COVID-19 vaccine updates

 - Jennifer Middleton, MD, MPH

In the last week, two pharmaceutical companies have released preliminary data indicating that their mRNA vaccines against the SARS-CoV-2 virus are efficacious and safe. Critics are arguing that these preliminary data releases only serve to drive up manufacturers' stock prices, but others are gladly grasping at their potential to help end the COVID-19 pandemic. Before these vaccines will be released to the United States (US) public, though, they must be evaluated by the Food and Drug Administration (FDA). 

To be approved by the FDA, vaccine manufacturers must prove their product's efficacy and safety through a rigorous, methodological process. First, manufacturers must submit an Investigational New Drug application, detailing the vaccine's proposed mechanism of action and previous animal model study results. Then,

Pre-marketing (pre-licensure) vaccine clinical trials are typically done in three phases, as is the case for any drug or biologic. Initial human studies, referred to as Phase 1, are safety and immunogenicity studies performed in a small number of closely monitored subjects. Phase 2 studies are dose-ranging studies and may enroll hundreds of subjects. Finally, Phase 3 trials typically enroll thousands of individuals and provide the critical documentation of effectiveness and important additional safety data required for licensing. 

As of November 12, 2020, the World Health Organization (WHO) was tracking 48 candidate vaccines. Nine of those candidate vaccines are in phase 3 trials, and two of them recently released interim data analyses. The Pfizer/BioNTech vaccine, BNT162b2, is currently in a phase 3 trial with over 43,000 participants; interim analysis suggests it is at least 90% effective. The National Institutes of Health (NIH)/Moderna vaccine, mRNA-1273, also in a phase 3 trial (the "COVE" trial) with over 30,000 participants, announced similar findings in their interim analysis with 94.5% effectiveness. 

Vaccine manufacturers can apply for an Emergency Use Authorization (EUA) to bypass the full approval process; the FDA has already issued EUAs during the pandemic for several SARS-CoV-2 diagnostic tests as well as for therapeutics such as baricitinib, remdesivir (in pediatric patients; already FDA-approved in adults), and convalescent plasma. (The FDA revoked the EUAs for hydroxychloroquine and chloroquine in June 2020.) The FDA has posted guidance for vaccine EUA applications and has pledged to make all submitted data for EUAs transparently available to the public. 

As Dr. Kenny Lin has previously pointed out on the blog, it's unlikely that a vaccine alone will stem the pandemic's tide; handwashing, social distancing, and face coverings remain essential. You can estimate the risk of an unknowingly COVID-19 infected person at your gathering using this online tool; you'll likely see why the Centers for Disease Control and Prevention (CDC) is recommending we only gather with immediate family for the upcoming Thanksgiving holiday. 

We'll continue to regularly update the AFP By Topic on Coronavirus Disease 2019 (COVID-19), and, as 2020 comes to a close, don't forget that the AAFP has a robust offering of CME learning activities about COVID-19. 

Mental health disorders are associated with COVID-19

- Kenny Lin, MD, MPH

Eight months ago, during the first wave of the pandemic, Dr. Jennifer Middleton discussed World Health Organization and Centers for Disease Control and Prevention (CDC)-recommended strategies and resources for optimizing mental health in health care workers, patients, and children. A CDC representative national survey conducted in late June found a strikingly high prevalence of symptoms of anxiety or depressive disorder (30.9%), trauma- and stressor-related disorder (26.3%) and new or increased substance use (13.3%). By comparison, a 2019 survey found that only 8.1% and 6.5% of people had symptoms of anxiety or depression, respectively. 1 in 10 respondents to this year's survey also reported having seriously considered suicide in the preceding 30 days, with disproportionately higher suicidality in younger adults (age 18-24 years), racial and ethnic minorities, essential workers, and unpaid adult caregivers.

In a recent commentary, Dr. Christine Moutier from the American Foundation for Suicide Prevention recommended several COVID-19-specific suicide prevention strategies that fuse clinical, health system, and policy interventions: reduce risk for people with mental illness or addiction; increase social connectedness; address risk at the moment of crisis; reduce access to lethal means; address COVID-19 increases in alcohol consumption and drug overdoses; mitigate financial strain; address domestic violence and unsafe environments; and prevent unsafe media and entertainment messaging on suicide.

The rise in anxiety, depression, stress, and suicidality coincided with the widespread conversion of office-based visits for behavioral and psychiatric conditions to telehealth, which may have restricted access to mental health care for existing and new patients. As three psychiatrists observed in a JAMA Viewpoint:

Patients with psychiatric disorders are particularly vulnerable to COVID-19 due to high rates of overweight, tobacco smoking, medical comorbidities, and poor self-care. ... Daily news of large-scale COVID-19–related disease and death in the community over months or years is almost certain to elevate psychiatric burden in the population. As such, the pattern of stress resembles that experienced by refugees or others exposed to chronic violence. ... A sustained increase in demand for psychiatric services may well exceed the existing capacity of the system over time and may last for years, depending on the course the pandemic takes.

Persons with prior psychiatric diagnoses may be at higher risk of death from COVID-19 infection. A cohort study of 1685 patients who were hospitalized with COVID-19 from February through April found that after controlling for demographics, medical comorbidities, and hospital location, patients with a psychiatric disorder were 1.5 times as likely to die as those with no psychiatric diagnosis. Citing a kinship network study that suggested that each COVID-19 death in the U.S. leaves nine bereaved close family members, some have suggested that primary care physicians screen relatives of persons who die from COVID-19 for symptoms of depression, prolonged grief, or post-traumatic stress disorder and provide evidence-based interventions if needed.

