Fauci: COVID-19 ‘vaccines, plural’ may complete trials by late 2020, early 2021
Anthony S. Fauci, MD, director of the National Institutes of Allergy and Infectious Disease, told ACR Convergence 2020 meeting attendees that multiple vaccine candidates are “fully enrolled” in phase 3 trials in the U.S.
“We have taken a strategic approach to vaccine development in the U.S.,” he said in his presentation.
The United States government is developing and testing six of 11 vaccine candidates under investigation worldwide. The strategic part of this approach involves “harmonization” of study protocols and common endpoints and laboratory parameters to “bridge” between the studies looking at the various vaccine products, according to Fauci.
There are three types of vaccines under investigation: nucleic acid, viral vector and protein subunit. Five of the six products being studied in the U.S. are fully enrolled in phase 3 trials, with results possible by the end of November or mid-December. At this point, it may be possible to know whether “we have a safe and effective vaccine or vaccines, plural,” Fauci said. He is “cautiously optimistic.”
Phase 1 trials showed “robust levels” of neutralizing antibodies for these products, and the positive outcomes have continued through the clinical trials process, according to Fauci. It is for this reason that front-line medical workers and high-risk populations may be able to be vaccinated by the end of 2020, with more doses administered in the early months of 2021.
The stakes for swift deployment of a safe and effective vaccine could not be higher. The current pandemic involves close to 50 million cases and 1.2 million fatalities worldwide, and some 10 million cases and 230,000 deaths domestically, according to Fauci. “In the U.S., we have been the hardest hit,” he said.
Understanding the history of coronaviruses
The research and development communities are benefiting from previous understanding of coronaviruses, according to Fauci. “We have had experience with coronaviruses now for decades and decades,” he said, explaining that these viruses account for around 15% to 30% of the common colds that circulate throughout the winter months.
Researchers developing vaccines and therapeutics built on knowledge gleaned from the SARS coronavirus pandemic of 2002 and the MERS coronavirus pandemic of 2012, which he noted continues to resurface from time to time.
The 2002 virus, SARS-CoV-1, is “phylogenetically proximal” to SARS-CoV-2, or COVID-19, according to Fauci. The key difference between the two viruses is the “high degree of efficiency in terms of transmission” of SARS-CoV-2, he said. This, in large part, has led to the “global pandemic of historic proportion, the likes of which we have not seen for the last 100 years.”
Fauci zeroed in on the “response and dynamics” of the response to the pandemic in the U.S. versus Europe. After the initial outbreak, the curve in Europe came “down to baseline,” but that never happened in the U.S., according to Fauci.
“Around June 19, there was a resurgence of cases due to the so-called reopening of the economy,” he said. Weekly rates decreased from 70,000 not to baseline, but to around 40,000, and then moved back up to around 80,000 cases per week.
One reason for the resurgence is that different states, regions and cities reopened with different protocols and regulations. But there were also disturbing general trends observed by phone tracking data and workplace activity. “People did not stay home,” Fauci said. “Visits to the grocery store and pharmacy stores did not go down as much as Europe.”
“On Nov. 4, we hit 100,000 cases in a single day,” he added.
Despite the challenges facing the U.S., Fauci stressed that, at the present moment, the resurgence in Europe is as bad or worse than it is domestically.
Mode of transmission
Ongoing infection rates are largely due to the previously mentioned efficient mode of transmission observed in SARS-CoV-2, according to Fauci. While droplets expelled from the mouth of an infected person to another person within 6 feet and indoors is the most likely way the infection is communicated, Fauci said that experts believe there is “some degree of aerosol spread.” However, the degree of this spread is unknown, nor is it known how long those smaller droplets remain in the air.
Despite the flood of contradictory information on the internet, basic public health strategies for mitigating transmission work, according to Fauci. He ran down the list that has become so familiar: wear a mask; keep a physical distance of at least six feet from others; avoid crowds, particularly indoors; conduct activities outdoors; and frequently wash your hands.
“If those five public health measures were adhered to universally and consistently across the country, we would not be having the degree of cases that we are currently seeing,” he said.
Recognizing the infection
Signs and symptoms are “very much like what we see in flu-like syndrome,” with the additional component of a “peculiar” loss of smell and taste in certain individuals, according to Fauci.
About 80% of those infected have mild to moderate symptoms, while 15% to 20% have more severe disease. Up to 40% have no symptoms at all.
There is wide variation in the case fatality rate, according to Fauci. It can be as low as 1% in some instances and as high as 25% in those who require mechanical ventilation.
High-risk groups include older individuals and those with underlying comorbidities such as diabetes, obesity, chronic obstructive pulmonary disorder (COPD), chronic heart disease or hypertension.
“The data with age are striking,” Fauci said, highlighting an “extraordinary disparity” in hospitalization rates for those aged 75 to 85 years compared with younger individuals.
However, people of any age with the aforementioned underlying comorbidity profile are at increased risk of severe or critical disease, or death.
Looking at manifestations of the virus, Fauci listed cardiac outcomes, acute respiratory distress syndrome, renal and neurological complications, along with hypercoagulopathy as events that may occur.
Of particular concern is multisystemic inflammatory syndrome, which has occurred in some 1,000 children worldwide and is often associated with hospitalization and mortality.
If there is another important concern for Fauci, it is the “profound” racial and ethnic disparities in incidence, severity of disease and hospitalizations among African American, Latinx, American Indian and Alaska Native populations compared to white populations.
But there is good news on the treatment front. The NIH has established a “living document” for expert consensus guidelines. While just two drugs are currently approved — remdesivir (Veklury, Gilead Sciences) for hospitalized individuals with lung involvement and dexamethasone for those requiring ventilation and other serious pulmonary complications — other antivirals, convalescent plasma, monoclonal antibodies and immunomodulators are all under investigation.
Fauci’s goal, and the goal of the recommendation document, is to “help and assist clinicians dealing with this disease to use the most updated data” in managing patients and, hopefully, preventing serious complications and mortality.