key: cord-0861978-339gk5jy
authors: Fernandes, Amanda; Chaudhari, Sonia; Jamil, Nadia; Gopalakrishnan, Geetha
title: COVID-19 vaccine commentary
date: 2021-01-27
journal: Endocr Pract
DOI: 10.1016/j.eprac.2021.01.013
sha: 168775751d38c906c1b0dd066cdd176c0e9c48a8
doc_id: 861978
cord_uid: 339gk5jy

nan

Rapid spread of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has affected millions of lives since its emergence in December 2019 in Wuhan, China. 1 Public health and mitigation measures, such as social distancing, masks, and hand washing to prevent the spread of SARS-CoV-2, has been met with some resistance and resulted in mixed success based on implementation efforts. 2 As a result, there has been a global urgency for vaccine development. Within a month of the outbreak, scientists sequenced the SARS-CoV-2 genome and used similarities between SARS-CoV-1 and SARS-CoV-2 to accelerate the vaccine discovery process. 3 Currently, there are over 180 vaccines in various stages of development worldwide. 4 Recently, 2 vaccines have received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) and 3 others are undergoing phase 3 clinical trials in the United States (US).

Currently available vaccines induce an immune response to the SARS-CoV-2 spike protein. 3 The spike protein on the SARS-CoV-2 engages cell-surface receptors to gain entry into host cells. The use of messenger RNA (mRNA) to encode the spike protein is a novel approach in vaccine development.

To facilitate the uptake of mRNA into cells, it is attached to a lipid nanoparticle. Once the mRNA enters the cell, the virus spike proteins are made to induce an immune response. 4 COVID-19 vaccines are the first mRNA vaccines to be studied in large scale clinical trials and approved for clinical use. Unlike other types of vaccines, mRNA vaccines are not infectious and do not incorporate into the host genome. They are also easier to manufacture synthetically once the genome sequence is known. 3, 4 However, vaccine distribution has been a challenge since approved mRNA vaccines require cold temperatures to maintain chemical integrity.

In the US, Operation Warp Speed (OWS) was formed to facilitate the development, manufacturing and distribution of vaccines. 5 In order to receive EUA, the vaccine must result in 50% fewer cases of symptomatic COVID-19 compared to placebo and report at least 2 months of safety data (ie, the anticipated timeframe for the development of vaccine-related complications). 6 The first vaccine to receive EUA from the FDA is the mRNA vaccine BNT162b2 by Pfizer and BioNTech. This 2 dose vaccine was found to be 95% effective in preventing severe COVID-19 infection. 7 The 43,538 trial participants included 8.4% of participants having diabetes and 35.1% meeting the criteria of obesity (defined as body mass index equal to or greater than 30.0 kg/m 2 ). Of note, vaccine efficacy against COVID-19 after the first dose was only 52%, with a median follow-up less than 21 days. The second vaccine was the mRNA-1273 from Moderna, which noted a vaccine efficacy of 94.1%. This trial enrolled approximately 30,000 participants, of whom 9.5% and 6.7% carried a diagnosis of diabetes and obesity, respectively. 8 Vaccine efficacy was 80% after the first dose, with a median follow-up of 28 days. Despite the efficacy for both vaccines after a single dose, 2 doses are recommended by the CDC at this time given the lack of data on the sustained protection after a single dose (Table) .

Both vaccines report a similar side effect profile, which includes both local (pain, erythema, swelling, and lymphadenopathy) and systemic side effects (fevers, headaches, myalgia, nausea, or vomiting) with no safety concerns (Table) . The first dose of the vaccine acts to prime the immune system, while the second dose strengthens the immune response. 7 Despite the progress to date, challenges with manufacturing and distribution remain. 5 Creative solutions to address vaccine availability are being debated, including a phased rollout and the use of a single versus dual vaccine dose. In the US, a phased rollout is underway based on risk profiles with health care providers, individuals over the age of 65 years, and patients with underlying medical conditions such as diabetes and obesity allocated to receive the vaccine in Phase 1. 6 Phase 2 aims to vaccinate all individuals over the age of 16 years who have previously not been vaccinated. Other endocrine patients at risk of developing severe complications, such as those with adrenal insufficiency, at risk for thyroid storm, or undergoing treatment for certain endocrine cancers, might also benefit from early vaccinations despite limited data. Contraindications to the vaccine are severe or immediate allergic reaction (eg, anaphylaxis) to a previous dose of mRNA COVID-19 vaccine or to polysorbate due to crossreactive hypersensitivity to polyethylene glycol in the vaccine. 11 Current recommendations also encourage immunocompromised individuals, pregnant/lactating people, and individuals with history of other allergies to receive the vaccine after risk assessment and appropriate counseling, given limited data. 11 At this time, neither vaccine is approved for use in children.

