Epidemiology effective treatments for PASC. Further, the severity of PASC, as measured by validated assessments of fatigue, pain, disability and health-related quality of life of those with PASC, was similar regardless of whether it was associated with a breakthrough or a non-breakthrough infection. The aetiology of PASC remains unknown but several factors have been hypothesised to influ- ence risk, including alterations in inflammatory cytokine profiles, cellular immune responses, reactivation of chronic viral infections and autoantibody formation. 40–46 Vaccination may reduce the risk of PASC by shortening the duration of viraemia, reducing the risk of severe COVID-19 and the associated hyper- inflammatory state, influencing the cellular immune response to acute infection, among other possible explanations. It is unclear whether the risk of PASC may increase with increasing time since vaccination; our study did not have sufficient power to address this question but it should be investigated further in future studies. Our study has several strengths. First, we used a systematic approach to identify patients with a prevalent diagnosis of a SARD at the time of SARS-CoV-2 infection. Second, we prospec- tively enrolled patients in RheumCARD to assess symptom dura- tion and vaccination status, collecting patient-reported outcomes unavailable from EHR data. Third, we used two complementary definitions of PASC and conducted multiple sensitivity analyses to confirm the robustness of our findings. Despite these strengths, our study has certain limitations. First, this study was conducted among participants who receive their care at MGB, which may limit generalisability to more diverse populations. Not all people invited to participate in RheumCARD completed a survey, but this should not affect our primary findings with regard to the risk of PASC among those who were or were not vaccinated prior to the acute infection. The proportion of current smokers was also low in our cohort; while consistent with prior estimates from similar populations, this may be a reflection of the type of patients who chose to participate. Second, the time between COVID-19 infection and survey completion was shorter among those with breakthrough infection because of the timing of the initiation of RheumCARD. While this could introduce recall bias whereby those with a non- breakthrough infection reported a longer duration of symptoms, we do not have reason to suspect this is likely. Further, our find- ings were similar in a sensitivity analysis where we limited the analysis to those who completed the surveys within 6 months of their index date. Also, similar proportions of patients in each group recalled flares of their underlying SARD following COVID-19 infection, suggesting no significant differential recall bias according to vaccination status. Third, some patients in the breakthrough group also received antiviral and other COVID-19 treatments which could impact our findings. However, in sensi- tivity analyses, we found that our observed trends persisted despite accounting for these differences. Fourth, based on the timing of infection, the variants most prevalent in those with breakthrough infections were Delta and Omicron. Due to the high vaccination rate in our cohort once vaccines became avail- able, we are unable to compare those with and without break- through infection with the same SARS-CoV-2 variant. Fifth, while we used the currently accepted research definitions of PASC, it is possible that the patient reports could reflect under- lying SARD activity, organ damage or be otherwise unrelated to COVID-19 resulting in overestimation of people truly expe- riencing prolonged COVID-19 symptoms. Future studies are needed to determine whether more homogeneous PASC subtypes may be present and to elucidate pathogenesis and possible treat- ments. Last, there are other PASC of varying severity including
thrombotic manifestations, neuropathy, cognitive dysfunction and others (sometimes referred to as ‘Long COVID-19’) that were not evaluated in this study; future studies could evaluate whether these are impacted by vaccination status, anticoagulant use, comorbidity burden and other factors. In conclusion, we found that patients with SARDs have shorter duration of COVID-19 symptoms and are less likely to have PASC at both 28 and 90 days if they are fully vaccinated prior to acute infection. These findings suggest that despite a higher risk of breakthrough infection, vaccination in patients with SARDs not only reduces the risk of severe acute outcomes but also long- term outcomes. Nonetheless, PASC remains common among patients with SARD, even after vaccination, and when present, the severity is similar to those who were either unvaccinated or partially vaccinated. Additional investigation is needed to deter- mine the aetiology and effective treatments of PASC in SARDs. Twitter Jeffrey A Sparks @jeffsparks Contributors NJP, JAS and ZSW had access to the study data, developed the figures and tables and vouch for the data and analyses. XF and YZ performed the statistical analyses and contributed to data quality control, data analysis and interpretation of the data. CC, KV, XF, XW, YK, GQ, SS, EPB, EK and KB contributed to data collection, data analysis and interpretation of the data. ZSW and JAS directed the work, designed the data collection methods, contributed to data collection, data analysis and interpretation of the data and had final responsibility for the decision to submit for publication. All authors contributed intellectual content during the draft and revision of the work and approved the final version to be published. ZSW accepts full responsibility for the finished work and/or the conduct of the study, had access to the data and controlled the decision to publish. JAS and ZSW contributed equally as last authors. ZSW assumes overall responsibility for the content as the guarantor. Funding NJP is funded by the Rheumatology Research Foundation (Scientist Development Award). YK is funded by the National Institutes of Health Ruth L. Kirschstein Institutional National Research Service Award (grant number T32 AR007530). ZSW is funded by NIH/NIAMS (grant numbers K23 AR073334 and R03 AR078938) and the Rheumatology Research Foundation (K Supplement). JAS is funded by NIH/NIAMS (grant numbers R01 AR077607, P30 AR070253, and P30 AR072577), the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Disclaimer The funders had no role in the decision to publish or preparation of this manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard University, its affiliated academic health care centers, or the Rheumatology Research Foundation, or the National Institutes of Health. Competing interests ZSW reports research support from Bristol-Myers Squibb and Principia/Sanofi and consulting fees from Zenas Biopharma, Horizon, Sanofi, Shionogi, Viela Bio, and MedPace. JS reports research support from the R. Bruce and Joan M. Mickey Research Scholar Fund, the Llura Gund Award for Rheumatoid Arthritis Research and Care, and Bristol-Myers Squibb. JS reports consulting fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer. NJP reports consulting fees from FVC Health and LLC. Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not applicable. Ethics approval This study involves human participants and was approved by This study was approved by the MGB Institutional Review Board (2020P000833). Participants gave informed consent to participate in the study before taking part. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available on reasonable request. Data are available on reasonable request to the corresponding author and appropriate ethical approvals. Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and
Patel NJ, et al . Ann Rheum Dis 2023; 82 :565–573. doi:10.1136/ard-2022-223439
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