Treatment Of Coronavirus Disease 2019 Research Articles

Administration of Lactobacillus plantarum GUANKE alleviates SARS-CoV-2-induced pneumonia in mice.

Most otherwise healthy individuals develop only mild or moderate symptoms of coronavirus disease 2019 (COVID-19) caused by current strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and virus replication is mainly confined to the upper respiratory tract; however, the virus can infect the lower respiratory tract and promote inflammation. Probiotic supplementation has been shown to reduce nasopharyngeal SARS-CoV-2 viral load, reduce the overall number and duration of symptoms, and attenuate inflammation in clinical trials. We showed that a novel L. plantarum GUANKE strain alleviated SARS-CoV-2-induced pneumonia in mice. The transcription and production of inflammatory cytokines were suppressed, and GUANKE moderately reduced the viral load. L. plantarum GUANKE has the potential to become a candidate drug for the treatment of COVID-19 or other viral respiratory infections.

Identifying Mechanism of RSV for the Treatment of COVID-19 and Idiopathic Pulmonary Fibrosis via Suppressing Inflammation Response Through IL-17 Signaling Pathway from the Perspectives of in silico Study.

Both coronavirus disease 2019 (COVID-19) and idiopathic pulmonary fibrosis (IPF) could cause severe pulmonary injury and have extremely dismal prognoses with a high risk of mortality. Resveratrol (RSV), a natural polyphenol, has promising potential in the treatment of viral infection and pulmonary fibrosis. The purpose of this research was to investigate the unclear mechanism of RSV as an anti-COVID-19 and IPF therapy. Utilizing relevant databases, the intersection of genes related to IPF, COVID-19, and possible RSV targets was discovered. Then the obtained targets were investigated using GO and KEGG analysis, TP and PPI network analysis. Furthermore, the binding affinities between core targets and RSV were calculated using molecular docking. The 1101 COVID-19 targets, 2166 IPF targets, and 341 RSV targets intersected with 21 overlapping targets. PPI network reveals the interactions among targets and TP network reveals interactions between targets and pathways. Five targets including JUN, CCL2, CXCL8, IL6, and SERPINE1 were identified as the core targets through two network analyses. GO analysis demonstrated chemotaxis, inflammatory response and angiogenesis were the significant pathophysiological processes. Combing TP network analysis and KEGG analysis, IL-17 signaling pathway was considered as the significant pathway. Except for JUN, molecular docking showed the binding energies of other four targets were lower than -5 kcal/mol indicating intimate interactions between RSV and other targets. Our research elucidate the targets, pathways and pathophysiological processes of RSV involved in effects of anti-COVID-19 and IPF, suggesting RSV could be a therapeutic candidate for reducing infection and fibrosis.

Possible mechanisms of SARS-CoV-2-associated myocardial fibrosis: reflections in the post-pandemic era.

Since December 2019, coronavirus disease 2019 (COVID-19) has been spreading worldwide with devastating immediate or long-term effects on people's health. Although the lungs are the primary organ affected by COVID-19, individuals infected with SARS-CoV-2 also develop systemic lesions involving multiple organs throughout the body, such as the cardiovascular system. Emerging evidence reveals that COVID-19 could generate myocardial fibrosis, termed "COVID-19-associated myocardial fibrosis." It can result from the activation of fibroblasts via the renin-angiotensin-aldosterone system (RAAS), transforming growth factor-β1 (TGF-β1), microRNAs, and other pathways, and can also occur in other cellular interactions with SARS-CoV-2, such as immunocytes, endothelial cells. Nonetheless, to gain a more profound insight into the natural progression of COVID-19-related myocardial fibrosis, additional investigations are necessary. This review delves into the underlying mechanisms contributing to COVID-19-associated myocardial fibrosis while also examining the antifibrotic potential of current COVID-19 treatments, thereby offering guidance for future clinical trials of these medications. Ultimately, we propose future research directions for COVID-19-associated myocardial fibrosis in the post-COVID-19 era, such as artificial intelligence (AI) telemedicine. We also recommend that relevant tests be added to the follow-up of COVID-19 patients to detect myocardial fibrosis promptly.

The Effect of COVID-19 on the Efferent Auditory System in Adults.

