Recommendations on SARS-CoV-2 vaccination in adult patients with rheumatic diseases.

Vaccination against coronavirus disease 2019 (COVID-19) has been promoted all over the world and has become an important measure to control the pandemic. Patients with rheumatic diseases are at high risk of 2019-nCoV severe infection, hence are the target population with high priority for vaccination. In 2021, under the leadership of the Chinese Rheumatology Association, the recommendations on SARS-CoV-2 vaccination for adult patients with rheumatic diseases in China were proposed based on the current data, in combination with international guidelines and experts' opinions.

Epidemiology and Clinical Management of Rheumatic Autoimmune Diseases in the COVID-19 Pandemic: A Review.

The coronavirus disease 2019 (COVID-19) has been in pandemic for more than 1 year, with serious negative effects produced worldwide. During this period, there have been a lot of studies on rheumatic autoimmune diseases (RADs) combined with COVID-19. The purpose of this study is to review and summarize these experiences. Pubmed, Web of science, Embase and the Cochrane library were searched from January 15, 2020 to July 15, 2021 using RADs and COVID-19 related keywords. Based on a comprehensive review of studies covering 16 countries, the prevalence of COVID-19 does not necessarily increase in RADs patients compared to the general population. In RADs population infected with COVID-19, a high proportion of female patients (54.44~95.2%), elderly patients (≥50y, 48~75.88%), and patients with pre-existing comorbidities (respiratory, 4.8~60.4%; endocrine, 8.52~44.72%; cardiovascular, 15.7~64.73%) were observed, although, this does not appear to have a decisive effect on disease severity. Many anti-rheumatic treatments have been extensively evaluated for their efficacy of treating COVID-19 in RADs patients, with TNF-α inhibitors and IL-6 receptor antagonist receiving more positive reviews. However, there is no conclusive information for most of the therapeutic regimens due to the lack of high-level evidence. Inflammatory markers or neutrophil-lymphocyte-ratio may be applied as indicators for clinical prognosis or therapeutic regimens adjustment. Thus, more research is still needed to address the prevalence, treatment, and clinical monitoring of RADs patients in COVID-19 pandemic.

Laboratory Predictors of COVID-19 Mortality: A Retrospective Analysis from Tongji Hospital in Wuhan.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly progressed to a global pandemic. Currently, there are limited effective medications approved for this deadly disease. OBJECTIVE: To investigate the potential predictors of COVID-19 mortality and risk factors for hyperinflammation in COVID-19. METHODS: Retrospective analysis was carried out in 1,149 patients diagnosed with COVID-19 in Tongji Hospital, Wuhan, China, from 1/13/2020 to 3/15/2020. RESULTS: We found significant differences in the rates of hyperuricemia (OR: 3.17, 95% CI: 2.13-4.70; p < 0.001) and hypoalbuminemia (OR: 5.68, 95% CI: 3.97-8.32; p < 0.001) between deceased and recovered patients. The percentages of hyperuricemia in deceased patients and recovered patients were 23.6% and 8.9%, respectively, which were higher than the reported age-standardized prevalence of 6.2% in Chinese population. Of note, the percentages of both IL-6 and uric acid levels in survived COVID-19 patients were above 90%, suggesting that they might be good specificity for indicators of mortality in COVID-19 patients. The serum level of uric acid (UA) was positively associated with ferritin, TNF-α, and IL-6 but not with anti-inflammatory cytokine IL-10. In addition, the levels of these proinflammatory cytokines in COVID-19 patients showed a trend of reduction after uric acid lowering therapy. CONCLUSIONS: Our results suggest that uric acid, the end product of purine metabolism, was increased in deceased patients with COVID-19. In addition, the serum level of uric acid was positively associated with inflammatory markers. Uric acid lowering therapy in COVID-19 patients with hyperuricemia may be beneficial.

COVID-19 infection in patients with connective tissue disease: A multicity study in Hubei province, China.

Novel Coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID-19 patients hospitalized in 23 centers affiliated to Hubei COVID-19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID-19 infection (p = 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts (p values were 0.033, < 0.001, and 0.071, respectively). Hydroxychloroquine therapy and low- to medium-dose glucocorticoids before COVID-19 diagnosis reduced the progression of COVID-19 to severe/critical conditions (p = 0.001 for hydroxychloroquine; p = 0.006 for glucocorticoids). Our data suggests that COVID-19 in CTD patients may be more severe compared to patients with AS or gout.

