No abstract

To evaluate the public interest in rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic. Google Trends was queried to analyze search trends in the United States for numerous rheumatic diseases and also the interest in a rheumatologist. Three 8-week periods in 2020 ((March 15-May 9), (May 10-July 4), and (July 5-August 29)) were compared to similar periods of the prior 4 years (2016-2019). Compared to a similar time period between 2016 and 2019, a significant decrease was found in the relative search volume for more than half of the search terms during the initial March 15-May 9, 2020 period. However, this trend appeared to reverse during the July 5-August 29, 2020 period where the relative volume for nearly half of the search terms were not statistically significant compared to similar periods of the prior 4 years. In addition, this period showed a significant increase in relative volume for the terms: Axial spondyloarthritis, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, Sjögren's syndrome, antiphospholipid syndrome, scleroderma, Kawasaki disease, Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis, and rheumatologist. There was a significant decrease in relative search volume for many rheumatic diseases between March 15 and May 9, 2020 when compared to similar periods during the prior 4 years. However, the trends reversed after the initial period ended. There was an increase in relative search for the term "rheumatologist" between July and August 2020 suggesting the need for rheumatologists during the COVID-19 pandemic. Policymakers and healthcare providers should address the informational demands on rheumatic diseases and needs for rheumatologists by the general public during pandemics like COVID-19.

No abstract

Motivations for the hierarchical assembly of protein complexes are diverse spanning biosensing, biomedical and bioreactor applications. The assembly processes should be simple, scalable, versatile, and biologically benign to minimize loss of component parts. A "plug and play" methodology comprising a generic linking apparatus may enable rapid design and optimization. One application that desires these qualities is metabolon construction wherein multiple enzymes are organized in defined pathways to mediate biochemical flux. Here, we propose a modular design by incorporation of crosslinking-compliant amino acid tags comprised of lysine or glutamine residues at the N- or C-termini of the to-be-assembled proteins. These amino acid tags enable covalent crosslinking using microbial transglutaminase (mTG). Modularity is demonstrated where stoichiometries and relative positions of enzymes and other functional proteins are altered. Construction of multifunctional complexes is demonstrated by crosslinking domains of different function and origin. Namely, we built a two-subunit quorum sensing (QS) biosynthetic metabolon on solid supports and altered stoichiometries of the limiting constituents to increase the overall rate of reaction. To display functionality beyond biosynthesis, we constructed a molecular communication 'device' (antibody binding Protein G-QS complex) to target bacterial cells and demonstrated tailored QS responses among targeted bacteria. We propose that this approach, solid phase mTG-mediated linkage of biological components, can be used for assembly within many environments including microreactors or lab-on-a-chip systems. Because the methodology is general, we envision construction of multi-functional protein complexes in a 'plug and play' fashion for a variety of biosensing and synthetic biology applications.

Objectives To determine the severity and outcome of COVID-19 among individuals with lupus as compared to controls. The secondary objective was to identify the risk association of sex, race, presence of nephritis, and use of various immunomodulators with COVID-19 outcomes. Methods Retrospective data of individuals with lupus with and without COVID-19 between January 2020 to May 2021 was retrieved from the TriNetX. A one-to-one matched COVID-19 positive control was selected using propensity score(PS) matching. We assessed several outcomes, including all-cause mortality, hospitalisation, intensive care unit (ICU) admission, mechanical ventilation, severe COVID, acute kidney injury (AKI), Haemodialysis, acute respiratory distress syndrome (ARDS), ischemic stroke, venous thromboembolism (VTE) and sepsis were assessed. Results We identified 2140 SLE patients with COVID-19, 29,853 SLE without COVID-19 and 732,291controls. Mortality within 30 days of COVID-19 diagnosis was comparable among SLE and controls [RR-1.26; 95%CI-0.85,1.8]. SLE with COVID-19 had a higher risk of hospitalisation [RR-1.28; 95% CI 1.14–1.44], ICU admission [RR-1.35; 95% CI 1.01–1.83], mechanical ventilation [RR- 1.58 95% CI 1.07–2.33], stroke [RR-2.18; 95% CI 1.32,3.60], VTE [RR-2.22; 95% CI 1.57–03.12] and sepsis [RR-1.37; 95% CI 1.06–1.78].Individuals with SLE who contracted COVID-19 had higher mortality, hospitalisation, ICU admission, mechanical ventilation, AKI, VTE and sepsis (p < 0.001) compared to SLE without COVID-19. Males with SLE had a higher risk of AKI [RR-2.05; 95% CI 1.27–3.31] than females. Lupus nephritis was associated with higher risk of hospitalisation [RR-1.36; 95% CI 1.05–1.76], AKI [RR-2.32; 95% CI 1.50–3.59] and sepsis [RR-2.07; 95% CI-1.12–3.83]. Conclusion The mortality of individuals with SLE due to COVID-19 is comparable to the general population but with higher risks of hospitalisation, ICU admission, mechanical ventilation, stroke, VTE and sepsis. The presence of nephritis increases the risk of AKI, thus probably increasing hospitalisation and sepsis

