mycophenolic-acid and Coronavirus-Infections

SARS-CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS-CoV-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on SARS-CoV-2 infection, and suggests guidelines for the management of immunosuppression.

Topics: Adaptive Immunity; Antiviral Agents; Betacoronavirus; Calcineurin Inhibitors; Contraindications, Drug; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Disease Susceptibility; Drug Interactions; Everolimus; Glucocorticoids; Humans; Immunity, Innate; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Pandemics; Pneumonia, Viral; Postoperative Complications; SARS-CoV-2; Sirolimus; TOR Serine-Threonine Kinases

COVID-19 has become a global concern. A large number of reports have explained the clinical characteristics and treatment strategies of COVID-19, but the characteristics and treatment of COVID-19 patient with systemic lupus erythematosus (SLE) are still unclear. Here, we report the clinical features and treatment of the first SLE patient with confirmed COVID-19 pneumonia. This was a 39-year-old woman, diagnosed with SLE 15 years ago, whose overall clinical characteristics (symptoms, laboratory tests, and chest CTs) were similar to those of the general COVID-19 patients. She continued to take the previous SLE drugs (doses of glucocorticoids, hydroxychloroquine, and immunosuppressive agents were not reduced) and was treated with strict antiviral and infection prevention treatment. After the first discharge, she got a recurrence of COVID-19 during her home isolation, and then returned to hospital and continued the previous therapy. Finally, this long-term immune suppressive patient's COVID-19 was successfully cured. The successful recovery of this case has significant reference value for the future treatment of COVID-19 patients with SLE. Key Points • COVID-19 patients with SLE is advocated to continue the medical treatment for SLE. • Hydroxychloroquine may have potential benefits for COVID-19 patients with SLE. • COVID-19 patients with SLE is prone to relapse, and multiple follow-ups are necessary.

Topics: Adult; Anti-Bacterial Agents; Antirheumatic Agents; Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Drug Combinations; Female; Glucocorticoids; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lopinavir; Lung; Lupus Erythematosus, Systemic; Moxifloxacin; Mycophenolic Acid; Pandemics; Pneumonia, Viral; Prednisone; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; Ritonavir; RNA, Viral; SARS-CoV-2; Tomography, X-Ray Computed

This review compares the clinical features, laboratory aspects and treatment options of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS).. Bats are the natural reservoirs of SARS-like coronaviruses (CoVs) and are likely the reservoir of MERS coronavirus (MERS-CoV). Although a small number of camels have been found to have positive nasal swabs by real-time polymerase chain reaction and to carry antibody against MERS-CoV, the transmission route and the intermediary animal source remain uncertain amongst the sporadic primary cases. Both SARS-CoV and MERS-CoV may cause severe respiratory failure and extrapulmonary features such as diarrhoea, whereas mild or asymptomatic cases also occur in both conditions. In comparison with SARS, patients with MERS are older with male predominance, more comorbid illness and relatively lower human-to-human transmission potential. Although the viral kinetics of MERS-CoV remain unknown, nosocomial infections of MERS occur early within the first week of illness of the index case, whereas those of SARS occurred mainly in the second week of illness when the patient's upper airway viral load peaks on day 10 of illness. In-vitro data suggest that interferon (IFN) with or without ribavirin and mycophenolic acid may inhibit MERS-CoV, whereas protease inhibitors and IFN have inhibitory activity against SARS-CoV.. Although there are some similarities in the clinical features, MERS progresses to respiratory failure much more rapidly than SARS. The higher case fatality rate of MERS is likely related to older age and comorbid illness. More studies are needed to understand MERS-CoV in order to guide public health infection control measures and treatment.

Topics: Age Distribution; Animals; Antiviral Agents; Camelus; Chiroptera; Coronavirus; Coronavirus Infections; Cross Infection; Diagnosis, Differential; Disease Progression; Female; Humans; Immunity, Innate; Infectious Disease Incubation Period; Interferons; Lung; Male; Middle East; Mycophenolic Acid; Public Health; Radiography; Real-Time Polymerase Chain Reaction; Ribavirin; Severe Acute Respiratory Syndrome; Sex Distribution; Viral Load

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption

Topics: Animals; Antiviral Agents; Betacoronavirus; Chlorocebus aethiops; Cloning, Molecular; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Evaluation, Preclinical; Drug Repositioning; HEK293 Cells; Host-Pathogen Interactions; Humans; Immunity, Innate; Mass Spectrometry; Molecular Targeted Therapy; Pandemics; Pneumonia, Viral; Protein Binding; Protein Biosynthesis; Protein Domains; Protein Interaction Mapping; Protein Interaction Maps; Receptors, sigma; SARS-CoV-2; SKP Cullin F-Box Protein Ligases; Vero Cells; Viral Proteins

Topics: Aged; Betacoronavirus; Cobicistat; Colchicine; Coronavirus Infections; COVID-19; Cytokines; Darunavir; Drug Combinations; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lopinavir; Male; Middle Aged; Mycophenolic Acid; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tacrolimus; Transplant Recipients; Treatment Outcome

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.