On the other hand, a diagnosis of COVID-19 may increase the risk for developing a mental health disorder. A retrospective cohort study that utilized electronic health record data from more than 62,000 U.S. patients between January 20 and August 1 found that COVID-19 survivors were more likely to have a first psychiatric diagnosis, a new psychiatric diagnosis, or a relapse of a previously stable diagnosis within 14 to 90 days than six other unrelated health events. However, this study design could not determine if these additional diagnoses were preexisting and unrecognized prior to COVID-19 infection or a direct consequence of the infection or medical management (including isolation at home or in the hospital).

Stress from COVID-19 pandemic fuels increased alcohol misuse

- Jennifer Middleton, MD, MPH

A survey of 1540 adults in the United States recently found that alcohol use has increased over the last year, especially in women:

On average, alcohol was consumed 1 day more per month by 3 of 4 adults. For women, there was also a significant increase of 0.18 days of heavy drinking (95% CI, 0.04-0.32 days)...an increase of 41% over baseline....For women there was an average increase in the Short Inventory of Problems scale of 0.09 (95% CI, 0.01-0.17 items)...representing a 39% increase, which is indicative of increased alcohol-related problems independent of consumption level for nearly 1 in 10 women.

Memes jesting about "mommy juice" abound right now, along with depictions of wine and coffee arguing regarding "who she loves more." These memes reflect the increasing normalization of alcohol as a coping mechanism but also trivialize the physical and psychological consequences of increased alcohol consumption. Excess alcohol use is linked with cardiovascular disease, several cancers, and intimate partner violence; it exacerbates depression and anxiety; and it can result in injuries, including motor vehicle accidents. An increase in these short- and long-term conditions will place further stress on individuals, families, workplaces, and healthcare systems already buckling under the weight of COVID-19. 

The pandemic has increased stress for countless individuals, and reports suggest women are bearing a disproportionate share. Women have been more likely to lose their jobs and are more likely to be primarily managing child care given decreased daycare access and increased virtual schooling. The pandemic's effect on women of color is even more profound. COVID-19 is widening gender-poverty gaps in the US and abroad. It's no surprise that alcohol misuse is increasing. 

The United States Preventive Services Task Force (USPSTF) recommends screening all adults for hazardous alcohol consumption and providing brief counseling to those who screen positive; we must urgently identify our patients who are using alcohol to cope with COVID-19 and offer help. 

There's an AFP By Topic on Alcohol Use Disorders if you'd like to read more, and this 2019 Community Blog post provides a brief overview of alcohol screening and treatment. The CDC also has a webpage with a lengthy list of resources for coping with increased stress due to COVID-19.

Advantages and limitations of mobile monitoring for cardiac arrhythmias

 - Kenny Lin, MD, MPH

During the first wave of the pandemic, when hydroxychloroquine was still thought to be an effective treatment for hospitalized patients with COVID-19 (subsequent studies have shown otherwise), some U.S. hospitals used personal electrocardiogram (ECG) devices to monitor these patients for drug-induced QT interval prolongation to conserve personal protective equipment and telemetry monitors. Such devices were already being used by patients with known cardiac conditions to monitor their heart rhythms in out-of-office settings.

As I discussed in a previous AFP Community Blog post, wearable devices such as the Apple Watch are also being studied to detect atrial fibrillation in asymptomatic primary care patients. In a 2019 study of more than 400,000 U.S. Apple Watch wearers with no self-reported history of atrial fibrillation, about 1 in 200 individuals received an irregular pulse notification and were scheduled for a telemedicine visit with a clinician to confirm study eligibility and triage those with urgent symptoms to the emergency department. Participants without urgent symptoms were mailed an ECG patch to wear for up to 7 days and then mail back to the study center.

Of the 450 participants who returned an ECG patch, 34% were confirmed to have atrial fibrillation, with a higher diagnostic yield in persons age 65 years or older. Of the 86 patients whose watches generated irregular pulse notifications when they were wearing the ECG patch, the positive predictive value for atrial fibrillation was 84%. In a survey completed at 90 days by patients who received an irregular pulse notification, 28% reported being prescribed a new medication, 33% were referred to a specialist, and 36% were recommended to have additional testing.

In the November 1 issue of American Family Physician, Dr. Madhavi Singh and colleagues reviewed the diagnostic test features of KardiaMobile, a $99 single-lead device that connects wirelessly to a smartphone app to generate an ECG tracing with automated interpretation. In studies of patients with known or suspected arrhythmias, KardiaMobile had greater than 90% sensitivity and specificity for atrial fibrillation or atrial flutter compared to a standard 12-lead ECG. However, no studies have compared its accuracy with a Holter or event monitor, and effects on patient outcomes are uncertain, particularly in populations at low risk for arrhythmias. (In 2018, the U.S. Preventive Services Task Force found insufficient evidence to assess the balance of benefits and harms of screening for atrial fibrillation, which has several potential downsides.) The authors concluded that similar to the Apple Watch, "further studies are needed before KardiaMobile can be recommended for use in seemingly healthy patients."