April 23, 2020
As we hear more and more about states and cities planning to re-open during this pandemic, how can myeloma patients plan to stay safe—if not necessarily at home?
First, myeloma patients should absolutely plan to stay home until it is safe to venture out in their locale. Second, to gauge when it might be safe to leave home, myeloma patients should closely monitor local information about COVID-19, such as infection numbers and plans for social distancing.
This week, new guidance has emerged to help us gradually transition to a new normal. It is easiest to pick up the news and recommendations where we left off last week, and update information and recommendations for: Testing, Tracing, and Treatment (the three Ts), the key components of safe re-opening strategies.
Myeloma patients will need to be tested for COVID-19 and/or COVID-19 antibodies before re-mingling in their local community and visiting their doctors and myeloma clinic personnel. For myeloma patients exposed to COVID-19, the antibody testing will be crucial to assessing ongoing immunity. For those not exposed, a COVID-19 screening test will be required as a baseline.
New Data About Spread in the Community
Several reports indicate that COVID-19 has been spreading in the community much longer than we first thought, extending back to early February and January, if not before. This means that many people, including myeloma patients, may have been infected and were never diagnosed. It is interesting and quite reassuring that myeloma patients most likely have been infected without incident, as opposed to many other at-risk groups in whom serious problems have emerged. New data again emphasize that major risk groups are those with high blood pressure (hypertension), obesity, and diabetes.
As noted below, increasing data indicate that myeloma therapies can be helpful, rather than increase risk factors for infection and/or complications. Even dexamethasone may be helpful to suppress the lung inflammation process, although due cautions are required since fever may also be suppressed.
Results of COVID-19 testing in individuals without symptoms indicate that about 50% of asymptomatic patients test positive and that they can readily spread infection. Approximately 5% of people in the total population have been exposed so far, according to current estimates, meaning that 95% are still at risk.
Implications of Flattening the Curve
Reducing the number of new COVID-19 patients, and particularly those needing hospitalization and/or ICU care, is an essential step toward creating a safe public environment for re-opening the country. The key point is that the number of new cases per day must be dropping and low, preferably under 100 (as a maximum) and as close to zero as possible. This allows broad testing to be implemented to assess the ongoing population spread of COVID-19.
In California, for example, as the curve flattens, and hospitalizations and ICU cases drop, the state this week announced plans to test between 60,000 to 80,000 people per day. With this approach, the number of new cases per day should be manageable and allow for contact-tracing in real time.
The Bottom Line for Testing
- High testing capacity is required to achieve safety.
- Antibody tests will, hopefully, reflect ongoing immunity.
- COVID-19 testing will allow proper guidance for quarantine/isolation (within a family, for example) or appropriate cautions about ongoing myeloma care.
- Testing and contact tracing will enable identification of any new clusters in the community, including asymptomatic but infectious individuals. This will be the basis for guidance in daily life.
2. Tracing Updates
To re-open our communities, it is essential to trace those individuals who have come into contact with those infected with COVID-19. What has such tracing revealed so far?
Sequencing Studies of COVID-19
A small study from China followed up on eleven patients in Hangzhou, a city east of Wuhan, the epicenter of the COVID-19 pandemic. Professor Li Lanjuan, a researcher at Zhejiang University, conducted deep sequencing of the coronavirus. Among the study’s many important observations:
six different mutations in the spike protein of COVID-19 (which is used by the virus to enter cells and is the basis for creating a vaccine) and dramatic differences in pathogenicity. Some virus strains were much more dangerous and spread widely, with up to 270 times greater virus load in the infected patients linked to more severe complications and outcomes. The sobering findings start to explain stark differences in outcomes between New York (very severe) and California (much less so) linked to different virus strains.
A larger sequencing study from Seattle again demonstrates the multiple strains of the virus at the molecular level and reveals that early U.S. deaths, dating back to February 6 and possibly before, were from a traveler from Wuhan, China. The sequencing showed that very early community spread was going on and contributing to cases not only in Washington state, but San Francisco and across the country. Cluster tracing in this elegant fashion illustrates that much earlier testing plus tracing will prevent this type of broad community spread.
California Serves As an Example
Current planning in California illustrates what is required to implement efficient tracing. It was announced this week that 10,000 tracers (or “connectors”) will be used to track contacts of all new COVID-19-positive cases.
