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Updates on COVID-19

A collection of articles covering COVID-19.

Friday, May 29, 2020

Dispersion: A lesser-known factor in COVID-19 transmissions

Almost everyone has heard of a church gathering in South Korea which left 37 people in the country infected by COVID-19. https://www.livescience.com/coronavirus-superspreader-south-korea-church.html Many have also heard of the biotechnology company Biogen’s role in spreading the novel coronavirus far and wide following the company’s leadership meeting in March. https://www.nytimes.com/2020/04/12/us/coronavirus-biogen-boston-superspreader.html That same month, more than half the 61 attendees at a choir practice in Washington state became infected with the virus. https://www.cbsnews.com/news/super-spreader-coronavirus/

Despite the fact that we have heard of so many such “superspreading” events, SARS-CoV-2 is not particularly adept at triggering outbreaks, according to research.

Two factors are critical to understanding how fast a pathogen such as a virus spreads in a population: one is the fairly well-known reproduction number, which denotes the average number of susceptible people in a population infected by a single infected individual. A reproduction number over the critical threshold of 1 ensures continued transmission ensuring disease persistence. While the reproduction number for SARS-CoV-2 is known to be three without enforcement of lockdowns and social distancing, reality is very different – some people transmit the disease to a lot more than three other individuals, while others (and this tends to be the norm with this virus), do not transmit it at all.

The second factor, which seems more significant in terms of COVID-19, is the dispersion factor; this number defines the extent to which the disease clusters. The dispersion factor determines the individual variation in the number of secondary cases that result from a primary or “index” case. In other words, if the dispersion factor is high, a small number of cases are disproportionately responsible for a large number of secondary cases, while a large number of patients may not transmit the disease at all. Low dispersion, on the other hand, results in a more constant growth of the epidemic, without a lot of variation in the number of secondary cases triggered by an index case.  

There isn’t a consensus yet on SARS-CoV-2’s dispersion factor. Researchers at the University of Bern have shown < https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.4.2000058> that the dispersion factor for COVID-19 is higher than for SARS and MERS, meaning it is less likely than the other two coronaviruses to have large superspreading clusters. The group mimicked the Chinese epidemic with varying combinations of the reproduction number and dispersion factor and compared their results to actual numbers before arriving at this conclusion. The high dispersion factor of the virus may mean that while we don’t see large superspreading events, concentrated clusters do occur, where a smaller number of patients cause a large proportion of infections.

Several studies <https://www.axios.com/coronavirus-superspreaders-7f91c28a-a68a-460b-93e7-43b3ddf1eddd.html> found evidence of substantial overdispersion of SARS-CoV-2, indicating that a relatively small number of patients are responsible for a large percentage of infections. One study in Hong Kong <https://www.researchsquare.com/article/rs-29548/v1> found that 20% of patients contributed to 80% of cases and another encompassing the Asia-Pacific region < https://wellcomeopenresearch.org/articles/5-67> revealed that roughly 10% of cases led to 80% of infections.

This could explain why the disease did not take off around the world very soon after its origin in China as well as its general irregularity in transmission in different regions of the world: isolated cases in certain countries failed to fuel large outbreaks while other regions saw an exponential number of cases from single cases.

There are other factors that determine whether the virus spreads quickly from a person – such as how loud a person is talking (or singing) < https://www.cnbc.com/2020/05/19/coronavirus-spread-by-talking-can-remain-in-air-researchers-find.html> and what stage of infection they are at when < https://www.sciencenews.org/article/coronavirus-covid-19-infection-contagious-days-before-symptoms-appear> attending so-called superspreading events. Some infected individuals may not yet be exhibiting symptoms or function as asymptomatic carriers <https://www.nytimes.com/2020/03/31/health/coronavirus-asymptomatic-transmission.html> while spreading the virus. These are all aspects known to contribute to transmissibility.

