Coronaviruses are constantly evolving, switching and expanding host species, and, in the last few decades, novel coronaviruses have emerged in humans, domestic animals, and wildlife. The SARS-CoV-2 virus itself is thought by some to have originated in bats, crossing over to intermediate animal hosts (snake or pangolin) before infecting humans [1] and resulting in the global pandemic which to date has killed over 6 million individuals worldwide. While a definitive origin has not been found, one leading hypothesis of the genesis of COVID transmission into humans is a zoonotic origin, i.e. from animals. 

So far, SARS-CoV-2 has infected a number of animals. In addition to domestic animals, infections have been found in wild animals including minks, ferrets, big cats, great apes, and white-tailed deer[2]. A few of these species have been identified to date as transmitting SARS-CoV-2 to humans. In the first year of the pandemic, studies demonstrated that mink were capable of infecting humans with the SARS-CoV-2 virus [3,4]. Thereafter, pet hamsters were shown to transmit SARS-CoV-2 to humans [5]. In addition, a case has also recently been published of transmission to humans from white-tailed deer, who are particularly vulnerable to SARS-CoV-2 infection [6,7]. Conversely, COVID-19 can be transmitted from humans to animals. Critically, this is likely to amplify viral mutagenesis, and, in turn, result in the re-infection of humans with more virulent forms of the virus [8].  

High density environments that favor interspecies interactions – such as farms, markets, and animal shelters and kennels – have likely precipitated the emergence and transmission of coronaviruses by generating a large enough animal population susceptible to coronavirus circulation and spillover across species [9]. This is directly supported by findings that COVID-19 is far more prevalent in kennels than the rest of the dog population [10]. In addition, commercial agriculture has also led to many domestic animals living close to humans, possibly driving the emergence of key viruses from cattle (OC43) and camelids (229E and MERS). Finally, the rise of domestic animals populations has also similarly contributed the spike in COVID transmission from animals to humans. This trend is exacerbated by the fact that when animals are kept under poor stressful conditions (e.g. in overcrowded environments or frequently being transported), their experienced stress weakens their immune systems, rendering them even more susceptible to infections [11].   

Accordingly, the concept of One Health – a blanket strategy calling for “the collaborative efforts of multiple disciplines working locally, nationally, and globally, to attain optimal health for people, animals and our environment” – has been highlighted by COVID-19 and reports of human-animal transmission. To this end, first, personnel working closely with wildlife should be trained to implement measures that reduce the risk of disease transmission between and across people and animals, per World Health Organization (WHO) directives. This should include good hygiene practices for hunters and butchers [12]. Second, the public should be educated about what to do when entering in contact with wildlife. As a general precaution, people should not approach wild animals, instead choosing to notify wildlife authorities if an animal needs help. Third, it is critical to safely dispose of food and other human waste to avoid attracting wildlife, and, if possible, keeping domestic animals away from wildlife as well, all the while reducing people’s dependence on domestic animals. Finally, collaboration between veterinarians and wildlife authorities should be encouraged. Such work should include promoting the monitoring of wildlife and, in the context of COVID-19 specifically, the sampling of wild animals known to be potentially susceptible to SARS-CoV-2, sharing all genetic sequence data, and reporting confirmed animal SARS-CoV-2 cases, among others [2]. 

Efforts to monitor coronaviruses in the wild are currently underway (including the Viral Genome Project and PREDICT programs). These are key to identifying new viruses with zoonotic potential and dissecting potential spillover pathways [13]. Further research is warranted, in addition, to more fully understand and respond to cross-species transmission dynamics [14]. 

