Predictors of COVID-19 severity and outcomes in Indian patients with rheumatic diseases: a prospective cohort study.

Objective: There is dearth of data regarding the outcomes of coronavirus disease 2019 (COVID-19) among rheumatic and musculoskeletal disease (RMD) patients from Southeast Asia. We report the clinicodemographic profile and identify predictors of COVID-19 outcomes in a large cohort of Indian RMD patients. Methods: This prospective cohort study, carried out at the Postgraduate Institute of Medical Education and Research, Chandigarh (a tertiary care centre in India), included RMD patients affected with COVID-19 between April 2020 and October 2021. Demographic and clinical and laboratory details of COVID-19 and underlying RMD were noted. Predictors of mortality, hospitalization and severe COVID-19 were identified using stepwise multivariable logistic regression. Results: A total of 64 severe acute respiratory syndrome coronavirus-2-infected RMD patients [age 41.5 (19-85) years; 46 (72%) females] were included. Eighteen (28%) patients had severe COVID-19. Twenty-three (36%) required respiratory support [11 (17%) required mechanical ventilation]. Thirty-six (56%) patients required hospitalization [median duration of stay 10 (1-42) days]; 17 (27%) required intensive care unit admission. Presence of co-morbidities [odds ratio (OR) = 4.5 (95% CI: 1.4, 14.7)] was found to be an independent predictor of COVID-19 severity. Co-morbidities [OR = 10.7 (95% CI: 2.5, 45.4)] and underlying lupus [OR = 7.0 (95% CI: 1.2, 40.8)] were independently associated with COVID-19 hospitalization. Ongoing rheumatic disease activity [OR = 6.8 (95% CI: 1.3, 35.4)] and underlying diagnosis of lupus [OR = 7.1 (95% CI: 1.2, 42.4)] and SSc [OR = 9.5 (95% CI: 1.5, 61.8)] were found to be strong independent predictors of mortality. Age, sex, underlying RMD-associated interstitial lung disease and choice of immunosuppressive therapy were not associated with COVID-19 severity or adverse outcomes. Conclusion: The presence of co-morbidities was independently associated with COVID-19 severity and hospitalization. Ongoing rheumatic disease activity and the presence of lupus or SSc independently predicted mortality. Age, sex, type of immunosuppressive therapy and presence of RMD-associated interstitial lung disease did not affect COVID-19 severity or outcomes in Indian RMD patients.

Recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination.

PURPOSE: To report recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination in two patients with quiescent disease activity for more than a year. METHODS: Retrospective observational case reports. RESULTS: Two patients (one female and one male) under follow-up for posterior uveitis having stable course with absence of ocular inflammation for more than a year presented with recurrence of choroiditis lesions 2-6 weeks following anti-SARS-CoV-2 vaccination. Both the patients were managed with intravitreal dexamethasone implant (Ozurdex®, Allergan, Inc., Irvine, CA, USA) and showed resolution of choroiditis lesions upon follow-up. CONCLUSIONS: Acute onset recurrence of inflammation, in absence of any change in health status or treatment suggests the potential role of vaccination being the trigger of this reactivation. Given large-scale vaccination against novel coronavirus- SARS-CoV-2, careful vigilance is warranted to pick up the disease recurrence in patients with posterior uveitis.

Vascular Implications of COVID-19: Role of Radiological Imaging, Artificial Intelligence, and Tissue Characterization: A Special Report.

The SARS-CoV-2 virus has caused a pandemic, infecting nearly 80 million people worldwide, with mortality exceeding six million. The average survival span is just 14 days from the time the symptoms become aggressive. The present study delineates the deep-driven vascular damage in the pulmonary, renal, coronary, and carotid vessels due to SARS-CoV-2. This special report addresses an important gap in the literature in understanding (i) the pathophysiology of vascular damage and the role of medical imaging in the visualization of the damage caused by SARS-CoV-2, and (ii) further understanding the severity of COVID-19 using artificial intelligence (AI)-based tissue characterization (TC). PRISMA was used to select 296 studies for AI-based TC. Radiological imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound were selected for imaging of the vasculature infected by COVID-19. Four kinds of hypotheses are presented for showing the vascular damage in radiological images due to COVID-19. Three kinds of AI models, namely, machine learning, deep learning, and transfer learning, are used for TC. Further, the study presents recommendations for improving AI-based architectures for vascular studies. We conclude that the process of vascular damage due to COVID-19 has similarities across vessel types, even though it results in multi-organ dysfunction. Although the mortality rate is ~2% of those infected, the long-term effect of COVID-19 needs monitoring to avoid deaths. AI seems to be penetrating the health care industry at warp speed, and we expect to see an emerging role in patient care, reduce the mortality and morbidity rate.