This study evaluated the effects of coronavirus disease 2019 (COVID-19) on the cochlea and auditory efferent system with transient evoked otoacoustic emissions (TEOAE) and contralateral suppression (CS). We aimed to evaluate the pre- and post-COVID-19 TEOAE and CS results in the same participants to reveal the effect of COVID-19 on the efferent auditory system. The CS measurement was performed twice for each participant before a diagnosis of COVID-19 and after treatment for COVID-19 as a within-subjects study design. All participants exhibited hearing thresholds below 25 dB HL at all frequencies and all participants demonstrated bilateral Type A tympanograms. The tests were performed in the linear mode using a double probe on the Otodynamics ILO292-II device. The CS of the otoacoustic emissions was measured at 65 dB peSPL TEOAE stimulus and 65 dB SPL broadband noise. All parameters including reproducibility, noise, and stability were considered during the measurements. The study included 11 patients (eight females and three males) aged between 20 and 35 years (mean age, 26 ± 3.66). Wilcoxon signed rank test and Spearman's correlation test were used for statistical analysis using the Statistical Package for the Social Sciences version 23.0. The Wilcoxon signed rank test showed that there was no significant difference between the pre-and post-COVID-19 TEOAE CS results in all tested frequencies and measurement parameters, 1000 to 4000 Hz, Z = -0.356, -0.089, -0.533, -0.533, -1.156, and p < 0.05. Although not statistically significant, the CS results obtained post-COVID-19 at all frequencies, except 4000 Hz, were lower than those before COVID-19. According to the overall TEOAE results after COVID-19, a statistically significant decrease was observed at 3000 Hz (Z = -2.847, p < 0.01) and 4000 Hz (Z = -2.401, p < 0.05) compared with the premeasurement. The study findings show that severe acute respiratory syndrome coronavirus 2 can affect the cochlea and the auditory efferent system in adults. Post-COVID-19 audiological evaluation can also be considered part of a general medical examination.

Novel Alkynylamide-Based Nonpeptidic Allosteric Inhibitors for SARS-CoV-2 3-Chymotrypsin-like Protease.

Although the coronavirus disease 2019 (COVID-19) crisis has passed, there remains a necessity for continuous efforts toward developing more targeted drugs and preparing for potential future virus attacks. Currently, most of the drugs received authorization for the treatment of COVID-19 have exhibited several limitations, such as poor metabolic stability, formidable preparation, and uncertain effectiveness. It is still significant to develop novel, structurally diverse small-molecule antiviral drugs targeting SARS-CoV-2 3-chymotrypsin-like protease (3CLpro). Herein, we report a class of alkynylamide-based nonpeptidic 3CLpro inhibitors that can be prepared conveniently by our previously developed one-pot synthetic method. The structure-activity relationships of alkynylamides as SARS-CoV-2 3CLpro inhibitors have been carefully investigated and discussed in this study. The two stereoisomers of the resulting molecules exhibit stereoselective interaction with 3CLpro, and the optimized compound (S,R)-4y inhibits 3CLpro with high potency (IC50 = 0.43 μM), low cytotoxicity, and acceptable cell permeability. Compound (S,R)-4y presents as a noncovalent inhibitor of 3CLpro against SARS-CoV-2 by the time-dependent inhibition assay (TDI) and mass spectrometry analysis. The Lineweaver-Burk plots, binding energy, surface plasmon resonance, and molecular docking studies suggest that (S,R)-4y specifically binds to an allosteric pocket of the SARS-CoV-2 3CLpro. These findings provide a novel class of nonpeptidic alkynylamide-based allosteric inhibitors with high selectivity against SARS-CoV-2 3CLpro featured by a simplified one-pot synthesis at room temperature in air.

Risk of COVID-19 infection in patients with NSCLC receiving EGFR-TKI targeted therapy during the first wave in China.

