Category: COVID-19

Introduction

Throughout the COVID-19 pandemic, our systems and institutions were tasked with quickly adapting their services to an increasingly virtual audience. This is particularly true of the medical world, where telemedicine rapidly became the go-to solution for socially-distanced medical needs.

Telemedicine, or telehealth, is the delivery of healthcare services through digital platforms, allowing patients to connect with their healthcare providers remotely. The ability to meet with physicians from the comfort of your home became a necessity during the COVID-19 pandemic, and since then, telemedicine has remained a key aspect of nationwide healthcare. According to Stephanie Watson at Harvard Health, “76 percent of hospitals in the U.S. connect doctors and patients remotely via telehealth, up from 35 percent a decade ago.”

While it promotes accessibility and convenience for patients and physicians alike, the drawbacks of telemedicine include quality concerns and potential technological barriers for certain demographics. This raises the question: Is telemedicine obsolete in a post-COVID world, or do the benefits of remote healthcare outweigh the costs?

Benefits

The primary benefit of telemedicine post-COVID is the increased accessibility to healthcare for populations in rural areas, those without reliable transportation, and immobile or busy patients. Patients without the privileges required to attend regular, in-person medical visits are much better accommodated by a virtual model. This system also increases convenience for the vast majority of patients, whether or not they fall into one of these demographics. 

During virtual visits, clinicians are also less likely to be exposed to infection or disease, further maximizing the care they are able to provide long-term. 

Additionally, telemedicine provides support for patients’ continuity of care, offering easier opportunities for follow-up appointments and check-ins for those with chronic conditions. Further, the implementation of telemedicine can reduce “medication misuse, unnecessary emergency department visits, and prolonged hospitalizations.” 

Drawbacks

Although telemedicine provides increased accessibility to healthcare, this doesn’t mean patients are taking advantage of it. According to a Stanford study, “increased telemedicine access is associated with a modest, 3.5% increase in the utilization of primary care.” While 3.5% translates to a large number of patients, it still represents a smaller population than expected.

One of the largest concerns regarding the wide implementation of telemedicine is the quality of care. The Institute of Medicine (US) Committee on Evaluating Clinical Applications of Telemedicine has identified three key quality issues: “overuse of care (e.g., unnecessary telemedicine consultations); underuse of care (e.g., failure to refer a patient for a necessary consultation); and poor technical or interpersonal performance (e.g., incorrect interpretation of pathology specimen or inattention to patient concerns).” 

Further, telehealth creates a digital divide, which causes particular difficulty in regard to older and low-income demographics. According to a Mayo Clinic study, the concordance of diagnoses between in-person and virtual appointments was 86.9%, and “for every 10-year increase in the patients’ age, the odds of receiving a concordant diagnosis by video telemedicine decreased by 9%.”

Physician’s Perspective

Dr. Maryam Kashi, a gastroenterologist with AdventHealth in Central Florida, operates on a hybrid model in providing patient care. Since 2020, she has run 2 days of in-person clinic and 3 days of virtual clinic each week. 

According to her own experience, Dr. Kashi believes that quality of care is held to the same standard in both in-person and virtual visits. She says that her hybrid model allows her to ensure that all patients with issues requiring physical exams or other in-person needs are able to be accommodated. Meanwhile, patients who only need a brief post-op check-in are able to meet with Dr. Kashi virtually at their convenience. 

Dr. Kashi contends that her current hybrid model, which includes a majority of virtual visits, elicits appreciative and receptive responses from patients as they experience greater convenience and access to healthcare. 

Conclusion

Telemedicine offers an accessible and efficient alternative to in-person care. While there are concerns regarding the quality of care and an obvious digital barrier, the great benefits of the service make a case for its continued usage beyond COVID restrictions. Hybrid models, like Dr. Kashi’s, ensure that patients are able to receive the care they need, regardless of physical or virtual limitations. Ultimately, adopting an inclusive system that includes telemedicine guarantees that the greatest number of patients acquire appropriate medical care.