Using Dogs to Sniff Out COVID-19
An interesting, low-tech approach to virus detection is being tried out in the UK, where they are using dogs (spaniels and Labrador retrievers) to sniff out COVID-19. This is amazing and could possibly blunt privacy concerns about proposed electronic methods for tracing. A more high-tech approach was outlined by Mark Zuckerberg this week. Researchers at Carnegie Mellon University created an opt-in symptoms survey, which was posted on Facebook. The self-reported responses are delivered directly to those researchers for analysis.
The Bottom Line:
- Efficient, rapid contact tracing is essential. Many details are still being worked out.
- Without results of tracing, a myeloma patient cannot safely re-enter the community at large.
- Tracing will both save lives and keep pressure off clinics and hospitals so that normal standard-of-care services can be safely provided.
- Awareness of new strains of COVID-19 will help direct resources to areas with more dangerous clusters of infection, which must be contained as rapidly as possible.
Containment is the only way to prevent a new surge in disease. We are already learning from new small surges in Harbin, China, and Singapore. These are cautionary outcomes which can guide re-opening strategies in the U.S. and elsewhere. Any situation in which large numbers of people congregate is a concern. These include nursing homes, cruise ships, and places where people live in close quarters. These will be targets for closer scrutiny and testing.
3. Treatment Implications As Communities Re-Open
While the goal is to shift back as soon as possible to standard-of-care recommendations for myeloma therapies, precautions by myeloma patients will continue for the foreseeable future.
This Week’s News About Treatments
We continue to learn about myeloma therapies being repurposed to treat COVID -19. The newest additions are:
- Aplidin, an eEF1A2 antagonist that in low doses inhibits virus replication
- Cyclosporine, a drug which can work like Actemra to shut down the cytokine storm linked to dangerous COVID-19 infections. Famed CAR T-cell researcher Dr. Carl June (University of Pennsylvania) this week announced a plan to test the drug, which is a pill that is very cheap to produce and already commercially approved as an immune therapy.
It is also remarkable to see all the refinements in attempting to provide improved care and outcomes for the sickest COVID-19 infected patients. Using a simple method to check blood oxygen (a pulse oximeter) can help detect early drops in oxygen before the patient is aware, enabling early intervention before there is a crisis.
An important study shows that hydroxychloroquine is not showing promise against COVID-19, despite high expectations by some. The results of a VA study of 368 patients (unfortunately, not randomized) showed significantly more deaths in patients receiving the malaria drug—not what we want to see. About 28% who were given hydroxychloroquine plus usual care died, versus 11% of those getting routine care alone. This underscores the need for ongoing trials to assess the value (or not) of all promising therapies.
A new vaccine being developed by researchers at Oxford University is moving forward. This novel approach promises to produce a vaccine in six months. Although there is some skepticism about the timeline, the many efforts around the world to develop a vaccine at lightning speed are encouraging.
The Bottom Line:
- Safe practices for patients are absolutely required to allow any return to a new normal.
- There are many encouraging results with treatments for COVID-19 patients that give hope that we will be able to better manage patients while we wait for a vaccine to become available.
Using Social Connections to Stay Strong: Always Look for the Silver Lining
As we remain physically isolated it is increasingly important to reach out and sustain social connections. We will get through this together, but there are many challenges ahead. We all need our “quaran-team” to serve as a sounding board and support system.
Every cloud has a silver lining. The fact that many more people have been infected with COVID-19 and recovered means that many more individuals have antibodies in their plasma which can be used to save others. The 500-plus ongoing clinical trials for COVID-19 treatments will likely produce several very useful therapies.
We are blessed that our healthcare professionals come to work every day, and that so many who serve on the frontlines put themselves at risk daily. We will be faced with the unfortunate reality that this won’t be the case around the world, as many will struggle to survive this enormous crisis.
But as we celebrate the 50th Anniversary of Earth Day this week, the planet is literally getting a breather, because industries and travel are shut down. Jellyfish are swimming in the canals of Venice and animals are roaming freely in our National Parks and around the world. And, as we have noted, spring is in full bloom, even in New York City’s Central Park.
We will get through this together!
Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.