We examined the factors influencing hospitalization and prognosis among patients with non-small cell lung cancer receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted therapy during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. In total, 267 patients diagnosed with NSCLC who were receiving treatment with third-generation EGFR-TKIs were included in our retrospective study. Data on patients' demographics, clinical characteristics, and survival were collected and analyzed. Over a mean follow-up of 18 months, 80.5% (215/267) of the patients contracted COVID-19, and 12.6% (27/215) of these patients were hospitalized for COVID-19 treatment. Vaccinated patients, those with body mass index (BMI) ≥22.3 kg/m2, and those with no comorbidities had lower rates of infection and hospitalization than unvaccinated patients, those with BMI <22.3 kg/m2, and those with comorbidities, respectively. Continued NSCLC treatment in patients with COVID-19 was identified as a risk factor for patient survival. NSCLC treatment can be continued for patients who received COVID-19 vaccines, those with higher BMI, and those without comorbidities during the COVID-19 epidemic, but treatment interruption might be required for patients during the active phase of infection.

Could Timed Targeting of the Circadian-Controlled NLRP3 Inflammasome Be a Potential Therapeutic Strategy for Treatment of COVID-19–Induced Encephalitis?

The new coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has several manifestations including neurological complications like encephalitis. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes, which are regulated by the circadian clock genes, are key signaling proteins that detect pathogenic microorganisms and sterile stressors and activate the pro-inflammatory cytokines such as interleukin-1β and -18 (IL-1β and IL-18). The disruption of circadian rhythms following SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) receptors in the capillary endothelium could lead to hyperactivation of the NLRP3 inflammasome, contributing to an enhanced inflammatory response in the central nervous system, thereby increasing susceptibility to or severity of coronavirus disease 2019 (COVID-19)-induced encephalitis. This review highlights the role of the circadian-controlled NLRP3 inflammasome in the pathogenesis of COVID-19-induced encephalitis and suggests targeting the NLRP3 circadian axis for timely intervention as a potential therapeutic target for the treatment of COVID-19-induced encephalitis.

Association of corticosteroid therapy with reduced acute kidney injury and lower NET markers in severe COVID-19: an observational study

BackgroundAcute kidney injury (AKI) is common in critical cases of coronavirus disease 2019 (COVID-19) and associated with worse outcome. Dysregulated neutrophil extracellular trap (NET) formation is one of several suggested pathophysiological mechanisms involved in the development of COVID-19 associated AKI. The corticosteroid dexamethasone was implemented as a standard treatment for severe COVID-19 as of June 2020. A sub-analysis of a prospective observational single center study was performed to evaluate the effect of corticosteroid treatment on AKI development and NET markers in critical cases of COVID-19.ResultsTwo hundred and ten adult patients admitted to intensive care at a tertiary level hospital due to respiratory failure or shock secondary to SARS-CoV-2-infection between March 13th 2020 and January 14th 2021 were included in the study. Ninety-seven of those did not receive corticosteroids. One hundred and thirteen patients were treated with corticosteroids [dexamethasone (n = 98) or equivalent treatment (n = 15)], but the incidence of AKI was assessed only in patients that received corticosteroids before any registered renal dysfunction (n = 63). Corticosteroids were associated with a lower incidence of AKI (19% vs 55.8%, p < 0.001). Fewer patients demonstrated detectable concentrations of extracellular histones in plasma when treated with corticosteroids (8.7% vs 43.1%; p < 0.001). Extracellular histones and in particular non-proteolyzed histones were observed more frequently with increasing AKI severity (p < 0.001). MPO-DNA was found in lower concentrations in patients that received corticosteroids before established renal dysfunction (p = 0.03) and was found in higher concentrations in patients with AKI stage 3 (p = 0.03). Corticosteroids did not ameliorate established AKI during the first week of treatment.ConclusionCorticosteroid treatment in severe COVID-19 is associated with a lower incidence of AKI and reduced concentrations of NET markers in plasma.

Dermatological manifestations, and drug-induced reactions in COVID-19 patients: an observational study from İstanbul, Turkiye