 

References  

 

1. Mahdy, M. A. A., Younis, W. & Ewaida, Z. An Overview of SARS-CoV-2 and Animal Infection. Frontiers in Veterinary Science (2020). doi:10.3389/fvets.2020.596391
2. Joint statement on the prioritization of monitoring SARS-CoV-2 infection in wildlife and preventing the formation of animal reservoirs. Available at: https://www.who.int/news/item/07-03-2022-joint-statement-on-the-prioritization-of-monitoring-sars-cov-2-infection-in-wildlife-and-preventing-the-formation-of-animal-reservoirs.
3. Pomorska-Mól, M., Włodarek, J., Gogulski, M. & Rybska, M. Review: SARS-CoV-2 infection in farmed minks – an overview of current knowledge on occurrence, disease and epidemiology. Animal (2021). doi:10.1016/j.animal.2021.100272
4. Munnink, B. B. O. et al. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science (80-. ). (2021). doi:10.1126/science.abe5901
5. Haagmans, B. L. & Koopmans, M. P. G. Spreading of SARS-CoV-2 from hamsters to humans. Lancet 399, 1027–1028 (2022). doi:10.1038/s41586-021-04353-x
6. Pickering, B. et al. Highly divergent white-tailed deer SARS-CoV-2 with potential deer-to-human transmission. bioRxiv 17 (2022). doi:10.1101/2022.02.22.481551
7. Hale, V. L. et al. SARS-CoV-2 infection in free-ranging white-tailed deer. Nat. 2022 6027897 602, 481–486 (2021).
8. He, S., Han, J. & Lichtfouse, E. Backward transmission of COVID-19 from humans to animals may propagate reinfections and induce vaccine failure. Environmental Chemistry Letters (2021). doi:10.1007/s10311-020-01140-4
9. Plowright, R. K. et al. Pathways to zoonotic spillover. Nature Reviews Microbiology (2017). doi:10.1038/nrmicro.2017.45
10. Naylor, M. J., Monckton, R. P., Lehrbach, P. R. & Deane, E. M. Canine coronavirus in Australian dogs. Aust. Vet. J. (2001). doi:10.1111/j.1751-0813.2001.tb10718.x
11. Oreshkova, N. et al. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020. Eurosurveillance (2020). doi:10.2807/1560-7917.ES.2020.25.23.2001005
12. CODE OF HYGIENIC PRACTICE FOR MEAT 1 CAC/RCP 58-2005. The National Institute for Communicable Diseases. Available at: https://www.nicd.ac.za/wp-content/uploads/2018/05/Code_of_Hygienic_Practice_for_Meat_CAC_RCP_58-2005.pdf
13. Global Virome Project. Available at: https://www.globalviromeproject.org/.
14. Animals and COVID-19 | CDC. Available at: https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/animals.html.

  

Despite policymakers’ efforts to reduce health care costs via a number of different means since the 1980s, the growth of health care cost as a fraction of the United States GDP has continued a steady upward trend. Even after extracting out supplemental COVID-19 funding, the ratio of health care expenditure to gross domestic product (GDP) surpassed 18% in 2020. Despite high levels of spending at both the country and individual level, the U.S. trails behind many other high-income nations in key metrics of health and the functioning of the health care system. 

 

Since 1960, health care spending as a fraction of the GDP has risen by an average of 2.2 percentage points per decade – in sharp contrast to the average increase of 1.1 percentage points per decade in other high-income countries. Interestingly, this rise has been rather non-linear. Increases were higher than average in response to the establishment of Medicare and Medicaid in the 1960s, but lower than average in response to managed-care expansion in the 1990s and in the 2010s. The overall increase in health care costs as a fraction of the U.S. GDP can be linked to some long-term trends, however, including an aging population [3] and the lack of institutional budgets to limit and guide spending.  

 

Although health care spending has been funneled into hospital care, physician services, and other personal health care, life expectancy has not improved rapidly. On the contrary, increases in the health care cost fraction of the U.S. GDP have taken a toll on individual well-being. Most median-income American worker salary increases in the last few decades have been absorbed by increased taxes, health care premiums, and out-of-pocket expenses [4]. This is exacerbated by the fact that programs such as Medicare have no legislative limits on spending – this results in hospitals increasing prices in response to rising costs, meaning consumers have to pay higher insurance premiums. This system has precipitated patient bankruptcies, leading to unpaid bills and budget crises for state and even the federal governments.  

