SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease : Results from the COVID-19 Global Rheumatology Alliance provider registry

Funding Information: members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the American College of Rheumatology (ACR), EULAR, the UK National Health Service (NHS), the National Institute for Health Research (NIHR), the UK Department of Health or any other organisation. Competing interests KLH reports she has received non-personal speaker’s fees from AbbVie and grant income from BMS, UCB and Pfizer, all unrelated to this manuscript; KLH is supported by the NIHR Manchester Biomedical Research Centre. LG reports personal consultant fees from AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis and UCB, and grants from Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi and Galapagos, all unrelated to this manuscript. AS reports research grants from a consortium of 14 companies (among them AbbVie, BMS, Celltrion, Fresenius Funding Information: Kabi, Gilead/Galapagos, Lilly, Mylan/Viatris, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis and UCB) supporting the German RABBIT register and personal fees from lectures for AbbVie, MSD, Roche, BMS, Lilly and Pfizer, all unrelated to this manuscript. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories among other institutions, such as AbbVie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi-Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal and UCB Pharma. EF-M reports personal consultant fees from Boehringer Ingelheim Portugal and that LPCDR received support for specific activities: grants from AbbVie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal, MSD, Celgene, Medac, Pharmakern and GAfPA; grants and non-financial support from Pfizer; and non-financial support from Grünenthal, outside the submitted work. IB reports personal consultant fees from AbbVie, Novartis, Pfizer and Janssen, all unrelated to this manuscript. JZ reports speaker fees from AbbVie, Novartis and Janssen/Johnson & Johnson, all unrelated to this manuscript. GR-C reports personal consultant fees from Eli Lilly and Novartis, all unrelated to this manuscript. JS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers: R01 AR077607, P30 AR070253 and P30 AR072577), and the R Bruce and Joan M Mickey Research Scholar Fund. JS has received research support from Amgen and Bristol Myers Squibb and performed consultancy for Bristol Myers Squibb, Gilead, Inova, Janssen and Optum, unrelated to this work. LW receives speaker’s bureau fees from Aurinia Pharma, unrelated to this manuscript. SB reports no competing interests related to this work. He reports non-branded consulting fees for AbbVie, Horizon and Novartis (all <$10 000). MGM has no competing interests related to this work. She serves as a patient consultant for BMS, BI JNJ and Aurinia (all <$10 000). RG reports no competing interests related to this work. Outside of this work she reports personal and/or speaking fees from AbbVie, Janssen, Novartis, Pfizer and Cornerstones and travel assistance from Pfizer (all <$10 000). JH reports no competing interests related to this work. He is supported by grants from the Rheumatology Research Foundation and has salary support from the Childhood Arthritis and Rheumatology Research Alliance. He has performed consulting for Novartis, Sobi and Biogen, all unrelated to this work (<$10 000). ESi reports non-financial support from Canadian Arthritis Patient Alliance, outside the submitted work. PS reports personal fees from the American College of Rheumatology/Wiley Publishing, outside the submitted work. ZW reports grant support from Bristol Myers Squibb and Principia/Sanofi and performed consultancy for Viela Bio and MedPace, outside the submitted work. His work is supported by grants from the National Institutes of Health. PMM has received consulting/speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this study. PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). PCR reports no competing interests related to this work. Outside of this work PCR reports personal fees from AbbVie, Atom Bioscience, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Kukdong, Novartis, UCB, Roche and Pfizer; meeting attendance support from BMS, Pfizer and UCB; and grant funding from Janssen, Novartis, Pfizer and UCB Pharma (all <$10 000). JY reports no competing interests related to this work. Her work is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155). Outside of this work, she has received research grants or performed consulting for Gilead, BMS Foundation, Pfizer, Aurinia and AstraZeneca. Funding Information: Twitter Jean Liew @rheum_cat, Loreto Carmona @carmona_loreto, Pedro M Machado @pedrommcmachado and Philip C Robinson @philipcrobinson Contributors All authors contributed to the study design, data collection, interpretation of results and review/approval of the final submitted manuscript. JL and MG are guarantors for this manuscript. Funding MG reports grants from the National Institutes of Health, NIAMS, outside the submitted work. KLH is supported by the NIHR Manchester Biomedical Research Centre. JS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers: R01 AR077607, P30 AR070253 and P30 AR072577), and the R Bruce and Joan M Mickey Research Scholar Fund. JH is supported by grants from the Rheumatology Research Foundation. ZW is supported by grants from the National Institutes of Health. PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). JY is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155). Publisher Copyright: ©Objective. While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2.  Methods. We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes. Results SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died. Conclusion. More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.publishersversionPeer reviewe