Aims: The systemic and respiratory clinical manifestations of coronavirus disease 2019 (COVID-19) include fever, cough, sneezing, sore throat, rhinitis, dyspnoea, chest pain, malaise, fatigue, anorexia, and headache. Moreover, cutaneous manifestations have been observed in 0.2% to 20.4% of cases. This investigation further explores the dermatological manifestations associated with COVID-19 and reactions induced by its pharmacological treatments. Conducted at a university hospital, the study examined 841 patients and identified skin manifestations in 1.5% of cases. It differentiates between symptoms directly attributed to the viral infection and those arising from treatment, highlighting the need for clinical vigilance and adaptability in managing these manifestations. COVID-19 has been linked to a wide range of clinical symptoms, extending beyond the well-known respiratory effects to include various dermatological manifestations. These manifestations, which range from mild rashes to severe conditions like vasculitis, may complicate diagnosis and management, particularly when similar symptoms are induced by therapeutic drugs used in COVID-19 treatment. Methods: This cross-sectional study included 841 patients treated in the COVID-19 outpatient and inpatient units of the university hospital between March and May 2020. The assessment involved clinical examinations and telemedicine consultations, focusing on differentiating between viral and drug-induced dermatological reactions. Results: Dermatological manifestations were observed in 1.5% of the 841 patients. Direct virus-related skin changes were noted in 1% (n=8) of patients, including maculopapular eruptions (50%, n=4) on the face and trunk, trunk-localized urticaria (25%, n=2), and purpuric lesions (12.5%, n=1) on the lower extremities. Drug-induced dermatological reactions were identified in 0.5% (n=5) of patients, featuring conditions such as bullous drug reactions, psoriasiform drug eruptions, hypertrichosis, and urticaria. Conclusion: These findings highlight the complex interplay between COVID-19 and its treatment, where both the virus and pharmacological agents can trigger significant dermatological reactions. The need for healthcare providers to consider both viral and drug-induced factors in the diagnosis and management of skin manifestations in COVID-19 patients is underscored. Further studies are essential to refine treatment protocols and reduce adverse dermatological outcomes.

Rhabdomyolysis-related acute kidney injury in patients with COVID-19.

Viral and bacterial infections may be complicated by rhabdomyolysis, which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnormalities to life-threatening conditions such as renal failure. Direct viral injury as well as inflammatory responses may cause rhabdomyolysis in the course of coronavirus disease 2019 (COVID-19). When presented with acute kidney injury (AKI), rhabdomyolysis may be related to higher morbidity and mortality. To compare rhabdomyolysis-related AKI with other AKIs during COVID-19. A total of 115 patients with COVID-19 who had AKI were evaluated retrospectively. Fifteen patients had a definite diagnosis of rhabdomyolysis (i.e., creatine kinase levels increased to > 5 times the upper normal range with a concomitant increase in transaminases and lactate dehydrogenase). These patients were aged 61.0 ± 19.1 years and their baseline creatinine levels were 0.87 ± 0.13 mg/dL. Patients were treated according to national COVID-19 treatment guidelines. They were compared with patients with COVID-19 who had AKI due to other reasons. For patients with rhabdomyolysis, creatinine reached 2.47 ± 1.17 mg/dL during follow-up in hospital. Of these patients, 13.3% had AKI upon hospital admission, and 86.4% developed AKI during hospital follow-up. Their peak C-reactive protein reached as high as 253.2 ± 80.6 mg/L and was higher than in patients with AKI due to other reasons (P < 0.01). Peak ferritin and procalcitonin levels were also higher for patients with rhabdomyolysis (P = 0.02 and P = 0.002, respectively). The mortality of patients with rhabdomyolysis was calculated as 73.3%, which was higher than in other patients with AKI (18.1%) (P = 0.001). Rhabdomyolysis was present in 13.0% of the patients who had AKI during COVID-19 infection. Rhabdomyolysis-related AKI is more proinflammatory and has a more mortal clinical course.

Sex differences in the outcome of critically Ill patients with COVID-19 - An international multicenter critical care consortium study

