By Chase Doyle
The COVID-19 pandemic has threatened the stability of healthcare systems around the world, but some patient populations are more vulnerable than others. In a two-part webinar hosted by OBR, Samuel Silver, MD, PhD, Professor of Internal Medicine/Hematology-Oncology at the University of Michigan Medical School and former Chairman of the NCCN Board of Directors, and Debra Patt, MD, MPH, MBA, Executive Vice President of Texas Oncology, discussed how oncology practices are responding to the crisis and preparing their clinics for the possibility of patient and provider infections.
Transmission and Incubation of SARS-CoV-2
Dr. Silver reported that the viability of the novel coronavirus varies depending on environmental conditions.1 In aerosols, SARS-CoV-2 can remain viable and infectious for approximately three hours; on plastic and stainless steel surfaces, it can remain viable up to 72 hours; on cardboard, however, no viable SARS-CoV-2 was measured after 24 hours; and on copper surfaces, the virus is viable for only four hours.
The incubation period of the virus also varies dramatically from patient to patient, said Dr. Silver, who noted that Chinese data have shown that 97.5% of patients who develop symptoms do so within 11.5 days, and the median incubation period to fever onset is 5.7 days. However, he also highlighted the tail end of this curve.
“Everyone talks about a two-week incubation period, but that is not absolute,” said Dr. Silver. “About 1% of patients will develop symptoms after 14 days. More importantly, a significant percentage of people who have the virus but remain asymptomatic can still transmit the disease, and we’re trying to learn more about those people.”
Researchers at Rockefeller University and the Howard Hughes Medical Institute are testing inherited genetic disorders that could lead to life threatening COVID-19 disease, specifically inborn errors of immunity among younger patients who develop severe infections.
“Host genetic vulnerability is obviously a big area of interest,” said Dr. Silver. “We’re still trying to determine why some young patients experience such difficulty with the virus, whereas other patients have no difficulty at all.”
Who Should Be Tested?
According to Dr. Silver, serologic testing will ultimately play an important role in understanding the epidemiology of COVID-19, especially in the asymptomatic population, but for diagnostic purposes, reverse transcription polymerase chain reaction (RT-PCR) is the standard test and it is highly sensitive and specific.
Due to a lack of resources, however, testing for the virus has become problematic. The Infectious Diseases Society of America (IDSA) recently published recommendations for diagnostic testing, which includes four different tiers of prioritization2:
- Tier 1: Critically ill patients in ICU-level care, individuals (including health care workers) with fever or respiratory symptoms who have had close contact to a confirmed case or recent travel to areas with high transmission; patients with respiratory symptoms or fevers who are immunosuppressed, elderly, have underlying chronic conditions, or an individual critical to pandemic response
- Tier 2: Hospitalized patients not in ICU and long-term care residents with unexplained fever and symptoms of lower respiratory tract infections
- Tier 3: Individuals in outpatient settings who are eligible for influenza testing, including individuals older than 50 and immunocompromised
- Tier 4: Individuals in communities being monitored by public health authorities
As Dr. Silver reported, Abbott Laboratories, which just introduced a “less expensive, less bulky” platform that can detect COVID-19 in as little as 5 minutes, may help ease some of the testing burden.
Managing Cancer Care
Early reports from Chinese investigators on patients with cancer who were infected with COVID-19 have identified nearly four-times higher risk of mechanical ventilation, ICU admission, and death compared with patients without cancer. Although the data are still limited, said Dr. Silver, oncologists intuit that their patients are at increased risk if infected and therefore must make difficult clinical decisions.
According to a special feature published in the JNCCN,3 solid tumor patients should likely proceed with adjuvant therapy with curative intent despite the threat of infection. Similarly, for patients with metastatic disease, treatment delays may lead to worsening performance status and loss of the window to treat. Considerations should include how delays from treatment may lead to admission for symptom palliation, which further stresses inpatient resources.
In addition, Dr. Silver said for patients with aggressive hematologic malignancy, there may be an urgency for life-saving therapy, including CAR T-cell therapy and stem cell transplantation, which cannot be delayed in many cases. For those suspected of being infected, however, transplants and cellular therapies should be delayed for a minimum of 14 days or until symptoms have resolved.
