Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
1.
BMC Pulm Med ; 22(1): 368, 2022 Sep 28.
Article in English | MEDLINE | ID: covidwho-2053891

ABSTRACT

BACKGROUND: The successful management of patients infected with coronavirus disease 2019 (COVID-19) with inhaled ciclesonide has been reported, however few studies have investigated its application among hospitalized patients. METHODS: This retrospective cohort study enrolled all adult patients admitted to our hospital with confirmed COVID-19 infection from May to June 2021. Critical patients who received mechanical ventilation within 24 h after admission and those who started ciclesonide more than 14 days after symptom onset were excluded. The in-hospital mortality rate was compared between those who did and did not receive inhaled ciclesonide. RESULTS: A total of 269 patients were enrolled, of whom 184 received inhaled ciclesonide and 85 did not. The use of ciclesonide was associated with lower in-hospital mortality (7.6% vs. 23.5%, p = 0.0003) and a trend of shorter hospital stay (12.0 (10.0-18.0) days vs. 13.0 (10.0-25.3) days, p = 0.0577). In subgroup analysis, the use of inhaled ciclesonide significantly reduced mortality in the patients with severe COVID-19 infection (6.8% vs. 50.0%, p < 0.0001) and in those with a high risk of mortality (16.4% vs. 43.2%, p = 0.0037). The use of inhaled ciclesonide also reduced the likelihood of receiving mechanical ventilation in the patients with severe COVID-19 infection. After multivariate analysis, inhaled ciclesonide remained positively correlated with a lower risk of in-hospital mortality (odds ratio: 0.2724, 95% confidence interval: 0.087-0.8763, p = 0.0291). CONCLUSIONS: The use of inhaled ciclesonide in hospitalized patients with COVID-19 infection can reduce in-hospital mortality. Further randomized studies in patients with moderate to severe COVID-19 infection are urgently needed.


Subject(s)
COVID-19 , Pregnenediones , Adult , COVID-19/drug therapy , Hospitalization , Humans , Pregnenediones/therapeutic use , Retrospective Studies
2.
J Pharmacol Sci ; 149(3): 81-84, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1796436

ABSTRACT

Ciclesonide (Cic) is approved as an inhalant for asthma and was clinically tested as a candidate therapy for coronavirus disease 2019 (COVID-19). Its active metabolite Cic2 was recently reported to suppress genomic RNA replication of severe acute respiratory syndrome coronavirus 2. In this study, we designed and synthesized a set of ciclesonide-acetal (Cic-acetal) derivatives. Among designated compounds, some Cic-acetal derivatives with a linear alkyl chain exhibited strong viral copy-number reduction activities compared with Cic2. These compounds might serve as lead compounds for developing novel anti-COVID-19 agents.


Subject(s)
Antiviral Agents , COVID-19 , Acetals/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Humans , Pregnenediones , RNA, Viral/genetics , RNA, Viral/pharmacology , SARS-CoV-2 , Virus Replication/genetics
5.
Clin Microbiol Infect ; 28(7): 1010-1016, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1739639

ABSTRACT

OBJECTIVES: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. METHODS: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. RESULTS: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. DISCUSSION: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.


Subject(s)
COVID-19 , Aged , COVID-19/drug therapy , Female , Humans , Male , Middle Aged , Outpatients , Oxygen , Pregnenediones , SARS-CoV-2 , Treatment Outcome
6.
JAMA Intern Med ; 182(1): 42-49, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1527389

ABSTRACT

Importance: Systemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear. Objective: To determine the efficacy of the inhaled steroid ciclesonide in reducing the time to alleviation of all COVID-19-related symptoms among nonhospitalized participants with symptomatic COVID-19 infection. Design, Setting, and Participants: This phase 3, multicenter, double-blind, randomized clinical trial was conducted at 10 centers throughout the US and assessed the safety and efficacy of a ciclesonide metered-dose inhaler (MDI) for treating nonhospitalized participants with symptomatic COVID-19 infection who were screened from June 11, 2020, to November 3, 2020. Interventions: Participants were randomly assigned to receive ciclesonide MDI, 160 µg per actuation, for a total of 2 actuations twice a day (total daily dose, 640 µg) or placebo for 30 days. Main Outcomes and Measures: The primary end point was time to alleviation of all COVID-19-related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30. Secondary end points included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19. Results: A total of 413 participants were screened and 400 (96.9%) were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female; 2 [0.5%] Asian, 47 [11.8%] Black or African American, 3 [0.8%] Native Hawaiian or other Pacific Islander, 345 [86.3%] White, and 1 multiracial individuals [0.3%]; 172 Hispanic or Latino individuals [43.0%]). The median time to alleviation of all COVID-19-related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). No participants died during the study. Conclusions and Relevance: The results of this randomized clinical trial demonstrated that ciclesonide did not achieve the primary efficacy end point of reduced time to alleviation of all COVID-19-related symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04377711.