While these findings may be attributed to our general lack of understanding of how SARS-CoV-2 operates, they also suggest specific methods of control. Since the virus is more likely to transmit among tightly connected groups of people in enclosed spaces, restricting crowds where superspreading is most likely to occur can have a huge impact on control measures. This is the rationale behind some scientists’ theory that simply limiting mass gatherings could bring COVID-19 down to a manageable level <https://www.wsj.com/articles/superspreader-events-offer-clue-on-curbing-coronavirus-11589977873>. Relaxing restraints on outdoor activities also seems advisable, given that the virus is mostly prone to superspreading indoors.

These guidelines are especially useful at a time when states and countries are beginning to ease their coronavirus restrictions and trying to balance economic interests with public health and security.

Monday, May 4, 2020

Nurse practitioners (NPs) have the training and experience to address the multiple healthcare needs of COVID-19 patients. Yet, due to confining laws limiting their scope of practice in several states, NPs and other advance practice registered nurses (APRNs) and physician assistants are unable to fully contribute their skills during this public health crisis.

Not surprisingly, some states, including Kentucky, Louisiana, New Jersey, New York and Wisconsin, have expanded scope of practice for APRNs amid the coronavirus crisis. An additional 12 states have modified existent laws to give more authority to providers with extra training.

This followed calls on state governors by the American Association of Nurse Practitioners and US Secretary of Health and Human Services Alex Azar to relax restrictions on scope of practice laws that limit NPs and physician assistants from providing much needed medical care. The move will expand patient access to healthcare as the country faces an unprecedented strain on health resources and workers.

Nurse practitioners have a number of skills that can be particularly helpful when dealing with the coronavirus pandemic: they have the ability to diagnose patients, interpret test results, and start patients on prescription and non-prescription treatments. They are also well trained in coordinating care and educating patients and caregivers, which are highly desirable skills during a public health emergency.

However, some states with strict scope of practice laws continue to function with these restrictions in place, denying APRNs the chance to care for patients amid the growing pandemic. In states with such laws, advance practice providers can only practice with a “collaborative agreement with a provider.”

Georgia is one such state. The state’s APRN practice laws are already among the strictest in the country. The four categories of APRNs—nurse practitioners, nurse anesthetists, nurse midwives, and clinical nurse specialists—need to have a protocol agreement with a supervising physician and additional supervision requirements to be able to practice in the Peach State.

Governor Brian Kemp has not taken steps to even temporarily suspend the state restrictions during the pandemic. This is despite urging by Secretary Azar, the United Advanced Practice Registered Nurses of Georgia (UAPRN), and the Georgia Coalition of Advanced Practice Registered Nurses (CAPRN).

“The leaders of the healthcare community in Georgia have sent letters and recommendations to the governor’s office without any response at all,” says Michelle Nelson, State President of UAPRN and co-director of Georgia CAPRN. “So his recommendation to open up the state was not based on the input of people on the frontlines, the physicians, and nurses.”

Not utilizing these qualified advance nurse practitioners (ANPs) to help combat the pandemic seems particularly short-sighted in light of the fact that the state is among the first to start reopening businesses, even while COVID-19 cases continue to rise and Georgia still ranks among the lowest in the country in per-capita testing for the virus. This goes against a three-phase plan recommended by the Trump administration, which suggests that states see 14 days of declining new infections before opening a wide range of businesses. Citing the need to allow revenue flow, Kemp, who was among the last of the nation’s governors to impose social-distancing guidelines, is one of the first to lift restrictions.

Healthcare workers must now brace themselves for the impact this is going to have on hospitals and patient care. “Since we have opened, we must anticipate that not only a second wave is coming, but that we are going to see a very big increase of what we already have with limited resources,” Nelson warns. “It is of the utmost importance to have as many hands on deck to make sure that people are able to get the appropriate care. Opening up the state is going to put further strain on our hospital systems – not just the workforce, but the resources in terms of personal protective equipment, which we already can’t secure in the amounts that we need.”

