tested positive for the COVID-19 virus. Regardless of the variant of the virus, patients with higher levels on the FIB-4 index were more likely to end up on a respirator.
Patients infected with the initial SARS-CoV-2 virus that sparked the COVID-19 pandemic have a higher rate of respiratory failure, but recent variants are less likely to lead to hospitalization. Studies earlier in the pandemic hinted that the Fibrosis-4 index might also help evaluate COVID-19 patients. This new analysis dives deeper, exploring the role of the FIB-4 index in understanding risk factors and guiding treatment decisions over the COVID-19 variants.
FIB-4 stands the test of time and continues to find new applications, said Richard Sterling, M.D., chief clinical officer of VCUs Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, the lead for clinical and translational science pilot programs at VCUs C. Kenneth and Dianne Wright Center for Clinical and Translational Research, and the studys corresponding author.
By incorporating measurements such as a patients age, liver enzymes and platelet count, the FIB-4 index can judge the severity of a patients liver disease. In the early 2000s, Sterling developed the index, now considered the gold standard worldwide as the initial screening test for most liver diseases. The FIB-4 index is a simple test recommended by leading liver, gastroenterology and endocrinology societies as a first-line test to screen for liver fibrosis.
The analysis in the current study sought to determine whether the FIB-4 index would be a useful tool related to newer variants of the coronavirus, including alpha, delta and the more recent omicron. The researchers reviewed data on 232,364 hospitalized patients, ages 1890, who tested positive for COVID-19 between April 27, 2020, and June 25, 2022, as part of the National COVID Cohort Collaborative.
The primary objective was to investigate the association between the FIB-4 index and the need for respiratory support, which often precedes a patients death. Additionally, the study explored the relationship between index measurements and the likelihood of a patients death within the first 30 days after falling ill.
The FIB-4 index was notably accurate, particularly during the wave of the delta variant, when the index had a 97% success rate in predicting those who would not need respiratory support and strongly associated in those who would.
Overall, regardless of the COVID-19 variant, patients with increased FIB-4 levels were 1.8 times more likely to require a respirator to breathe for them.
Even when adjusting for other health factors like diabetes, cardiac issues, respiratory disease and obesity, the FIB-4 indexs reliability remained valuable in differentiating between patients with multiple illnesses who may require respirators and those who are less likely to need such intervention.
The power of the FIB-4 index also helped predict whether patients would survive more than a month. Patients across the different virus variants who had elevated FIB-4 levels faced an increased risk of dying within 30 days after falling ill. (The review found that 25,250 patients died in that period.) This implies that the FIB-4 index serves as a holistic indicator of a patients overall health and prognosis.
As the COVID-19 pandemic continues, and as the virus evolves in transmissibility, severity, symptoms and response to vaccines, the FIB-4 index has emerged as a valuable tool for understanding patients risks for future variants and as a simple tool for front-line providers to help identify respiratory disease severity from COVID-19.
This project was supported in part by the Biostatistics, Epidemiology and Research Design core of the C. Kenneth and Dianne Wright Center for Clinical and Translational Research (award No. UL1TR002649 from the National Center for Advancing Translational Sciences).
The investigation of virus tenacity in the environment plays a crucial role in enhancing our understanding of potential transmission routes for infectious diseases. Our study focused on assessing the tenacity of airborne FCoV and FCoV in dried organic matrices on surfaces. Overall, airborne FCoV showed a remarkable level of stability over a wide range of RH conditions. However, it is important to note that relative humidity has an impact on FCoV stability. The virus showed higher stability at both low and high RH levels, whereas medium RH conditions (around 5060%) were associated with a higher probability of decay. Remarkably, FCoV remained infectious for over 7h in the airborne state at medium RH levels. Moreover, on surfaces, FCoV showed the ability to remain infectious for extended periods, even up to several months. The stability on surfaces was influenced by factors such as temperature and the presence of organic material.
