Update to Chapter 194: Common Viral Respiratory Infections

In the ~1 year since the beginning of the COVID-19 pandemic, there have been >75 million cases and ~1.7 million deaths globally. The United States still leads all other nations, with >17 million cases and 311,000 deaths thus far; the country is adding more than 1 million cases each week and more than 3000 additional deaths each day. On the backdrop of these sobering numbers, two different vaccines have now been approved for emergency use in the United States, with many other countries already having approved a COVID-19 vaccine or expected to do so soon. Although SARS-CoV-2 continues to wreak havoc on individuals, health care systems, and economies, the largest mass immunization campaign the world has ever seen has now begun.

Epidemiology

• Although early studies suggested that ~30% of SARS-CoV-2-infected pregnant women required hospitalization, Adhikari and colleagues (2020) have found that the vast majority of pregnant women do not develop serious complications or deliver newborns who are infected with the virus. Of >3300 pregnant women followed in the Dallas, Texas, area between March and August of 2020, 252 tested positive for COVID-19 during pregnancy. The overwhelming majority (95%) either were asymptomatic or had mild symptoms, and only 13 of the women (5%) developed severe pneumonia. Importantly, there was no increase in adverse pregnancy-related outcomes between those women with or without COVID-19. Two other studies similarly found no increase in the rate of stillbirths during the COVID-19 pandemic.

• Genomic studies are beginning to uncover specific genes that are associated with severe disease. Zhang and colleagues (2020) performed a focused comparison of the genomes of 659 individuals with severe COVID-19 and 534 individuals with benign infection and found that loss-of-function mutations in the type I interferon pathway are associated with severe disease. In a separate study, the same group (Bastard et al, 2000) found that autoantibodies against type I interferons were more common in patients with severe disease. Finally, Pairo-Castineira and colleagues (2020) performed a genomic analysis of 2200 critically ill COVID-19 patients in the United Kingdom and found that mutations in 5 genes (OAS, DPP9, IFNAR2, TYK2, and CCR2) associated with antiviral immunity and lung inflammation are linked to severe COVID-19 disease.

• The United States Centers for Disease Control and Prevention (CDC) recently updated their guidance regarding the duration of quarantine for those who are exposed to COVID-19. Exposed individuals may now exit quarantine after 7 days if they remain asymptomatic and have a negative polymerase chain reaction or antigen test for SARS-CoV-2 at day 5 or later; in the absence of testing, the quarantine can end after 10 days if the individual remains asymptomatic. The CDC notes that a 14-day quarantine is still optimal. The inclusion of these shorter durations comes with increased risk of a false negative; however, the hope is that these revised guidelines may increase overall adherence with quarantining after exposure.

Treatment

• Although observational data initially suggested that convalescent plasma may be an effective treatment for COVID-19, recently published controlled trials refute this idea. Simonovich and colleagues (2020) randomized 333 patients in a 2:1 ratio to convalescent plasma or placebo, with the primary outcome being the patient's clinical status 30 days after the intervention. There was no difference between the groups in a 6-point ordinal scale used to rate outcome and mortality, or in outcomes at 7 or 14 days. Of note, study participants had symptoms for ~1 week prior to enrollment, so it is possible that earlier intervention and/or a different patient population might benefit from convalescent plasma. However, given that vaccines are now available, it is not clear that there will be a significant role for convalescent plasma moving forward.

• Results from large phase 3 trials are now available for 3 different vaccines, all of which have been found to be highly effective. Importantly, these trials focused on the development of symptomatic disease as their endpoint. It is still unclear to what degree these vaccines protect against asymptomatic infection and, therefore, ongoing transmission of the virus.

  • Polack and colleagues (2020) demonstrated that Pfizer's mRNA-based vaccine (BNT162b2) confers 95% protection against COVID-19 after 2 doses. A total of 43,548 participants were randomized to vaccine or placebo, and there were 162 and 8 COVID-19 cases in the placebo and vaccine groups, respectively, that occurred ≥7 days after the second dose. There were no significant differences in vaccine efficacy across different age, sex, racial, or ethnic groups, and there was no increased incidence in serious adverse events.

    • Of note, there were insufficient data to determine whether the vaccine protects against severe COVID-19 disease given the low number of cases overall: there were a total of 10 such cases with onset after the first dose, with 9 in the placebo group and 1 in the vaccine group. This strong trend toward protection is promising, and the lack of statistical significance is a reflection of the low number of severe disease cases overall, not an indication that the vaccine does not protect against severe disease.

    • The vaccine has 52% efficacy after the first dose, with protection beginning as soon as 12 days after the first dose.

    • In the first week of this vaccine's rollout in the United States and in the United Kingdom, there have been at least 3 cases of anaphylaxis/severe allergic reaction to the vaccine. In all 3 cases, the individuals recovered without incident with appropriate medical therapy. However, these findings underscore the need to observe patients for at least 15 minutes after vaccination, with a longer duration for those with a history of anaphylaxis.

  • Moderna's vaccine (mRNA-1273) also has completed a phase 3 trial and was found to confer 94.1% protection, with 185 and 11 COVID-19 cases in the placebo and vaccine groups, respectively (out of >28,000 participants). Similar to the Pfizer vaccine, there were no significant differences in efficacy across different age, sex, racial, or ethnic groups.

    • This vaccine was found to significantly protect against severe COVID-19 disease as well as more mild disease: there were 30 cases of severe disease in the placebo group with none in the vaccine group.

    • The Moderna vaccine is also effective after the first dose. An analysis of those who only received one dose of the vaccine at the time of the interim analysis demonstrated a vaccine efficacy of 80%, with 51% efficacy within the first 2 weeks after the first dose and 92% efficacy for >14 days after the first dose.

    • There is a suggestion that this vaccine may prevent some asymptomatic infections after the first dose. Among those participants who were SARS-CoV-2 seronegative at the beginning of the trial, 38 in the placebo group and 14 in the vaccine group seroconverted before the second dose. Although these numbers are small, it holds promise that there may be a reduction in asymptomatic infection, particularly after both doses of the vaccine are given.

  • Voysey and colleagues (2020) report that a chimpanzee adenovirus-vectored vaccine (AZD1222) made jointly by AstraZeneca and Oxford University had an overall efficacy of 70%. In this interim analysis, results from 11,636 trial participants were pooled from 4 different studies. A small subset of patients (n = 1367) inadvertently received a lower dose (LD) of vaccine for the first immunization and then a standard dose for the second immunization. In this subgroup, the vaccine efficacy was 90%; those patients who received the standard dose (SD) for both immunizations had a vaccine efficacy of 62%. It is not clear why the LD/SD regimen had such a notably different efficacy from the SD/SD regimen.

    • The LD/SD regimen had 59% efficacy against asymptomatic infection, while the SD/SD regimen conferred only 4% protection against asymptomatic infection.

    • Investigators are continuing to work on why the LD/SD regimen is more effective, and additional larger trials with this regimen are likely.

  • The United Arab Emirates and Bahrain have approved a COVID-19 vaccine made by the Chinese company Sinopharm. They report that the vaccine is 86% effective, although the underlying clinical trial data have not been made public for others to review.

References