Managing ANCA-associated vasculitis during COVID-19 pandemic: a single-center cross-sectional study.

The objective of the study is to report the outcomes of COVID-19 in ANCA-associated vasculitis (AAV) patients. This was a registry-based observational study conducted at a tertiary care center in north India. AAV patients with at least one follow-up visit between March 2020 and September 2021 were included. Demographic features, clinical manifestations, disease activity, and treatment details of underlying AAV were noted in all patients. Details of COVID-19 infection including severity, treatment, and outcomes were noted. Predictors of COVID-19 severity were determined using univariate analysis. A total of 33 (18.3%) out of 180 AAV patients contracted COVID-19 infection. Moderate COVID-19 infection was seen in 33.3% and severe or critical infection was seen in 36.3% of patients. Seventeen patients (51.5%) required supplemental oxygen therapy. Nine patients had active disease at the time of COVID-19 infection and three of them died due to COVID-19 infection. The risk of COVID-19 infection and its severity did not differ between patients receiving different immunosuppressants including rituximab induction. Hypothyroidism (p = 0.046) and ocular (p = 0.038) involvement due to AAV predicted the development of moderate to severe/critical COVID-19. Three (9.1%) patients died from COVID-19 and the rate of AAV flare after COVID-19 was similar to that in non-COVID-19 patients (15.3/100 person-year vs. 15.6/100 person-year, p = 0.95). Majority of the patients with AAV had moderate to severe or critical COVID-19 infection. The rate of death due to COVID-19 in AAV is higher than in general population. Use of standard remission induction regimens did not lead to increased risk of COVID-19 infection in our AAV cohort.

The Application and Patient-Reported Experience of Telephone Consultations in Elective Foot and Ankle Orthopaedic Surgery: 12-Month Follow-up.

BACKGROUND: Telemedicine offers convenient and affordable health care, overcoming the logistical challenges of face-to-face encounters. Clinicians increasingly relied on telemedicine during the global pandemic. To assess the ongoing role for telemedicine in orthopaedics, we prospectively analyzed the failure rate, safety and patient-reported experience of telephone consultations for 12 months. METHODS: 265 telephone Foot/Ankle consultations were conducted in April 2020 and were prospectively analyzed over 12 months. The primary outcome measure was the rate of failed telephone consultations. A consultation was deemed unacceptable if the patient did not answer, if the clinician could not reach a conclusion or if any outcome changed over 12 months. Secondary outcome measures included patient-reported satisfaction and time saved by avoiding a face-to-face visit. RESULTS: A clinical decision was reached in 84% of follow-up telephone consultations and 64% of new patient consultations (P = 0.001). Sixty-six percent were managed with nonoperative therapies, 16% were discharged, and 11% were added to the waiting list for surgery. The reasons for failing to achieve a clinical decision included failure to contact the patient (12.8%), inappropriate discharge with subsequent rereferral (1.9%), and insufficient clinical information (1.5%). Overall, 84.7% of patients reported that the telephone consultation was highly useful and 71.9% would recommend it to a friend or family member. Patients reported a mean time saving of 120 minutes. CONCLUSION: Based on our experience, we provide recommended criteria for the safe and practical use of telephone consultations and suggest versatile patient care pathways into which a telephone consultation can be incorporated. LEVEL OF EVIDENCE: Level IV, prospective cohort series (noncomparative).

ANCA-associated vasculitis following ChAdOx1 nCoV19 vaccination: case-based review.

For the foreseeable future, vaccines are the cornerstone in the global campaign against the Coronavirus Disease-19 (COVID-19) pandemic. As the number and fatalities due to COVID-19 decline and the lockdown anywise rescinded, we recognize an increase in the incidence of autoimmune disease post-COVID-19 vaccination. However, the causality of the most vaccine-induced side effects is debatable and, at best, limited to a temporal correlation. We herein report a case of a 51-year-old gentleman who developed Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) 2 week post-COVID-19 vaccination. The patient responded favorably to oral steroids and rituximab. Additionally, we conducted a case-based review of vaccine-associated AAV describing their clinical manifestations and treatment response of this emerging entity.