FCoV was used as a surrogate for SARS-CoV-2 in our study. Working with infectious pathogens of biosafety level 3 (SARS-CoV-2) is only possible in a limited number of laboratories, and especially with virus aerosols, it is very challenging. FCoV, on the other hand, can be studied under biosafety level 2 (BSL2) conditions, making it a safer and more cost-efficient option. FCoV belongs to the genus Alphacoronavirus, while SARS-CoV-2 is a Betacoronavirus. Although they share only 44.044.5% similarity at their nucleotide level3, previous research has shown that non-zoonotic animal coronaviruses like FCoV, canine coronavirus (CCV), transmissible gastroenteritis virus (TGEV) or mouse hepatitis virus (MHV) could be a suitable surrogate for survival of zoonotic SARS-CoVs27,28,29. To the best of our knowledge, this is the first study investigating the tenacity of FCoV in aerosols and on surfaces.
Our aerosol experiments were conducted in an aerosol chamber with a volume of 7m3, allowing individual airflows and climatic conditions. The chamber has been previously utilized in a study investigating the stability of Escherichia coli in aerosols30. Other studies investigating pathogen stability in aerosols, including SARS-CoV-2, have utilized a rotating drum, as described by Goldberg et al.14,31, to generate a dynamic aerosol. Our chamber offers a good opportunity to create a more realistic setting for exploring pathogen behavior within a room. To investigate FCoV stability, we worked with both dynamic (air exchange) and static (no air exchange) aerosol setups.
We observed a slight U-shaped trend in the stability of FCoV in dynamic aerosols at different RH levels, indicating that FCoV was more likely to decay at medium RH levels, ranging from 50 to 60%. This U-shaped pattern has also been observed for other enveloped viruses, including TGEV and influenza virus32,33. However, studies on human coronaviruses have shown varying results. For example, Sars-CoV and MERS have been found to be more stable at medium humidity levels34,35. Oswin et al. demonstrated that at low humidity levels, the initial stability decreases significantly but then remains relatively stable compared to higher humidity levels. If this initial decrease is neglected, a U-shaped pattern could also be observed21. Overall, coronaviruses in the aerosol state appear to be more stable than influenza or filoviruses at medium humidity levels34. When comparing studies on stability of viruses at different humidity levels, it is important to consider the medium used, as significant differences in stability can arise due to this factor. The most important fact to take into consideration when talking about the relationship between stability of viruses and RH is the microenvironment of the droplet and therefore the medium in which it resides36. Simulating human respiratory fluids accurately is still challenging due to the unknown exact components and concentrations. Therefore, many studies used cell culture medium such as DMEM as a model medium. One previous study compared DMEM with porcine respiratory fluid (PRF) and found that they differed greatly in the NA:K ratio. In addition, PRF contained significantly more protein37. It is important to note that studies using simulated respiratory fluids or real respiratory fluids instead of model medium have shown differences in virus stability38. These studies suggest that virus stability might be underestimated in most cases34,36,39,40. To make studies more representative, changes should be made to the virus suspension medium in further aerovirology studies37.
In our study, we modified DMEM by supplementing it with 10% FBS as a protein source, as respiratory droplets contain a variety of salts and proteins41,42. Yang et al. investigated the influence of different model media on the stability of Influenza A viruses in droplets, comparing DMEM and PBS, each with or without the addition of 5% FBS as a protein source. In general, they found better viability in DMEM than in PBS especially at medium and low RH36. Notably, the addition of FBS significantly affected virus stability at medium RH levels, suggesting a protective effect of proteins43,44. When a droplet leaves the respiratory tract, it evaporates by approximately half its original size depending on the ambient RH. This leads to a high concentration of substances within the droplet, such as salts, which are usually harmless but can become toxic to the virus. This effect is only relevant at medium RH levels just before the salts crystallize36. The exact RH at which the salts crystallize (efflorescence RH) depends on the droplet's composition and medium45. These findings support our own observations, as we observed a slight decrease in stability at medium RHs in the aerosol. Overall, we observed a high stability of FCoV in the aerosol, likely due to the presence of 10% FBS. The dynamic aerosol setup aimed to simulate a ventilated room where a virus emitter is present. The results indicate that the ambient RH in a room can significantly impact the stability of the emitted virus in the aerosol and thus its transmission potential. To minimize the risk of infection, it is advisable to keep the relative humidity at medium levels in indoor places.
