Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases

Cook, Claire; Patel, Naomi J; D’Silva, Kristin M; Hsu, Tiffany; DiIorio, Michael; Prisco, Lauren; Martin, Lily; Vanni, Kathleen M M; Zaccardelli, Alessandra; Todd, Derrick J.; Sparks, Jeffrey A.; Wallace, Zachary S

doi:10.1136/annrheumdis-2021-221326

Cited by 81 publications

(83 citation statements)

References 6 publications

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“…This mirrors an increase in breakthrough cases throughout the globe. [18][19][20]32 Our study showed a statistically significant higher risk of getting infected before vaccination, as compared to after vaccination, and the overall COVID-19 related hospitalizations were lower among the fully vaccinated. However, among those who did get COVID-19 after being fully vaccinated, the hospitalization rate was not statistically different compared to those who had it before vaccination.…”

Section: Discussionmentioning

confidence: 95%

Clinical and Virologic Factors associated with Outcomes of COVID-19 before and after Vaccination among Veterans: Retrospective Analysis from Six New England States

Lee

Cosenino

Kyriakides

et al. 2022

Preprint

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Background: A region-wide analysis of COVID-19 outcomes in New England has not been done. We aimed to characterize clinical, demographic, and vaccination status affecting COVID-19 clinical outcomes and describe viral epidemiology. Methods: Clinical variables of Veterans with COVID-19 in Veterans Administration healthcare systems in six New England states from April 8, 2020, to September 2, 2021 were correlated with outcomes of 30-day mortality, non-psychiatric hospitalization, intensive care unit admission (ICU-care), and post-vaccination infection. We sequenced 754 whole viral genomes and 197 partial genomes. Results: Of 4,170 Veterans with COVID-19, 81% were White, 8% women, mean age was 60.1+17.7 years, and 2,399 became fully vaccinated. Overall, 19% Veterans needed hospitalization, 2.8% required ICU-care, and 3.7% died. Veterans with post-vaccination COVID-19 were older, with higher rates of tobacco/drug use, CKD, and malignancy, and 0.38% died. Among the unvaccinated, ICU-care and mortality correlated with age, while hospitalization correlated with age, male sex, black race, drug use, chronic heart disease, COPD, CKD, and chronic liver disease. Age, CKD, and alcohol use correlated with hospitalization in vaccinated patients. Most New England Veterans (>97%) were infected with B.1 sub-lineages with the D614G mutation in 2020 and early 2021. B.1.617.2 lineage (71%) predominated after July 2021, including the post-vaccination infections. Conclusion: In New England Veterans with mean age of 60 years, age and CKD significantly correlated with hospitalization regardless of vaccination-status. Age correlated with mortality and ICU-care among the unvaccinated. The Delta variant of SARS-CoV-2 (B.1.617.2) dominated post-vaccination infections.

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Section: Discussionmentioning

confidence: 95%

Clinical and Virologic Factors associated with Outcomes of COVID-19 before and after Vaccination among Veterans: Retrospective Analysis from Six New England States

Lee

Cosenino

Kyriakides

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…While vaccination has been the central strategy in preventing or dampening the viral pandemic [49], vaccination is clearly less effective in certain circumstances exacerbated by the emergence of new SARS-CoV-2 variants which may limit or shorten the impact of certain vaccine therapies [50][51][52]. In addition, there remains an important sub-set of individuals, typically with compromized immune systems, that respond less well to vaccines [53][54][55], thus necessitating the development of additional antiviral strategies. In those regions of the world claiming a level of pandemic-control, a new and growing epidemic of patients suffering from longer-term post-infection complications, often referred to by the catch-all "long-COVID", is being increasingly reported.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal Human Antibodies That Recognise the Exposed N and C Terminal Regions of the Often-Overlooked SARS-CoV-2 ORF3a Transmembrane Protein