Subject(s)
COVID-19/drug therapy , Pregnenediones/standards , Administration, Inhalation , Adolescent , Adult , Ambulatory Care Facilities/organization & administration , Ambulatory Care Facilities/statistics & numerical data , Ambulatory Care Facilities/trends , COVID-19/epidemiology , Double-Blind Method , Female , Glucocorticoids/standards , Glucocorticoids/therapeutic use , Humans , Male , Metered Dose Inhalers , Middle Aged , Outpatients/statistics & numerical data , Pregnenediones/therapeutic use
8.
BMJ ; 375: e068060, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1495140

ABSTRACT

OBJECTIVE: To determine if inhaled and intranasal ciclesonide are superior to placebo at decreasing respiratory symptoms in adult outpatients with covid-19. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: Three Canadian provinces (Quebec, Ontario, and British Columbia). PARTICIPANTS: 203 adults aged 18 years and older with polymerase chain reaction confirmed covid-19, presenting with fever, cough, or dyspnoea. INTERVENTION: Participants were randomised to receive either inhaled ciclesonide (600 µg twice daily) and intranasal ciclesonide (200 µg daily) or metered dose inhaler and nasal saline placebos for 14 days. MAIN OUTCOME MEASURES: The primary outcome was symptom resolution at day 7. Analyses were conducted on the modified intention-to-treat population (participants who took at least one dose of study drug and completed one follow-up survey) and adjusted for stratified randomisation by sex. RESULTS: The modified intention-to-treat population included 203 participants: 105 were randomly assigned to ciclesonide (excluding two dropouts and one loss to follow-up) and 98 to placebo (excluding three dropouts and six losses to follow-up). The median age was 35 years (interquartile range 27-47 years) and 54% were women. The proportion of participants with resolution of symptoms by day 7 did not differ significantly between the intervention group (42/105, 40%) and control group (34/98, 35%); absolute adjusted risk difference 5.5% (95% confidence interval -7.8% to 18.8%). Results might be limited to the population studied, which mainly included younger adults without comorbidities. The trial was stopped early, therefore could have been underpowered. CONCLUSION: Compared with placebo, the combination of inhaled and intranasal ciclesonide did not show a statistically significant increase in resolution of symptoms among healthier young adults with covid-19 presenting with prominent respiratory symptoms. As evidence is insufficient to determine the benefit of inhaled and intranasal corticosteroids in the treatment of covid-19, further research is needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT04435795.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Ambulatory Care/methods , COVID-19/drug therapy , Pregnenediones/administration & dosage , Administration, Inhalation , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Double-Blind Method , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Intention to Treat Analysis , Male , Middle Aged , Pregnenediones/therapeutic use , Self Report , Treatment Outcome , Young Adult
9.
Neurobiol Dis ; 156: 105422, 2021 08.
Article in English | MEDLINE | ID: covidwho-1267874