Blood shortages are also leading to transplantation delays across the country. Dr. Silver reported, many blood banks in the U.S. are down to a 1-day blood supply. As such, most centers are delaying all autologous transplants for myeloma and many for lymphoma as well as transplants for non-malignant disorders like sickle cell that may be deemed non-emergent.
The list of potential COVID-19 therapeutics in development or in clinical trial may be long, said Dr. Silver, but providers still “know very little about what to do”. This list includes4:
- Remdesivir: a novel nucleotide analog with activity against multiple SARS in vitro and in animal studies. There are clinical trials and expanded access, said Dr. Silver, so there is “tremendous interest in this agent”.
- Chloroquine or Hydroxychloroquine: anti-malarial drugs that have shown in vitro activity against coronaviruses, including SARS-CoV-2. Hematologists should watch out for glucose-6-phosphate dehydrogenase (g6pd) deficiency, said Dr. Silver, who noted that the recommendation of the University of Michigan is to not use these the agents outside of a clinical trial.
- Lopinavir/ritonavir or Darunavir/cobistat: randomized placebo controlled studies showed no benefit compared to standardized care for either combination of HIV drugs.
- Tocilizumab, Sarilumab (interleukin-6 inhibitors): inflammation is a serious issue in critically ill patients, said Dr. Silver, who noted that several interleukin inhibitors, including IL-1 inhibitors, are being explored in clinical trials. Secondary hemophagocytic lymphohistiocytosis can occur in critically ill patients, he cautioned.
- Convalescent plasma: a recent publication from China reported that five patients on ventilators became afebrile within three days of starting convalescent plasma. This treatment is “certainly promising”, said Dr. Silver.
Although the U.S. Food and Drug Administration has found no scientific evidence connecting the use of non-steroidal anti-inflammatory drugs (NSAIDs) to worsening COVID-19 system, Dr. Silver noted that many providers are opting to use Tylenol instead. It may also be prudent to avoid corticosteroids, he said.
Coordination and Communication
Invoking the ‘blitz spirit’ of the British during World War II, Dr. Patt said that the most important thing for providers to do is “keep calm and carry on”, and this can be facilitated by coordinating efforts and managing communications, both internally and externally.
“I strongly recommend sending daily newsletters to staff with updates to guidelines to ensure that you’re compliant with current CDC recommendations,” said Dr. Patt. “We’ve also tried to facilitate external communication to patients by posting information on the Texas Oncology website and patient portals.”
With respect to managing patients, Dr. Patt recommended delaying routine follow-ups to decrease clinic volume and reduce risk to the highest risk patients. Similarly, patients who are on active treatment that may not be as timely should delay therapy.
“I’ve decreased my clinic volume by 80%,” said Dr. Patt. “It’s important to preserve clinic safety for the patients on active treatment who really need it. It also means my staff are exposed to fewer patients, and it’s easier to manage the social distancing norms that we’ve had to adopt.”
According to Dr. Patt, however, risk/benefit analysis for the timing of interventions may be highly variable for every patient, and each case should be considered individually. Although cancer generally needs to be treated in a timely manner, there are treatments that one can forgo, said Dr. Patt, and certain procedures may be staged to minimize hospital length of stay.
Recognizing that hospitals will soon be the highest proportion of concentrated risk, some surgeons are also triaging cases to an ambulatory care facility instead of doing them in the hospital setting.
For patients with active illness in the acute care setting, Dr. Patt and colleagues have instituted a nursing triage system augmented with physician support. Nurses are empowered to triage patients with COVID-19 symptoms, quarantine them, and potentially send them to the hospital when appropriate.
According to Dr. Patt, however, when at all possible, Texas Oncology is managing potentially infectious patients through telehealth to not put staff and patients at risk. They are also offering telehealth visits to all patients as an option to avoid unnecessary trips to the clinic.
