Lessons Learned from the COVID-19 Coalition
The biweekly webinars hosted by renowned health care thought leaders provide resources to improve patient outcomes during COVID-19. Here's a recap of the first 5 discussions.
On September 10, 2020, MJH Life Sciences™ introduced the COVID-19 Coalition, a partnership with renowned health care thought leaders across multiple medical disciplines. The coalition will present biweekly webinars that give providers resources to improve patient outcomes during the coronavirus disease 2019 (COVID-19) pandemic. The first 5 webinars addressed issues related to influenza and COVID-19, myths and controversies, treatments, vaccines and prophylactic therapies, and long-term physical and psychological effects.
Moderator Angela L. Rasmussen, PhD, of Columbia University Mailman School of Public Health; Andreas Handel, PhD, of the College of Public Health at the University of Georgia; and Juliet Morrison, PhD, of the University of California, Riverside, participated in this webinar on September 15, 2020.
COVID-19 and Influenza: A Tale of 2 Viral Pathogens
Rasmussen noted that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses have distinct taxonomy, genomics, and evolutionary origin, as well as modes of entry into and replication inside the cell. In addition, the higher mutation rate of the influenza virus is related to its ability to reassort its genome. She added that SARS-CoV-2 appears to have a stronger effect on the central nervous system and gastrointestinal tract and infects the cardiovascular system directly. Pathogenic strains of the influenza virus, on the other hand, affect the cardiovascular system through the increased entry of macrophages. Rasmussen also noted that the differential pattern of pathway induction in the immune response suggests that these viruses induce distinct host responses. She added that case reports show coinfection of SARS-CoV-2 and influenza does occur, but the effect on disease severity is unclear. “We need more data from a broader range of patients,” she concluded.
Population-level Patterns of COVID-19 and Influenza: What Should We Expect?
Handel said that behavior changes and the nonpharmaceutical interventions (NPIs) implemented for COVID-19 have likely had an effect on the influenza rate. He pointed to data showing that rates in the 2019-2020 season were lower than expected in multiple countries which, along with lower test positivity rates in China and a minimal number of influenza-related hospitalizations in Australia, suggests a true decrease in influenza cases (versus reduced reporting of cases). He concluded that key factors that will dictate the interaction between COVID-19 and influenza in the long-term include the effects of a COVID-19 vaccine on influenza vaccine uptake, NPIs, and individual behavior patterns; development of a universal flu vaccine; and COVID-19 treatments.
Influenza and COVID-19 Vaccines
Morrison noted that although several COVID-19 vaccines are currently in phase 3 trials, their rapid development has contributed in part to high levels of vaccine hesitancy among the general public. She added that this skepticism has prompted vaccine developers to make a historic pledge stating that they will uphold the integrity of the scientific process, and ensure that regulatory filings and approvals are up to par and no corners are being cut. Morrison cited the example of AstraZeneca putting their trial on hold when a participant developed an illness that may have been related to the vaccine. She concluded that educating the public about the perceived threat of COVID-19 and the effectiveness and safety of the vaccines that become available are key to fighting vaccine hesitancy.
Moderator Saskia V. Popescu, PhD, MPH, infectious disease epidemiologist and infection preventionist in Phoenix, Arizona; Emily Ricotta, PhD, MSc, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; and Angela L. Rasmussen, PhD, addressed common COVID-19 myths and controversies in a COVID-19 Coalition webinar on September 29, 2020.
MYTH 1: “SARS-CoV-2 is totally airborne”
Rasmussen said that SARS-CoV-2 is primarily transmitted through short-range respiratory droplets or aerosols between individuals in close contact for long periods of time. “The word ‘airborne’ is often misleading because a lot of times people think of long-range transmission,” she said.
Ricotta added, “We need to be clearer in the way that we’re communicating this, and I think that’s where some of the confusion has come in.” However, both panelists agreed that these discrepancies in definition do not affect current recommendations for preventing transmission (such as mask usage).
MYTH 2: “Herd immunity is achievable through natural infection”
Ricotta said that herd immunity through natural infection would likely require 40% to 70% of the population to be infected and have sustained immunity. In addition, as not all the long-term effects of COVID-19 are known, many people would be put at risk with this strategy. Rasmussen added that global herd immunity through natural infection has not been achieved for any pathogen and does not keep the pathogen out of the environment in the long-term.
MYTH 3: “We can’t trust data quality”
Ricotta said that the data source, consistency in data reporting, interruptions in data collection, and consistency in criteria for positivity can affect data. “It’s not necessarily the quality of data. You just have to be really careful when you’re working with and interpreting them,” she said.
Rasmussen added that communicating with the public about the appropriate use of mathematical models has been a “tremendous challenge.” They’re only as good as the information that goes into building them at the time, and that’s constantly changing.”
