Disentangling post-vaccination symptoms from early COVID-19

Abstract

Background: Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app. Design: We conducted a prospective observational study in UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (other than local symptoms at injection site) and were tested for SARS-CoV-2, aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were also recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models including UK testing criteria. Findings: Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. A majority of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue). Interpretation: Post-vaccination side-effects per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2, to prevent community spread. Funding: Zoe Limited, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Alzheimer's Society, Chronic Disease Research Foundation, Massachusetts Consortium on Pathogen Readiness (MassCPR).

Combined assessment of S‐ and N‐specific IL‐2 and IL‐13 secretion and CD69 neo‐expression for discrimination of post–infection and post‐vaccination cellular SARS‐CoV‐2‐specific immune response

“…Accordingly, the mere fact that a particular patient had survived COVID‐19 or had been vaccinated with an mRNA‐ or vector‐based SARS‐CoV‐2 vaccine does not guarantee with certainty that the respective individual has also developed a protective humoral and cellular immunity. Moreover, recent data have shown that post‐vaccination side‐effects may not be differentiable with high accuracy from COVID‐19 by solely applying symptom profiles or machine‐derived algorithms 27 . This may be especially a problem if PCR tests were not performed in the time period directly after vaccination, since vaccination itself (especially during the first 3 days after vaccination) may cause fever and fatigue, symptoms also associated with mild COVID‐19 infection 9 .…”

SARS-CoV-2 post-vaccination adverse reports: A review

“…Большой обзор посвящен побочным эффектам мРНК-вакцин [6]. Следует отметить сложность интерпретации краткосрочных поствакцинальных эффектов, связанных с возможной интерференцией с симптомами ранней стадии недиагностированного COVID-19 [7].…”