COVID-19 in 2021—Continuing Uncertainty

Abstract

UncertaintyMore than a year has passed since the first confirmed case of SARS-CoV-2 infection in the US was reported on January 20, 2020.What followed was an unprecedented year with nearly 30 million documented infections and more than 500 000 excess deaths in the US due to SARS-CoV-2.Alongside this devastation is the successful development and deployment of multiple safe and effective vaccines. 1o date, almost 80 million doses of vaccine have been administered in the US with some experts suggesting that the extent of disease, including the number of deaths, will continue to decline between now and summer.Yet moving to the next phase of the pandemic remains a challenge; clinicians and patients have many questions that may not have clear answers.This Viewpoint summarizes the current best evidence to some of these complex questions.Which Vaccine Is Best and How Should They Be Deployed?Currently,2mRNAvaccines(createdbyPfizer-BioNTech and Moderna) and 1 adenovirus-vectored vaccine (Janssen/Johnson & Johnson) have received Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA).These vaccines have proven to be safe and highly effective in preventing severe COVID-19 and death and likely also prevent transmission. 1he Janssen vaccine is the first adenovirusvectored vaccine to be evaluated and to receive EUA by the FDA.This vaccine uses a cold virus (Ad26) engineered to carry the genetic code of the SARS-CoV-2 spike protein.As a single-dose vaccine, it offers practical advantages in terms of deployment and scale-up.However, comparing the different vaccines is more difficult with respect to efficacy.The 2 mRNA vaccines have similar efficacy of approximately 95% for the prevention of symptomatic COVID-19 and nearly 100% efficacy in preventing death from COVID-19 after 2 doses. 1 However, neither of these vaccines were tested when more recently identified SARS-CoV-2 variants like B.1.1.7 and B.1.135were the predominant ones in circulation.The Janssen vaccine was 66% protective against moderate to severe COVID-19 although this varied by geographic location: 72% protective in the US while only 57% protective in South Africa, reflecting the various variants in each country. 2 However, the vaccine was 85% protective against severe disease and 100% protective against hospitalization and death from COVID-19 without geographic differences. 2t present, given the differences between the 3 vaccines, which vaccine should individuals receive?Initially the answer is that they should receive whichever vaccine is available when they become eligible.However, as supplies become less of a limitation, it may be that for groups with higher risk of severe disease and complications (eg, older adults, immunocompromised people), the mRNA vaccines would provide an advan-

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