When both ends meet a case report of Crohn\u27s disease in a patient with systemic lupus erythematosus

Background: Inflammatory bowel disease (IBD) is an uncommon autoimmune condition affecting Filipinos. Its association with systemic lupus erythematosus (SLE) is even more unusual. The immunological background of both diseases is thought to explain the mechanism of this rare association.1 Objective: To present an unusual case of lower gastrointestinal bleeding in a patient with SLE Setting: A tertiary training hospital in Cavite, Philippines Case Summary: A 29 year old Filipina with 11 years history of SLE developed a recent flare of lupus nephritis. She also presented with bloody diarrhea and anemia. Bleeding was initially attributed to thrombocytopenia or to platelet dysfunction due to renal insufficiency. Colonoscopy revealed superficial ulcerations on the terminal ileum, asymmetric granulomatous/cobblestone mucosa at various levels where punctuate ulcerations were actively bleeding which are consistent with Crohn\u27s disease. The patient was treated with mesalazine and methylprednisolone pulse with note of resolution of lower gastrointestinal bleeding. Significance: This report highlights the importance of considering a wide range of differentials in dealing with complications of systemic lupus erythematosus. Further, it illustrates the supreme importance of endoscopic evaluation for patients with gastrointestinal bleeding

Implementation of Practical Surface SARS-CoV-2 Surveillance in School Settings.

Surface sampling for SARS-CoV-2 RNA detection has shown considerable promise to detect exposure of built environments to infected individuals shedding virus who would not otherwise be detected. Here, we compare two popular sampling media (VTM and SDS) and two popular workflows (Thermo and PerkinElmer) for implementation of a surface sampling program suitable for environmental monitoring in public schools. We find that the SDS/Thermo pipeline shows superior sensitivity and specificity, but that the VTM/PerkinElmer pipeline is still sufficient to support surface surveillance in any indoor setting with stable cohorts of occupants (e.g., schools, prisons, group homes, etc.) and may be used to leverage existing investments in infrastructure. IMPORTANCE The ongoing COVID-19 pandemic has claimed the lives of over 5 million people worldwide. Due to high density occupancy of indoor spaces for prolonged periods of time, schools are often of concern for transmission, leading to widespread school closings to combat pandemic spread when cases rise. Since pediatric clinical testing is expensive and difficult from a consent perspective, we have deployed surface sampling in SASEA (Safer at School Early Alert), which allows for detection of SARS-CoV-2 from surfaces within a classroom. In this previous work, we developed a high-throughput method which requires robotic automation and specific reagents that are often not available for public health laboratories such as the San Diego County Public Health Laboratory (SDPHL). Therefore, we benchmarked our method (Thermo pipeline) against SDPHL's (PerkinElmer) more widely used method for the detection and prediction of SARS-CoV-2 exposure. While our method shows superior sensitivity (false-negative rate of 9% versus 27% for SDPHL), the SDPHL pipeline is sufficient to support surface surveillance in indoor settings. These findings are important since they show that existing investments in infrastructure can be leveraged to slow the spread of SARS-CoV-2 not in just the classroom but also in prisons, nursing homes, and other high-risk, indoor settings

SARS-CoV-2 Distribution in Residential Housing Suggests Contact Deposition and Correlates with Rothia sp.

Monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on surfaces is emerging as an important tool for identifying past exposure to individuals shedding viral RNA. Our past work demonstrated that SARS-CoV-2 reverse transcription-quantitative PCR (RT-qPCR) signals from surfaces can identify when infected individuals have touched surfaces and when they have been present in hospital rooms or schools. However, the sensitivity and specificity of surface sampling as a method for detecting the presence of a SARS-CoV-2 positive individual, as well as guidance about where to sample, has not been established. To address these questions and to test whether our past observations linking SARS-CoV-2 abundance to Rothia sp. in hospitals also hold in a residential setting, we performed a detailed spatial sampling of three isolation housing units, assessing each sample for SARS-CoV-2 abundance by RT-qPCR, linking the results to 16S rRNA gene amplicon sequences (to assess the bacterial community at each location), and to the Cq value of the contemporaneous clinical test. Our results showed that the highest SARS-CoV-2 load in this setting is on touched surfaces, such as light switches and faucets, but a detectable signal was present in many untouched surfaces (e.g., floors) that may be more relevant in settings, such as schools where mask-wearing is enforced. As in past studies, the bacterial community predicts which samples are positive for SARS-CoV-2, with Rothia sp. showing a positive association. IMPORTANCE Surface sampling for detecting SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is increasingly being used to locate infected individuals. We tested which indoor surfaces had high versus low viral loads by collecting 381 samples from three residential units where infected individuals resided, and interpreted the results in terms of whether SARS-CoV-2 was likely transmitted directly (e.g., touching a light switch) or indirectly (e.g., by droplets or aerosols settling). We found the highest loads where the subject touched the surface directly, although enough virus was detected on indirectly contacted surfaces to make such locations useful for sampling (e.g., in schools, where students did not touch the light switches and also wore masks such that they had no opportunity to touch their face and then the object). We also documented links between the bacteria present in a sample and the SARS-CoV-2 virus, consistent with earlier studies

SARS-CoV-2 Distribution in Residential Housing Suggests Contact Deposition and Correlates with Rothia sp.

UNLABELLED: Monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on surfaces is emerging as an important tool for identifying past exposure to individuals shedding viral RNA. Our past work has demonstrated that SARS-CoV-2 reverse transcription-quantitative PCR (RT-qPCR) signals from surfaces can identify when infected individuals have touched surfaces such as Halloween candy, and when they have been present in hospital rooms or schools. However, the sensitivity and specificity of surface sampling as a method for detecting the presence of a SARS-CoV-2 positive individual, as well as guidance about where to sample, has not been established. To address these questions, and to test whether our past observations linking SARS-CoV-2 abundance to Rothia spp. in hospitals also hold in a residential setting, we performed detailed spatial sampling of three isolation housing units, assessing each sample for SARS-CoV-2 abundance by RT-qPCR, linking the results to 16S rRNA gene amplicon sequences to assess the bacterial community at each location and to the Cq value of the contemporaneous clinical test. Our results show that the highest SARS-CoV-2 load in this setting is on touched surfaces such as light switches and faucets, but detectable signal is present in many non-touched surfaces that may be more relevant in settings such as schools where mask wearing is enforced. As in past studies, the bacterial community predicts which samples are positive for SARS-CoV-2, with Rothia sp. showing a positive association. IMPORTANCE: Surface sampling for detecting SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is increasingly being used to locate infected individuals. We tested which indoor surfaces had high versus low viral loads by collecting 381 samples from three residential units where infected individuals resided, and interpreted the results in terms of whether SARS-CoV-2 was likely transmitted directly (e.g. touching a light switch) or indirectly (e.g. by droplets or aerosols settling). We found highest loads where the subject touched the surface directly, although enough virus was detected on indirectly contacted surfaces to make such locations useful for sampling (e.g. in schools, where students do not touch the light switches and also wear masks so they have no opportunity to touch their face and then the object). We also documented links between the bacteria present in a sample and the SARS-CoV-2 virus, consistent with earlier studies

Comparison of heat-inactivated and infectious SARS-CoV-2 across indoor surface materials shows comparable RT-qPCR viral signal intensity and persistence.