BackgroundSex differences in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) susceptibility, illness severity, and hospital course are widely acknowledged. The effects of sex on outcomes experienced by patients with severe Coronavirus Disease 2019 (COVID-19) admitted to the intensive care unit (ICU) remains unknown. ObjectivesTo determine the effects of sex on ICU mortality in patients with COVID-19 MethodsThis retrospective analysis of an international multi-center prospective observational database included adults admitted to ICU for treatment of acute COVID-19 between 1st January 2020 and 30th June 2022. The primary outcome was ICU mortality. Multivariable Cox regression was used to ascertain the hazard of death (Hazard Ratio=HR) adjusted for pre-selected covariates. The secondary outcome was sex differences in complications of COVID-19 during hospital stay. ResultsOverall, 10,259 patients (3,314 females, 6,945 males) were included with a median age of 60 (interquartile range [IQR]=49–68) and 59 (IQR=49–67) years, respectively. Baseline characteristics were similar between sexes. More females were non-smokers (65% vs. 44 %, p < 0.01) and obese (39% vs. 30 %, p < 0.01), compared to males. Also, males received greater ICU intervention (mechanical ventilation, prone ventilation, vasopressors, and tracheostomy) than females. Males had a greater hazard of death (compared to females, HR=1.14; 95 % CI=1.02–1.26). Adjustment for complications during hospital stay did not alter the hazard of death (HR=1.16; 95 % CI=1.05–1.28). Males had a significantly elevated hazard of death among patients who received ECMO (HR=1.24; 95 % CI=1.01–1.53). Male sex was associated with cardiac arrest (adjusted OR [aOR]=1.37; 95 % CI=1.16–1.62) and PE (aOR=1.28; 95 % CI=1.06–1.55). ConclusionAmong patients admitted to ICU for severe COVID-19, males experienced higher severity of illness and more frequent intervention than females. Ultimately, the hazard of death was moderately elevated in males compared to females despite greater PE and cardiac arrest.

The role of convalescent plasma and hyperimmune immunoglobulins in the COVID-19 pandemic, including implications for future preparedness.

When Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks. A scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment. This review included the latest Cochrane systematic review update on 30-day mortality and safety. We also covered use in pediatric and immunocompromised patients, as well as the logistic challenges faced in donor recruitment and plasma collection in general. Challenges for low resource countries were specifically highlighted. A major challenge is the high donation frequency required from first-time donors to ensure a safe product, which minimizes the risk of transfusion-transmitted infectious. This is particularly difficult in low- and middle- income countries due to inadequate infrastructure and insufficient blood product supplies. High-certainty evidence indicates that convalescent plasma does not reduce mortality or significantly improve clinical outcomes in patients with moderate to severe COVID-19 infection. However, CCP may provide a viable treatment for patients unable to mount an endogenous immune response to SARS-CoV-2, based on mostly observational studies and subgroup data of published and ongoing randomized trials. Convalescent plasma has been shown to be safe in adults and children with COVID-19 infection. However, the efficacy in pediatric patients remains unclear. Data on efficacy and safety of CCP are still underway in ongoing (randomized) studies and by reporting the challenges, limitations and successes encountered to-date, research gaps were identified to be addressed for the future. This experience serves as a valuable example for future pandemic preparedness, particularly when therapeutic options are limited, and vaccines are either being developed or ineffective due to underlying immunosuppression.

Assessment of factors associated with self-medication practices during the COVID-19 pandemic in southwestern Ethiopia: a community-based cross-sectional survey

BackgroundSelf-medication practices involve the use of medications without healthcare professional requests. The threat of coronavirus disease 2019 (COVID-19) caused the practice of a fittest to survive action, with the assumption that something is better than nothing. Moreover, owing to the lack of effective treatment for COVID-19, the general public has shifted toward self-medication and symptomatic treatment, with approximately 80% of people stockpiling medication for use during the pandemic. Thus, this study aimed to assess the factors associated with self-medication practices during the COVID-19 pandemic crisis in southwestern Ethiopia.MethodsA community-based cross-sectional study design was employed at selected drug retail outlets in southwestern Ethiopia for 415 community pharmacy clients from July 1, 2021, to September 1, 2021. Purposive sampling techniques were employed to select five drug retail outlets on the basis of high patient flows, and we took the study participants until the required quota allotted to each selected drug retail outlet had been filled. Bivariable and multivariable logistic regression analyses were employed to identify factors associated with self-medication. AORs with 95% CIs were used to report associations, and the level of significance was set at P < 0.05. Results: Self-medication was significantly associated with being female (AOR 3.51, 95% CI 1.04–12.41), having a college education or above (AOR 47, 95% CI 4.32–55.21), time wastage at public health facilities (AOR 2.71, 95% CI 3.47–5.21), being afraid of contracting COVID-19 (AOR 0.006, 95% CI 0.004–0.185), and having high fees at public health facility (AOR 0.006, 95% CI 0.004–0.185). The most frequently used medications to treat or prevent the COVID-19 pandemic were analgesics (42.4%) and cold medicines (29.5%). Headache (22.2%), fever (13.2%), respiratory infection (14.3%), and cold (21.4%) were the most frequently reported symptoms of the COVID-19 pandemic.ConclusionThis study revealed high self-medication practices among study area residents during the COVID-19 pandemic. The primary reasons for self-medication in the context of COVID-19 are fear of the pandemic and time wastage at public health facilities. Therefore, special attention should be given to educating public and health care providers on the types of illnesses that can be self-diagnosed and self-treated and the types of drugs to be used for self-medication.

