Treatment Of Coronavirus Disease 2019 Research Articles

Exploring the Molecular Mechanism of Niuxi-Mugua Formula in Treating Coronavirus Disease 2019 via Network Pharmacology, Computational Biology, and Surface Plasmon Resonance Verification.

In China, Niuxi-Mugua formula (NMF) has been widely used to prevent and treat coronavirus disease 2019 (COVID-19). However, the mechanism of NMF for treating COVID-19 is not yet fully understood. This study aimed to explore the potential mechanism of NMF for treating COVID- 19 by network pharmacology, computational biology, and surface plasmon resonance (SPR) verification. The NMF-compound-target network was constructed to screen the key compounds, and the Molecular Complex Detection (MCODE) tool was used to screen the preliminary key genes. The overlapped genes (OGEs) and the preliminary key genes were further analyzed by enrichment analysis. Then, the correlation analysis of immune signatures and the preliminary key genes was performed. Molecular docking and molecular dynamic (MD) simulation assays were applied to clarify the interactions between key compounds and key genes. Moreover, the SPR interaction experiment was used for further affinity kinetic verification. Lipid and atherosclerosis, TNF, IL-17, and NF-kappa B signaling pathways were the main pathways of NMF in the treatment of COVID-19. There was a positive correlation between almost the majority of immune signatures and all preliminary key genes. The key compounds and the key genes were screened out, and they were involved in the main pathways of NMF for treating COVID-19. Moreover, the binding affinities of most key compounds binding to key genes were good, and IL1B-Quercetin had the best binding stability. SPR analysis further demonstrated that IL1B-Quercetin showed good binding affinity. Our findings provided theoretical grounds for NMF in the treatment of COVID-19.

Diphyllin elicits a doubled-pronged attack on the entry of SARS-CoV-2 by inhibiting cathepsin L and furin

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, posing serious threats to global health. Effective broad-spectrum antiviral drugs for the treatment of COVID-19 are not sufficiently available. In the present study, we investigated the antiviral activity of the natural lignan diphyllin (PubChem CID 100492) against different SARS-CoV-2 variants and explored the underlying molecular mechanisms. We found that diphyllin dose-dependently inhibits the SARS-CoV-2 spike (S)-mediated entry into different types of cells. The potent inhibition was evident against spike proteins derived from the original SARS-CoV-2 and from variants of concern such as Alpha, Beta, Delta or Omicron. Accordingly, diphyllin also significantly inhibited the in vitro infection of a clinical SARS-CoV-2 virus isolate. Mechanistically, diphyllin simultaneously inhibited the endosomal entry of SARS-CoV-2 by neutralizing the endosomal acidification and reducing the activity of the cysteine protease cathepsin L (CTSL) as well as S-meditated cell surface entry by impairing furin activity. Collectively, our findings establish diphyllin as novel inhibitor of CTSL and furin proteases, resulting in a double-pronged attack on SARS-CoV-2 entry along endosomal as well as cell surface routes. Therefore, diphyllin has the potential to be advanced as an inhibitor of SARS-CoV-2 entry.

Research progress of spike protein mutation of SARS-CoV-2 mutant strain and antibody development.

The coronavirus disease 2019 (COVID-19) is a respiratory disease with a very high infectious rate caused by the Severe Acute Respiratory Syndrome Coronavirus-2(SARS-CoV-2). Because SARS-CoV-2 is easy to mutate, the continuous emergence of SARS-CoV-2 variant strains not only enhances the infectivity of the SARS-CoV-2 but also brings great obstacles to the treatment of COVID-19. Neutralizing antibodies have achieved good results in the clinical application of the novel coronavirus pneumonia, which can be used for pre-infection protection and treatment of novel coronavirus patients. This review makes a detailed introduction to the mutation characteristics of SARS-CoV-2, focusing on the molecular mechanism of mutation affecting the infectivity of SARS-CoV-2, and the impact of mutation on monoclonal antibody therapy, providing scientific reference for the prevention of SARS-CoV-2 variant strains and the research and development of antibody drugs.