Managing comorbidities in Covid-19 patients: A drug utilization study in a COVID-dedicated hospital in Northern India.

INTRODUCTION: In the prevailing COVID-19 pandemic, the Indian healthcare system has worked hard towards restricting the adverse outcomes to the least possible figures. The present study aims to share the experience of a COVID-dedicated tertiary care government hospital in Northern India of managing COVID-19 patients with comorbidities. METHODOLOGY: A retrospective, observational study was conducted in a COVID-dedicated tertiary health care government hospital in Northern India. Details on sociodemographic data, hospital admission data, and drug utilization pattern of all laboratory-confirmed COVID-19 patients of all age groups, either gender, having comorbidity (s), and admitted between April and September, 2020 were noted and evaluated. RESULTS: Among the total study participants (N = 406), 2868 drugs were prescribed. Out of these, 2336 were used for the management of symptoms of COVID-19 and 532 were used for the management of coexistent comorbidity (s). For COVID-19 symptoms, the most commonly prescribed class of drugs were antimicrobials (853, 36.52%), followed by nonsteroidal antiinflammatory drugs (374, 16.01%), proton pump inhibitors (299, 12.80%), antihistamines (232, 9.93%), immunosuppressant drugs (103, 4.41%), and others. For comorbidities most commonly prescribed were antihypertensive (310, 58.60%) drugs, followed by antidiabetic drugs (166, 31.38%), bronchodilators (34, 6.43%), thyroid hormones (11, 2.08%), immunosuppressant drugs (7, 1.32%). CONCLUSION: The most frequently prescribed antihypertensives were calcium channel blockers (CCBs) and least prescribed was beta blocker+CCB. Among the antidiabetic drugs, most frequently prescribed was insulin and least prescribed was DPP-4 inhibitors and Biguanide+DPP-4 inhibitor both.

Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial.

OBJECTIVES: There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX. METHODS: This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat. RESULTS: 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen. CONCLUSION: A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially. TRIAL REGISTRATION NUMBER: CTRI/2018/12/016549.

Low-dose radiation therapy for COVID-19 pneumonia: a pilot study.

OBJECTIVES: The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no specific effective treatment for COVID-19. The major cause of death in COVID-19 is severe pneumonia leading to respiratory failure. Radiation in low doses (<100 cGy) has been known for its anti-inflammatory effect and therefore, low dose radiation therapy (LDRT) to lungs can potentially mitigate the severity of pneumonia and reduce mortality. We conducted a pilot trial to study the feasibility and clinical efficacy of LDRT to lungs in the management of patients with COVID-19. METHODS: From June to Aug 2020, we enrolled 10 patients with COVID-19 having moderate to severe risk disease [National Early Warning Score (NEWS) of ≥5]. Patients were treated as per the standard COVID-19 management guidelines along with LDRT to both lungs with a dose of 70cGy in single fraction. Response assessment was done based on the clinical parameters using the NEWS. RESULTS: All patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3 to 7 days. One patient, who was a known hypertensive, showed clinical deterioration and died 24 days after LDRT. No patients showed the signs of acute radiation toxicity. CONCLUSION: The results of our pilot study suggest that LDRT is feasible in COVID-19 patients having moderate to severe disease. Its clinical efficacy may be tested by conducting randomized controlled trials. ADVANCES IN KNOWLEDGE: LDRT has shown promising results in COVID-19 pneumonia and should be researched further through randomized controlled trials.

Managing Active Iupus Nephritis During COVID-19 Pandemic.