MYTH 4: “There is no asymptomatic transmission”
Rasmussen said that distinguishing asymptomatic from presymptomatic transmission and estimating the prevalence of asymptomatic cases, which is a substantial source of transmission, has been difficult. This is because most asymptomatic cases are based on self-reported data, symptoms can develop after a positive test, and people may not recognize that mild, nonspecific symptoms are related to COVID-19.
MYTH 5: “Any SARS-CoV-2 vaccine won’t be safe”
Rasmussen said the purpose of clinical trials is to ensure vaccine safety and efficacy. Ricotta added that postmarket evaluation of vaccines is performed and possible vaccine-associated events are reported in a tracking system. Although vaccines have risks, Ricotta said they are often considered acceptable relative to the risks associated with the disease.
MYTH 6: “Young people can’t get sick”
According to Ricotta, although young patients often have fewer symptoms than older patients, some require hospitalization and have had blood clots, strokes, and myocarditis. Rasmussen added that symptoms in children can be vague and difficult to associate with COVID-19, and she and Popescu pointed out that cases in children may be underreported.
MYTH 7: “COVID-19 antibodies wane”
The immune system response to SARS-CoV-2 immunoglobulin G (IgG) is consistent with that of other viruses, Rasmussen said. Memory immune cells likely persist, even if IgG decreases to undetectable levels, and assumptions about long-term immunity cannot be made based on antibody levels.
MYTH 8: “Hydroxychloroquine is a miracle drug”
Rasmussen said that none of the high-quality randomized controlled trials and observational studies show a clinical benefit for prophylaxis or treatment, and the drug can cause ocular problems or cardiac arrhythmias.
MYTH 9: “COVID-19 is no worse than the flu”
Although both viruses affect the respiratory tract and have similar modes of transmission, comparing COVID-19 to influenza is “like comparing apples to oranges, ” Ricotta said. Getting tested for both viruses is important to guide treatment. Rasmussen added that aside from the fundamental differences in the viruses, the 2 diseases should not be compared because of the differences in treatment and vaccination recommendations.
This October 13, 2020, webinar included moderator Jason Pogue, PharmD, of the University of Michigan College of Pharmacy; Susan L. Davis, PharmD, of Wayne State University; and Jason C. Gallagher, PharmD, of Temple University School of Pharmacy.
Davis said that although updated results showed differences in mortality at day 15, illness severity, hospital stay, and time to recovery are also important measures to consider when deciding whether to give remdesivir. Additionally, the guidelines for use from the National Institutes of Health and the Infectious Diseases Society of America were based on the drug’s limited availability early in the pandemic. The increase in availability and advent of new therapies since then may change when and which patients receive the drug, according to Davis.
The panelists stated that a wide range of patients, including those with minimal need for supplemental oxygen, would likely benefit from dexamethasone. Gallagher cautioned against making assumptions about when a patient is in the “inflammatory phase” of the disease, given that knowledge about its clinical course is continuing to evolve. Moving forward, he recommended focusing on clinical data when assessing clinical benefit from dexamethasone.
Although an emergency use authorization (EUA) was given, Gallagher said the data from the nonrandomized Mayo Clinic Expanded Access Program are difficult to interpret. Further, he remarked that the benefits appear to be primarily in patients who have not produced their own antibodies to SARS-CoV-2. Davis noted that the primary intention of the program was to improve access for patients and that it was not designed as a clinical trial. Pogue added that convalescent plasma may have lower levels of antibodies than the levels the patient has produced.
Although the data published in press releases appear promising, Davis said such data from pharmaceutical companies is insufficient for rational decision-making in the clinic. When companies apply for an EUA, closer communication with the FDA can expedite additional treatment options in a pandemic, but a completed clinical trial is necessary for an agent’s widespread use in the clinical setting, she continued.
“EUA is a tool for a health emergency,” said Davis. “It is not a replacement for the normal drug approval process.”
Gallagher added that monoclonal antibodies may predict progression in patients who are readmitted to the hospital but the logistical challenges, such as the need for intravenous infusion, will likely limit their overall impact on reducing transmission and improving outcomes.
Moderator Margaret A. Liu, MD, CEO of PAX Therapeutics and chairman of the board of the International Society for Vaccines; Myron S. Cohen, MD, head of monoclonal antibody clinical testing in the COVID-19 Prevention Trials Network; and Lawrence (Larry) Corey, MD, head of vaccine testing in the COVID-19 Prevention Trials Network, participated in this webinar, held October 27, 2020.
