Day: August 27, 2021

Viral Load Alone not Indicative of COVID Transmission Risk

SARS-CoV-2 viruses (yellow) infecting a human cell. Credit: NIH

Viral load as determined by cycle threshold (Ct) has limited utility in guiding decisions regarding isolation and quarantine of COVID patients, according to a study of COVID cases in university students.

Though some in vitro studies indicate that virus load levels in infected individuals affects the successful rate of virus transmission, whether the viral load carried at the individual level can determine transmissibility was unknown. In this study published in The Journal of Molecular Diagnostics, university students underwent regular testing and contact tracing after positive tests, and significant overlap in cycle thresholds (Ct) was found between spreaders and nonspreaders. This brings into question using Ct values to determine transmission rates, with even those with low viral loads able to transmit the virus.
Real-time RT-PCR Ct values represent the number of amplification cycles required for the target gene to exceed a threshold level. Ct values are therefore inversely related to viral load and can provide an indirect method of quantifying the copy number of viral RNA in the sample; however, the use of Ct values as a proxy of viral load is influenced by the assay itself (correlation would stand in the linear dynamic range of the specific RT-PCR assay used) and factors within the sample matrix that can affect amplification efficiency

“We wanted to find whether there was a scientifically sound way to quickly triage students with potential high-risk exposure to COVID positive students for quarantine,” explained co-lead authors Patrice Delafontaine, MD, Department of Medicine, and Xiao-Ming Yin, MD, PhD, Departments of Pathology and Laboratory Medicine, Tulane University School of Medicine. “Some studies have found that the Ct value of the RT-PCR assay is a surrogate for infectivity, and cutoff Ct values have been proposed as a way to guide isolation practices. Through testing and contact tracing, we found that Ct value could not predict transmissibility. We should not overlook positive patients with low viral load, and all positive patients should be quarantined.”

A high-throughput SARS-CoV-2 surveillance testing program was established at Tulane University to support isolation and contact tracing efforts at the campus. Students were tested twice weekly and asked about symptoms they may be experiencing. Contact tracers spoke to all positive case subjects to identify close contacts.
The study looked at 7440 patients who were screened between September 1, 2020 and October 31, 2020, among whom 602 positive cases were identified. From this group, 195 index cases were identified with one or more reported close contacts, who were then tested during their mandated 14-day quarantine period for evidence of transmission from the associated index cases. Of these index cases, 48.2% had at least one contact who became COVID positive, whereas 51.8% of the index cases were nonspreaders with no contacts who subsequently tested positive. Mean Ct values of the spreaders and the nonspreaders were nearly identical.

The researchers then reversed approach, where index cases were traced for 481 students undergoing quarantine due to known exposure to the disease. Eighteen percent of the students became positive during their quarantine. Index cases for the 481 quarantined students were considered spreaders if they were linked to one or more quarantine students with a positive test result, or nonspreaders if they were associated only with students with negative test results. Mean Ct values of the spreader and the nonspreader groups were similar.

The researchers next identified and evaluated 375 positive cases to assess the relationship between symptom presentation and Ct values. Reported symptoms included lethargy, fever, headache, cough, runny nose and gastrointestinal symptoms. Mean and median Ct values were lower in symptomatic cases than in asymptomatic cases, indicating a higher viral load, This suggests that infections with a higher viral load could more often lead to symptom development, or that symptomatic individuals tend to have higher viral loads or maintain their viral loads for a longer period of time. Ct levels may be useful at a population level, in association with symptomatic presentation, to indicate the likelihood of transmission. These values may thus have epidemiologic or surveillance importance.

“Taken together, these index cases suggest that Ct values alone do not predict transmission risk and reporting of Ct values at the individual level, such as by setting a cutoff value of 32, would provide little diagnostic value for case management,” note Dr. Delafontaine and Dr. Yin. “A sensitive and robust SARS-CoV-2 diagnostic testing method is needed to effectively control viral transmission by maximizing the ability to identify and quarantine even those with a low level of virus.”

Source: Elsevier

Inconsistent PrEP Use for HIV in High-risk Groups

HIV infecting a human cell. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases/NIH

A large, in-depth look at US patients taking HIV-prevention drug therapy found strong adherence soon after patients get the prescription, but less consistent use thereafter, particularly among groups considered to be high-priority.