ABSTRACT

Synthetic glucocorticoids (sGCs) such as dexamethasone (DEX), while used to mitigate inflammation and disease progression in premature infants with severe bronchopulmonary dysplasia (BPD), are also associated with significant adverse neurologic effects such as reductions in myelination and abnormalities in neuroanatomical development. Ciclesonide (CIC) is a sGC prodrug approved for asthma treatment that exhibits limited systemic side effects. Carboxylesterases enriched in the lower airways convert CIC to the glucocorticoid receptor (GR) agonist des-CIC. We therefore examined whether CIC would likewise activate GR in neonatal lung but have limited adverse extra-pulmonary effects, particularly in the developing brain. Neonatal rats were administered subcutaneous injections of CIC, DEX or vehicle from postnatal days 1-5 (PND1-PND5). Systemic effects linked to DEX exposure, including reduced body and brain weight, were not observed in CIC treated neonates. Furthermore, CIC did not trigger the long-lasting reduction in myelin basic protein expression in the cerebral cortex nor cerebellar size caused by neonatal DEX exposure. Conversely, DEX and CIC were both effective at inducing the expression of select GR target genes in neonatal lung, including those implicated in lung-protective and anti-inflammatory effects. Thus, CIC is a promising, novel candidate drug to treat or prevent BPD in neonates given its activation of GR in neonatal lung and limited adverse neurodevelopmental effects. Furthermore, since sGCs such as DEX administered to pregnant women in pre-term labor can adversely affect fetal brain development, the neurological-sparing properties of CIC, make it an attractive alternative for DEX to treat pregnant women severely ill with respiratory illness, such as with asthma exacerbations or COVID-19 infections.


Subject(s)
Cerebellum/drug effects , Cerebral Cortex/drug effects , Glucocorticoids , Lung/drug effects , Pregnenediones/pharmacology , Prodrugs/pharmacology , Signal Transduction/drug effects , Animals , Animals, Newborn , Anti-Inflammatory Agents/pharmacology , Body Weight/drug effects , Brain/drug effects , Brain/growth & development , COVID-19/drug therapy , Dexamethasone/pharmacology , Female , Mice , Mice, Inbred C57BL , Myelin Basic Protein/biosynthesis , Organ Size/drug effects , Pregnancy , Rats , Rats, Sprague-Dawley , Receptors, Glucocorticoid/drug effects
10.
Endocr J ; 68(4): 477-484, 2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1204140

ABSTRACT

We provide the details of the successful management of a patient with active Cushing's disease complicated with coronavirus disease 2019 (COVID-19) pneumonia. The patient was a 27-year-old Japanese female healthcare worker who was scheduled to undergo pituitary surgery for Cushing's disease. She had been in close contact with an undiagnosed patient infected with COVID-19 and then developed COVID-19 pneumonia. Despite a lack of known risk factors associated with severe COVID-19 infection, the patient's dyspnea worsened and her respiratory condition deteriorated, as indicated by the need for 7 L/min oxygen supply by mask to maintain her oxygen saturation at >90%. Medical treatment was initiated to control hypercortisolism by the 'block and replace' regimen using steroidogenesis inhibitors and hydrocortisone. The COVID-19 pneumonia improved with multi-modal treatment including antiviral therapy. One month later, after a negative severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) test result and with appropriate protection against virus transmission to medical staff in the operating room and daily medical care nurses, trans-sphenoidal surgery was performed by our highly experienced pituitary surgeon. One month after the surgery, the patient's basal ACTH and cortisol levels and urinary free cortisol were all under the detection limit. Surgical remission was expected. Since hypercortisolism due to active Cushing's disease may worsen a COVID-19 infection, multi-disciplinary management that includes appropriate and prompt treatment strategies is mandatory in such cases.


Subject(s)
Amides/administration & dosage , Benzamidines/administration & dosage , COVID-19/therapy , Guanidines/administration & dosage , Metyrapone/administration & dosage , Pituitary ACTH Hypersecretion/therapy , Pregnenediones/administration & dosage , Pyrazines/administration & dosage , ACTH-Secreting Pituitary Adenoma/complications , ACTH-Secreting Pituitary Adenoma/drug therapy , Adenoma/complications , Adenoma/drug therapy , Adult , COVID-19/complications , COVID-19/pathology , Combined Modality Therapy , Dihydrotestosterone/administration & dosage , Dihydrotestosterone/analogs & derivatives , Disease Progression , Female , Health Personnel , Heparin/administration & dosage , Humans , Japan , Neurosurgical Procedures , Pituitary ACTH Hypersecretion/blood , Pituitary ACTH Hypersecretion/complications , Pituitary ACTH Hypersecretion/pathology , SARS-CoV-2/physiology , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage
11.
Bioorg Med Chem Lett ; 43: 128052, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1196690

ABSTRACT

Ciclesonide is an inhaled corticosteroid used to treat asthma and is currently undergoing clinical trials for treatment of coronavirus disease 2019 (COVID-19). An active metabolite of ciclesonide, Cic2, was recently reported to repress severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomic RNA replication. Herein, we designed and synthesized a few types of ciclesonide analogues. Cic4 (bearing an azide group) and Cic6 (bearing a chloro group) potently decreased SARS-CoV-2 viral replication and had low cytotoxicity compared with Cic2 (bearing a hydroxy group). These compounds are promising as novel therapeutic agents for COVID-19 that show significant antiviral activity.