Another challenge facing vaccine rollout and uptake has been vaccine hesitancy. In a recent survey conducted by the Pew Research Center, only 60% of respondents said that they would get the vaccine if one were available to them. Demographic and regional variations were noted, with only 54% of women (vs 67% men), 42% Blacks (vs 61% Whites, vs 83% Asians), 55% lowincome families (vs 71% high-income), and 50% Republican-leaning individuals (vs 69% Democratleaning) reporting acceptance of COVID-19 vaccination. 12 These differences are not unique to the United States and exist worldwide. 2 Experts currently estimate that approximately 80% of the J o u r n a l P r e -p r o o f population will need to be vaccinated to gain adequate herd immunity. 2 Hesitant attitudes toward vaccines will only hinder the development of herd immunity. Further complicating the need for urgent vaccination, scientists are now tracking 2 more infectious variants of SARS-Co-V2, B.1.1.7 (British variant) and 501Y.V2 (South African variant). While Pfizer recently announced that their vaccine is effective against these new variants, 13 concerns remain that with ongoing mutations, our current vaccines may not be effective and periodic revaccination maybe required.

Historically, vaccines have revolutionized the care of many communicable diseases. 6 Campaigns to vaccinate at-risk individuals have been the key. This is especially true for those living with diabetes and the influenza vaccine. There is a significant difference in the uptake of influenza vaccination in individuals with diabetes compared to age-controlled individuals without diabetes. 14 With the introduction of mRNA vaccines, we are in a unique position as endocrinologists to help combat the current vaccine hesitancy in our patients who are at high risk of developing COVID-19. Several studies have noted that COVID-19 has a higher incidence in patients with diabetes and obesity as well as those over the age of 65. For instance, a case series done in New York that included 5700 patients revealed that 33.8% of these patients had diabetes. Furthermore, there is increase risk in severity of illness from COVID-19 in these individuals, leading to more hospitalizations, intensive care unit admissions, longer length of hospital stay, and death. [15] [16] [17] During this crisis, what can we do as endocrinologists?

All patients who are evaluated in our practice should be assessed for their willingness to take the COVID-19 vaccine. For patients with negative views toward the vaccine, we should be ready to address their concerns regarding side effects and to answer questions about the rapidity of vaccine development and the use of mRNA technology. As the number of cases of COVID-19 increases in the United States, patients will likely know someone who has developed COVID-19 or will have contracted COVID-19 themselves. It is likely that these personal connections and stories are going to have a bigger impact on vaccination decisions than statistics. 18 Consumer behavior has long been driven by identity and has driven many sales models. We can use a similar approach when trying to increase vaccine uptake in our patient population. 18 During the first phase of vaccine rollout, many health care workers utilized social media to post personal images of vaccination. Social media and personal connections played a big role in increasing confidence in the vaccine. We need to carry this forward into our practice. A wearable token that identifies health care workers as "vaccinated against COVID-19" will help boost public trust in the vaccine. Surveys of the general population have shown that intent and trust in getting vaccinated increases as people see others getting vaccinated. 18 Endocrinologists have been in the forefront of vaccination strategies, as we led efforts to vaccinate our patients with diabetes against infections such as influenza and pneumococcal diseases. Now, we are called upon once again to educate our diabetic as well as our nondiabetic patients on the risk-benefit of COVID-19 vaccinations. With the pandemic intensifying, our role as endocrinologists is simple -to help develop herd immunity starting with our most vulnerable population.

The authors have no multiplicity of interest to disclose.

J o u r n a l P r e -p r o o f 

SARS-CoV-2 transmission from people without COVID-19 symptoms

Challenges in creating herd immunity to SARS-CoV-2 infection by mass vaccination. The Lancet

SARS-CoV-2 vaccines in development

A comparison of plasmid DNA and mRNA as vaccine technologies. Vaccines (Basel)

Developing safe and effective Covid vaccines -Operation Warp Speed's strategy and approach

The granting of emergency use designation to COVID-19 candidate vaccines: implications for COVID-19 vaccine trials

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine -United States

Maintaining safety with SARS-CoV-2 vaccines

Interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States

Intent to get a COVID-19 vaccine rises to 60% as confidence in research and development process increases

Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera

Flu vaccination coverage

Patients with diabetes are at higher risk for severe illness from COVID-19

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area

Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region

Beyond politics -Promoting Covid-19 vaccination in the United States