 

A number of interventions should be and have been made to reduce the cost of health care in the U.S. First, individual lifestyle factors can be improved to decrease the need to access health care. According to the American Medical Association (AMA), lifestyle modifications can reduce annual health care costs by nearly $2,700 per participant. Individuals and patients need to be well-educated about, and abide by, guidelines for a healthy lifestyle and available resources to this end, and access to and the effectiveness of interventions can be improved [5].  

 

At a systems level, reforming key administrative processes can also reduce costs. Prior authorization processing, managed care, deductibles and co-payments, standard electronic transactions, and bundled-payment programs are all areas that can be targeted. In many other Organization for Economic Cooperation and Development (OECD) countries, health care organizations adopt fixed budgets tied to tax revenue and general economic growth, resulting in a more stable ratio of health care expenditures to GDP [1].  

 

With the health care cost fraction of GDP reaching 18%, in stark contrast to the average 12% in other high-income countries, efforts need to continue to be made to reduce the growth of health care spending. Crucially however, this must be implemented in parallel with the adoption of novel, effective technologies and deliberate efforts to improve the quality of clinical care.  

 

References 

1. Skinner, J., Cahan, E. & Fuchs, V. R. Stabilizing Health Care’s Share of the GDP. N. Engl. J. Med. 386, 709–711 (2022). doi:10.1056/NEJMp2114227
2. Khan, T., Tsipas, S. & Wozniak, G. Medical Care Expenditures for Individuals with Prediabetes: The Potential Cost Savings in Reducing the Risk of Developing Diabetes. Popul. Health Manag. 20, 389–396 (2017). doi:10.1089/pop.2016.0134
3. Why Are Americans Paying More for Healthcare? Available at: https://www.pgpf.org/blog/2022/02/why-are-americans-paying-more-for-healthcare.
4. Auerbach, D. I. & Kellermann, A. L. A decade of health care cost growth has wiped out real income gains for an average US family. Health Aff. (2011). doi:10.1377/hlthaff.2011.0585
5. The AMA can help you prevent type 2 diabetes | AMA Prevent Diabetes. Available at: https://amapreventdiabetes.org/.

As the COVID-19 pandemic continues, at-home Covid tests have become more common. This article will explore everything that you should know about at-home tests, ranging from when to take them to how to obtain them.

 

When Should I Take an At-Home Covid Test?

 

It is a common misconception that people should only take Covid self-tests when they suspect that they have already been infected by the virus. While laboratory PCR tests are more appropriate when a person has already been exposed to the virus, medical professionals advise people to take at-home rapid antigen tests for assurance purposes [1]. It is a good idea to regularly take antigen tests to catch infections early and subsequently isolate oneself before spreading the disease to other people [2]. Both antigen and PCR tests are available in at-home capacities, although the latter must be sent to a laboratory for results [3].

 

What Is the Difference Between Antigen and PCR Tests?

 

Real-time reverse transcription polymerase chain reaction (PCR) tests are the more sensitive form of COVID-19 tests [4]. This means that, compared to antigen tests, they are better at detecting infections, and this applies to both at-home tests and tests at clinics [3]. However, they may come back positive for a mean of 17 days and, in some cases, as long as three months after the typically 9-day infection period has ended [3]. As mentioned, individuals can swab themselves at home, but PCR rests require processing using special equipment [4]. As a result, they have to be sent to a laboratory, so results come back more slowly [4].

 

By contrast, rapid antigen tests can display results within minutes [2]. These tests are convenient because they can be taken at home [1]. They are highly specific, which suggests that they produce very few false positives, but their false negative rate is as high as 20%, compared to PCR tests’ 10% [3]. Accordingly, people who believe that they may have COVID-19 but tested negative according to a rapid antigen test should take a supplementary PCR test [1].

 

What Should I Keep in Mind When Administering an At-Home Test?

 

Before using a COVID-19 self-test, you should store all test items according to the manufacturer’s directions on the label [1]. This includes complying with the appropriate storage temperature ranges and making sure to clean and sanitize any objects that may come into contact with the test, as well as your hands [1]. When swabbing, you must take care not to contaminate the sample; otherwise, the test could display inaccurate results [3]. After taking a test, you should not reuse any of the testing objects [1]. Rather, they should be thrown away, and, afterward, you should clean any surfaces that came into contact with the testing materials and wash your hands once more [1].