In anticipation of this, Governor Kemp did issue an executive order, which expedites nursing students for graduation and enables retired nurses to rejoin the workforce. Graduate nurses who are waiting to take their nursing exams are allowed to get a temporary license through the Georgia Board of Nursing. In addition, out-of-state doctors, nurses, and pharmacists can obtain temporary licensures to practice in Georgia.

“I applaud the governor’s motivations in trying to get as many nurses back into the workforce but something very important that he missed is the ANPs,” says Nelson. “They are working every day, they are experienced, they are skilled, they are licensed, and they are certified to be able to provide high level care. Why not allow them to be able to work to the highest levels of their ability? If you truly care about making sure that Georgians are getting optimal healthcare, why are you overlooking a significant subset of the nursing workforce that is up and ready?”

An unexpected result of the coronavirus pandemic has been the loss of jobs among healthcare workers – with fewer and fewer people needing other routine care amid the pandemic, doctor’s offices and clinics around the country have shut down. 

“Surgery centers and hospitals have furloughed ANPs, fired them, doctor’s offices have closed down, and let them go,” Nelson laments. “These are people without work—and instead of bringing them into other areas where they can work, we are inviting graduates and retired people and even nurses from other states to come and work here. What about the people who are already working here that are ready, willing, and able?”

While some physicians have seen a drop in the number of patients due to COVID-19 with fewer patients going to the doctor, there are still a number of hard-to-access and rural communities in Georgia that struggle due to lack of adequate care. Imposing collaborative agreements for NPs prevents geographic access to care in these regions. “People who are not infected but may have other primary care issues—what are we doing to put healthcare providers in place to take care of these people?” asks Nelson. “A lot of physicians have closed down their offices. And there are many counties in Georgia that have no healthcare providers, hospitals, or doctors’ offices. People have to drive to neighboring counties to get care. We should at least put something in place in these communities.”

Lifting restrictions on ANPs and enabling them to practice without physician supervision would allow them to move to regions where care is most needed.

“We are requesting at least temporarily–although we should do this permanently–for lifting of restrictions on our ability to practice to the highest levels of our training, certification, and licensure,” Nelson states. “We are asking to be able to go into communities, particularly in rural areas where there are no healthcare providers, and to set up popup clinics to deliver healthcare, if nothing else.”

With the aim of improving Georgians’ access to medical care, state legislators have introduced bills to broaden the scope of practice for non-physicians with advanced training every year to no avail. These attempts have come up short against resistance from medical provider groups who want to keep things as they are.

“We get significant opposition from the medical association of Georgia which has a lot of sway over legislators, so they fight us tooth and nail over releasing these restrictions,” explains Nelson. “The restrictions we have now dictate that a physician has to supervise ANPs even in their own practices and that they don’t have any more than four ANPs to supervise. So, even if we were able to hire more ANPs, we have to pay physicians a fee to be the supervising physician–that is typically about a thousand dollars a head per month, which could easily add up to $40,000-60,000 a year. So you can see why physicians are so dead set against ANPs being able to work without supervision.”

These limitations are motivating nurses to leave Georgia and practice in states with lighter restrictions. APRNs who work at VA hospitals and military bases in Georgia are governed by federal regulations and hence allowed full practice authority without the need for physician supervision. States that allow full practice authority to APRNs have had no reason for concern.  

As Nelson affirms, “Twenty-two states have moved to the full practice authority model. Not one of them has revoked them. None of them have said that ANPs are not working or are unsafe. We have decades of data and research that show that we are able to provide safe, quality, and effective healthcare and are able to handle 80-90% of the cases that come to any primary care physician’s office. And we are also trained to know that if it something is beyond our scope of practice or expertise, we must appropriately refer it to a physician or specialist.”

Now more than ever, it seems critical to remove these restrictions and empower this highly trained healthcare workforce to contribute to an unprecedented crisis.