According to Cohen, key advantages of monoclonal antibody therapy include the ability to offer immediate protection to exposed or unvaccinated individuals in high-risk settings, provide an option for patients unlikely to respond to or who are allergic to a vaccine, and stop viral replication and disease progression. Several phase 3 trials are ongoing for monoclonal antibody therapies, including one (NCT04452318) that is evaluating the efficacy of REGN10933 + REGN10987 (which prevents the receptor binding domain of the spike protein from reaching the ACE2 receptor) for preventing infection in the household contacts of individuals who test positive for COVID-19. Another is the BLAZE-2 trial (NCT04497987), which is investigating the antibody LY-CoV555 for preventing infection in residents and staff of skilled nursing and assisted living facilities.
Corey said that several features of SARS-CoV-2, including its relatively high infection cure rate, mutation rate of 2 base pairs per month with little variation in neutralizing areas of the spike protein, and recent evidence of past infection protecting against acquisition, have made COVID-19 vaccine development more straightforward than that for HIV.
The conceptual framework for COVID-19 vaccine development involves developing multiple vaccine platforms (protein-, viral vector–, and RNA-based) and having a coordinated effort from the US government to involve global vaccine manufacturing companies, said Corey. He also emphasized the importance of having a common data safety monitoring board for these efficacy trials using different vaccine platforms, with decisions for a given candidate based on the context of the other trials.
According to Corey, the main goal of these trials is to evaluate each candidate vaccine for safety and efficacy for reducing COVID-19 disease, with approximately 30,000 individuals enrolled per trial; measure 150 disease end points; enroll Black, Latinx, and tribal communities; and evaluate vaccines in epidemiologic settings of individuals at greatest risk for complications based on comorbidities, age, and race.
“COVID-19 vaccines provide the leading approach for changing the societal and medical complications of the COVID-19 pandemic. A vaccine that protects from medically complicated COVID-19 disease would provide enormous help in relieving the uncertainty that accompanies work, travel, and gatherings with family, friends, and community,” said Corey.
Moderator Tina Q. Tan, MD, of Feinberg School of Medicine at Northwestern University; Carlos del Rio, MD, of Emory School of Medicine and Grady Health System; and Colleen Cicchetti, PhD, executive director of the Center for Childhood Resilience, participated in this November 12, 2020, webinar.
Tan pointed out that although most children and infants generally present with mild or no symptoms, they may have persistent and long-term symptoms even if they have mild illness and no underlying medical conditions. Multisystem inflammatory syndrome in children is the most serious and can result in long-term cardiac, neurologic, and gastrointestinal problems.
Long-Term Health Consequences of Covid-19
Del Rio estimated that 10% to 15% of patients do not recover quickly based on findings from the COVID Symptom Study, and the persistence of symptoms is independent of age, comorbidity burden, and severity of acute illness. He added that cardiac injury, myocarditis, arrhythmias, cardiogenic shock, and thromboembolic disease may occur in the acute phase. These can lead to myocardial fibrosis or scarring, arrhythmias with cardiac arrest outside the hospital setting, and cardiomyopathy in the postacute phase. Pneumonia, acute respiratory distress syndrome, and hypoxic respiratory failure can occur during the acute phase and be followed by restrictive lung disease in the postacute setting. In addition, major mood swings and “brain fog” can persist for several months. Del Rio added that renal function may also be compromised long-term, with persistent kidney dysfunction or requirement for dialysis even in patients who did not require renal replacement therapy during hospitalization. Finally, he cited emotional and behavioral concerns, including feelings of isolation and loneliness, a sense of hopelessness, and ongoing psychological effects, and identified the need for an integrated research agenda to conduct observational studies and randomized trials and a multidisciplinary approach to treatment in post–COVID-19 clinics.
The Uninvited Guest: Promoting Mental Health & Wellness During COVID-19
Cicchetti said that issues related to the COVID-19 pandemic, racism, and economic downturn in 2020 have contributed to multiple layers of stress in many individuals. Ongoing mental health challenges for many individuals include a sense of inequity, structural racism, heightened exposure to stress and trauma, social isolation and disconnection, limited access to community programs and support, changes to routine and structure, barriers to accessing health care and other services, and educational disruptions for children.
Cicchetti emphasized the importance of providers addressing stress directly with clients using tools such as Stoddard and Kaufman’s Coronavirus Impact Scale and the UCLA Brief COVID-19 Screen for Child/Adolescent PTSD. She recommended that parents respond to their children using principles of trauma-informed care, including creating a safe environment, building relationships and connectedness, and supporting and teaching emotional regulation. She added that the majority of children will do well, and often look to parents for coping strategies and leadership during times of crisis. Create a sense of predictability and establish routines to enhance children’s safety and security, she suggested, as well as providing them with love and support. Additionally, allowing them to ask questions, supporting their emotional regulation, and letting them figure out how to support themselves with self-care activities will help them reduce stress, cope with challenges, and enhance their sense of well-being.