Tan

Patton

Munro

et al. 2021

Viruses

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ORF3a has been identified as a viroporin of SARS-CoV-2 and is known to be involved in various pathophysiological activities including disturbance of cellular calcium homeostasis, inflammasome activation, apoptosis induction and disruption of autophagy. ORF3a-targeting antibodies may specifically and favorably modulate these viroporin-dependent pathological activities. However, suitable viroporin-targeting antibodies are difficult to generate because of the well-recognized technical challenge associated with isolating antibodies to complex transmembrane proteins. Here we exploited a naïve human single chain antibody phage display library, to isolate binders against carefully chosen ORF3a recombinant epitopes located towards the extracellular N terminal and cytosolic C terminal domains of the protein using peptide antigens. These binders were subjected to further characterization using enzyme-linked immunosorbent assays and surface plasmon resonance analysis to assess their binding affinities to the target epitopes. Binding to full-length ORF3a protein was evaluated by western blot and fluorescent microscopy using ORF3a transfected cells and SARS-CoV-2 infected cells. Co-localization analysis was also performed to evaluate the “pairing potential” of the selected binders as possible alternative diagnostic or prognostic biomarkers for COVID-19 infections. Both ORF3a N and C termini, epitope-specific monoclonal antibodies were identified in our study. Whilst the linear nature of peptides might not always represent their native conformations in the context of full protein, with carefully designed selection protocols, we have been successful in isolating anti-ORF3a binders capable of recognising regions of the transmembrane protein that are exposed either on the “inside” or “outside” of the infected cell. Their therapeutic potential will be discussed.

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“…We systematically identified all SARD participants with SARS-CoV-2 confirmed by PCR, nucleocapsid antibody, or antigen testing (from March 1, 2020 to November 3, 2021 for this analysis) at Mass General Brigham (MGB) HealthCare system in the greater Boston, Massachusetts area, as previously described (2,9,(11)(12)(13)(14). This was supplemented by referrals from rheumatologists of participants who were diagnosed outside of the MGB system.…”

Section: Study Populationmentioning

confidence: 99%

DMARD disruption, disease flare, and prolonged symptom duration after acute COVID-19 among participants with rheumatic disease: A prospective study

DiIorio

Cook

Vanni

et al. 2022

Preprint

Self Cite

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Objective: To describe disease-modifying antirheumatic drug (DMARD) disruption, rheumatic disease flare/activity, and prolonged COVID-19 symptom duration among COVID-19 survivors with systemic autoimmune rheumatic diseases (SARDs). Methods: We surveyed patients with SARDs after confirmed COVID-19 at Mass General Brigham to investigate post-acute sequelae of COVID-19. We obtained data on demographics, clinical characteristics, COVID-19 symptoms/course, and patient-reported measures. We examined baseline predictors of prolonged COVID-19 symptom duration (defined as lasting ≥28 days) using logistic regression. Results: We analyzed surveys from 174 COVID-19 survivors (mean age 52 years, 81% female, 80% White, 50% rheumatoid arthritis) between March 2021 and January 2022. Fifty-one percent of 127 respondents on any DMARD reported a disruption to their regimen after COVID-19 onset. For individual DMARDs, 56-77% had any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41%. Global patient-reported disease activity was worse at the time of survey than before COVID-19 (mean 6.6, SD 2.9 vs. 7.6, SD 2.3, p<0.001). Median time to COVID-19 symptom resolution was 14 days (IQR 9,29). Prolonged symptom duration of ≥28 days occurred in 45%. Hospitalization for COVID-19 (OR 3.54, 95%CI 1.27-9.87) and initial COVID-19 symptom count (OR 1.38 per symptom, 95%CI 1.17-1.63) were associated with prolonged symptom duration. Respondents experiencing prolonged symptom duration had higher RAPID3 scores (p=0.007) and more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms. Conclusion: DMARD disruption, SARD flare, and prolonged symptom duration were common in this prospective study of COVID-19 survivors, suggesting substantial impact on SARDs after acute COVID-19.

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Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases

Cited by 81 publications

References 6 publications

Clinical and Virologic Factors associated with Outcomes of COVID-19 before and after Vaccination among Veterans: Retrospective Analysis from Six New England States

Clinical and Virologic Factors associated with Outcomes of COVID-19 before and after Vaccination among Veterans: Retrospective Analysis from Six New England States

Monoclonal Human Antibodies That Recognise the Exposed N and C Terminal Regions of the Often-Overlooked SARS-CoV-2 ORF3a Transmembrane Protein

DMARD disruption, disease flare, and prolonged symptom duration after acute COVID-19 among participants with rheumatic disease: A prospective study

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