Public health investigations of COVID-19 vaccine breakthrough cases : case investigation protocol
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Public health investigations of COVID-19 vaccine breakthrough cases : case investigation protocol

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      As of the end of March 2021, >30 million coronavirus disease 2019 (COVID-19) cases and >546,000 COVID-related deaths had been reported in the United States.1 Safe and effective COVID-19 vaccines are an important tool in controlling the pandemic. The U.S. Food and Drug Administration (FDA) has issued Emergency Use Authorization (EUA) for three COVID-19 vaccines.2 In large, randomized controlled trials, each vaccine was safe and efficacious for preventing symptomatic, laboratory-confirmed COVID-19 disease.3–5 There were no statistically significant differences in efficacy by age, gender, race, or comorbidities. Despite the high level of efficacy, a small number of breakthrough cases occurred. The phase 3 studies have not yet identified risk factors for vaccine breakthrough cases; however, approximately 44,000 people received the FDA-authorized vaccines during the clinical trials and follow-up is ongoing. In addition, several other COVID-19 vaccines are in late-stage development.6

      As FDA-authorized COVID-19 vaccines are administered more broadly, it will be important to monitor breakthrough cases to identify unexpected trends or clustering in the patients (i.e., demographics, geography, underlying medical conditions, time since vaccine receipt, and clinical severity), the administered vaccine (i.e., type, dosing, lot, storage, and handling), or infecting virus (i.e., variant strains and mutations). While some studies have found that neutralizing antibodies persist for months following natural infection with SARS- CoV-2, others have detected some waning immunity over time.7-9 Some of the FDA-authorized COVID-19 vaccines require strict temperature control.10-12 Vaccine failures could result from partial vaccine degradation due to inadequate cold chain or other issues during shipping, storage, or administration. The current FDA-authorized vaccines, and the majority COVID-19 vaccines in late-stage development, target the SARS-CoV2 spike glycoprotein.6,13 In recent months, five SARS-CoV-2 variants of concern have emerged that contain mutations in the spike glycoprotein (i.e., B.1.1.7, B.1.351, P.1, B.1.427, and B.1.429).14-16 The B.1.1.7 lineage was first detected in the United Kingdom, the B.1.351 lineage was first identified in South Africa, the P.1 lineage was identified in travelers from Brazil, and the B.1.427, and B.1.429 lineages emerged in California. Preliminary data suggest these variant strains may be more transmissible or cause increased severity of disease.14-17 At least one in vitro study suggests the B.1.351 variant might be neutralized less effectively by convalescent plasma from patients infected with other strains of SARS-CoV-2.17,18 There is mixed evidence regarding whether these variant strains are less susceptible to vaccine-induced immunity.19-25 However, it will be important to detect vaccine breakthrough cases that may result from shifts in the susceptibility of circulating viral strains.

      This protocol can be used to guide public health investigations of COVID-19 vaccine breakthrough cases. We aim to capture both symptomatic and asymptomatic infections. Characterization of vaccine breakthrough cases could provide the first indication that a vaccine is less effective in certain demographic groups or that vaccine-induced immunity is waning and booster doses may be needed. Clustering of cases among vaccinated persons by time, geographic area, or lot could help identify an issue in manufacturing, shipping, handling, or administration. Evaluating SARS-CoV-2 strains that cause vaccine breakthrough cases provides one way to monitor for variant strains that could result in lower vaccine efficacy.Publication date from document properties.


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