During the pandemic, laboratories across the world worked hard to improve current diagnostic testing methods. The main method, quantitative polymerase chain reaction (qPCR) turns a small quantity of DNA into a larger amount and uses fluorescent dyes to indicate the presence or absence of viral genetic material. However, this method falls short in the following ways:

1. It requires expensive equipment and reagents, along with trained personnel.
2. It requires temperature cycles, so it cannot be performed at a single temperature.
3. It takes time. Depending on the initial amount of target present, a qPCR test can take as long as 90 minutes.

At the University of Florida, PhD student Long T. Nguyen, working under Dr. Piyush Jain, has developed a rapid, single temperature COVID-19 diagnostic test that provides results in under 30 minutes. Amazingly, the test distinguishes between five COVID variants, achieves amplification, and RNA to DNA conversion all in one “pot.” Finally, the results can be read on a mobile phone.

The system they used is based on a detection system found in bacteria. Bacteria contain natural immune systems called CRISPR Cas, which function to create both a memory of past viral infections, along with a defense system once these viruses come back. Cas is a protein which is sometimes described as “a pair of molecular scissors,” capable of cutting DNA or RNA fragments, while CRISPR contains complementary sequences to attacking viruses and acts as a “molecular GPS,” helping Cas find a certain target. For this reason, it is also called a Guide RNA.

Some Cas proteins locate their target and only make cuts around the target DNA/RNA; this is called cis cleavage. Others go on a “cutting frenzy.” After finding the target and cutting, the Cas protein starts cutting up other DNA or RNA fragments surrounding it, termed trans cleavage. Cas9 proteins, famous for genetic engineering, employ cis cleavage and only cut DNA. Cas12 and Cas13 proteins utilize trans cleavage, cutting DNA and RNA respectively. All bacteria have adapted their own systems, with slight variations, allowing scientists to harness each’s individual powers.

Cas12 and Cas13 proteins are at the forefront of diagnostic research. Their cutting frenzy may not be great for gene editing, but recent innovation has found that FQ reporters, or fluorescent quenchers, can be used to detect a signal with light. These reporters are dampened by a piece of RNA or DNA located between the fluorescent and quencher. Once cut, they glow and show a light on a fluorescent reader. If a Cas12 or Cas13 protein detects its target, it will cut the target then rapidly start cutting the FQ reporters nearby.

CRISPR RNA, shortened as crRNA, can be “programmed” to target any part of a target sequence. Specifically for the virus that causes COVID-19, there is a highly conserved region called the N gene. Since this same sequence is found across all variants, it can indicate the presence of the virus, but does not distinguish between mutated strains. The Jain lab identified mutated regions on each of the five variants: Alpha, Beta, Gamma, Delta, and Omicron, and created crRNAs which were complementary to each of these mutated regions. 

They then had to choose the optimal Cas protein, which could withstand higher temperatures. This was necessary because amplification occurs at high temperatures, ranging from 55-70°C. BrCas12b comes from a thermophilic bacterium found in hot springs and was the optimal choice.

Detection is completed in under 30 minutes and patient samples with a higher viral load (i.e., they had more SARS-CoV-2 virions present in their sample), exhibited 100% accuracy with about 95% sensitivity in distinguishing variants. The figure below, from Long et. al shows the incredible accuracy which comes from this detection. The colored titles, “Alpha, Beta, etc.” are the variant present in the patient sample, while the x-axis shows the crRNA used. For instance, it was expected that if a patient contained the Beta strain, only the Beta crRNA would show high signal.

Most studies combining RT-LAMP with a CRISPR reaction have extremely low sensitivity and difficulty distinguishing a positive sample. The use of specifically BrCas12b, a less studied Cas protein, allowed the Jain lab to circumvent many of the problems others have had combining the two. The applicability of this research extends far beyond COVID-19 detection. Any RNA or DNA detection could be done utilizing this research, simply by changing the sequence located on the crRNA.

Moreover, the Jain lab aims to create portable and cheap methods for testing. They proposed an inexpensive lens which can be attached to any mobile phone camera. In a dark setting, the lens, which costs less than $5 can shine light of a specific wavelength on a sample with the added CRISPR Cas reagent and glow in the presence of COVID-19.