The study, published in JAMA Network Open, examined data from 13 906 members of Kaiser Permanente referred for pre-exposure prophylaxis, or PrEP, therapy between 2012 and 2019. The study found certain groups were more likely to stop taking PrEP: young people, Black and Latino individuals, women, and people with substance use disorders.

The findings suggest targeted strategies are needed to support use of this effective prevention in high-risk groups, said lead author Carlo Hojilla, RN, PhD, a research fellow with the Kaiser Permanente Northern California Division of Research.

“The findings have important implications that suggest access to health care is a great way to get people in the door, but we need more effective strategies for making sure people who have an ongoing need for PrEP stay on the medication,” said Dr Hojilla. “These are groups we want to reach, and we need innovative approaches to keep them engaged in PrEP care.”

Some 88% of patients referred for HIV prevention care received a PrEP prescription, and most (98%) of them filled their initial prescriptions. “These findings were encouraging,” Dr Hojilla said. “Kaiser Permanente has managed to do really well increasing uptake of PrEP therapy.”
However, significant inconsistency in use was seen with about half of users discontinuing PrEP at least once; 60% of those filled a prescription again though the study did not explore the reasons for this. Some users may have discontinued PrEP because of a decrease in risk for HIV acquisition, the authors speculated. Medical mistrust, stigma, homophobia, and transphobia as barriers to PrEP uptake and persistence in some communities have been documented in prior studies. Cost was known to be a concern for some, and the study was done before PrEP was provided at no cost, Dr Hojilla said.

The study was also done before the introduction of a new dosing scheme known as 2-1-1, or on-demand, which allows the user to take PrEP only around the time of a potential exposure to HIV, with a similar level of effectiveness as daily dosing. It’s possible that some of the discontinuation reflected in the study was from patients who opted to not take the drug daily because they had only occasional risk exposure, even prior to 2-1-1 dosing being formally recommended, said senior author Jonathan Volk, MD, an infectious disease specialist with The Permanente Medical Group.

No new HIV infections were seen in those remaining on PrEP, the study found. “This shows how incredibly well PrEP works when taken,” Dr Volk said. “But there are important opportunities for us to maximise the population level impact of this vital therapy. To do this, we need to avoid attrition along the care continuum, especially by assisting patients to stay on PrEP throughout periods of risk for HIV acquisition.”

Source: Kaiser Permanente

Heart Attack Survivors can Extend Healthy Lifespan

Photo by Ketut Subiyanto on Pexels

If patients follow lifestyle advice and medications after a heart attack, it could add seven healthy years of life, according to a new study.

“Most heart attack patients remain at high risk of a second attack one year later,” explained study author Dr Tinka Van Trier of Amsterdam University Medical Centre. “Our study suggests that improving both lifestyles and medication use could lower this risk, with a gain in many years of life without a cardiovascular event.”

A previous study showed that 80–90% of the risk of a heart attack can be modified by managing factors such as smoking, unhealthy diet, abdominal obesity, inadequate physical activity, hypertension, diabetes and raised blood lipid levels. Two main strategies are used: lifestyle change and medication.

However, risk factors are rarely reduced sufficiently after a heart attack, even in programmes aiming to help patients improve their lifestyles and optimise their medication. Therefore, residual risk is high to very high in a large number of patients. Dr Van Trier said: “This study was conducted to quantify this residual risk and estimate the extent to which it could be lowered with optimal management.”

The study pooled data from 3230 patients, average age 61 and 24% women, that had a heart attack or received a stent or bypass surgery. At an average of one year after the cardiac event, 30% continued smoking, 79% were overweight, and 45% reported insufficient physical activity. Only 2% of attained treatment targets for blood pressure, LDL cholesterol, and glucose levels with 40% having hypertension and 65% having high LDL cholesterol. Preventative medication use was common: 87% used antithrombotic medications, 85% took lipid lowering drugs and 86% were on blood pressure lowering drugs.

The researchers calculated the lifetime risk of a heart attack, stroke, or death from cardiovascular disease and estimated changes in healthy years when lifestyle or medication was changed or optimised. 

The estimated average residual lifetime risk for cardiovascular disease mortality was 54%. If all targets in the model were met, this risk would drop to 21%.