Biological components are integrated with electronic devices to create microsystems with novel functions and chitosan, a naturally occurring biopolymer, can play a significant role as an interface material. Chitosan can be electrodeposited within confined geometries by cathodic charge and appropriate electrode design and proteins can be conjugated to chitosan. However, conjugation chemistries can be slow and chitosan, a polycationic polysaccharide, enables non-specific binding in biofabrication processes. There is a need to speed up the assembly process and reduce non-specific binding. Here, we have developed a two-step methodology that accelerates protein assembly, reduces background and increases specificity. We first ''coated'' the surface of chitosan with a Lys-Tyr-Lys (KYK) tripeptide in a slow step using tyrosinase-mediated conjugation chemistry and then conjugated proteins with C-terminal glutamine-tags to the saturating KYK tripeptide via transglutaminase. As a demonstration, we assembled a functioning two-enzyme bacterial metabolic pathway on an electrode chip. Results indicated a fivefold decrease in non-specific binding and an improvement in signal to noise ratio from 0.3 to 20. This transglutaminase-mediated approach is simple and quick, it requires no chemical reagents, no printing or stamping devices; it employs biological components and is biologically benign to the component parts-all characteristics of biofabricated devices.

CKD and kidney failure are important comorbidities that are associated with unfavorable outcomes in patients with coronavirus disease 2019 (COVID-19) (1,2). Patients with CKD/kidney failure also have a disproportionate burden of other comorbidities (e.g., coronary artery disease, hypertension, and diabetes mellitus), which are associated with more severe presentations of COVID-19 (2). We investigated the effect of CKD/kidney failure on COVID-19 using propensity matching to account for significant comorbidities. In this cohort study, we included patients $18 years of age diagnosed with COVID-19 between January 20, 2020 and September 10, 2020 identified via real-time search and analysis of .49 million patients (inpatients and outpatients) from 33 health care organizations participating in a global health research network called TriNetX (Cambridge, MA). Patients with COVID-19 were confirmed using COVID-19-specific diagnostic criteria recommended by the World Health Organization and the Centers for Disease Control and Prevention. Patients with COVID-19 were divided into cohorts (CKD or no CKD) on the basis of presence of CKD or kidney failure identified via validated International Classification of Diseases-10th modification codes prior to the date of COVID-19 diagnosis. Propensity matching was done for age, sex, race, and multiple comorbidities, including obesity, hypertension, diabetes, ischemic heart disease, heart failure, chronic lung disease, cerebrovascular disease, and nicotine and alcohol use, using a greedy neighbor-matching algorithm to balance the baseline characteristics between the study groups. Primary outcome tested was 30-day all-cause mortality post-COVID-19 diagnosis. Secondary outcomes tested were hospitalization and need for mechanical ventilation. Subgroup analyses were reported for different CKD stages: patients with stage 2 (mild), stages 3 and 4 (moderate), or stage 5/kidney failure (severe) and included need for KRT in the mild/ moderate CKD group. All statistical analyses were performed using TriNetX with standard methodology previously reported (3). A total of 152,463 patients with COVID-19 were identified (CKD: 8810 [inclusive of kidney failure]; non-CKD: 143,653). The CKD cohort was older (67615 versus 46618 years; P,0.001) and had higher proportions of men (52% versus 44%; P,0.001), people of Black race (35% versus 21%; P,0.001), and comorbid

Introduction/objective The general public may utilize online information through search engines for implications and risks of some anti-rheumatic drugs. These drugs have been used in the management of coronavirus disease 2019 (COVID-19) and associated inflammatory sequelae or cytokine storm of infection. Therefore, the objective of this study was to investigate the population-level interest in anti-rheumatic drugs during the COVID-19 era, by analyzing changes in Google search frequency data. Method To obtain the relative search volume (RSV) of anti-rheumatic drugs, we queried Google Trends for 78 search terms representing non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, antigout agents, conventional disease-modifying anti-rheumatic drugs (DMARDs), immunosuppressants, biologics, and Janus kinase (JAK) inhibitors within the USA. Three 8-week periods in 2020 (March 15–May 9), (May 10–July 4), and (July 5–August 29) representing the initial- and short-term periods were compared to overlapping periods of the preceding 3 years (2017–2019). Results We found statistically significant increases in RSV for colchicine, hydroxychloroquine, tocilizumab (and its brand name-Actemra), and anakinra, and statistically significant decreases among brand names of immunosuppressive agents (i.e., mycophenolate mofetil, azathioprine, cyclophosphamide, tacrolimus, cyclosporine) during both the initial- and short-term COVID-19 periods as compared to overlapping periods of the preceding 3 years. Conclusion There were significant increases in RSV of colchicine, hydroxychloroquine, tocilizumab, and anakinra during both initial- and short-term COVID-19 periods when compared to overlapping periods of the preceding 3 years reflecting a heightened level of information-seeking on these drugs during the pandemic. Rheumatologists should address this increase in informational demand. Further research assessing medium- and long-term interest in anti-rheumatic drugs is required to increase our knowledge on this new pandemic. Key Points •This study was aimed to investigate the population-level interest in anti-rheumatic drugs in the COVID-19 era, by analyzing changes in Google search frequency data. •Significant increases were seen in relative searches for colchicine, hydroxychloroquine, tocilizumab, and anakinra during both initial and short-term COVID-19 periods when compared to similar periods of 2017–2019 reflecting a heightened level of information-seeking on these drugs during the pandemic. •Rheumatologists should address this increase in informational demand for colchicine, hydroxychloroquine, tocilizumab, and anakinra.