Smart system of disease management for patient follow-up and medication refill during the COVID-19 epidemic period: a multicentre retrospective cohort study

Background An outbreak of coronavirus disease 2019 (COVID-19) started in December, 2019. The epicentre, Wuhan in Hubei Province, was in lockdown. From Jan 23, 2020, most hospitals in Wuhan only focused on patients with COVID-19, and patients with chronic diseases could not visit their physicians in clinic and had no access to prescriptions. Smart System of Disease Management (SSDM) is a series of mobile applications for chronic disease management that includes both patient and physician interfaces. After training in clinic, patients regularly do a disease activity assessment, and input data from lab tests as well as their medication. The data is then synchronised to the mobile of the responsible physician. The physician can then do an online consultation and renew prescriptions on the basis of real-time data from his or her patients. We aimed to establish the feasibility and effects of SSDM in maintaining effective interactions between patients and physicians in Hubei province during the COVID-19 epidemic period. Methods Based on the SSDM database, we did a multicentre retrospective cohort study of patients with rheumatic disease in Hubei province in China. SSDM had been widely used across China since 2015. To study the influence of interruption of routine care by the COVID-19 epidemic for patients with rheumatic disease, we included patients registered with SSDM from Hubei Province. Data on patient disease activities, online consultations, and prescription refilling, as well as surveys on satisfaction about the online service were extracted from Jan 23, 2020 to Feb 27, 2020, acting as the study group, and data from the same period during 2018 and 2019 were also extracted as a control. Inclusion criteria included a confirmed diagnosis of rheumatic disease and disease duration of at least 3 months. Patients were excluded from the study if they declined participation or discontinued before completion of the survey. For patients with rheumatoid arthritis, achieving a disease activity score with 28 joints (DAS28) of less than 3·2 was considered to be a treat-to-target (T2T) status. For patients with systemic lupus erythematosus, a disease activity index-2000 (SLESAI-2K) score of less than 4 was the main target of the lupus low disease-activity state (LLDAS). We compared the T2T and LLDAS prevalence during the epidemic period of 2020 with that of 2018 and 2019. All statistical analyses were done with Python version 3.7.4. We used descriptive and frequency statistics (percentage) to describe baseline demographic information and clinical information. Comparison of ratio variables between two groups was done with a χ2 test. Findings By Feb 27, 2020, a total of 173 560 adult patients (46 861 [27%] men and 126 699 [73%] women) with rheumatic disease from 860 hospitals across China registered and routinely used SSDM since 2015. Patients were encouraged to upload their data and do a disease activity self-assessment every 1–3 months. 10 441 (6%) of 173 560 patients (3237 [31%] with rheumatoid arthritis and 1566 [15%] with systemic lupus erythematosus) were managed by 176 rheumatologists from 42 hospitals in Hubei province. From Jan 23, 2020 to Feb 27, 2020, 69 rheumatologists from 28 hospitals provided 1451 patients with 1692 consultations and supplied 566 (39%) of them with continued medication, which included 55 commonly used therapeutic drugs for rheumatic diseases. 247 (8%) of 3237 patients with rheumatoid arthritis during the 2020 epidemic and 350 (9%) in same period during 2018 and 2019 did the DAS28 self-assessments, and T2T was 47% in 2020 compared with 50% in 2018 and 2019, (p=0·53). 293 (19%) of 1566 patients with systemic lupus erythematosus in 2020 and 210 (16%) in 2018 and 2019 did the SLESAI-2K self-assessments, and LLDAS was 60% in 2020 compared with 47% in 2018 and 2019 (p=0·03). Surveys showed that 100% of patients were satisfied with the interactions, which prevented the risk of cross-infection and discontinuation of medication. Interpretation Patients with rheumatism can maintain accessibility to good c re in the era of the COVID-19 epidemic by using SSDM for consultations and medication refills. The clinical outcomes, at least for both rheumatoid arthritis and systemic lupus erythematosus, are not compromised. Funding None.

COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study.