Dr Van Trier said: “The findings show that despite current efforts to reduce the likelihood of new events after a heart attack, there is considerable room for improvement. Our analysis suggests that the risk of another cardiovascular event could, on average, be halved if therapies were applied or intensified. For individual patients, this would translate into gaining an average of 7.5 event-free years.”

Source: European Society of Cardiology

Many Respiratory Diseases Are Borne by Aerosols

Photo by Britanny Colette on Unsplash

As the COVID pandemic forced a close study of airborne transmission, new evidence has challenged the idea that many respiratory pathogens besides SARS-CoV-2 were only carried in the large respiratory droplets from coughs and sneezes of infected individuals. Rather, they also spread through virus-laden microscopic respiratory aerosols.

In a review published in Science, Chia Wang and colleagues discussed recent research regarding airborne transmission of respiratory viruses and how an improved understanding of aerosol transmission will enable better-informed controls to reduce and mitigate airborne transmission.

Most respiratory pathogens were until recently assumed to spread largely in large droplets expirated from an infectious person or transferred from contaminated surfaces. Public health recommendations in mitigating viral spread has, thus far, been guided by this understanding.

It is also known however, that a number of respiratory pathogens, such as influenza and the common cold, spread through infectious respiratory aerosols, which can remain suspended in the air, travelling further and for much longer, infecting those that inhale them.

According to a growing body of evidence, much of which gained from studying the spread of COVID, airborne transmission may be a more dominant mode of respiratory virus transmission than previously thought. Here, Wang et al. highlight how infectious aerosols are generated, travel throughout an environment and deliver their viral payloads to hosts. Before COVID, the maximum size for droplets to be classified as aerosols was 5 micrometres, but this has now been updated to 100 micrometres, because up to this size, droplets can remain suspended in the air for up to 5 seconds from a height of 1.5m and travel one metre to be inhaled by another.

The deal with this under-appreciated threat, the authors described ways to mitigate aerosol transmission at long and short ranges, including improvements to ventilation and airflows, air filtration, UV disinfection and personal face mask fit and design.

Source: News-Medical.Net

Drone-delivered Defibs Beat Ambulances to Cardiac Arrests

Photo by David Bartus from Pexels

In a unique pilot project in Sweden, drones were used to deliver defibrillators to real-life alerts of suspected cardiac arrest. The drones were dispatched in more than a fifth of the emergencies and arrived on target and ahead of the ambulance in most cases. 

”This is the first time in the world that a research group can report results from a study where drones flew defibrillators to location of real-life alerts of suspected cardiac arrest,” says lead researcher Andreas Claesson, associate professor at the Center for Resuscitation Science at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.

With sudden cardiac arrest, every minute counts. Currently, the odds of surviving an out-of-hospital cardiac arrest are 10 percent. However, with early CPR and a shock from an automated external defibrillator (AED), the chances of survival could reach 50-70 percent but response time needs to improve. In 2019 the median response time from alert to ambulance arrival for out-of-hospital cardiac arrest (OHCA) in Sweden was 11 minutes.  
To try and reach cardiac arrest victims sooner, researchers investigated using the rapid dispatch of drone-carried defibrillators in parallel with ambulances. Drones are already used in some countries to dispatch medicines and medical supplies to remote rural regions, The study, conducted in mid-2020 in western Sweden, describes an integrated method where emergency operators, drone pilots and air traffic control worked together to facilitate the dual response.

The drones took off in response to 12 out of 53 alerts of suspected cardiac arrest over a four-month period, successfully delivering an AED to the site in 11 of those cases. In seven of those cases, the drones arrived before the ambulance, with a median time benefit of 1 minute and 52 seconds. However, no drone-delivered defibrillators were attached to the patients before ambulances arrived.

“Even if none of the AEDs were used this time, our study shows that it is possible to use drones to transport defibrillators in a safe way and with target precision during real-life emergencies,” said first-author Sofia Schierbeck, PhD student at the Center for Resuscitation Science at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet. “A precondition for their future use is that the dispatcher takes initiative and instructs people on site to quickly collect and attach the AED in order to help the person with cardiac arrest.”

More work is needed to increase the dispatch rate and time benefits. For instance, in 2020 the drones were grounded if it was dark, rainy or the winds were too strong. The software system was also configured to avoid routes above densely populated areas, meaning that some alerts were too far out of range.