A Cluster of Diutina catenulata Funguria in Patients with Coronavirus Disease 2019 (COVID-19) Hospitalized in a Tertiary Reference Hospital from Rio de Janeiro, Brazil.

During the COVID-19 pandemic, fungal infections, especially pulmonary aspergillosis, mucormycosis, and invasive candidiasis, have emerged as a significant health concern. Beyond Candida albicans, the most common cause of invasive candidiasis, other rare ascomycetous yeast species have been described in tertiary care units, potentially posing a broader health threat. We have isolated, from September 2020 to June 2021, nine Diutina catenulata strains from urine samples of six patients. This was intriguing as this fungus had not been previously identified in our institution, nor after June 2021. Therefore, we decided to outline the clinical features of the patients with this rare pathogen, to describe phenotypic characteristics, including antifungal susceptibility profiles, of this yeast species and to identify the genetic makeup through whole-genome sequencing analysis to evaluate if this was a cluster of genetically similar D. catenulata isolates in our institution. The strains were identified through MALDI-TOF MS analyses and Sanger sequencing of two rDNA regions. All patients yielding D. catenulata from urine samples needed ventilator support and used urinary catheters during hospitalization for treatment of COVID-19. None of them had received COVID-19 vaccines. Morphological and biochemical profiles of the nine strains were largely consistent, although fluconazole susceptibility varied, ranging from 4 to 32μg/mL. Phylogenomic analysis revealed minimal genetic variation among the isolates, with low intrapopulation variation, supported by the identification of only 84 SNPs across all strains. Therefore, we propose that the yeast strains isolated were part of a cluster of D. catenulata funguria in the context of COVID-19.

Examination of SARS-CoV-2 RNA in joint synovial fluid of patients with COVID-19 and acute knee arthritis.

It has not yet been fully established that there is coronavirus disease 2019 (COVID-19) involvement in the synovial fluid and it remains a topic of debate. The aim of this study was to evaluate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in knee joint synovial fluid of patients with COVID-19. This retrospective study was conducted with an initial screening of patients who were admitted to a tertiary pandemic hospital due to COVID-19 symptoms, and underwent treatment for COVID-19 between March and June 2020. A total of 2476 patients were hospitalized or received treatment for a possible diagnosis of COVID-19. While the RT-PCR test was positive in 318 patients (12.8%), 2158 (87.2%) were computed tomography positive but reverse transcription-polymerase chain reaction (RT-PCR) negative. Twelve patients were consulted due to acute joint effusion. Of five patients with knee joint effusion and a positive RT-PCR test, the synovial tissue RT-PCR test was positive in only one patient. This paper is the first to show the presence of SARS-CoV-2 in synovial fluid. This can be considered of importance for the determination and elimination of the route of transmission, thereby preventing further development and spread of the disease.

Clinical profiles and mortality predictors of hospitalized patients with COVID-19 in Ethiopia

