Update to Chapter 194: Common Viral Respiratory Infections

There have now been >55 million cases of COVID-19 in the world, with >1.3 million deaths. The United States has had ~12 million cases with >250,000 deaths, and the country is now accruing >1 million new cases each week with the number of new daily cases approaching 200,000. These numbers dwarf all previous peaks and are almost certainly a direct result of colder weather with people spending more time indoors, with fears that these numbers will only worsen as the weather continues to get colder. In the midst, though, of this impending “dark winter,” there are early reports that vaccines are highly effective against COVID-19.

Epidemiology

• Letizia and colleagues (2020) investigated SARS-CoV-2 transmission among Marine recruits. All recruits (N = 1848) were instructed to self-quarantine at home for 2 weeks followed by a 2-week supervised quarantine period that included mask wearing, social distancing, and daily temperature and symptom monitoring. At the beginning of the supervised quarantine period, 16 recruits (0.9%) tested positive for SARS-CoV-2, with only 1 being symptomatic. Additional testing performed on days 7 and 14 identified an additional 35 positive cases, only 4 of whom had any symptoms in the week preceding the positive test. Additional analysis revealed 6 different transmission clusters among 18 recruits. Interestingly, no SARS-CoV-2 infections were identified as a result of the daily symptom monitoring. Taken together, this study highlights that the vast majority of infections in young adults (83% of subjects were 18–20 years old) are asymptomatic and that transmission is difficult to completely stop even with strict quarantine measures.

• Given the rapidly increasing number of cases throughout the country, the U.S. Centers for Disease Control and Prevention (CDC) has recommended against travel for the Thanksgiving holiday and that people should refrain from celebrating with those outside their immediate household. Although no formal announcement has yet been made about the December holidays, it seems likely that a similar recommendation will be made.

Treatment

• The World Health Organization (WHO) is recommending against the use of remdesivir in patients hospitalized with COVID-19, qualifying this guidance as weak or conditional (www.bmj.com/content/370/bmj.m3379). Although a National Institutes of Health (NIH)-sponsored study (ACTT-1) found that remdesivir treatment shortened hospitalization time, neither it nor a newer, yet-unpublished study sponsored by the WHO (SOLIDARITY) found that remdesivir improved mortality. Moreover, SOLIDARITY, which included ~10 times the number of patients as ACTT-1, found that remdesivir did not influence the hospital course of patients with COVID-19. These updated guidelines from the WHO reflect the lack of evidence supporting improvement in any clinically relevant parameter, although they acknowledge that there is not sufficient evidence to state that remdesivir is ineffective either. Given the very recent presentation of the results from the SOLIDARITY trial, guidelines from other agencies (e.g., NIH, Infectious Diseases Society of America) have not yet incorporated them into their recommendations.

  • Remdesivir received full approval by the U.S. Food and Drug Administration (FDA) (beyond the initial emergency use authorization) for all hospitalized patients >12 years of age. Although the disappointing results from the SOLIDARITY trial were known for a week prior to this approval, the FDA’s approval was based only on the NIH’s ACTT-1 trial along with two industry-sponsored trials. Although the FDA can later withdraw its approval for either safety or efficacy concerns, this approval will likely require any future clinical trial in the United States to compare new therapies against remdesivir instead of a placebo.

• The FDA has given emergency use authorization (EUA) for bamlanivimab, a monoclonal antibody against the spike protein of SARS-CoV-2, for patients ≥12 years of age and who are at high risk for progressing to severe disease and/or hospitalization. Specifically, it is not authorized for patients who either are already hospitalized or require oxygen therapy due to COVID-19. This EUA was based on the interim analysis of a phase 2 clinical trial in which patients were randomized to placebo or one of three different doses of bamlanivimab. Although there was no difference in viral load reductions from baseline to day 11, there was a reduction in hospitalizations and emergency room visits observed in patients who received bamlanivimab (3% vs 10%), with no difference between the various doses of bamlanivimab.

Prevention

• The CDC has recently updated their guidance on mask-wearing to include the fact that wearing a mask protects the wearer in addition to others with whom the individual is in close contact.

• The CDC previously defined a “close contact” as one who had a single ≥15-min exposure within 6 ft to an individual who tested positive for SARS-CoV-2, but they have now expanded this definition to be exposure within 6 ft for a total of ≥15 min (can be in multiple episodes).

• Both Pfizer and Moderna have publicly reported that their independently developed vaccines have ~95% efficacy based on interim data analysis of large phase 3 clinical trials. (Detailed data from the trials are not yet publicly available and have not been peer reviewed.) Both vaccines target the spike protein, which is similarly targeted by several other vaccines currently in phase 3 trials. The finding that both of these vaccines have such high efficacy—the FDA had previously stated that they wanted at least 50% efficacy—offers promise that these additional spike protein–targeted vaccines will be similarly effective. Furthermore, vaccines from both Pfizer and Moderna are based on mRNA, a technology that has never before been used in vaccine development. If these are truly successful vaccines, this approach for generating vaccines may fundamentally streamline development of new vaccines for any future outbreak of a novel pathogen.

  • Pfizer has submitted their data to the FDA for emergency use authorization, and Moderna is expected to do the same imminently.

  • Although development of effective vaccines was the first major hurdle, distribution and mass administration of the vaccines both represent major challenges. Some of these vaccines require storage at –80°C, which will complicate their distribution in both high- and low-resource countries.

References