Topics: Betacoronavirus; Ceftriaxone; Coronavirus Infections; COVID-19; Cytokines; Glomerulonephritis, IGA; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tacrolimus; Treatment Outcome

Topics: Abatacept; Coronavirus Infections; COVID-19; Cyclosporine; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lung; Male; Middle Aged; Mycophenolic Acid; Pandemics; Pneumonia, Viral; Prednisone; Radiography, Thoracic; Tomography, X-Ray Computed; Treatment Outcome

This is a report of a case with mucous membrane pemphigoid (MMP) with severe eye involvement and concurrent COVID-19 treated successfully using simultaneous high dose intravenous immunoglobulin (IVIg) and anti-viral treatment as hydroxychloroquine, lopinavir/ritonavir, and ribavirin. He had finished a 2-g cycle of rituximab (RTX) in late January. He was receiving mycophenolate mofetil (MMF) for one month and 30 mg prednisolone for three months until his hospitalization. Prednisolone was tapered to 15 mg when current COVID-19 was suspected, considering his recent cough, dyspnea, and fever.

Topics: Adult; Anti-Bacterial Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Deprescriptions; Diabetes Mellitus, Type 2; Drug Combinations; Drug Therapy, Combination; Humans; Hypertension; Immunoglobulins, Intravenous; Immunologic Factors; Iran; Lopinavir; Male; Mycophenolic Acid; Oseltamivir; Pandemics; Pemphigoid, Benign Mucous Membrane; Pneumonia, Viral; Prednisolone; Ritonavir; Rituximab; SARS-CoV-2; Tomography, Spiral Computed

Topics: Adult; Aged; Aged, 80 and over; Antirheumatic Agents; Azathioprine; Betacoronavirus; Clinical Laboratory Techniques; Cohort Studies; Coronavirus Infections; Cough; COVID-19; COVID-19 Testing; Cyclosporine; Diarrhea; Dysgeusia; Dyspnea; Fatigue; Female; Fever; Glucocorticoids; Humans; Hydroxychloroquine; Immunosuppressive Agents; Incidence; Intensive Care Units; Italy; Lupus Erythematosus, Systemic; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Olfaction Disorders; Pandemics; Pneumonia, Viral; Prednisone; Respiratory Distress Syndrome; SARS-CoV-2; Telemedicine

Topics: Adolescent; Adrenal Cortex Hormones; Anemia, Hemolytic, Autoimmune; Benzoates; Betacoronavirus; Coronavirus Infections; COVID-19; Erythrocyte Transfusion; Humans; Hydrazines; Male; Mycophenolic Acid; Oxygen; Pandemics; Pneumonia, Viral; Pyrazoles; SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is a novel infectious disease and became a global issue. Treatment of COVID-19 especially in solid organ transplant recipients is empirical and controversial, especially the adjustment of the immunosuppressants.. A 29-year-old kidney transplant recipient with the symptoms of COVID-19 pneumonia.. COVID-19 pneumonia after kidney transplantation.. He was treated with modified immunosuppressants (unchanged dose of tacrolimus and oral corticosteroids while discontinuing mycophenolate mofetil (MMF)), antibiotics, interferon α-2b inhalation and traditional Chinese medicine.. He recovered from COVID-19 pneumonia after 29 days of hospitalization. And the renal function (measured as blood urea nitrogen, serum creatinine, and urine protein) returned to normal.. In certain group of COVID-19 (e.g., mild to moderate cases, young patients without comorbidities), a reduction instead of an overall withdrawal of immunosuppressant in kidney transplant recipients is feasible.

Topics: Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drugs, Chinese Herbal; Humans; Immunosuppressive Agents; Interferon alpha-2; Kidney Transplantation; Male; Mycophenolic Acid; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome

In this study, the anti-severe acute respiratory syndrome coronavirus-2 (anti-SARS-CoV-2) activity of mycophenolic acid (MPA) and IMD-0354 was analyzed. These compounds were chosen based on their antiviral activities against other coronaviruses. Because they also inhibit dengue virus (DENV) infection, other anti-DENV compounds/drugs were also assessed. On SARS-CoV-2-infected VeroE6/TMPRSS2 monolayers, both MPA and IMD-0354, but not other anti-DENV compounds/drugs, showed significant anti-SARS-CoV-2 activity. Although MPA reduced the viral RNA level by only approximately 100-fold, its half maximal effective concentration was as low as 0.87 µ m, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets the coronaviral papain-like protease and an in-depth study on its mechanism of action would be useful in the development of novel anti-SARS-CoV-2 drugs.