Furthermore, our study demonstrated that FCoV remained infectious in static aerosols for over 7h with a half-life of 34.8min. The static aerosol setup aimed to simulate an enclosed room without regular air exchange, where a virus was released for a specific duration. During these experiments, we considered the possible natural loss of virus due to sedimentation. We observed a 31.4% loss of infectious virus through sedimentation, which occurred within the initial 10min and was than constant over the subsequent 7h. Moreover, the particle count remained stable throughout the entire experiment, indicating that virus-containing particles relevant for aerosol transmission remained suspended in the aerosol. It is known that aerosol particles <5m, which are relevant for inhalation, remain suspended as droplet nuclei in the air for hours, while larger droplets >10m settle to the ground within minutes due to gravity11,12,46. However, re-aerosolization of these sedimented infectious virus particles may also occur. In these experiments, the RH averaged 33%. Previous studies on related viruses have found that SARS-CoV-1 and SARS-CoV-2 remain stable in aerosols for over 3h, with respective half-lives of 1.1 and 1.2h, at an RH of 65%14. Similarly, MERS-CoV was found to be infectious in aerosols for over 3h35. In our study, we observed that FCoV has a half-life of 34.8min in aerosols and was detectable for over 7h. There was one other research group that investigated the stability of SARS-CoV-2 in aerosols over a longer period and found infectious virus after 16h at an average RH of 53%. However, this was a single observation without replication18. Comparing the half-lives of SARS-CoV-2 and FCoV indicates that both exhibit relatively short durations, suggesting similar behavior in aerosol stability. Observed differences may be more likely attributed to different aerosol generation processes and sampling methods. When considering influenza A viruses, their infectivity in aerosols varies lasting from 1 to 24h, depending on RH levels. Furthermore, influenza A viruses adapted to animals tend to demonstrate longer stability compared to human influenza A viruses47,48. It is important to note that comparisons between these studies are challenging due to variations in RH levels and medium used, as both factors strongly influence the stability of airborne viruses, as mentioned earlier. In general, our findings underscore the potential risk of aerosol transmission of enveloped respiratory viruses, especially in enclosed and unventilated environments over an extended period. This aligns with previous studies that have demonstrated aerosol transmission of SARS-CoV-2 between animals using hamsters as an animal model49,50.
At optimal environmental conditions the recovery rate of airborne FCoV was approximately 13% in our study. Several factors may have an influence on recovery rates of airborne viruses, including inactivation during aerosolization, loss through sedimentation, as well as sampling losses. We assume that our ultrasonic nebulizer and the aerosilization settings used resulted in the production of a suitable viral aerosol. In a study by Kim et al. various nebulizers and settings like pressure and nebulization time were tested to evaluate their impact on the stability of TGEV, and it was concluded that the stability of TGEV was not significantly affected32. Dhla et al. emphasized the importance of selecting an appropriate sampling method, as it can influence the stability of viruses in the sample. Since there is no generally recommended virus air sampling method, the choice of air sampler needs to be individually determined based on the specific experimental setup51. Most commonly used air samplers for collecting SARS-CoV-2 include filters, impactors, cyclone samplers and impingers52. For our experiments we chose the Coriolis cyclone air sampler. Previous studies aiming to detect SARS-CoV-2 in hospitals or healthcare settings have also utilized cyclone samplers due to their high collection volume53,54,55,56. While SARS-CoV-2 RNA has been detected in these studies, the identification of infectious SARS-CoV-2 was reported in only a few cases. It should be noted that cyclone samplers may be less efficient in detecting low levels of viruses compared to other air samplers, as the centrifugal forces affecting the viruses during collection could potentially cause stress57. However, in our study, we worked with high concentrations of viruses in a controlled environment, which made the Coriolis sampler suitable for our purposes, and we were able to detect infectious viruses.