Subject(s)
COVID-19/drug therapy , Pregnenediones/pharmacology , RNA, Viral/antagonists & inhibitors , SARS-CoV-2/drug effects , COVID-19/virology , Glucocorticoids/pharmacology , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , Virus Replication/genetics
12.
Curr Probl Cancer ; 45(6): 100739, 2021 12.
Article in English | MEDLINE | ID: covidwho-1163605

ABSTRACT

We describe a case of coronavirus disease 2019 (COVID-19) in a patient with mixed cellularity classical Hodgkin lymphoma (cHL) undergoing brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) therapy. A 43-year-old man presented to our hospital with a complaint of fever, for which he was diagnosed with COVID-19 after a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and antiviral therapy with favipiravir and ciclesonide was started subsequently. The fever persisted for the first few days of treatment, but his respiratory status was stable, and he became asymptomatic and afebrile on day 9. Although the PCR tests remained positive, he met the updated discharge criteria of the World Health Organization (WHO) on day 12. However, his fever recurred, and his condition worsened on day 16. A chest X-ray showed a new opacity. It is likely that favipiravir and ciclesonide treatment probably did not completely eliminate the virus in the patient, and therefore the infection persisted. We added remdesivir from day 21, and the improvement was remarkable. He was discharged on day 29 after two consecutive PCR test results were negative. PCR tests are not mandatory for the updated WHO discharge criteria. However, even after antiviral therapy, COVID-19 patients with hematologic malignancies may have prolonged active infection with impaired viral excretion. Depending on the background disease and comorbidities, there may be some patient populations for whom it is not appropriate to simply comply with the current discharge criteria. Therefore, more emphasis may be needed on PCR examinations.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Hodgkin Disease/complications , Hodgkin Disease/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Brentuximab Vedotin/therapeutic use , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Dacarbazine/therapeutic use , Disease Progression , Doxorubicin/therapeutic use , Humans , Male , Pregnenediones/therapeutic use , Pyrazines/therapeutic use , Time Factors , Vinblastine/therapeutic use
13.
Adv Respir Med ; 89(1): 79-81, 2021.
Article in English | MEDLINE | ID: covidwho-1143738

ABSTRACT

As no definitive therapy or vaccine is yet available for COVID-19, in a desperate attempt repurposed drugs are being explored as an option. A drug repurposing study identified Ciclesonide as a potential candidate. We reviewed the available evidence and clinical trials on the use of Ciclesonide in COVID-19. At present the evidence is limited to a report of three cases. However, five clinical trials are underway, and their results will help in elucidating the role of Ciclesonide in COVID-19.


Subject(s)
COVID-19/drug therapy , Drug Repositioning , Glucocorticoids/therapeutic use , Pregnenediones/therapeutic use , Administration, Inhalation , Clinical Trials as Topic , Female , Humans , Male , Treatment Outcome
14.
Yakugaku Zasshi ; 140(12): 1495-1500, 2020 Dec 01.
Article in Japanese | MEDLINE | ID: covidwho-794044

ABSTRACT

Achieving appropriate inhalation in patients with coronavirus disease 2019 (COVID-19) is a common challenge in the use of repurposed metered-dose inhaler (MDI) formulations. The purpose of this study was to evaluate the effect of five valved holding chambers (VHCs) on the inhalation of ciclesonide from Alvesco MDI. The aerodynamic particle size distribution of ciclesonide discharged from Alvesco MDI was evaluated using a Next Generation Impactor in the presence and absence of VHCs. The use of VHCs retained or slightly increased the amount of ciclesonide in the fine particle diameter range (aerodynamic particle size below 3 µm) (FPD) and reduced the amount at the induction port after coordinated inhalation. However, the use of VHC reduced the FPD of the formulation by increasing the time between the MDI discharge and the pump suction by various degrees among the five VHCs. These results indicated that use of the VHCs and minimizing the inhalation delay time should ensure sufficient inhalation of ciclesonide particles.