India is seeing a rapid rise in coronavirus disease-2019 (COVID-19). Immunosuppression is a possible risk factor for severe COVID-19, although their exact interaction is unclear. A total of 13 cases with active lupus nephritis (LN, with or without extra-renal manifestations) were managed with intense immunosuppression between January 2020 and June 2020 during the COVID-19 pandemic at our center. There were no other comorbidities in any patient. All patients received hydroxychloroquine as a part of standard of care. Vigorous precautionary measures were taken for preventing infection in all. One patient developed acute respiratory distress syndrome but was tested negative for COVID-19. None of the other 12 patients developed symptoms suggestive of COVID-19. We report safe management of patients with active LN with intense immunosuppression along with vigorous precautions amidst the COVID-19 pandemic. The role of hydroxychloroquine along with timely precautions needs to be further explored as protective measures against COVID-19 among systemic lupus erythematosus patients.

Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic review and meta-analysis.

OBJECTIVES: The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates. METHODS: Electronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes. RESULTS: Twenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9-89.0, I2 = 90%) as compared to a single dose (69.3, 52.4-82.3, I2 = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02-0.13, I2 = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6-96.9, I2 = 0%), spondyloarthropathy (95.6, 95% CI: 83.4-98.9, I2 = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4-94.2, I2 = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1-88.9, I2 = 85%), and vasculitis (70.5, 95% CI: 52.9-83.5, I2 = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70-90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy. CONCLUSION: Seroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.

Mesenchymal stem cells in SARS-CoV-2 infection: A hype or hope.

COVID-19 is a serious viral infection that struck the world in December 2019 starting from Wuhan in China, spreading subsequently to all over the world. The disease has baffled scientists and doctors worldwide in terms of its presentation, behaviour, and treatment options till now. A low mortality rate is the only relief we get so far from COVID-19 in terms of numbers. Treatment options have gradually streamlined to steroids and very few FDA approved antiviral as well as plasma therapy and supportive treatment. Monoclonal antibodies are used to tide over any impending cytokine storm but are not equally effective in all patients. Ventilation support is invariably required for moderate to severe disease varying from a simple High Flow non-rebreathing mask to BiPAP (Bilevel Positive Airway Pressure) and HFNO (High-Flow Nasal Oxygen) extending to full-fledge ventilation via a Mechanical Ventilator. Because of the non-availability of satisfactory treatment so far, many researchers from different biomedical fields are looking for alternative therapeutic strategies to manage the pandemic. One such therapeutic approach showing a ray of hope to combat COVID-19 infection is Mesenchymal stem cell therapy. Mesenchymal cells have immunomodulatory, anti-inflammatory as well as regenerative properties and various preliminary studies have shown that MSCs can reverse the lung damage and overcome the cytokine storm incited by COVID-19 infection. Also, it has improved the recovery rate of critically ill patients on mechanical ventilation. In this review, we will discuss the possibility and relevance of MSCs in COVID-19 treatment and preview of various MSCs clinical trials.

Managing ANCA-associated vasculitis during the COVID-19 pandemic: results from an online survey.

Management of ANCA-associated vasculitis (AAV) during the COVID-19 pandemic poses unique therapeutic challenges. An online survey was conducted to understand physician's choices for treating AAV during the COVID-19 pandemic. Web-based survey featuring nineteen questions was circulated amongst physicians across various specialties. The responses regarding immunosuppressive therapy for remission induction and maintenance, COVID-19 testing, and preventive measures were recorded. A total of 304 responses were recorded. Most of the respondents were from India (83.9%) and comprised rheumatologists (66%) in practice for ≥ 5 years (71%). Though a majority preferred Rituximab or intravenous cyclophosphamide (CYC) as a remission induction agent, a significant proportion opted for oral CYC and mycophenolate mofetil (MMF) also. Only one-third wanted to test for COVID-19 before initiating immunosuppressive therapy in patients with organ/life-threatening manifestations. Rituximab was the most favored maintenance therapy (47%), followed by azathioprine, MMF, and methotrexate. The results of this focused survey of managing AAV patients depict the real-world dilemmas and physicians' choices in this setting.

Major Thrombotic Event Despite Anticoagulation in a Patient With COVID-19.

The outbreak of coronavirus disease 2019 (known as COVID-19), which started in Wuhan, China in December 2019, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has been associated with both venous and arterial thromboembolism likely secondary to significant cytokine activation and inflammation. Reports on the incidence of thrombotic complications, however, are not well documented. Our case will examine a young man diagnosed with COVID-19 who developed an acute, severe bilateral saddle pulmonary embolism while on prophylactic dose anticoagulation after being admitted to the hospital and treated for two weeks with significant improvement.