We observed that 31.4% of the infectious virus sedimented onto the ground or surfaces within the first 10min in the static aerosol. This finding highlights the potential risk of contact transmission and the importance of studying virus infectivity on commonly encountered surfaces. We focused on stainless steel surfaces, which are frequently found in public buildings and clinical settings and are frequently touched. Previous studies have shown that CoVs exhibit greater stability on non-porous surfaces like metal, glass or plastic compared to porous surfaces, such as paper or fabrics58,59. Furthermore, viruses tend to be more stable at lower humidity levels and temperatures59. In our study, we demonstrated that FCoV remained infectious for 1958days at 20C and low RH, with the organic load significantly influencing the virus's stability. Comparatively, SARS-CoV-2 remained infectious on stainless steel surfaces for 47days at room temperature, while MERS and Sars-CoV-1 remained infectious for 2days14,15,35,60,61. TGEV and MHV, other non-zoonotic CoVs, remained infectious at room temperature for 3days at 50% RH and up to 28days at 20% RH27. It is important to note that differences in the results of various studies may occur due to varying medium used. While most of these studies were conducted using cell culture medium, we enriched our medium with 10g/L yeast extract/BSA or 3g/L sheep blood/BSA, representing a high organic load according to the guidelines for virus inactivation studies on nonporous surfaces62. Exhaled droplets that would sediment on surfaces consist of respiratory tract residues, saliva and organic material from the environment, resulting in a high organic load. Other studies added a tripartite soil load (mucin, BSA and tryptone) following international standard ASTM to the medium and found increased stability of SARS-CoV-2 on stain-less steel surfaces at 20C for 1428days, indicating a protective effect of the organic load16,63. Therefore, we would suggest using a high organic load, such as ASTM Internationals standardized tripartite soil load64, for further studies to avoid underestimating the stability of these viruses in the environment. However, it should be taken into consideration that stability may differ in dried human respiratory fluids. Regarding the influence of temperature, we found that infectious FCoV was detectable at 4C and 50% RH for 54167days, depending on the organic load. Only few studies have investigated CoVs stability at temperatures below 20. Notably, Onianwa et al. observed a reduction in infectiousness of the Delta variant of SARS-CoV-2 at 24C and 65% RH in the first 2.5h, while no reduction was observed at 4C and 85% RH within 2.5h65. TGEV and MHV also remained infectious at 4C for over 28days at all tested RHs, with the lowest losses observed at 20% RH27. Interestingly, we observed prolonged infectivity with yeast extract at 4C, although the reason for this difference remains unclear.
Like in aerosols, evaporation, and thus RH, plays an important role in terms of virus stability in droplets that sediment. French et al. studied the interplay of droplet volume and RH on surfaces and found that loss of infectivity was slower and more affected by RH in larger droplets (50L) than in small droplets (1L)66. Studies investigating stability of CoVs on surfaces, including our study, all used larger droplet volumes, which are not in line with realistically expelled droplet volumes (<0.5L) and may lead to different conclusions about virus stability. Another limitation of our study design is that we could not regulate the RH at the storage place and therefore could not distinguish between the influence of temperature and RH after drying. However, French et al. found that that viral decay during the wet phase was higher than during the dry phase regardless of RH66. In our experiment, all germ carriers were dried under controlled conditions for 45min, allowing us to neglect the influence of RH during the wet phase. Thus, the observed differences in stability may be primarily attributed to temperature and variations in organic load.
In summary, our study demonstrated that FCoV could remain infectious in the airborne state for hours and on surfaces up to months, with the duration depending on environmental conditions. Factors such as RH, temperature, and the presence of organic material significantly impact the pathogen's infectivity outside the host. Comparing studies on virus stability is challenging due to the lack of standardized experimental setups and medium used in these investigations. Additionally, reproducing respiratory fluids in the laboratory is difficult as their exact composition is still unknown. However, existing evidence suggests that viruses may exhibit even greater stability in respiratory fluids. It can be stated that aerosol transmission as well as droplet and contact transmission are possible transmission routes for coronaviruses under various environmental conditions over an extended period. Whether an infection occurs depends on many other factors, such as the viral load in the environment, the minimum infection dose,and the immune state of individuals. Especially enclosed, poorly ventilated rooms and low RH environments may pose a higher risk of infection due to the accumulation and better stability of these enveloped viruses. Given that, different pathogens respond uniquely to environmental conditions based on their biological and physical properties, it is essential to study a wide range of viruses to identify and understand potential correlations. The exact mechanisms that lead to the inactivation or protection of enveloped viruses by environmental components remain unknown and require further research. Our study suggests that FCoV could be a valuable surrogate for studying the behavior of zoonotic coronaviruses like SARS-CoV-2 in the environment. Although surrogates could offer valuable insights into the stability and persistence of these viruses outside the host, enhancing our understanding of zoonotic transmission dynamics, it remains crucial to directly investigate the actual virus.