Post-COVID-19 pneumonia: Long-term radiographic and spirometric outcomes

Objectives: This study aimed to evaluate the long-term radiographic and spirometric outcomes in patients who survived Coronavirus Disease 2019 (COVID-19) pneumonia in Brazzaville, with a focus on identifying the prevalence and contributing factors to persistent pulmonary sequelae. Materials and Methods: A cross-sectional study was conducted in multiple COVID-19 treatment centers in Brazzaville. A total of 52 patients, with a median age of 49.5 years, were assessed at least six months after recovery. Thoracic computed tomography (CT) scans were used to evaluate radiographic abnormalities, while spirometry assessed ventilatory function. Factors contributing to these abnormalities were analyzed, including age, comorbidities, and the severity of the acute illness. Results: Radiographic analysis revealed that 42.3% of patients had abnormal thoracic CT scans, with common findings including ground-glass opacities (52.2%), atelectasis (39.1%), and traction bronchiectasis (13%). Spirometric analysis revealed that 71.1% of patients had ventilatory disorders and predominantly restrictive patterns (51.4%). Advanced age, comorbidities (such as diabetes and hypertension), and the use of mechanical ventilation were significantly associated with radiographic abnormalities. Persistent respiratory symptoms, including chronic cough and dyspnea, were reported by 32.7% of patients, and 44.2% experienced impaired quality of life. Conclusion: These findings underscore the importance of long-term follow-up for COVID-19 pneumonia survivors, particularly those with persistent symptoms or comorbidities. Regular monitoring of respiratory function through spirometry and imaging is essential to managing long-term sequelae and improving patients’ quality of life.

Clinical Benefits of Sustained Oral Nirmatrelvir/Ritonavir Use for the Outpatient Treatment of COVID-19: Findings from the Taiwanese Health Authority Perspective Using a Decision Tree Modeling Approach.

Despite the observed clinical benefits of nirmatrelvir/ritonavir (NMV/r), it is uncertain whether Taiwan will continue covering NMV/r for high-risk individuals with mild-to-moderate coronavirus disease 2019 (COVID-19). This analysis assessed the impact of sustained utilization of NMV/r on COVID-19-associated healthcare resource utilization (HCRU) and mortality from the Taiwanese health authority perspective (THAP). A decision tree model estimated the incremental number of clinical events associated with NMV/r utilization over a 30-day period. Model results compared (1) a base case using current rates of NMV/r from the THAP, and (2) a hypothetical scenario assuming the current supply of NMV/r is not extended in Taiwan. NMV/r utilization rates included 80% and 0% in the base case and hypothetical scenario, respectively. Outcomes included the number of hospitalizations involving a general ward (GW) stay, intensive care unit (ICU) stay, and mechanical ventilation (MV) use, as well as the number of bed days, symptom days, and hospitalization deaths. Based on epidemiologic data, 150,255 patients with COVID-19 were eligible for treatment from the THAP. In the hypothetical scenario, HCRU increased by 175% compared to the base case, including increases in hospitalizations involving GW, ICU, and MV use (differences: 2067; 623; 591, respectively), bed days (difference: 51,521), symptom days (difference: 51,714), and deaths (difference: 480). Findings indicate that sustained utilization of NMV/r from the THAP reduces the clinical burden of mild-to-moderate COVID-19 through the reduced incidence of COVID-19-related HCRU and deaths.

Real-world use of multiplex point-of-care molecular testing or laboratory-based molecular testing for influenza-like illness in a 2021 to 2022 US outpatient sample.

While molecular testing is recommended for symptomatic patients suspected of having coronavirus disease 2019 (COVID-19), limited data are available examining real-world use of tests for severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the impact of SARS-CoV-2 testing on patient outcomes. In this retrospective cohort study using de-identified administrative claims data in the Optum Labs Data Warehouse, we identified 2 groups of patients with ≥1 outpatient claims with a procedure code for SARS-CoV-2 testing between January 2021 and September 2022. Group 1 had ≥1 claims with CPT code 0240U or 0241U ("Xpert Xpress") (N = 51,602); Group 2 had ≥1 claims for laboratory-based molecular testing (N = 317,192). Outcomes assessed on the identification date and through the 90-day follow-up included claims evidence of use of SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) tests, diagnosis of active COVID-19, influenza, or RSV, and use of treatments (antivirals for COVID-19, influenza, and RSV and other treatments for COVID-19 and RSV). Patients in Group 1 had fewer tests for SARS-CoV-2, influenza, or RSV (mean ± standard deviation 1.6±1.4 versus 2.6±2.6, standardized difference -0.45), faster time to diagnosis of COVID-19 (median 0 versus 4 days, standardized difference -0.27) or influenza (median 0 versus 5 days, standardized difference -0.74), and faster time to treatment of COVID-19, influenza, or RSV (median 1 versus 5 days, standardized difference 0.16) than patients in Group 2. In this nationwide real-world study of outpatient testing, use of point-of-care molecular multiplex SARS-CoV-2 testing resulted in fewer claims for SARS-CoV-2, influenza, and RSV tests, faster time to diagnosis, and faster time to treatment than laboratory-based molecular testing.