“It’s time to put patients and communities first,” Nelson asserts. “And it is high time that we decide to not let the special interests, finances, and pocket books of a few dictate the health and wellbeing of the citizens of Georgia.”

 

 

Tuesday, April 28, 2020

As the COVID-19 pandemic continues, the correlation between obesity and patient outcomes becomes clearer to the scientific community.1 This link appears related to the diminished immune response and viral pathogenicity in patients with obesity. Current understanding of the pathogenesis is that obesity contributes to the cytokine storm immune response in patients infected with COVID-19. A large study recently confirmed that patients with obesity were not only more likely to need mechanical ventilation but were also more likely to require vasopressors.2 A BMI above 30 seems to increase a patient’s risk of intensive care and all-cause mortality from COVID-19, and appears to be the most prevailing underlying condition for those hospitalized with COVID-19.3

The importance of addressing modifiable risk factors such as exercise and diet cannot be underestimated in this pandemic. Evidence continues to validate the importance of a healthy BMI to reduce morbidity and mortality with COVID-19. The direct practice implication here is the potential consideration of BMI as a pivotal vital sign. The data from COVID-19 mortality suggest that addressing elevated BMI on each patient encounter is equally as important as any other elevated vital sign. NPs are in a unique position to provide holistic patient care by indicating lifestyle changes that support a healthy BMI for patients.


References:

1. Carter SJ, Baranauskas MN, Fly AD. Considerations for obesity, vitamin D, and physical activity amidst the COVID-19 pandemic. Obesity (Silver Spring). [ePub. April 16, 2020.]

2. Goyal P, Choi JJ, Pinheiro LC, et al. Clinical characteristics of COVID-19 in New York City. New Engl J Med. [ePub. April 17, 2020.]

3. Centers for Disease Control and Prevention. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019—COVID-NET, 14 States, March 1-30, 2020. Morbid Mortal Weekly Rep. 2020;69(15):458-464.

Wednesday, April 22, 2020

covid 19 virus and people.jpg

In the wake of the coronavirus disease (COVID-19) pandemic and the increased need for healthcare providers, states have opened a window for Advanced Practice Registered Nurses (APRNs) to respond to the increased demand for workforce expansion and care of higher acuity patients.  If you live in one of the states that have been hit hardest from the COVID-19 pandemic, you have been working nonstop for weeks to months depending on your location.  Hospitals and primary care providers alike have had to change their approach to delivering care to be able to meet the needs of patients while keeping vulnerable populations safe.  This has resulted in some providers switching from face-to-face visits to online platforms (telemedicine models).  The learning curve has been steep at times, but patients are thankful for the opportunity to continue the connection with their healthcare providers while following social distancing guidelines and staying safely at home.

For hospital and acute care providers, the situation has rapidly developed into scenarios where staff are needed to cross train in preparation for the surge of COVID-19 positive patients.  Many states prepared for increased intensive care unit (ICU) beds, increased mechanical ventilators, as well as increased acquisition of personal protective equipment (PPE), which are already in short supply.  

The increased demand for providers has resulted in temporary emergency proclamations across the country by state Governors (AANP, 2020), which have included the following:

  • Temporary Work Permits for Reinstatement Applicants
  • APRN Collaborative Agreement Requirements Lifted
  • Physician Supervision of CRNAs (certified registered nurse anesthetists) Removed
  • Clinical Education Requirements Modified
  • Provisional Licenses for Exam Applicants and Temporary Work Permits for Endorsement Applicants

Only five states (Kentucky, Louisiana, New Jersey, New York, Wisconsin) have temporarily suspended all APRN practice agreement requirements. These executive orders state a date of expiration but Governors have the authority to extend those dates.