UNLABELLED: Environmental monitoring in public spaces can be used to identify surfaces contaminated by persons with COVID-19 and inform appropriate infection mitigation responses. Research groups have reported detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on surfaces days or weeks after the virus has been deposited, making it difficult to estimate when an infected individual may have shed virus onto a SARS-CoV-2 positive surface, which in turn complicates the process of establishing effective quarantine measures. In this study, we determined that reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection of viral RNA from heat-inactivated particles experiences minimal decay over seven days of monitoring on eight out of nine surfaces tested. The properties of the studied surfaces result in RT-qPCR signatures that can be segregated into two material categories, rough and smooth, where smooth surfaces have a lower limit of detection. RT-qPCR signal intensity (average quantification cycle ( Cq )) can be correlated to surface viral load using only one linear regression model per material category. The same experiment was performed with infectious viral particles on one surface from each category, with essentially identical results. The stability of RT-qPCR viral signal demonstrates the need to clean monitored surfaces after sampling to establish temporal resolution. Additionally, these findings can be used to minimize the number of materials and time points tested and allow for the use of heat-inactivated viral particles when optimizing environmental monitoring methods. IMPORTANCE: Environmental monitoring is an important tool for public health surveillance, particularly in settings with low rates of diagnostic testing. Time between sampling public environments, such as hospitals or schools, and notifying stakeholders of the results should be minimal, allowing decisions to be made towards containing outbreaks of coronavirus disease 2019 (COVID-19). The Safer At School Early Alert program (SASEA) [1], a large-scale environmental monitoring effort in elementary school and child care settings, has processed &gt; 13,000 surface samples for SARS-CoV-2, detecting viral signals from 574 samples. However, consecutive detection events necessitated the present study to establish appropriate response practices around persistent viral signals on classroom surfaces. Other research groups and clinical labs developing environmental monitoring methods may need to establish their own correlation between RT - qPCR results and viral load, but this work provides evidence justifying simplified experimental designs, like reduced testing materials and the use of heat-inactivated viral particles

Analysis of SARS-CoV-2 RNA Persistence across Indoor Surface Materials Reveals Best Practices for Environmental Monitoring Programs.

Environmental monitoring in public spaces can be used to identify surfaces contaminated by persons with coronavirus disease 2019 (COVID-19) and inform appropriate infection mitigation responses. Research groups have reported detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on surfaces days or weeks after the virus has been deposited, making it difficult to estimate when an infected individual may have shed virus onto a SARS-CoV-2-positive surface, which in turn complicates the process of establishing effective quarantine measures. In this study, we determined that reverse transcription-quantitative PCR (RT-qPCR) detection of viral RNA from heat-inactivated particles experiences minimal decay over 7 days of monitoring on eight out of nine surfaces tested. The properties of the studied surfaces result in RT-qPCR signatures that can be segregated into two material categories, rough and smooth, where smooth surfaces have a lower limit of detection. RT-qPCR signal intensity (average quantification cycle [Cq]) can be correlated with surface viral load using only one linear regression model per material category. The same experiment was performed with untreated viral particles on one surface from each category, with essentially identical results. The stability of RT-qPCR viral signal demonstrates the need to clean monitored surfaces after sampling to establish temporal resolution. Additionally, these findings can be used to minimize the number of materials and time points tested and allow for the use of heat-inactivated viral particles when optimizing environmental monitoring methods. IMPORTANCE Environmental monitoring is an important tool for public health surveillance, particularly in settings with low rates of diagnostic testing. Time between sampling public environments, such as hospitals or schools, and notifying stakeholders of the results should be minimal, allowing decisions to be made toward containing outbreaks of coronavirus disease 2019 (COVID-19). The Safer At School Early Alert program (SASEA) (https://saseasystem.org/), a large-scale environmental monitoring effort in elementary school and child care settings, has processed &gt;13,000 surface samples for SARS-CoV-2, detecting viral signals from 574 samples. However, consecutive detection events necessitated the present study to establish appropriate response practices around persistent viral signals on classroom surfaces. Other research groups and clinical labs developing environmental monitoring methods may need to establish their own correlation between RT-qPCR results and viral load, but this work provides evidence justifying simplified experimental designs, like reduced testing materials and the use of heat-inactivated viral particles

Safer at school early alert: an observational study of wastewater and surface monitoring to detect COVID-19 in elementary schools

BackgroundSchools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown.MethodsThe objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 to March&nbsp;2021.FindingsIn 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88%-98%); 67% were associated with a positive wastewater sample (95% CI: 57%-77%), and 40% were associated with a positive surface sample (95% CI: 29%-52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples.InterpretationPassive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy.FundingCounty of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control