COVID-19 infection in children with blood cancer: A systematic review.

Blood cancer is the most common type of cancer and the leading cause of death by disease past infancy among children. Children with blood cancer are vulnerable population to viral infections such as coronavirus disease 2019 (COVID-19). To estimate the incidence of COVID-19 in children with blood cancer and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with blood cancer with COVID-19 illness. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of COVID-19 in children with blood cancer, published from December 1, 2019 to April 30, 2023, with English language restriction. Of the 3077 papers that were identified, 155 articles were included in the systematic review (83 case report, 54 cohort and 18 case-series studies). Studies involving 1289 children with blood cancer with confirmed COVID-19 were analysed. Leukaemias (1141 cases) were the most frequent types of blood cancer observed in children who developed COVID-19, followed by non-Hodgkin's lymphomas (59 cases), Hodgkin's lymphomas (36 cases), Langerhans cell histiocytosis (7 cases), myelodysplastic syndrome (7 cases) and myeloid neoplasm (1 case). Among all 1289 blood cancer paediatric cases who transmitted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some children were documented to be admitted to the intensive care unit (ICU) (n = 175, 13.6%), intubated and placed on mechanical ventilation (MV) (n = 111, 8.6%), suffered acute respiratory distress syndrome (ARDS) (n = 144, 11.2%) or died (n = 111, 8.6%). Overall, COVID-19 in children with different types of blood cancer resulted in no or low severity of disease in 78.6% of all included cases (COVID-19 severity: asymptomatic = 238, mild = 601, or moderate = 171). Treatment for COVID-19 was not necessary in a small number of children with blood cancer (n = 94, 7.3%). Fatality in children with blood cancer with COVID-19 was reported in any of the included blood cancer categories for leukaemias (n = 99/1141, 8.7%), non-Hodgkin's lymphomas (n = 7/59, 11.9%), Hodgkin's lymphomas (n = 2/36, 5.5%), myelodysplastic syndrome (n = 1/7, 14.3%) or myeloid neoplasm (n = 1/1, 100%). Fatality rate in children with blood cancer infected with SARS-CoV-2 was the highest in patients with Hispanic ethnicity (n = 44/111, 39.6%) and COVID-19-related fatality was highest in male patients (76.5% of deceased patients). Most studies reported to alter the intensity and regimen of anticancer treatment in children with blood cancer during course of SARS-CoV-2 infection, however, many studies have reported to successfully treat COVID-19 without any changes to the anticancer treatment. Globally, leukaemias were the most prevalent and myeloid neoplasms were the least prevalent blood cancer types in children who developed SARS-CoV-2 infection. Children with blood cancer infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the healthy pediatric populations. Mortality in children with blood cancer and infected with SARS-CoV-2 was highest in cases belonging to male gender and Hispanic ethnicity. However, children with blood cancer tend to have milder COVID-19 symptoms and are less likely to be hospitalized and have better prognosis when compared to adults. Continuation of anticancer treatment in individual paediatric blood cancer patients with COVID-19 seems to be possible.

In Vitro Characterization of Inhibition Function of Calcifediol to the Protease Activity of SARS-COV-2 PLpro.

Vitamin D3 and its metabolites calcifediol have been recommended as effective drugs for novel coronavirus disease 2019 (COVID-19) therapy in many studies, since the outbreak of this global dramatic pandemic. In this study, we made a striking discovery that Calcifediol demonstrates robust inhibitive effect on the of the papain-like cysteine protease (PLpro), a critical proteolytic enzyme for the severe acute respiratory syndrome coronavirus-2(SARS-COV-2), through a small-scale FRET-based screening experiment. The practical bindings of Calcifediol to PLpro were also demonstrated by several in vitro interaction studies. All the evidence had revealed the inhibition might be caused by the targeted binding event. Consequently, our discovery represents a significant finding that the beneficial therapeutic impact of Calcifediol on COVID-19 may be attributed not only to its immunoregulatory properties but also to its inhibition of PLpro. This finding strongly bolsters the case for the clinical use of Vitamin D3 and its derivative Calcifediol in the treatment of COVID-19.

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.

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.