BACKGROUND: In the ongoing COVID-19 pandemic, the susceptibility of patients with rheumatic diseases to COVID-19 remains unclear. We aimed to investigate susceptibility to COVID-19 in patients with autoimmune rheumatic diseases during the ongoing COVID-19 pandemic. METHODS: We did a multicentre retrospective study of patients with autoimmune rheumatic diseases in Hubei province, the epicentre of the COVID-19 outbreak in China. Patients with rheumatic diseases were contacted through an automated telephone-based survey to investigate their susceptibility to COVID-19. Data about COVID-19 exposure or diagnosis were collected. Families with a documented history of COVID-19 exposure, as defined by having at least one family member diagnosed with COVID-19, were followed up by medical professionals to obtain detailed information, including sex, age, smoking history, past medical history, use of medications, and information related to COVID-19. FINDINGS: Between March 20 and March 30, 2020, 6228 patients with autoimmune rheumatic diseases were included in the study. The overall rate of COVID-19 in patients with an autoimmune rheumatic disease in our study population was 0·43% (27 of 6228 patients). We identified 42 families in which COVID-19 was diagnosed between Dec 20, 2019, and March 20, 2020, in either patients with a rheumatic disease or in a family member residing at the same physical address during the outbreak. Within these 42 families, COVID-19 was diagnosed in 27 (63%) of 43 patients with a rheumatic disease and in 28 (34%) of 83 of their family members with no rheumatic disease (adjusted odds ratio [OR] 2·68 [95% CI 1·14-6·27]; p=0·023). Patients with rheumatic disease who were taking hydroxychloroquine had a lower risk of COVID-19 infection than patients taking other disease-modifying anti-rheumatic drugs (OR 0·09 [95% CI 0·01-0·94]; p=0·044). Additionally, the risk of COVID-19 was increased with age (adjusted OR 1·04 [95%CI 1·01-1·06]; p=0·0081). INTERPRETATION: Patients with autoimmune rheumatic disease might be more susceptible to COVID-19 infection than the general population. FUNDING: National Natural Science Foundation of China and the Tongji Hospital Clinical Research Flagship Program.

A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab.

Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition.

Clinical features of rheumatic patients infected with COVID-19 in Wuhan, China.

OBJECTIVE: The clinical features of rheumatic patients with coronavirus disease 2019 (COVID-19) have not been reported. This study aimed to describe the clinical features of COVID-19 in rheumatic patients and provide information for handling this situation in clinical practice. METHODS: This is a retrospective case series study. Deidentified data, including gender, age, laboratory and radiological results, symptoms, signs, and medication history, were collected from 2326 patients diagnosed with COVID-19, including 21 cases in combination with rheumatic disease, in Tongji Hospital between 13 January and 15 March 2020. RESULTS: Length of hospital stay and mortality rate were similar between rheumatic and non-rheumatic groups, while the presence of respiratory failure was more common in rheumatic cases (38% vs 10%, p<0.001). Symptoms of fever, fatigue and diarrhoea were seen in 76%, 43% and 23% of patients, respectively. There were four rheumatic patients who experienced a flare of rheumatic disease during hospital stay, with symptoms of muscle aches, back pain, joint pain or rash. While lymphocytopaenia was seen in 57% of rheumatic patients, only one patient (5%) presented with leucopenia in rheumatic cases. Rheumatic patients presented with similar radiological features of ground-glass opacity and consolidation. Patients with pre-existing interstitial lung disease showed massive fibrous stripes and crazy-paving signs at an early stage. Five rheumatic cases used hydroxychloroquine before the diagnosis of COVID-19 and none progressed to critically ill stage. CONCLUSIONS: Respiratory failure was more common in rheumatic patients infected with COVID-19. Differential diagnosis between COVID-19 and a flare of rheumatic disease should be considered. TRIAL REGISTRATION NUMBER: ChiCTR2000030795.

The immunology of COVID-19: is immune modulation an option for treatment?

In December, 2019, an outbreak of COVID-19 emerged in Wuhan, China and quickly spread globally. As of May 7, 2020, there were 3 672 238 confirmed infections and 254 045 deaths attributed to COVID-19. Evidence has shown that there are asymptomatic carriers of COVID-19 who can transmit the disease to others. The virus incubation time shows a wide range (0-24 days) and the virus displays a high infectivity. It is therefore urgent to develop an effective therapy to treat patients with COVID-19 and to control the spread of the causative agent, severe respiratory syndrome coronavirus 2. Repurposing of approved drugs is widely adopted to fight newly emerged diseases such as COVID-19, as these drugs have known pharmacokinetic and safety profiles. As pathological examination has confirmed the involvement of immune hyperactivation and acute respiratory distress syndrome in fatal cases of COVID-19, several disease-modifying anti-rheumatic drugs (DMARDS), such as hydroxychloroquine and tocilizumab, have been proposed as potential therapies for the treatment of COVID-19. In this Review, we discuss the immunological aspects of COVID-19 and the potential implication of DMARDs in treating this disease.