 

Where Can I Get a COVID-19 At-Home Test?

 

At-home tests are available at some grocery stores, local pharmacies, and online [5]. Prices can be around 11 dollars, though some are more expensive [5]. For free tests, people in the United States can visit COVIDtests.gov to order up to 8 free at-home tests per household [6].

 

Conclusion

 

By making it easier to determine whether you have been infected by the novel coronavirus, at-home Covid tests can help reduce the overall infection rate [2]. Consequently, each household should keep a couple of tests readily available.

 

References

 

[1] K. Rogers, “What you should know about taking an at-home Covid-19 test,” CNN, Updated February 2, 2022. [Online]. Available: https://www.cnn.com/2021/12/17/health/how-to-at-home-covid-19-test-wellness/index.html/.

 

[2] M. Johnson-León et al., “Executive summary: It’s wrong not to test: The case for universal, frequent rapid COVID-19 testing,” eClinicalMedicine, vol. 33, February 2021. [Online]. Available: https://doi.org/10.1016/j.eclinm.2021.100759.

 

[3] A. Crozier et al., “Put to the test: use of rapid testing technologies for covid-19,” BMJ, vol. 372, no. 208, p. 1-7, February 2021. [Online]. Available: https://doi.org/10.1136/bmj.n208.

 

[4] R. W. Peeling et al., “Scaling up COVID-19 rapid antigen tests: promises and challenges,” The Lancet, vol. 21, no. 9, p. e290-e295, September 2021. [Online]. Available: https://doi.org/10.1016/S1473-3099(21)00048-7.

 

[5] Center for Medicare & Medicaid Services, “How to get your At-Home Over-The-Counter COVID-19 Test for Free,” CMS, Updated January 12, 2022. [Online]. Available: https://www.cms.gov/how-to-get-your-at-home-OTC-COVID-19-test-for-free.

 

[6] T. Keith, “You can order free COVID tests from the government again,” NPR, available March 7, 2022. [Online]. Available: https://www.npr.org/2022/03/07/1085022030/you-can-order-free-covid-tests-from-the-government-again.

Ergonomic considerations are key to the success of ultrasound-guided diagnostics [1] and medical interventions that require very fine control. Head movements in particular may inconvenience surgeons and result in technical difficulties, and there remains a significant failure rate for first pass interventions. Wearable devices that can be attached to smart glasses, consisting of a head-mounted display which projects the ultrasound screen in front of the operator’s eye, allow surgeons to keep their eyes and attention fixed on the surgical field. Research has shown that such smart glasses, which are both ergonomic and affordable, can improve the success rate of ultrasound-guided procedures.

 

Various studies in the last few years have contributed to highlighting the benefits of such smart glasses. A 2019 study first assessed the use of smart glasses in the context of ultrasound-guided peripheral venous access [2]. The research was carried out as a randomized, crossover-design simulation study in which emergency medicine residents attempted ultrasound-guided peripheral venous access on a pediatric patient with or without the use of smart glasses. Results demonstrated that the use of smart glasses, though not improving procedural time or the number of skin punctures and needle restrictions, significantly reduced the number of operator head movements.

 

A study shortly thereafter in 2020 examined the use of smart glasses equipped with augmented reality representing ultrasound information, alongside other real-time data such as endoscopic data [3]. The findings suggested that augmented reality can improve trauma surgery interventions. In particular, it improved the efficiency of surgery, reducing the operating time and minimizing the radiation exposure of clinical personnel and patients alike.

 

Most recently, a study from 2021 looked into the success rate of ultrasound-guided pediatric radial arterial catheterization [4]. The work was carried out as a prospective, single-blinded, randomized controlled, single-center study focused on pediatric patients under 2 years of age requiring radial artery cannulation under general anesthesia. Results demonstrated that smart glasses-assisted ultrasound-guided radial artery catheterization improved first-attempt success rates, procedure time, and overall complication rates. It also improved ergonomic satisfaction.