This is a perfect time for all APRNs to document our effectiveness in the face of this coronavirus pandemic and reach out to our consumers, patients, and legislators to stress the positive components for all stakeholders of full practice authority for all APRNs in all states.  The benefits for continuing the ability to practice at the top of our scope of practice are too many to count, but ones we need to highlight are:

  • Increased access to quality healthcare providers
  • Decreased costs to patients and healthcare systems and states that embrace this model
  • Increased number of providers to manage the increased chronicity of disease in our outpatient population
  • Increased providers to care for increased acuity and increased co-morbid burden of our in-patient population
  • Increased providers for vulnerable populations and underserved areas, including rural

In 1918, nurses played a pivotal role in the Spanish flu pandemic that killed about 675,000 Americans and up to 50 million people worldwide.  Today, advances in science, technology, and healthcare have made the world much safer. However, the following modern developments have also put the world at risk for pandemics:

  • Growth in the world's population
  • Urbanization with increased population density
  • Increased global travel and integration
  • Changes in land use (loss of animal habitats)
  • Increasing emergence of transmission of viral disease from animals/ domestication
  • Greater exploitation of the natural environment
  • Mutations and adaptations of organisms
  • Engineering or re-creation of disease-causing organisms in laboratories
  • Breakdown in public trust of governments, scientists, the media, public health, health systems, and health workers in many countries
  • Health misinformation from easily accessible sources
  • Insufficient global preparedness and support for a pandemic health crisis by governments at all levels (Global Preparedness Monitoring Board, 2019; Madhav et al., 2018).

APRNs should connect with their local, regional, state, and national organizations to advocate for continuing the waivers for practice, and permanent removal of barriers to full practice authority. Joining an organization, paying dues, contributing money to political action committees, participating in advocacy activities, and communicating with administrators, and local and state elected officials and legislators are ways every APRN can help keep the focus on the value of our practice and the benefits to patients of full practice authority for APRNs. And we do this by collecting data to demonstrate impact and effectiveness. Monitor and collect outcome data in those states that have relaxed restrictions during the pandemic that will enable us to demonstrate our outcomes of providing extraordinary care in extraordinary circumstances.  The current practice environment in states with temporary executive orders that waive barriers during the pandemic should be the "new definition" and our "new normal" for how we practice in every state all the time.  

There are few times in our country's history that provide such opportunities in which we can take a stand. 2020 is the Year of the Nurse and Midwife and it could not be a better time to be an advanced practice nurse and to be able to own our strengths and highlight our abilities to impact patient care and outcomes. The time to act is now.


REFERENCES

American Association of Nurse Practitioners (AANP). COVID-19 state emergency response: temporarily suspended and waived practice agreement requirements. 2020. www.aanp.org/advocacy/state/covid-19-state-emergency-response-temporarily-suspended-and-waived-practice-agreement-requirements.

Global Preparedness Monitoring Board. A world at risk: annual report on global preparedness for health emergencies. Geneva, Switzerland: World Health Organization. 2019. https://apps.who.int/gpmb/annual_report.html

Madhav N, Oppenheim B, Gallivan M, Mulembakani P, Rubin E, Wolfe N. Pandemics: risks, impacts, and mitigation. In DT Jamison, H Gelband, S Horton, P Jha, R Laximinarayan, CN Mock, & R Nugent (Eds.), Disease control priorities: improving health and reducing poverty (3rd ed.) (pp. 315-345), Vol 9. Washington, DC: World Bank. 2018. http://documents.worldbank.org/curated/en/527531512569346552/pdf/121615-PUB-HOLD-embargo-date-is-12-6-2017-ADD-BOX-405304B.pdf


Authors:

Sheila D. Melander, PhD, APRN-BC, FCCM, FAANP, FAAN
Associate Dean of MSN and DNP Faculty and Practice Affairs
University of Kentucky College of Nursing

Jamesetta A. Newland, PhD, FNP-BC, FAANP, DPNAP, FAAN
Editor-in-chief, The Nurse Practitioner
Clinical Professor Emerita, New York University Rory Meyers College of Nursing

Monday, April 20, 2020

HTN Image.jpg

Older age, diabetes, and heart disease are seen to be the most common risk factors for severe cases of coronavirus infection. Much has been made of the connection between hypertension and Covid-19 since reports suggest that the novel coronavirus disproportionately affects people with such cardiovascular conditions.

