COVID-19: Overview of rheumatology fellows.

SARS-COV-2 infection has spread worldwide since it originated in December 2019, in Wuhan, China. The pandemic has largely demonstrated the resilience of the world's health systems and is the greatest health emergency since World War II. There is no single therapeutic approach to the treatment of COVID-19 and the associated immune disorder. The lack of randomised clinical trials (RCTs) has led different countries to tackle the disease based on case series, or from results of observational studies with off-label drugs. We as rheumatologists in general, and specifically rheumatology fellows, have been on the front line of the pandemic, modifying our activities and altering our training itinerary. We have attended patients, we have learned about the management of the disease and from our previous experience with drugs for arthritis and giant cell arteritis, we have used these drugs to treat COVID-19.

Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 2: Inactivated Vaccines.

BACKGROUND AND AIMS: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years. CONCLUSIONS: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.

COVID-19 among heart transplant recipients in Germany: a multicenter survey.

AIMS: Heart transplantation may represent a particular risk factor for severe coronavirus infectious disease 2019 (COVID-19) due to chronic immunosuppression and frequent comorbidities. We conducted a nation-wide survey of all heart transplant centers in Germany presenting the clinical characteristics of heart transplant recipients with COVID-19 during the first months of the pandemic in Germany. METHODS AND RESULTS: A multicenter survey of all heart transplant centers in Germany evaluating the current status of COVID-19 among adult heart transplant recipients was performed. A total of 21 heart transplant patients with COVID-19 was reported to the transplant centers during the first months of the pandemic in Germany. Mean patient age was 58.6 ± 12.3 years and 81.0% were male. Comorbidities included arterial hypertension (71.4%), dyslipidemia (71.4%), diabetes mellitus (33.3%), chronic kidney failure requiring dialysis (28.6%) and chronic-obstructive lung disease/asthma (19.0%). Most patients received an immunosuppressive drug regimen consisting of a calcineurin inhibitor (71.4%), mycophenolate mofetil (85.7%) and steroids (71.4%). Eight of 21 patients (38.1%) displayed a severe course needing invasive mechanical ventilation. Those patients showed a high mortality (87.5%) which was associated with right ventricular dysfunction (62.5% vs. 7.7%; p = 0.014), arrhythmias (50.0% vs. none; p = 0.012), and thromboembolic events (50.0% vs. none; p = 0.012). Elevated high-sensitivity cardiac troponin T- and N-terminal prohormone of brain natriuretic peptide were significantly associated with the severe form of COVID-19 (p = 0.017 and p < 0.001, respectively). CONCLUSION: Severe course of COVID-19 was frequent in heart transplanted patients. High mortality was associated with right ventricular dysfunction, arrhythmias, thromboembolic events, and markedly elevated cardiac biomarkers.

Pan­cancer analysis of transmembrane protease serine 2 and cathepsin L that mediate cellular SARS­CoV­2 infection leading to COVID-19.

Severe acute respiratory syndrome (SARS) coronavirus­2 (SARS­CoV2) is the cause of a new disease (COVID­19) which has evolved into a pandemic during the first half of 2020. Older age, male sex and certain underlying diseases, including cancer, appear to significantly increase the risk for severe COVID­19. SARS­CoV­2 infection of host cells is facilitated by the angiotensin­converting enzyme 2 (ACE­2), and by transmembrane protease serine 2 (TMPRSS2) and other host cell proteases such as cathepsin L (CTSL). With the exception of ACE­2, a systematic analysis of these two other SARS­CoV2 infection mediators in malignancies is lacking. Here, we analysed genetic alteration, RNA expression, and DNA methylation of TMPRSS2 and CTSL across a wide spectrum of tumors and controls. TMPRSS2 was overexpressed in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), uterine corpus endometrial carcinoma and uterine carcinosarcoma, with PRAD and READ exhibiting the highest expression of all cancers. CTSL was upregulated in lymphoid neoplasm diffuse large B­cell lymphoma, oesophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, lower grade glioma, pancreatic adenocarcinoma, skin cutaneous melanoma, stomach adenocarcinoma, and thymoma. Hypo­methylation of both genes was evident in most cases where they have been highly upregulated. We have expanded on our observations by including data relating to mutations and copy number alterations at pan­cancer level. The novel hypotheses that are stemming out of these data need to be further investigated and validated in large clinical studies.

Tocilizumab for severe COVID-19: a systematic review and meta-analysis.

This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31-1.22; I2 = 68%]. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33-6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14-4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.

Incidental COVID-19 in a heart-kidney transplant recipient with malnutrition and recurrent infections: Implications for the SARS-CoV-2 immune response.

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID-19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present a simultaneous heart-kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non-healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS-CoV-2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS-CoV-2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure.

Coronavirus Disease (COVID-19) in Kidney and Liver Transplant Patients: A Single-Center Experience.