BackgroundStudying the characteristics of hospitalized Coronavirus Disease 2019 (COVID-19) patients is vital for understanding the disease and preparing for future outbreaks. The aim of this study was to analyze and describe the clinical profiles and factors associated with mortality among COVID-19 patients admitted to Jimma Medical Center COVID-19 Treatment Center (JMC CTC) in Ethiopia.MethodsAll confirmed COVID-19 patients admitted to JMC CTC between 17 April 2020 and 05 March 2022 were included in this study. Socio-demographic data, clinical information, and outcome variables were collected retrospectively from medical records and COVID-19 database at the hospital. Bivariable and multivariable analyses were performed to determine factors associated with COVID-19 severity and mortality. A P-value < 0.05 was considered statistically significant.ResultsA total of 542 confirmed COVID-19 patients were admitted to JMC CTC, of which 322 (59.4%) were male. Their median age was 48 years (IQR 32–64). About 51% (n = 277) of them had severe COVID-19 upon admission. Patients with hypertension [AOR: 2.8 (95% CI: 1.02–7.7, p = 0.046)], diabetes [AOR: 8.8 (95% CI: 1.2–17.3, p = 0.039)], and underlying respiratory diseases [AOR: 18.8 (95% CI: 2.06–71.51, p = 0.009)] were more likely to present with severe COVID-19 cases. Overall, 129 (23.8%) died in the hospital. Death rate was higher among patients admitted with severe disease [AHR = 5.5 (3.07–9.9) p < 0.001)] and those with comorbidities such as hypertension [AHR = 3.5 (2.28–5.41), p < 0.001], underlying respiratory disease [AHR = 3.4 (1.97–5.94), p < 0.001], cardiovascular disease (CVDs) [AHR = 2.8 (1.73–4.55), p < 0.001], and kidney diseases [AHR = 3.7 (2.3–5.96), p < 0.001].ConclusionAbout half of COVID-19 cases admitted to the hospital had severe disease upon admission. Comorbidities such as hypertension, diabetes, and respiratory diseases were linked to severe illness. COVID-19 admissions were associated with high inpatient mortality, particularly among those with severe disease and comorbidities.

Visual analysis on ferroptosis and its cross-talk to coronavirus disease 2019 (COVID-19)

BackgroundFerroptosis is a new type of programmed cell death. Although ferroptosis has been studied in various aspects, there has been no visual analysis of ferroptosis in coronavirus disease 2019 (COVID-19) to date. It is still a global health concern of the COVID-19 pandemic worldwide, three years after its outbreak. Yet the emergence of the mutant strain Omicron has caused a fourth wave of infections in many countries. The pathogenesis of COVID-19 is still undergoing extensive exploration, which holds paramount importance in mitigating future epidemics. MethodsFor this study, CiteSpace 6.2 R4 software was used for bibliometric and visual atlas analysis of ferroptosis-related research, and the Genecards database was used to mine ferroptosis and COVID-19-related genes. ResultsWe found increasing studies about ferroptosis. China and the United States have demonstrated robust scientific innovation over recent years, with extensive collaboration between their institutions and authors. Ferroptosis and COVID-19 were seen to have 13 shared genes, which may be new targets for the treatment of COVID-19 in the future. Most of the shared genes are enriched in tumor necrosis factor (TNF) pathways. The majority of those genes are up-regulated under the cellular response to oxidative stress. Genes including Tumour necrosis factor (TNF), RELA proto-oncogene (RELA), Activating transcription factor 4 (ATF4), Cytochrome b-245 beta chain (CYBB), Jun proto-oncogene (JUN), Mitogen-activated protein kinase 1 (MAPK1) and Heme oxygenase 1 (HMOX1), maybe a breakthrough for ferroptosis and COVID‐19. Whilst previous research has shown there to be a relationship between ferroptosis and COVID‐19, the specific role of ferroptosis remained unclear. Our study aimed to analyze the research status of ferroptosis and its relationship with COVID-19, to provide a useful reference for further prevention and treatment of COVID-19. Overall, uncovering the role of ferroptosis in SARS-CoV-2 infection is important for the development of new treatment strategies for COVID-19.

Paxlovid for the treatment of COVID-19: a systematic review and meta-analysis.

Paxlovid (nirmatrelvir/ritonavir) is a new oral antiviral drug that is used for coronavirus disease 2019 (COVID-19) and is administered to patients with mild to moderate disease for five consecutive days. This meta-analysis aimed to evaluate the efficacy of Paxlovid in COVID-19 patients. PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify relevant publications up to 9 March 2023. Three randomized controlled trial (RCT) studies, one prospective cohort study, and 25 retrospective cohort studies were identified for the meta-analysis. There was a significant difference between the Paxlovid and control groups in terms of hospitalization (RR = 0.53; 95% CI: 0.24-0.69, p < 0.001), all-cause mortality (RR = 0.36; 95% CI: 0.27-0.50, p < 0.001), hospitalization or death (RR = 0.50; 95% CI: 0.37-0.67, p < 0.001), intensive care unit admission (RR = 0.45; 95% CI: 0.27-0.73, p = 0.001), and emergency department visits (RR = 0.67; 95% CI: 0.54-0.83, p < 0.001). However, no significant difference was found between the two groups in terms of COVID-19 rebound (OR = 1.18; 95% CI: 0.82-1.68, p = 0.37). In addition, the Paxlovid group had a significantly shorter hospital length of stay (weighted mean difference WMD = -1.11; 95% CI, -1.81, -0.41; I2 > 50%, p < 0.05), and polymerase chain reaction negative conversion time (WMD = -2.75; 95% CI, -3.60, -1.89, I2 > 50%, p < 0.05) than that of the control group. Paxlovid can be considered an effective therapeutic agent for treating patients with COVID-19.