Patients with severe symptoms of Covid-19—often requiring mechanical ventilation and intensive care, and some succumbing to death—consistently exhibit comorbidities such as hypertension and cardiovascular disease. Hypertension was seen to be the most frequent coexisting condition in one of the largest studies from China, which involved 1,099 patients. The prevalence of hypertension among these patients was 15%.

Correlation between Covid-19 and hypertension

However, recent research published in the Journal of the American Medical Association Cardiology warns that the correlation maybe overstated. "I don't think these conditions are overrepresented [in Covid-19 patients]," says Franz Messerli, senior author of the paper with affiliations at Bern University Hospital in Bern, Switzerland and the Division of Cardiology at Mount Sinai Health Medical Center in New York. "We looked at two big studies with H1N1 flu and they also quote-unquote "show overrepresentation of hypertension and diabetes." Basically, these two conditions have become so common and so prevalent. Hypertension is a common comorbidity for anything, not just for Covid-19."

Another recent paper in the New England Journal of Medicine (NEJM), notes that the 15% estimate in the abovementioned study from China is actually lower than the coexistence of hypertension among other viral infections, such as viral pneumonia, influenza, and Middle East Respiratory Syndrome, as well as in the general Chinese population. Moreover, the researchers note that hypertension is usually prevalent in infective illnesses and in patients with advancing age; the latter remains the strongest predictor of fatality from Covid-19.

The RAAS system and Covid-19

The renin–angiotensin–aldosterone system (RAAS) is responsible for several important human physiological processes. The respiratory syndrome coronaviruses—SARS-CoV-1 that caused the SARS epidemic in the early 2000s and SARS-CoV-2, which is responsible for the current Covid-19 pandemic—interact with the RAAS through angiotensin-converting enzyme 2 (ACE2), which counters RAAS activation within the body. More importantly, ACE2 acts as a receptor for both SARS viruses, and this interplay has long been implicated in virus infectivity. SARS-CoV-2 engages with and uses ACE2 for entry into target cells.

However, not enough is known about the interactions between the RAAS and Covid-19. "This is an evolving topic," Scott Solomon of Boston's Brigham and Women's Hospital and senior author of the NEJM paper said in an email. "There are some data to suggest that the RAAS might play a role in acute respiratory distress syndrome (ARDS) and even some data that blocking the RAAS can attenuate ARDS in animal models, but minimal human data are available."

The effect of hypertension drugs on the coronavirus

The overrepresentation of hypertension patients among those afflicted with the novel coronavirus has triggered concerns about the use of RAAS inhibitors—which include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs)—often used in the medical management of these conditions.

Animal studies have shown that ACE2 is substantially increased in mice treated with ACEIs and ARBs. This has led to the concern that ACEIs and ARBs taken by hypertension patients could potentially exacerbate COVID-19 infection by increasing ACE2 levels. "We know that in certain patients, ACE2 is upregulated and this upregulation could predispose them to enhanced infectivity because obviously the coronavirus seems to connect with the ACE2 receptor," says Messerli. But he cautions that this is still theoretical. "We don't know for a fact that this is happening – so far it has not been documented."

Solomon reinforces this point. "There are no good data that RAAS inhibitors are harmful in this population at the moment. We are awaiting well-controlled observational data. Some have raised theoretic concerns but there are no data yet to support either withdrawing RAAS inhibitors from patients prophylactically or even when they have Covid-19, unless clinical circumstances warrant it." He and his co-authors observe that many of the Covid-19 patients included in the Chinese study were probably not being treated with RAAS inhibitors – only 30 to 40% of Chinese patients are treated with any antihypertensive therapy, with those treated with RAAS inhibitors being as low as 25-30%.