Topics: Animals; Antiviral Agents; Benzamides; Betacoronavirus; Chlorocebus aethiops; Coronavirus Infections; COVID-19; Dengue Virus; Humans; Mycophenolic Acid; Pandemics; Pneumonia, Viral; SARS-CoV-2; Vero Cells; Virus Replication

Topics: Adult; Betacoronavirus; Cholinesterase Inhibitors; Coronavirus Infections; COVID-19; Disease Progression; Female; Glucocorticoids; Humans; Hypercapnia; Hypoxia; Immunoglobulins, Intravenous; Immunologic Factors; Myasthenia Gravis; Mycophenolic Acid; Pandemics; Plasma Exchange; Pneumonia, Viral; Prednisone; Pyridostigmine Bromide; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2; Severity of Illness Index; Thymectomy; Tomography, X-Ray Computed

Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies.. We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate.. Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients.. Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.

Topics: Adult; Aged; Aged, 80 and over; Allografts; Antimalarials; Betacoronavirus; Coronavirus Infections; COVID-19; Enzyme Inhibitors; Female; Graft Rejection; Humans; Hydroxychloroquine; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; New York City; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Transplant Recipients

Various interferon (IFN)-inducible transmembrane (IFITM) proteins are known to be expressed in human tissues though only IFITM 1-3 are inducible by IFN. Numerous studies have shown that activation of IFITM3 could suppress infection by influenza and coronaviruses such as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In view of the potential application of IFITM proteins' induction to target SARS-CoV-2 infection that causes COVID-19, this article layout insights into the known antiviral mechanisms and therapeutic agents related to IFITM. Blocking viral entry through various mechanisms and the potential application of the FDA approved immunosuppressant agent, mycophenolic acid, as inducer of IFITM3 are among those discussed.

Topics: Animals; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Immunosuppressive Agents; Interferons; Membrane Proteins; Mycophenolic Acid; Pandemics; Pneumonia, Viral; RNA-Binding Proteins; SARS-CoV-2

Topics: Anti-Infective Agents; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Monitoring, Immunologic; Mycophenolic Acid; Oxygen Inhalation Therapy; Pandemics; Pneumonia, Viral; Prednisolone; SARS-CoV-2; Tacrolimus; Treatment Outcome

Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia.. In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered.. Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival.. Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.

Topics: Aged; Alanine Transaminase; Coronavirus Infections; Female; Health Personnel; Humans; Immunosuppressive Agents; Logistic Models; Lung; Male; Middle Aged; Middle East Respiratory Syndrome Coronavirus; Multivariate Analysis; Mycophenolic Acid; Polymerase Chain Reaction; Retrospective Studies; Saudi Arabia; Severity of Illness Index; Tertiary Care Centers; Treatment Outcome

Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged to cause fatal infections in patients in the Middle East and traveler-associated secondary cases in Europe and Africa. Person-to-person transmission is evident in outbreaks involving household and hospital contacts. Effective antivirals are urgently needed.. We used small compound-based forward chemical genetics to screen a chemical library of 1280 known drugs against influenza A virus in Biosafety Level-2 laboratory. We then assessed the anti-MERS-CoV activities of the identified compounds and of interferons, nelfinavir, and lopinavir because of their reported anti-coronavirus activities in terms of cytopathic effect inhibition, viral yield reduction, and plaque reduction assays in Biosafety Level-3 laboratory.. Ten compounds were identified as primary hits in high-throughput screening. Only mycophenolic acid exhibited low EC50 and high selectivity index. Additionally, ribavirin and interferons also exhibited in-vitro anti-MERS-CoV activity. The serum concentrations achievable at therapeutic doses of mycophenolic acid and interferon-β1b were 60-300 and 3-4 times higher than the concentrations at which in-vitro anti-MERS-CoV activities were demonstrated, whereas that of ribavirin was ∼2 times lower. Combination of mycophenolic acid and interferon-β1b lowered the EC50 of each drug by 1-3 times.. Interferon-β1b with mycophenolic acid should be considered in treatment trials of MERS.

Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Communicable Diseases, Emerging; Coronavirus; Coronavirus Infections; Disease Outbreaks; Drug Discovery; High-Throughput Screening Assays; Humans; Interferons; Mycophenolic Acid; Ribavirin; Vero Cells; Viral Load; Viral Plaque Assay