Potential of 6′‑hydroxy justicidin B from Justicia procumbens as a therapeutic agent against coronavirus disease 2019

BackgroundSince the onset of the coronavirus disease 2019 (COVID-19) pandemic, remarkable advances have been made in vaccine development to reduce mortality. However, therapeutic interventions for COVID-19 are comparatively limited despite these intensive efforts. Furthermore, the rapid mutation capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a characteristic of its RNA structure, has led to the emergence of multiple variants, necessitating a shift from a predominantly vaccine-centric approach to one that encompasses therapeutic strategies. 6′-Hydroxy justicidin B (6′-HJB), an arylnaphthalene lignan isolated from Justicia procumbens, a traditional Chinese medicine, is known for its antiviral properties. Hypothesis/PurposeThe aim of the present study was to assess the effectiveness and safety of 6′-HJB against SARS-CoV-2 in order to determine its potential as a therapeutic agent against COVID-19. MethodsThe efficacy of 6′-HJB was evaluated both in vitro using Vero and Calu-3 cell lines and in vivo using ferrets. The safety assessment included toxicokinetics, safety pharmacology, and Good Laboratory Practice (GLP)-compliant toxicity evaluations following single- and repeated-dose toxicity studies in dogs. ResultsThe anti-SARS-CoV-2 efficacy of 6′-HJB was evaluated through dose-response curve (DRC) analysis using immunofluorescence; 6′-HJB demonstrated superior inhibition of SARS-CoV-2 growth and lower cytotoxicity than remdesivir. In SARS-CoV-2-infected ferret, 6′-HJB showed efficacy comparable to that of the positive control, Truvada. Further GLP toxicity studies corroborated the safety profile of 6′-HJB. Single-dose and 4-week repeated oral toxicity studies in Beagle dogs demonstrated minimal harmful effects at the highest dosages. The lethal dose of 6′-HJB exceeded 2,000 mg kg-1 in Beagle dogs. Toxicokinetic and GLP safety pharmacology studies demonstrated no adverse effects of 6′-HJB on metabolic processes, respiratory or central nervous systems, or cardiac functions. ConclusionThis research highlights both the antiviral efficacy and safety profile of 6′-HJB, underscoring its potential as a novel COVID-19 treatment option. The potential of 6′-HJB was demonstrated using modern scientific methodologies and standards.

The PARP inhibitor rucaparib blocks SARS-CoV-2 virus binding to cells and the immune reaction in models of COVID-19.

To date, there are limited options for severe Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus. As ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host; we have, here, assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19. The effects of PARP inhibitors on virus uptake were assessed in cell-based experiments using multiple variants of SARS-CoV-2. The binding of rucaparib to spike protein was tested by molecular modelling and microcalorimetry. The anti-inflammatory properties of rucaparib were demonstrated in cell-based models upon challenging with recombinant spike protein or SARS-CoV-2 RNA vaccine. We detected high levels of oxidative stress and strong PARylation in all cell types in the lungs of COVID-19 patients, both of which negatively correlated with lymphocytopaenia. Interestingly, rucaparib, unlike other tested PARP inhibitors, reduced the SARS-CoV-2 infection rate through binding to the conserved 493-498 amino acid region located in the spike-ACE2 interface in the spike protein and prevented viruses from binding to ACE2. In addition, the spike protein and viral RNA-induced overexpression of cytokines was down-regulated by the inhibition of PARP1 by rucaparib at pharmacologically relevant concentrations. These results point towards repurposing rucaparib for treating inflammatory responses in COVID-19.