June 18, 2020
The top story of the week is, undoubtedly, the new study from the U.K. showing that dexamethasone, the ever-present myeloma therapy, is effective in very sick patients with COVID-19 infection. But equally important this week is that we are increasingly faced with a barrage of conflicting guidance about how to stay safe during the COVID-19 pandemic. To help you process all this information, I offer a science 101 primer: how to understand information that can save your life.
The U.K. RECOVERY (Randomized Evaluation of COVID-19 thERapY) clinical trial was part of a study of 11,500 patients from over 175 NHS (National Health Service) hospitals. A total of 2,014 patients received 6 milligrams of dexamethasone daily for 10 days. (Compare this to the 20 to 40 milligrams of dexamethasone taken weekly in “low-dose” myeloma treatment.)
Use of dexamethasone significantly improved survival for both patients on ventilators and those requiring oxygen. Patients with earlier disease did not benefit, and, as myeloma patients are aware, steroids such as dexamethasone must be used with due cautions in the face of infections.
Although final analyses and peer review have not yet occurred, an urgent letter was sent to U.K. hospitals from the Chief Medical Officers of England, Scotland, Wales and Northern Ireland instructing physicians that dexamethasone use be considered a standard of care option. Of note, the antiviral drug remdesivir is also being made available in the NHS system, although all studies with hydroxychloroquine have been abandoned.
The benefit with dexamethasone is not only great news for COVID-19 patients struggling with lung complications, but helpful and interesting news for myeloma patients. The cytokine storm that occurs with COVID-19 lung disease is very similar to that which occurs with CAR T-cell therapy in patients with aggressive or very active myeloma. It should therefore not be surprising that myeloma therapies (as I have noted) have varying degrees of benefit against COVID-19 infection. This means, broadly speaking, that continuing with myeloma therapy is extremely important to control the disease and should not raise undue concerns about increased COVID-19 risks—and in some cases, such as with dexamethasone, may even be helpful.
Understanding Science to Survive: Avoid Red Herrings
A second wave of COVID-19 in China
Officials in Beijing, China shut down a seafood market after dozens of people tested positive for COVID-19. Of the initial 53 individuals testing positive, 7 had symptoms, and 6 of the 7 either worked at the Xinfadi market or had visited the market. This outbreak is an example of when understanding science starts to be important. Forty environmental samples were collected from the Xinfadi market. Great alarm emerged when positive samples came from the chopping boards used to process imported salmon. In what many consider a dramatic overreaction, all imports of salmon from Norway were immediately banned.
Professor Ben Cowling, head of epidemiology and biostatistics at Hong Kong University, called the link to salmon a “red herring.” Salmon do not sustain growth of COVID-19 and are not a source of COVID-19. The fish actually tested negative, as would be expected, since they are transported in a frozen state guaranteed to destroy any virus. There have been no COVID-19 outbreaks at source salmon farms in Europe.
This is where a standard test for evaluating science comes into play: reductio ad absurdum—reducing to the ridiculous. The COVID-19 is on the salmon cutting board not because it came from the salmon but because the employee, symptomatic and testing positive for COVID-19, most likely coughed or sneezed onto the board (as well as into the air). Salmon and other fish, meat, lamb, fruit and vegetables are NOT sources of COVID-19, nor virus transmission.
The original source of COVID-19 infection was from individuals infected because they lived and worked in southwest China’s Yunnan province, close to the border with Myanmar and Laos, where there are many horseshoe bats that carry the coronavirus. Spread of coronaviruses from bats to local residents has been well established and studied for years. This led to the original infection in Wuhan, which spread in the bustling live food market in the center of that city. However, the new outbreak in Beijing is from a new imported strain (or clade) from Europe, coming from person-to-person community spread. So, where did the COVID-19 come from?
This is when the whole testing, tracing, quarantine protocol becomes crucial. Only a few of the infected individuals had traveled outside of Beijing recently. This means that a new focus of community spread started at the Xinfadi market. The market employs 10,000 people and supplies 90% of produce to the region—not just seafood, but meat, lamb, fruit and vegetables.
The virus has been sequenced and is a mutation coming from Europe, NOT from Wuhan, the original epicenter of COVID-19. So, there had been community spread of a European strain of COVID-19. The individual source of this outbreak has not yet been identified, but probably resulted from some travel encounter not documented, which was suddenly the source of a super-spreader event. Other examples of these super-spreader events have occurred in meat-packing plants and nursing homes, where people are congregated in close quarters.
This is what we have now seen repeatedly. Although most infected individuals only infect a few (one to three) others, super spreaders with a heavier load of virus or perhaps a more virulent strain can infect dozens, even hundreds, of people at a single mass event or location. These super spreaders pop up over time and are the major sources of sustaining the pandemic. Such events have caused serious infections and deaths in an alarming fashion.
It is a top priority to both identify super spreaders and prevent all such events. The Xinfadi market outbreak is a striking new example of this phenomenon and the area is now in a “soft lockdown” in order to shut down this serious new surge, with the potential to shut down a large portion of China’s economy.
At an international level, leaders have provided excellent guidance for public safety around the world. Outstanding results have been achieved in New Zealand, Taiwan, Korea and Iceland, for example. Women leaders have done a great job!
In Turkey, a very practical approach has also been quite effective. The strategy is for young, healthy individuals (who are at low risk of COVID-19 complications) to return to work to keep the economy going, while the more elderly, at-risk individuals stay safe at home. Mass meetings and gatherings are prohibited. Nursing homes, the site of virulent COVID-19 outbreaks in the U.S., are rare in Turkey, where the elderly stay with their families. With Turkey’s approach, infections and deaths have been lower than expected and the country is functioning.
The key is to have a plan — a strategy of some sort to inform and guide people. There is no perfect plan, but it is essential to have a basic approach that can be fine-tuned to achieve better results.
In the U.S., where, unfortunately, we have no plan or strategy, studies in both Boston and San Francisco have confirmed multiple sources of ongoing community spreading events. The virus has come directly from China, Europe, and elsewhere in the U.S.
How can one avoid becoming part of a super-spreader event as many areas of the country both reopening and seeing spikes in community infection?
- Avoid all mass gatherings.
- Wear a mask whenever out on public. Recent data confirm a five-fold reduction in the risk of transmission wearing a mask. You are not only protecting others but also yourself.
- Avoid poorly ventilated, crowded spaces to limit the opportunity for air spread in any fashion. The major source of COVID-19 infection is through direct transmission in the air. Plastic barriers are definitely helpful in public spaces (check-out counters, pick-up areas, pharmacies).
- Assume that anyone you do not know is a source of COVID-19.
- Focus on outdoor activities. Direct transmission is rare in outside spaces.
- Continue to practice physical distancing and careful hand washing.
- Exercise caution around family members or friends who are active in the community.
- Avoid mass transit of all types for now.
- Continue to socially network with friends and family. At this point, many of those whom you know and trust have been quarantined for many weeks to months. This means they are an exceptionally low risk as a source of COVID-19 (as, most likely, are you)
Following these tips, you can tune out most of the political noise that only distorts the real information. Unfortunately, these days you must be your own best advocate.
I hope this week’s information helps.
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®.