 

Interestingly, the use of smart glasses is beginning to extend beyond ultrasound-guided procedures. A 2020 prospective, randomized study sought to assess the feasibility of using smart glasses in the context of fluoroscopically guided minimally invasive spinal instrumentation surgery [5]. The study, which examined posterior lumbar interbody fusion, found that smart glasses did not significantly reduce the number of surgeon head turns and both the operative and radiation exposure times. Additional studies will provide a more complete picture.

 

Research has shown that the use of smart glasses in ultrasound-guided procedures improves first-attempt success rates, enhances ergonomic ease, minimizes procedure time, and decreases complication rates. However, certain challenges remain. First, future research will need to focus on developing faster data transfer algorithms to achieve higher spatial and temporal resolutions. Second, the glasses can be heavy, and applied research will need to focus on developing lighter smart glasses. Finally, work is required to elucidate more in depth how smart glasses might affect patient safety and health care professionals in a range of complex care environments [6].

 

References 

 

1. Maas, S., Ingler, M. & Overhoff, H. M. Using smart glasses for ultrasound diagnostics. Curr. Dir. Biomed. Eng. (2015). doi:10.1515/cdbme-2015-0049
2. Lim, H. et al. Use of smart glasses for ultrasound-guided peripheral venous access: A randomized controlled pilot study. Clin. Exp. Emerg. Med. (2019). doi:10.15441/ceem.19.029
3. Lal, A., Hu, M. H., Lee, P. Y. & Wang, M. L. A novel approach of using AR and smart surgical glasses supported trauma care. arXiv (2020).
4. Jang, Y. E. et al. Smart Glasses for Radial Arterial Catheterization in Pediatric Patients: A Randomized Clinical Trial. Anesthesiology (2021). doi:10.1097/ALN.0000000000003914
5. Matsukawa, K. & Yato, Y. Smart glasses display device for fluoroscopically guided minimally invasive spinal instrumentation surgery: A preliminary study. J. Neurosurg. Spine (2021). doi:10.3171/2020.6.SPINE20644
6. Romare, C. & Skär, L. Smart glasses for caring situations in complex care environments: Scoping review. JMIR mHealth and uHealth (2020). doi:10.2196/16055

Over 100,000 people currently sit on organ transplant waitlists ¹; about 6,000 die annually while waiting for a kidney, heart or lung. Xenotransplantation, a procedure involving transplants of live nonhuman cells, tissues, or organs (or such human tissues that have come into ex vivo contact with live nonhuman tissues) into humans, is thus of tremendous clinical promise and potential. While not a novel method – many clinical xenotransplantation attempts have been made in the last few centuries ², the challenges of xenotransplantation are significant but being steadily being overcome.

Despite its considerable benefits, nonhuman tissue transplants present a significant risk in light of the potential infection of recipients with foreign infectious agents, in addition to their potential transmission to the general human population ³. Advances in gene-editing tools (for example, genetically engineering pigs to make their tissues more resistant to human immune responses) and immunosuppressive therapy have particularly contributed to making clinical xenotransplantation more viable.

A number of xenotransplantation successes have been documented between nonhuman animals. In preliminary research studies, a life-supporting genetically engineered pig kidney functioned in a monkey for over a year ⁴, and genetically engineered orthotopically-placed pig hearts have maintained the lives of baboons for 6 months ⁵.

Xenotransplantation has also been met with budding success from nonhuman animal cells, tissues, and organs to humans. Pig cells have been a particularly viable transplantation agent to this end. Pig pancreatic islets can be used to treat diabetes, for example, while fetal porcine neural stem cells can be applied to Parkinson cell therapy. In parallel, pig skin can be transplanted to help burn victims ³.

1905 saw the first serious attempt at organ xenotransplantation, when slices of rabbit kidney were transplanted into a child with chronic kidney disease who was dying of renal insufficiency ⁶. The two first decades of the 20th century consequently saw a flurry of subsequent xenotransplantation efforts involving primate, pig and lamb organs, among others.