OBJECTIVES: The novel 2019 coronavirus (COVID-19) was first described in December 2019 in Wuhan, China and subsequently announced as a pandemic on March 12, 2020. In several studies, solid-organ transplant recipients were reported to have higher risk for COVID-19. Here, we aimed to determine the frequency of COVID-19 in our kidney and liver transplant patients. MATERIALS AND METHODS: Our study included 583 transplant patients who were admitted to our outpatient transplant clinics and emergency departments between March 1 and May 1, 2020. Seventy-four of them were liver transplant recipients (46 male, 28 female, of which 14 were pediatric and 60 were adult patients) and 509 of them were kidney transplant recipients (347 male, 162 female, of which 16 were pediatric and 493 were adult patients). We retrospectively evaluated demographic characteristics, currently used immunosuppressant treatment, present complaints, treatment and diagnosis of comorbid diseases, and results of COVID-19 tests. RESULTS: Of 583 transplant recipients, 538 were seen in our outpatient transplant clinics and 45 were seen in our emergency departments. Of these, 18 patients who had had cough and fever were evaluated by respiratory clinic doctors, and nasopharyngeal swab samples were taken. One kidney transplant recipient had a positive COVID-19 test; he was followed with home isolation. He received treatment with hydroxychloroquine (400 mg/day). The other 17 patients had negative tests. There were no mortalities due to COVID-19. CONCLUSIONS: Transplant patients also got affected during the COVID-19 pandemic. According to the data of our centers, this effect is not much more different from the normal population. We recommend that transplant recipients should be warned in terms of personal hygiene and should be closely monitored by organ transplant centers. If there is an indication for hospitalization, they should be followed in an isolated unit, with no aggressive changes made to immunosuppressive doses unless necessary.

Incidence and Immunologic Analysis of Coronavirus Disease (COVID-19) in Hemodialysis Patients:A Single-Center Experience.

OBJECTIVES: COVID-19 is a great threat to the modern world and significant threat to immunocompromised patients, including patients with chronic renal failure. We evaluated COVID-19 incidence among our hemodialysis patients and investigated the most probable immune mechanisms against COVID-19. MATERIALS AND METHODS: Baskent University has 21 dialysis centers across Turkey, with 2420 patients on hemodialysis and 30 on peritoneal dialysis. Among these, we retrospectively evaluated 602 patients (257 female/345 male) with chronic renal failure receiving hemodialysis as renal replacement therapy; 7 patients (1.1%) were infected with SARS-CoV-2. We retrospectively collected patient demographic characteristics, clinical data, and immunological factors affecting the clinical course of the disease. We divided patients into groups and included 2 control groups (individuals with normal renal functions): group I included COVID-19-positive patients with normal renal function, group II included COVID-19-positive hemodialysis patients, group III included COVID-19-negative hemodialysis patients, and group IV included COVID-19-negative patients with normal renal function. Lymphocyte subsets in peripheral blood and typing of human leukocyte antigens were analyzed in all groups, with killer cell immunoglobulin like receptor genes analyzed only in COVID-19-positive patients and healthy controls. RESULTS: No deaths occurred among the 7 COVID-19-positive hemodialysis patients. Group I patients were significantly older than patients in groups II and III (P = .039, P = .030, respectively) but not significantly different from group IV (P = .060). Absolute counts of natural killer cells in healthy controls were higherthan in other groups (but not significantly). ActivatedT cells were significantly increased in both COVID-19-positive groups versus COVID-19-negative groups. Groups showed significant differences in C and DQ loci with respect to distribution of alleles in both HLA classes. CONCLUSIONS: Although immunocompromised patients are at greater risk for COVID-19, we found lower COVID-19 incidence in our hemodialysis patients, which should be further investigated in in vitro and molecular studies.

Optimal Management of Acute Lymphoblastic Leukemia (ALL) in Adult Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic.

The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. In December 2019, an outbreak of atypical pneumonia known as COVID-19 was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), is characterized by rapid human-to-human transmission. Acute lymphoblastic leukemia (ALL) patients are often in need for intensive chemotherapy to induce remission that will be complicated with prolonged period of cytopenias. They are often recalled to the hospital for treatment and disease surveillance. These patients may be immunocompromised due to the underlying malignancy or anti-cancer therapy. ALL patients are at higher risk of developing life-threatening infections. Several factors increase the risk of infection and the presence of multiple risk factors in the same patient is common. Cancer patients had an estimated 2-fold increased risk of contracting SARS-CoV-2 than the general population. With the World Health Organization declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such pandemic on ALL patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the optimal management of ALL patients in any infectious pandemic. In this review, we will address the potential challenges associated with managing ALL patients during the COVID-19 infection pandemic with suggestions of some practical approaches, focusing on screening asymptomatic ALL patients, diagnostic and response evaluation and choice of chemotherapy in different scenarios and setting and use of hematopoietic stem cell transplantation (HSCT).

Management of transplant patients outside hospital during COVID-19 epidemic: A Chinese experience.

Coronavirus disease 2019 (COVID-19) pandemic poses an increasing challenge for transplant community. Aggressive management measures are conductive to improve compliance and to lower the risk of intra-hospital infection. In this Personal Viewpoint essay, we shared experiences about management strategies of transplant patients outside hospital amid the epidemic. With the aid of Cloud Clinic service and telemedicine care, transplant patients could be regularly followed up and get medical consultation online. Furthermore, personal health education and mental health assistance are enrolled in our practice.