This is why Solomon does not recommend that patients be taken off RAAS inhibitors just yet. "First, in patients who are on RAAS inhibitors as guideline directed therapy—in the case of heart failure and post-myocardial infarction in particular—we believe that withdrawal would be potentially harmful and should be avoided," he says. "For hypertension alone, we do have several options for treatment, but based on the available data I would not recommend withdrawal of these agents at this time either prophylactically or even in patients with Covid-19 (although this decision has to be made on the ground, since blood pressure could be an issue in patients with severe disease). This is also the recommendation of the American Heart Association, the American College of Cardiology, Heart Failure Society of America, and the European Society of Cardiology."

Messerli warns though, that reading about such possible associations could spread alarm among those afflicted with the coronavirus. "The problem is if patients read that some medications—such as ARBs and to a lesser extent ACEIs—increase the activity of ACE2, it can cause anxiety. Probably around 50 million people worldwide use ACEIs and ARBs. That could lead to a lot of stress for people." That said, he also recommends that patients continue the same medication they are on as much as possible, except at the expense of patients abandoning their medications.

"If the patient really has high anxiety levels, then there is a risk they may discontinue the medication without doctor's orders," Messerli says. "If that's a concern, it's a big risk. They may have heart failure and end up in the emergency room – that's not a good scenario. So if the patient is really very concerned, I would simply suggest to switch to a direct renin inhibitor, which downregulates the renin-angiotensin system and one study showed that it also downregulates ACE2. I cannot vouch for the soundness of the study. But this way you get all the benefits of renin-angiotensin blockade while downregulating ACE2. We state clearly in the paper that this should be a temporary switch – this should not be done permanently but just to relieve anxiety during this time."

Could RAAS inhibitors be beneficial to Covid-19 patients?

Two forms of ACE2 exist in the human body – a transmembrane protein functions as a receptor for SARS-COV-2's spike protein, and a soluble form, which circulates in small amounts in the blood. Understanding the interaction between the Covid-19 virus and these two forms of the enzyme could go a long way toward understanding the process of viral infection. 

A recent study showed that patients with Covid-19-associated pneumonia had higher levels of serum angiotensin II, and these levels correlated with increased viral load and lung injury. One hypothesis based on this observation is that the binding of SARS-CoV-2 to ACE2 may mitigate ACE2 activity, which leads to RAAS activation and increased angiotensin II, which results in pulmonary complications and risk of lung injury. Modulation of the RAAS by ACEIs and ARBs could thus lead to increased expression of ACE2, which could relieve some of the above symptoms.

However, this is merely a hypothesis. "We don't know that RAAS inhibitors would be beneficial at the moment," says Solomon. "ACE2 is the enzyme by which the virus enters cells. When the virus utilizes this enzyme to get into the cell, the activity of the enzyme is reduced and thus its main function, to counterbalance activation of the RAAS, is attenuated. This might have deleterious effects and might promote unchecked local RAAS activation. That is why some have speculated that RAAS inhibitors could in fact be beneficial. But this needs to be tested in clinical trials."

Another theory is that increasing soluble forms of ACE2 within the body may provide competition to SARS-CoV-2, thus slowing viral entry into cells. "Experimentally and clinically, it has been shown with other viruses that the outcome of viral pneumonia is mitigated in patients who are on ACEIs or ARBs," says Messerli. "So once you are infected, it's good to be on ACE inhibitors or ARBs, though this is still speculation at this point."

These two propositions indicate that ACEIs and ARBs may help Covid-19 patients by increasing ACE2 levels. Studies are underway to test if the ability of ACE2 to bind to SARS-CoV-2 could present potential therapeutic options for Covid-19.

But as Messerli noted, coronavirus research changes every day. "I can only say what is the state of the art as of today; tomorrow it may already be different. This is a very fast changing environment."