“Since this study was completed, we have identified several areas of improvement,” Andreas Claesson said. “In April this year, we began a follow-up study with a more optimised system. In that study, we want to test if we can use the drones in more alerts and reduce the response time further and thereby increase the time benefit as compared to the ambulance. Every minute without treatment in the early stages reduces the chance of survival by around 10 percent, and that is why we believe this new method of delivery has the potential to save lives.”

The results are published in the European Heart Journal.

Source: Karolinska Institute

The Complex Web of South African Vaccine Hesitancy

Photo by Mika Baumeister on Unsplash

A review of surveys towards COVID vaccines in South Africa has revealed that there are multiple factors at work, with an underlying scepticism towards vaccines in general that appears to be growing in the very face of the pandemic.

The findings, published in Expert Review of Vaccines, highlight the multi-faceted and unique aspects of vaccine hesitancy in South Africa, such as men being more likely to reject a vaccine.

Vaccine hesitancy is not new; two years before the emergency of COVID the World Health Organization identified it as a top ten threat to health, underscored by outbreaks of preventable diseases such as measles.

A previous review of 126 surveys in 2020 found a global decline of COVID vaccine acceptance from 70% in March to 50% by October. Vaccine hesitancy has been an obstacle in South Africa for a long time: it was a factor in various measles outbreaks from 2003 to 2011, and it became more apparent during the nation-wide school HPV vaccination programme begun in 2014.

The researchers searched for surveys on COVID vaccine hesitancy in South Africa up until 15 March 2021, with sample sizes ranging from 403 to 75 518.

Unlike elsewhere, men are more hesitant
In a survey by Ask Africa, men were more likely to distrust vaccines (39%) than women (26%). Of the women who would refuse, there was a higher percentage who would  However, women were more likely to take the vaccine even if they thought it was unsafe. The authors cautioned that this result should be interpreted with caution; however, Department of Health deputy director Dr Nicholas Crisp also recently pointed this out, suggesting that more recent survey data helped inform his opinion.
Curiously, this is in contrast to other COVID studies and other vaccine studies in general, which indicate that women are more hesitant than men when it comes to vaccines in general. 

Age, race, education, geographical location
Three of the studies found that age may be important, with older adults having less concerns and/or being more accepting of COVID vaccination. 

The COVID-19 Democracy survey found that people 55 or older were more likely to take the vaccine (74%) compared to those 18 to 24 years old (63%).
The same survey found that white adults were the least likely racial group to accept vaccination, with only 56% willing to be vaccinated compared to 69% of black African adults. Education was another factor, with just 59% of tertiary educated people willing to be vaccinated compared to 72% of this who did not complete high school.

Council for Medical Schemes (CMS) survey found that vaccine acceptance was higher (83%) in urban suburban settings compared to other settings (73% and 78%).

Doubts about safety significant
Three rounds of Ipsos survey data showed a huge drop in acceptance from 64% in July/August and 68% in October to 53% in December. Of those not accepting, concern about side effects as a reason rose from 30% in October to 65% in December.

The Ask Afrika survey indicated that stopping the roll-out of the AstraZeneca vaccine early this year reduced both levels of trust in vaccine safety and confidence in the process. 

Of particular concern were several surveys indicating South African antipathy to all vaccines; in the Ipsos surveys, about a quarter refusing COVID vaccines were also opposed to vaccines in general. Thus, this hesitancy to COVID vaccines, the authors suggest, is just the tip of the iceberg of South African vaccine hesitancy.  Indeed, the Africa CDC survey indicated that at least one in five South Africans were less likely to get vaccinated in general than before the pandemic.

More research and targeted messaging needed
Overall, the authors found about a third of the adult South African public is hesitant towards COVID vaccines. Age, race, education, geographic locations and possibly gender all influence the social nature of vaccine acceptance in South Africa.

The authors conclude that responding to vaccine hesitancy, including COVID vaccine hesitancy, requires a better understanding of the often complex and multi-layered issues influencing vaccination views and practices, and tailoring interventions accordingly. Individualistic, decontextualised, and ‘one-size-fits-all’ approaches are unlikely to have great success.

Source: Expert Review of Vaccines