This culminated in the successful transplantation, in 1997, of a pig’s heart, lungs and kidneys into a terminally ill individual in India. The patient was a 32-year-old man who had failed to respond to conventional surgery; he remarkably survived for 7 days, dying thereafter from multiple infections ⁷.

The last few years saw another series of xenotransplantation breakthroughs. In 2021, a pig kidney was successfully transplanted into a brain-dead recipient. Partly because the pig’s thymus gland was transplanted as well, there were no indications of immediate immune rejection ⁸.

Most recently, in 2022, a 57-year-old successfully survived a surgery in which he received a heart from a 1-year-old pig in which the enzymes underpinning the production of hyperacute organ rejection antigens had been gene-edited out. The U.S. medical regulator granted special permission for the procedure, which is not currently approved, given that the patient would have otherwise died – and the surgery marked the first of its kind ⁹.

Since preclinical studies in nonhuman primates can take up to 4 years and are relatively expensive, 3D bioprinting has emerged as a particularly promising technology in this context ¹⁰. In particular, the scaffold-free 3D-bioprinting of pig organ models using genetically engineered pig cells can quickly and cheaply generate organ-specific 3D models. In parallel, organ-specific bioprinting can also be used to better understand different immunogenic responses, helping to advance the field of nonhuman tissue transplants ¹¹.

Ethical questions surrounding the clinical use of nonhuman tissue for transplants are being raised worldwide – to which end the U.S. Food and Drug Administration published comprehensive guidelines in 2003 ¹². While it remains unclear what type of evidence is considered sufficient, national regulatory authorities must shape regulations such as to enable safe, thorough, informative clinical trials well supported by preclinical data.

Recent clinical breakthroughs have been paving the way for the future of xenotransplantation, marking a step forward toward solving the problem of human organ shortage ¹³.

 

References

 

1. Organ Donation Statistics | organdonor.gov. Available at: https://www.organdonor.gov/learn/organ-donation-statistics.
2. Deschamps, J. Y., Roux, F. A., Saï, P. & Gouin, E. History of xenotransplantation. Xenotransplantation (2005). doi:10.1111/j.1399-3089.2004.00199.x
3. Xenotransplantation | FDA. Available at: https://www.fda.gov/vaccines-blood-biologics/xenotransplantation.
4. Kim, S. C. et al. Long-term survival of pig-to-rhesus macaque renal xenografts is dependent on CD4 T cell depletion. Am. J. Transplant. (2019). doi:10.1111/ajt.15329
5. Längin, M. et al. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature (2018). doi:10.1038/s41586-018-0765-z
6. Toledo-Pereyra, L. H. & Lopez-Neblina, F. Xenotransplantation: a view to the past and an unrealized promise to the future. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation (2003). doi:10.1034/j.1399-0039.2002.00003.x
7. Why the US Pig Heart Transplant Was Different From the 1997 Assam Doc’s Surgery – The Wire Science. Available at: https://science.thewire.in/the-sciences/university-maryland-pig-heart-xenotransplant-dhani-ram-baruah-1997-failed-surgery-arrest/.
8. Progress in Xenotransplantation Opens Door to New Supply of Critically Needed Organs | NYU Langone News. Available at: https://nyulangone.org/news/progress-xenotransplantation-opens-door-new-supply-critically-needed-organs.
9. Man gets genetically-modified pig heart in world-first transplant – BBC News. Available at: https://www.bbc.com/news/world-us-canada-59944889.
10. Cooper, D. K. C. Financial support for xenotransplantation research. Xenotransplantation (2019). doi:10.1111/xen.12483
11. Li, P. et al. The potential role of 3D-bioprinting in xenotransplantation. Current Opinion in Organ Transplantation (2019). doi:10.1097/MOT.0000000000000684
12. Tissue Guidances | FDA. Available at: https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/tissue-guidances.
13. Lu, T., Yang, B., Wang, R. & Qin, C. Xenotransplantation: Current Status in Preclinical Research. Frontiers in Immunology (2020). doi:10.3389/fimmu.2019.03060