Subject(s)
COVID-19/drug therapy , Drug Repositioning , Inhalation Spacers , Metered Dose Inhalers , Pregnenediones/administration & dosage , Administration, Inhalation , Humans , Particle Size
15.
J Virol ; 95(1)2020 12 09.
Article in English | MEDLINE | ID: covidwho-968111

ABSTRACT

Here, we screened steroid compounds to obtain a drug expected to block host inflammatory responses and Middle East respiratory syndrome coronavirus (MERS-CoV) replication. Ciclesonide, an inhaled corticosteroid, suppressed the replication of MERS-CoV and other coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), in cultured cells. The 90% effective concentration (EC90) of ciclesonide for SARS-CoV-2 in differentiated human bronchial tracheal epithelial cells was 0.55 µM. Eight consecutive passages of 43 SARS-CoV-2 isolates in the presence of ciclesonide generated 15 resistant mutants harboring single amino acid substitutions in nonstructural protein 3 (nsp3) or nsp4. Of note, ciclesonide suppressed the replication of all these mutants by 90% or more, suggesting that these mutants cannot completely overcome ciclesonide blockade. Under a microscope, the viral RNA replication-transcription complex in cells, which is thought to be detectable using antibodies specific for nsp3 and double-stranded RNA, was observed to fall in the presence of ciclesonide in a concentration-dependent manner. These observations indicate that the suppressive effect of ciclesonide on viral replication is specific to coronaviruses, highlighting it as a candidate drug for the treatment of COVID-19 patients.IMPORTANCE The outbreak of SARS-CoV-2, the cause of COVID-19, is ongoing. New and effective antiviral agents that combat the disease are needed urgently. Here, we found that an inhaled corticosteroid, ciclesonide, suppresses the replication of coronaviruses, including betacoronaviruses (murine hepatitis virus type 2 [MHV-2], MERS-CoV, SARS-CoV, and SARS-CoV-2) and an alphacoronavirus (human coronavirus 229E [HCoV-229E]), in cultured cells. Ciclesonide is safe; indeed, it can be administered to infants at high concentrations. Thus, ciclesonide is expected to be a broad-spectrum antiviral drug that is effective against many members of the coronavirus family. It could be prescribed for the treatment of MERS and COVID-19.


Subject(s)
COVID-19/metabolism , Pregnenediones/pharmacology , RNA, Double-Stranded/biosynthesis , RNA, Viral/biosynthesis , SARS-CoV-2/physiology , Virus Replication/drug effects , Animals , COVID-19/drug therapy , Chlorocebus aethiops , Dogs , HeLa Cells , Humans , Madin Darby Canine Kidney Cells , Vero Cells
16.
J Microbiol Immunol Infect ; 54(1): 109-112, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-813695

ABSTRACT

No specific therapy is available for COVID-19. We report the effectiveness and adverse effects of triple therapy with hydroxychloroquine, azithromycin, and ciclesonide in patients with COVID-19 pneumonia. The clinical condition of the patients improved within 5 days in response to the therapy.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Pregnenediones/therapeutic use , Aged , COVID-19/epidemiology , Drug Therapy, Combination , Female , Humans , Liver/drug effects , Male , Middle Aged , SARS-CoV-2/drug effects , Tokyo/epidemiology
17.
Clin Rheumatol ; 39(11): 3171-3175, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-730357

ABSTRACT

We treated two patients with severe respiratory failure due to coronavirus disease 2019 (COVID-19). Case 1 was a 73-year-old woman, and Case 2 was a 65-year-old-man. Neither of them had a history of autoimmune disease. Chest computed tomography scans before the antiviral therapy showed bilateral multiple patchy ground-glass opacities (GGO) consistent with COVID-19 pneumonia. The GGO regressed over the course of the antiviral treatment; however, new non-segmental patchy consolidations emerged, which resembled those of interstitial lung disease (ILD), specifically collagen vascular disease-associated ILD. We tested the patients' sera for autoantibodies and discovered that both patients had high anti-SSA/Ro antibody titers. In Case 1, the patient recovered with antiviral therapy alone. However, in Case 2, the patient did not improve with antiviral therapy alone but responded well to corticosteroid therapy (methylprednisolone) and made a full recovery. The relationship between some immunological responses and COVID-19 pneumonia exacerbation has been discussed previously; our discovery of the elevation of anti-SSA/Ro antibodies suggests a contribution from autoimmunity functions of the immune system. Although it is unclear whether the elevation of anti-SSA/Ro antibodies was a cause or an outcome of aggravated COVID-19 pneumonia, we hypothesize that both patients developed aggravated the COVID-19 pneumonia due to an autoimmune response. In COVID-19 lung injury, there may be a presence of autoimmunity factors in addition to the known effects of cytokine storms. In patients with COVID-19, a high level of anti-SSA/Ro52 antibodies may be a surrogate marker of pneumonia severity and poor prognosis.