“The emergent need was to reduce the risk of seeing acute care patients, but the long-term need for telemedicine is something that may persist for months,” said Dr. Patt. “It offers our patients an opportunity to see and visit with their clinician without necessarily having to come and wait in our waiting room… Telemedicine is a tool that could help cancer care navigate this crisis effectively.”
In the last week alone, Dr. Patt and colleagues on-boarded over 400 physicians and 150 advanced practice providers to their telemedicine platform, VSEE Messenger (the patient-facing platform is VSee Clinic).
“We went from five visits per day to 80 visits per day in less than a week, and yesterday we saw over 500 visits through the telemedicine platform in a single day,” said Dr. Patt. “I’ve even been rounding in the hospital by telehealth.”
As visitors are no longer allowed in Texas Oncology clinics, critical conversations with family members of patients who are dying of cancer must also be managed with telehealth. Dr. Platt noted that up to 13 people at different sites can be invited on her platform so that family conferences can still take place.
Although telemedicine is “absolutely necessary” during the crisis, Dr. Patt acknowledged that not all patients are capable of using HIPPA-compliant platforms. For patients with connectivity issues, she said, the phone is still a useful resource for telehealth visits and follow-up, but HIPPA-compliant platforms are preferred.
Utilization of telehealth services has also been bolstered by what Dr. Patt called “unprecedented policy changes” related to the COVID-19 pandemic. All Medicare beneficiaries can now be seen in their home and can be billed, including both new and established patient visits, and there will be laxity on co-pay collection. Many commercial payers are also starting to cover telehealth platforms.
Changes in the Hospital Environment
One of the biggest changes to the hospital environment is the need to confirm adequate personal protective equipment (PPE). According to Dr. Patt, there is a shortage of N95 masks for providers conducting COVID-19 testing, but even general masks and gowns could be in limited supply.
“Make sure that you are checking your supply chain and anticipating your supply needs,” she emphasized. “Your staff may suddenly all want to have masks. It’s important to consider what can be used from the general office supply and what can potentially be used from home.”
Administrators may also consider altering the staffing model to rotate staff. According to Dr. Patt, Texas Oncology has adopted a staggered model of staffing in which clinic employees work for five days in a row followed by five days at home, which keeps them out of the clinic for nine in case they develop symptoms.
“By spacing staffing, you can allow people to work from home, and also continue to have appropriate staffing,” she explained. “As community prevalence goes up, having infected healthcare workers will greatly impact our ability to care for patients.”
Finally, said Dr. Patt, practicing social distancing is critical for healthcare workers as well. Conducting staff meetings virtually is a critical way to facilitate communication without putting providers at increased risk of infection, and virtual tumor boards are “more important now than ever”.
“I could not endorse telemedicine more,” said Dr. Patt. “I think that communities that can embrace telemedicine and do it efficiently and effectively will save their cancer patients by providing them service during this incredible time of need. I also think it’s a really useful way to do family conferences, support groups, nutrition services, and patient navigation.”
In order to serve clinicians and researchers with guidance on malignant and non-malignant topics during the COVID-19 pandemic, the American Society of Hematology has created a resource webpage that was highly recommended by Dr. Silver: https://www.hematology.org/covid-19.
JNCCN Special Feature
Managing Cancer Care During the COVID-19 Pandemic: Agility and Collaboration Toward a Common Goal. https://jnccn.org/view/journals/jnccn/aop/article-10.6004-jnccn.2020.7560/article-10.6004-jnccn.2020.7560.xml
Clinical Guides/General Info
Maps & Tracking
Telemedicine Fact Sheet
- Van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17.
- COVID-19 Prioritization of Diagnostic Testing. https://www.idsociety.org/globalassets/idsa/public-health/covid-19-prioritization-of-dx-testing.pdf. Accessed March 31, 2020.
- Ueda M, Martins R, Hendrie PC, et al. Managing Cancer Care During the COVID-19 Pandemic: Agility and Collaboration Toward a Common Goal. J Natl Compr Canc Netw. 2020 Mar 20:1-4.
- Kalil AC. Treating COVID-19-Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics. JAMA. 2020 Mar 24.