Effect of SARS CoV-2 Infection among Potential Liver Transplant Recipients and Living Donors on the Outcome of Living Donor Liver Transplantation

Abstract Background Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a substantial risk of morbidity and mortality. Liver transplantation has faced unique challenges due to COVID-19 all over the world. There is a scarce data on the effects of SARS-CoV-2 infection in candidates awaiting liver transplantation or potential donors who proved to have SARS CoV-2 infection based on clinical and/or positive RT- PCR test and/or radiological data. Objective To describe the effect of preoperative SARS-CoV 2infection in potential candidates and living donors on the outcome of living donor liver transplantation (LDLT). Patients and Methods Combined retrospective and prospective pilot cohort study carried out at Ain Shams Center for Organ Transplantation (ASCOT). 74 LDLT recipients & their donors were included, who underwent LDLT operation during the interval between January 2020 and august 2022. were classified into two groups: Group A: included candidate recipients and/or living donor who had preoperative SARS-CoV-2 infection and Group B (control group): included candidate recipients and/or living donor who didn't have preoperative SARS-CoV-2 infection. The two groups were followed post LDLT for a minimum duration of 6 months and maximum duration of 2.5 years. Their data were analysed and compared. Results Among the 74 LDLT recipients, 10 recipients (13.5%) & 8 donors (10.8%) had confirmed preoperative SARS-COV2. The mean age of the recipients was 46.90 ± 14.15 years old with male prevalence, and the majority had mild respiratory symptoms of preoperative COVID-19. Two patients have specific treatment for COVID-19 with remdesivir or steroid therapy and supplemental oxygen and 8 patients received only symptomatic treatment. The median time between SARS Cov2 infection and LT in our series was 6.5 months. there was no significant difference between candidates/recipients who had preoperative COVID-19 (group-a) and those who hadn’t (group-b), regarding the preoperative, operative and postoperative characteristics apart from significantly shorter duration of operation and higher incidence of early postoperative desaturation in ICU in (group a, 20% vs 1.6% in group b patients, p: 0.006) Table (1). The mean age of the living donors of group a was 30.25 ± 7.07, all had mild preoperative COVID 19 disease which didn’t affect significantly their operative and postoperative course Table (2). Conclusion Mild preoperative COVID-19 disease didn’t affect significantly the postoperative course of recipients for LDLT. Donors with completely resolved mild preoperative COVID-19 disease can safely donate for LDLT.

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.

Computational Insights into Kaempferol and Luteolin: Potential Mitigators of the Omicron B.1.1.529 SARS-CoV-2 Variant

Abstract The coronavirus disease 2019 (COVID-19) has been circulating in the local and global population. Among the SARS-CoV-2 variants, the Omicron strain tends to be detected in the recent genomic surveillance studies. Despite being a manageable disease, recovered patients may experience post-COVID-19 conditions such as cough (50.6%), fatigue (45.8%), and memory loss (37.4%). While developing an updated vaccine for COVID-19 is time-consuming, the in-silico discovery of phytoconstituents that bind to the SARS-CoV-2 receptor binding domain (RBD), may provide insights on the potential of edible plants as complementary treatments. This study aimed to investigate and compare the ligand-protein interactions of phytoconstituents and COVID-19 treatment drug, remdesivir, to the SARS-CoV-2 spike protein. The molecular docking results indicated that kaempferol and luteolin could potentially mitigate COVID-19, as they exhibited higher RBD-binding affinities than remdesivir.

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.

ORGANIZATION OF PERINATAL CARE IN UKRAINE DURING THE COVID-19 PANDEMIC

The purpose: analysis of the organization of perinatal care in Ukraine during the COVID-19 pandemic. Materials and methods. The research materials were the legislative base of Ukraine on the specified issue, the following research methods were used: bibliosemantic and the method of structural-logical analysis. The results. In Ukraine, organizational measures, most clinical aspects, in particular case identification, hospitalization according to clinical criteria, groups at risk of developing complications of the disease, provision of non-specific treatment, etc., are regulated by the order of the Ministry of Health of Ukraine dated 03/28/2020 No. 722 "Organization of medical care for patients with coronavirus disease ( COVID-19)", and are implemented in health care institutions by developing clinical patient routes and local protocols. The treatment of coronavirus disease and vaccination of pregnant women is regulated by general regulatory documents, separate legal acts regarding the management of pregnant women and their vaccination were not adopted. The impact of the pandemic on perinatal care and the course of pregnancy in uninfected women remains poorly researched. Conclusions. Health services must develop plans to minimize the impact of both infections and appropriate restrictions on pregnant women, maintain the effectiveness of perinatal care in the face of outbreaks of dangerous quarantine infections, while continuing to provide both routine and emergency obstetric care.