Subject(s)
Antibodies, Antinuclear/immunology , Coronavirus Infections/immunology , Lung Diseases, Interstitial/immunology , Pneumonia, Viral/immunology , Respiratory Insufficiency/immunology , Aged , Amides/therapeutic use , Antiviral Agents/therapeutic use , Benzamidines , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/drug therapy , Female , Glucocorticoids/therapeutic use , Guanidines/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Male , Methylprednisolone/therapeutic use , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/drug therapy , Pregnenediones/therapeutic use , Pyrazines/therapeutic use , Recovery of Function , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/immunology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed
18.
Virus Res ; 290: 198089, 2020 12.
Article in English | MEDLINE | ID: covidwho-634875

ABSTRACT

We investigated whether reduced lymphocyte count, could predict the development of severe COVID-19. We also examined whether ciclesonide could prevent the development of severe COVID-19 among patients with the predictors. This was a retrospective cohort study. Of the 30 included patients, 12, 14, and 4 were allocated to severe pneumonia, non-severe pneumonia, and non-pneumonia groups, respectively. The group of the low level of lymphocyte counts of the sixth day after onset was significantly intubated approximately three days later. The incidence of the severe pneumoniae requiring intubation are significantly lower in the patients treated with ciclesonide than without it (11.18 % vs 83.33 %, p = 0.0033). The lymphocyte count after ciclesonide treatment in the non-severe pneumonia group was significantly higher (p = 0. 0156) than before. The lymphocyte count could be used to identify patients that may develop severe COVID-19. Treatment with ciclesonide may prevent the development of severe COVID-19.


Subject(s)
COVID-19/blood , COVID-19/drug therapy , Glucocorticoids/therapeutic use , Lymphocytes/pathology , Pregnenediones/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/pathology , Female , Humans , Lymphocyte Count , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , Young Adult
19.
J Infect Chemother ; 26(10): 1100-1103, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-627186

ABSTRACT

We report a coronavirus disease 2019 (COVID-19) case with rheumatoid arthritis taking iguratimod. The patient who continued iguratimod therapy without dose reduction was treated with ciclesonide had an uneventful clinical course, but prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed after resolution of symptoms. The effects of disease-modifying antirheumatic drugs (DMARDs) and ciclesonide on clinical course and viral shedding remain unknown and warrant further investigation.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Betacoronavirus , Chromones/therapeutic use , Coronavirus Infections/complications , Pneumonia, Viral/complications , Pregnenediones/therapeutic use , Sulfonamides/therapeutic use , Adult , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/complications , COVID-19 , Coronavirus Infections/diagnosis , Female , Humans , Pandemics , Pneumonia, Viral/diagnosis , RNA, Viral , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Thorax/diagnostic imaging , Virus Shedding
20.
BMJ Case Rep ; 13(7)2020 Jul 01.
Article in English | MEDLINE | ID: covidwho-622599

ABSTRACT

Since December 2019, coronavirus disease 2019 (COVID-19) has been an international public health emergency. The possibility of COVID-19 should be considered primarily in patients with new-onset fever or respiratory tract symptoms. However, these symptoms can occur with other viral respiratory illnesses. We reported a case of severe acute respiratory syndrome coronavirus 2 and influenza A virus coinfection. During the epidemic, the possibility of COVID-19 should be considered regardless of positive findings for other pathogens.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Influenza A virus/isolation & purification , Influenza, Human/complications , Influenza, Human/diagnosis , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Amides/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Coinfection , Coronavirus Infections/drug therapy , Diagnosis, Differential , Glucocorticoids/therapeutic use , Humans , Influenza, Human/economics , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pregnenediones/therapeutic use , Pyrazines/therapeutic use , Radiography , Real-Time Polymerase Chain Reaction , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL