more than 14 days after the second dose. Vaccine efficacy was 70.4% overall, but surprisingly was lower in the SD/ SD arm (62.1%) versus the LD/SD arm (90.0%). While zero COVID-19-related hospital admissions occurred in vaccine recipients, ten occurred in the control groups, two of which were severe. Regarding safety, no serious adverse events or deaths associated with treatment in vaccine recipients. The Janssen vaccine, Ad26.COV2.S, is a recombinant vector vaccine that uses a human adenovirus to express the SARS-CoV-2 spike protein. This vaccine requires only a single injection and can be stored in a refrigerator for months. Initial safety profile was established with data from published phase 1 and 2 trials, 25 and the vaccine is currently being evaluated as part of the ENSEMBLE trial. 26 ENSEMBLE is a phase 3, randomized, double-blinded trial in which participants receive either the single dose vaccine or placebo. The study included 44,325 participants recruited from study sites including Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa, and the United States and was able to evaluate efficacy in locations with emerging variants. Although data from this study have not yet been published, NIH reported on a preliminary analysis of 468 participants who developed symptomatic Covid-19. 27 Reportedly the vaccine has 66% efficacy at preventing development of moderate to severe Covid-19 at 28 days post vaccination, with a level of 72% protection in the United States. Notably, efficacy of 85% at preventing severe/critical Covid-19 was observed across all regions, and there were no deaths in the vaccine arm relative to five COVID-19 deaths in the placebo arm. Complete safety data are forthcoming. The Novavax vaccine (NVX-CoV2373) is a recombinant SARS- CoV2 spike protein nanoparticle vaccine with Matrix-M1 adjuvant. It has been studied as a two-dose vaccine series administered 21 days apart. Phase 1-2 trial data have been published establishing the safety of the vaccine and showing a robust immune response, inducing a high titer of antibodies in excess of that seen in the convalescent serum of symptomatic Covid-19 patients. 28 Although Phase 3 data have not yet been published, the manufacturer has released results of a preliminary analysis of UK phase 3 trial. 29 The trial enrolled more than 15,000 participants, ages 18-84. The primary endpoint was symptomatic COVID-19 (polymerase chain reaction [PCR]-confirmed) occurring at least 7 days following second vaccine dose. Initial, recently reported results were based on the first 62 Covid-19 cases in trial participants, with 56 being in the placebo group and 6 in the vaccine group. Based on these numbers, an efficacy of 89.3% was reported. Notably the trial was conducted in a region with wide circulation of the UK virus variant, which was detected in 50% of participants with PCR confirmed symptomatic Covid-19. Post-hoc analysis suggested 95.6% efficacy against the original Covid-19 strain and 85.6% against the new variant. Although no specific data on
adverse events in the phase 3 trial have been released, it was reported that adverse events requiring medical attention occurred at low levels and were evenly distributed between the intervention and placebo group.
VACCINES TO PREVENT ASYMPTOMATIC INFECTION
Early promising data provide biological plausibility that vaccines will prevent not only disease and progression to severe COVID-19, but also asymptomatic infection and therefore stand to limit asymptomatic transmission. Earlier nonhuman primate (NHP) models have examined the airways of macaques following vaccination with both the Novavax and Janssen vaccines. 30,31 These studies demonstrated low or no detectable RNA in respiratory tracts of macaques following vaccination. The University of Oxford/AstraZeneca study evaluated for asymptomatic infection in addition to the aforementioned outcomes. Although the total number of cases was small (n=69), there was a signal for efficacy in preventing asymptomatic transmission (58.9% efficacy in LD/SD group and 3.8% in SD/SD group). A more recent analysis of “real- world” data on the Pfizer vaccine roll-out in Israel has demonstrated an encouraging finding, that is, that viral loads are significantly reduced in those who have been vaccinated. 32 The study, which has not yet been published as peer-reviewed, was able to examine post-vaccination infections via laboratory data. The authors compared the mean viral load for infections that occurred on days 12-28 following the first vaccine dose to viral loads of uninfected controls and found a four-fold reduction in the samples from vaccinated individuals. This finding offers provides hope that asymptomatic transmission will also be reduced with vaccination, which is critical to achieving herd immunity. TREATMENT
The push to find effective treatments for COVID-19 has been a race against time, as more sickness, death, and economic devastation occur with each passing day. Initial attempts at repurposing already existing pharmacologic agents in order to treat COVID-19 were unfortunately not met with great success. Lopinavir-ritonavir, 33–35 azithromycin, 36,37 hydroxychloroquine 35–38 were studied due to reported in vitro activity; however, in subsequent trials these agents were not shown to have significant benefit in symptomatic improvement or mortality. However, there are exceptions, for example remdesivir and dexamethasone (see below). Fortunately, our treatment arsenal now includes more than a few different therapeutic options, and our management of COVID-19 has improved since early 2020, as evidenced by declining mortality over time. This section will focus on pharmaceutical interventions to treat COVID-19 symptoms and improve outcomes, and includes a discussion of SARS- 18
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