Kicking off the American Association for Cancer Research (AACR) Virtual Meeting: COVID-19 and Cancer earlier this week, Anthony Fauci, MD, gave the keynote lecture, “Coronavirus Infections: More Than Just the Common Cold.” As Dr. Fauci told listeners, “[COVID-19]—and other infectious diseases—represent a perpetual challenge for which we have to be perpetually prepared.”
Anthony Fauci, MD
David Tuveson, MD, PhD, FAACR
AACR President-Elect David Tuveson, MD, PhD, FAACR, who introduced Dr. Fauci, listed his many awards and accomplishments, noting that Dr. Fauci has spent 52 years at the National Institutes of Health (NIH), 36 of them as Director of the National Institutes of Allergy and Infectious Diseases, and has advised six consecutive Presidents of the United States.
“His impact goes beyond the medical field. His combination of scholarship, leadership, and his tireless work ethic have established him as a beacon of knowledge and truth,” Dr. Tuveson stated.
Historical Perspective
Dr. Fauci explained that coronaviruses are not just human infections—that bats and other animals are intermediate hosts and serve as viral reservoirs. In the past, four coronaviruses were found to be responsible for common winter colds. Later, coronaviruses evolved as causes of potential pandemics: in 2002, severe acute respiratory syndrome (SARS), and in 2012, Middle East Respiratory Syndrome (MERS).
SARS was transmitted from a bat to a civet cat and then to humans. It then became transmissible from human to human, but the spread of SARS was contained by isolation and infection control. Ultimately more than 8,000 cases were identified worldwide, with close to 800 deaths.
“By June and July of 2003, there were no cases [of SARS]. The virus was contained purely by public health measures [isolation and quarantine] without drugs and vaccines,” Dr. Fauci said.
In 2012, MERS emerged as another potential pandemic in Saudi Arabia. MERS was transmitted from a bat, to a camel, to humans, and infected considerable numbers of people.
“The fatality rate was 35%. About 80% of the cases occurred in Saudi Arabia, and, unlike SARS, it is still smoldering but is moderately well controlled,” Dr. Fauci said.
COVID-19: ‘No End in Sight’
Although SARS coronavirus 2—COVID-19—has close phylogenetic proximity to SARS coronavirus 1, it is more widely transmissible, so far causing almost 14 million cases globally and 583,000 deaths, “with no end in sight,” he said. The United States is the hardest hit of all the countries, with 3.4 million cases and 136,000 deaths as of July 20, 2020.
Some unique aspects of COVID-19 have been identified, but many questions about the virus remain. It is known that transmission is primarily respiratory, direct from person to person, and usually occurs in close contact situations. Respiratory droplets are thought to be the main culprit, but there is also considerable interest in aerosol transmission, which would have an impact on spread closer than the 3 to 6 feet considered necessary for respiratory transmission, Dr. Fauci noted. Although COVID-19 is detected in other bodily fluids of humans and in animals, these factors have an uncertain role in transmission.
The virus has “protean manifestations,” including fever, cough, flu-like symptoms, shortness of breath, and myalgias. “It is now known that loss of smell and taste precedes the onset of respiratory symptoms,” Dr. Fauci noted. A variety of other manifestations have been reported.
Wide Spectrum of Severity
“Of all the viruses I have dealt with, I am impressed by the extraordinarily wide spectrum of disease, ranging from asymptomatic to mild [in bed for a few days], more severe [in bed for a few weeks with postviral syndromes], to hospitalization and intensive care, need for ventilation, and death,” he continued.
“Of all the viruses I have dealt with, I am impressed by the extraordinarily wide spectrum of disease [caused by the coronavirus]….”— Anthony Fauci, MD
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One obstacle to contact tracing is that—surprisingly—it is now known that 25% to 40% of COVID-19–infected individuals are asymptomatic. About 81% of cases of COVID-19 are mild to moderate, 14% are severe, and 5% are critical. The case fatality rate is 2.3%, “but this is likely below 1% if you account for the high percentage of asymptomatic infected individuals,” Dr. Fauci said.
Older adults are at highest risk for COVID-19, as are people of any age with underlying conditions such as chronic kidney disease, chronic obstructive pulmonary disease, immunocompromised status, diabetes, and sickle cell disease. Other medical circumstances may confer risk as well, including the use of glucocorticosteroids, pregnancy, hypertension, and human immunodeficiency virus infection. It is well known that COVID-19 disproportionately affects hospitalization and death of minority patients in the United States.
COVID-19 also has a wide range of manifestations and, as experience is gained with the pandemic, more manifestations have emerged. These include acute respiratory distress, acute cardiac injury, acute kidney injury, neurologic disorders, hypercoagulability leading to thromboembolic complications, and multisystem inflammatory syndrome in children (resembling Kawasaki disease).
Excess of Cancer Deaths
The intersection between COVID-19 and cancer is an important aspect of the pandemic. The toll includes the potential for an estimated excess of 10,000 deaths from breast and colorectal cancer due to delayed or no screening, Dr. Fauci told the audience.
Testing for COVID-19 includes molecular tests using genetic material, antigen tests to detect proteins from the virus (a more recent test), and antibody tests to detect proteins in blood made in response to infection with the virus. The list of potential therapeutics includes remdesivir, other broad-spectrum antivirals, convalescent plasma, repurposed drugs, host modifiers, immune-based therapies, and monoclonal antibodies. Remdesivir is furthest along in development, and dexamethasone has been found to reduce 28-day mortality in ventilated patients and those who need oxygen, rather than early in the course of infection.
There are many unanswered questions about COVID-19. To make useful information readily available, the NIH has initiated a “living” document online that includes regularly updated treatment guidelines for COVID-19. These resources can be accessed at www.Covid19treatmentguidelines.nih.gov.
The bottom line for prevention is physical distance and personal hygiene. “Wash hands, avoid close contact, use a face covering, clean inanimate objects,” Dr. Fauci said.
Vaccine Candidates
A number of candidate vaccines are being investigated and are directly or indirectly supported by the NIH. Dr. Fauci said there is an effort within the NIH to collaborate and harmonize the approach using common protocols, common primary and secondary endpoints, and compatible and interchangeable lab data.
Three main platforms are being studied: nucleic acid, an mRNA-based approach; viral vector; and protein subunit. Phase I and II trials of several of these products have been completed, and an mRNA-1273 vaccine will enter phase III trials at the end of July 2020.
A recent phase I study published online in The New England Journal of Medicine showed that mRNA-1273 could induce robust neutralizing antibodies at a similar level to what is seen in the convalescing serum of patients with COVID-19.1 This study, in 45 healthy volunteers, supported further development of this vaccine.
“It’s not clear if this candidate is better. It’s just ahead of the others [in trial development],” Dr. Fauci said.
DISCLOSURE: Dr. Fauci reported no conflicts of interest.
REFERENCES
1. Jackson LA, Anderson EJ, Rouphael NG, et al: An mRNA vaccine against SARS-CoV-2: Preliminary report. N Engl J Med. July 14, 2020 (early release online).
