m6A Regulator-Mediated Methylation Modification Patterns and Characteristics in COVID-19 Patients.

Background: RNA N6-methyladenosine (m6A) regulators may be necessary for diverse viral infectious diseases, and serve pivotal roles in various physiological functions. However, the potential roles of m6A regulators in coronavirus disease 2019 (COVID-19) remain unclear. Methods: The gene expression profile of patients with or without COVID-19 was acquired from Gene Expression Omnibus (GEO) database, and bioinformatics analysis of differentially expressed genes was conducted. Random forest modal and nomogram were established to predict the occurrence of COVID-19. Afterward, the consensus clustering method was utilized to establish two different m6A subtypes, and associations between subtypes and immunity were explored. Results: Based on the transcriptional data from GSE157103, we observed that the m6A modification level was markedly enriched in the COVID-19 patients than those in the non-COVID-19 patients. And 18 essential m6A regulators were identified with differential analysis between patients with or without COVID-19. The random forest model was utilized to determine 8 optimal m6A regulators for predicting the emergence of COVID-19. We then established a nomogram based on these regulators, and its predictive reliability was validated by decision curve analysis. The consensus clustering algorithm was conducted to categorize COVID-19 patients into two m6A subtypes from the identified m6A regulators. The patients in cluster A were correlated with activated T-cell functions and may have a superior prognosis. Conclusions: Collectively, m6A regulators may be involved in the prevalence of COVID-19 patients. Our exploration of m6A subtypes may benefit the development of subsequent treatment modalities for COVID-19.

Comparative effectiveness and safety of 32 pharmacological interventions recommended by guidelines for coronavirus disease 2019: a systematic review and network meta-analysis combining 66 trials.

BACKGROUND: The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19. METHODS: Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20-0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60-2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20-5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk. CONCLUSIONS: COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.

Myelodysplastic syndrome in a 30-year-old man with coronavirus disease 2019 (COVID-19): a diagnostic challenge.

BACKGROUND: Myelodysplastic syndromes (MDS) mainly occur in the elderly but can rarely affect younger individuals too. The correct diagnosis relies on careful morphologic evaluation, cytogenetic/molecular results, and excluding reactive conditions mimicking MDS. We present the clinical, pathologic, cytogenetic, and molecular features of a case of MDS with excess blasts-2 (MDS-EB-2) in a 30-year-old male who was found to have pancytopenia during his hospitalization for coronavirus disease 2019 (COVID-19) and discuss the diagnostic challenges of MDS in patients with COVID-19. CASE PRESENTATION: A 30-year-old man presented to an outside hospital with fever, chills, weakness, coughing spells, dizziness and shortness of breath and was diagnosed with bilateral pneumonia due to COVID-19. At the outside hospital, he was found to be pancytopenic, and a subsequent bone marrow aspiration and biopsy raised concern for a COVID-19 induced hemophagocytic lymphohistiocytosis. In addition, MDS could not be ruled out. The patient was thus referred to our institute for further management. The patient's peripheral blood showed pancytopenia with occasional dysplastic neutrophils and a few teardrop cells. Given the diagnostic uncertainty, a bone marrow aspiration and a biopsy were repeated revealing a hypercellular bone marrow with erythroid hyperplasia, megakaryocytic hyperplasia, trilineage dysplasia, increased blasts (13%), many ring sideroblasts, and mild to moderate myelofibrosis, consistent with MDS-EB-2. Chromosomal analysis revealed isochromosome 14. Next generation sequencing demonstrated SF3B1 K700E mutation. DISCUSSION AND CONCLUSION: The diagnosis of MDS can be challenging, particularly in young patients. Cytopenia and myelodysplastic features have been reported in COVID-19 patients, making the diagnosis of MDS more elusive. A careful pathologic examination of the bone marrow with ancillary studies including flow cytometry, immunohistochemistry, and cytogenetic and molecular studies in combination with a thorough clinical evaluation, leads to the accurate diagnosis.

Clinical and radiologic features of the first cured Coronavirus disease 2019 (COVID-19) patient in Guangzhou City, China.

To determine changes in clinical and radiologic findings associated with Coronavirus disease 2019 (COVID-19) from diagnosis to recovery, we retrospectively reviewed the diagnosis and treatment records of the first patient cured of COVID-19 in Guangzhou. A 55-year-old woman from Wuhan was admitted to the hospital isolation ward with the chief complaint of "cough for 11 days and once fever 8 days ago" on January 22, 2020. COVID-19 was laboratory confirmed by reverse transcription polymerase chain reaction (RT-PCR) assay, and she received conventional antiviral therapy, such as moxifloxacin, traditional Chinese medicine, and arbidol. Repeat chest-computed tomography (CT) scans were performed on days 13 and 19 of her illness. The former showed radiologic findings, including ground-glass opacities (GGOs), which revealed viral pneumonia; the latter revealed that the previous lesions had been significantly absorbed. The lesions on CT scans were consistent with the changes in the course of disease. Some drugs, such as traditional Chinese medicine and arbidol, might play an important role in the recovery of COVID-19 patients. This study provides some new insights into the formulation of a timely and effective diagnostic and therapeutic strategy to cure patients with COVID-19.