Progression Of Coronavirus Disease 2019 Research Articles

Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection.

Many factors may influence the risk of being infected by SARS-CoV-2, the coronavirus responsible for coronavirus disease 2019 (COVID-19). Exposure to the virus cannot explain the variety of an individual's responses to the virus and the high differences of effect that the virus may cause to some. While a person's preexisting condition and their immune defenses have been confirmed to play a major role in the disease progression, there is still much to learn about hosts' genetic makeup towards COVID-19 susceptibility and risk. The host genetic makeup may have direct influence on the grade of predisposition and outcomes of COVID-19. In this study, we aimed to investigate the presence of relevant genetic single nucleotide polymorphisms (SNPs), the peripheral blood level of IL6, vitamin D and arterial blood gas (ABG) markers (pH, oxygen-SpO2 and carbon dioxide-SpCO2) on two groups, COVID-19 (n = 41, study), and the healthy (n = 43, control). We analyzed cytokine and interleukin genes in charge of both pro-inflammatory and immune-modulating responses and those genes that are considered involved in the COVID-19 progression and complications. Thus, we selected major genes, such as IL1β, IL1RN (IL-1 β and α receptor) IL6, IL6R (IL-6 receptor), IL10, IFNγ (interferon gamma), TNFα (tumor necrosis factor alpha), ACE2 (angiotensin converting enzyme), SERPINA3 (Alpha-1-Antiproteinase, Antitrypsin member of Serpin 3 family), VDR (vitamin D receptor Tak1, Bsm1 and Fok1), and CRP (c-reactive protein). Though more research is needed, these findings may give a better representation of virus pleiotropic activity and its relation to the immune system.

Subgenomic RNAs and Their Encoded Proteins Contribute to the Rapid Duplication of SARS-CoV-2 and COVID-19 Progression.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently widespread throughout the world, accompanied by a rising number of people infected and breakthrough infection of variants, which make the virus highly transmissible and replicable. A comprehensive understanding of the molecular virological events and induced immunological features during SARS-CoV-2 replication can provide reliable targets for vaccine and drug development. Among the potential targets, subgenomic RNAs and their encoded proteins involved in the life cycle of SARS-CoV-2 are extremely important in viral duplication and pathogenesis. Subgenomic RNAs employ a range of coping strategies to evade immune surveillance from replication to translation, which allows RNAs to synthesize quickly, encode structural proteins efficiently and complete the entire process of virus replication and assembly successfully. This review focuses on the characteristics and functions of SARS-CoV-2 subgenomic RNAs and their encoded proteins and explores in depth the role of subgenomic RNAs in the replication and infection of host cells to provide important clues to the mechanism of COVID-19 pathogenesis.

Association of COVID-19 patient's condition with fasting blood glucose and body mass index: A retrospective study.

The COVID-19 pandemic broke out in 2019 and rapidly spread across the globe. Most of the severe and dead cases are middle-aged and elderly patients with chronic systemic diseases. This study aimed to assess the association between fasting blood glucose (FPG) and body mass index (BMI) levels in patients with coronavirus disease 2019 (COVID-19) under different conditions. Experimental-related information (age, gender, BMI, and FPG on the second day of admission) from 86 COVID-19 cases (47 males and 39 females) with an average age of (39 ± 17) years was collected in April and November 2020. These cases were divided into three groups according to the most severe classification of each case determined by the clinical early warning indicators of severe-critically illness, the degree of progression, and the treatment plan shown in the diagnosis and treatment plan of COVID-19 pneumonia. Statistical models were used to analyze the differences in the levels of FPG and BMI, age, and gender among the three groups. 1. Experimental group: 21 patients with asymptomatic or and mild symptoms (group A), 45 patients with common non-progression (group B), and 20 patients with common progression and severe symptoms (group C). 2. The age differences among the three groups were statistically significant and elderly patients had a higher risk of severe disease (t= 4.1404, 3.3933, 9.2123, P= 0.0001, 0.0012, 0.0000). There was a higher proportion of females than males in the normal progression and severe disease cases (χ2= 5.512, P= 0.019). 3. The level of FPG was significantly higher in group C than in group A (t= 3.1655, P= 0.0030) and B (t= 2.0212, P= 0.0475). The number of diabetes or IFG in group C was significantly higher than in group A (χ2= 5.979, P= 0.014) and group B (χ2= 6.088, P= 0.014). 4. BMI was significantly higher in group C than in groups A (t= 3.8839, P= 0.0004) and B (t= 3.8188, P= 0.0003). The number of overweight or obese patients in group C was significantly higher than in groups A (χ2= 8.838, P= 0.003) and B (χ2= 10.794, P= 0.001). 5. Patients' age, gender, and FPG were independent risk factors for COVID-19 disease progression (β= 0.380, 0.191, 0.186; P= 0.000, 0.034, 0.045). The levels of FPG and BMI were significantly increased in the population with common progressive and severe COVID-19. FPG and age are independent risk factors for the progression of COVID-19.

Prognostic value of procalcitonin in cancer patients with coronavirus disease 2019.

Many biomarkers have been studied to assist in the risk stratification and prognostication of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Procalcitonin (PCT), a circulating precursor of the hormone calcitonin, has been studied with mixed results as a predictor of severe coronavirus disease 2019 (COVID-19) in the general population; however, to date, no studies have focused on the utility of PCT in predicting disease severity and death from COVID-19 in the cancer population. We conducted a retrospective study of cancer patients hospitalized with COVID-19 at a comprehensive cancer center over a 10-month period who had PCT recorded on admission. We assessed associations between variables of clinical interest and the primary outcomes ofprogression of COVID-19 and death during or within 30days of hospitalization using univariable and multivariable logistic regression. The study included 209 unique patients. In the univariate analysis, elevated PCT on admission was associated with higher odds of progression of COVID-19 or death (Odds ratio [OR] 1.40, 95% CI 1.08-1.93) and mortality alone (OR 1.53, 95% CI 1.17-2.11). In multivariate regression, PCT remained significantly associated with progression or death after holding chronic kidney disease (CKD) status constant (OR 1.40, 95% CI: 1.08, 1.93, p=0.003). Similarly, the association of PCT and death remained significant after adjusting for age (OR 1.54, 95% CI: 1.17-2.15). In hospitalized COVID-19 patients with underlying cancer, initial PCT levels on admission may beassociated with prognosis, involving higher odds of progression of COVID-19 and/or mortality.

Circular RNAs as emerging regulators in COVID-19 pathogenesis and progression.

Coronavirus disease 2019 (COVID-19), an infectious acute respiratory disease caused by a newly emerging RNA virus, is a still-growing pandemic that has caused more than 6 million deaths globally and has seriously threatened the lives and health of people across the world. Currently, several drugs have been used in the clinical treatment of COVID-19, such as small molecules, neutralizing antibodies, and monoclonal antibodies. In addition, several vaccines have been used to prevent the spread of the pandemic, such as adenovirus vector vaccines, inactivated vaccines, recombinant subunit vaccines, and nucleic acid vaccines. However, the efficacy of vaccines and the onset of adverse reactions vary among individuals. Accumulating evidence has demonstrated that circular RNAs (circRNAs) are crucial regulators of viral infections and antiviral immune responses and are heavily involved in COVID-19 pathologies. During novel coronavirus infection, circRNAs not only directly affect the transcription process and interfere with viral replication but also indirectly regulate biological processes, including virus-host receptor binding and the immune response. Consequently, understanding the expression and function of circRNAs during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will provide novel insights into the development of circRNA-based methods. In this review, we summarize recent progress on the roles and underlying mechanisms of circRNAs that regulate the inflammatory response, viral replication, immune evasion, and cytokines induced by SARS-CoV-2 infection, and thus highlighting the diagnostic and therapeutic challenges in the treatment of COVID-19 and future research directions.

Exploration of blood-derived coding and non-coding RNA diagnostic immunological panels for COVID-19 through a co-expressed-based machine learning procedure.

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) is the causative virus of the pandemic coronavirus disease 2019 (COVID-19). Evaluating the immunological factors and other implicated processes underlying the progression of COVID-19 is essential for the recognition and then the design of efficacious therapies. Therefore, we analyzed RNAseq data obtained from PBMCs of the COVID-19 patients to explore coding and non-coding RNA diagnostic immunological panels. For this purpose, we integrated multiple RNAseq data and analyzed them overall as well as by considering the state of disease including severe and non-severe conditions. Afterward, we utilized a co-expressed-based machine learning procedure comprising weighted-gene co-expression analysis and differential expression gene as filter phase and recursive feature elimination-support vector machine as wrapper phase. This procedure led to the identification of two modules containing 5 and 84 genes which are mostly involved in cell dysregulation and innate immune suppression, respectively. Moreover, the role of vitamin D in regulating some classifiers was highlighted. Further analysis disclosed the role of discriminant miRNAs including miR-197-3p, miR-150-5p, miR-340-5p, miR-122-5p, miR-1307-3p, miR-34a-5p, miR-98-5p and their target genes comprising GAN, VWC2, TNFRSF6B, and CHST3 in the metabolic pathways. These classifiers differentiate the final fate of infection toward severe or non-severe COVID-19. The identified classifier genes and miRNAs may help in the proper design of therapeutic procedures considering their involvement in the immune and metabolic pathways.

Reduced Risk of Progression from Non-Severe to Severe COVID-19 in Hospitalized Dialysis Patients by Full COVID-19 Vaccination.

Coronavirus disease 2019 (COVID-19) vaccination reduces the risk of progression to severe COVID-19 in the general population. To examine that preventive effect in dialysis patients, the association of vaccination status with severe COVID-19 progression was investigated in this retrospective observational study conducted from December 2020 to May 2022 of 100 such patients hospitalized for non-severe COVID-19 at Inoue Hospital (Suita, Japan). Fifty-seven were fully vaccinated, defined as receiving a COVID-19 vaccine second dose at least 14 days prior to the onset of COVID-19, while 43 were not. Among all patients, 13 (13.0%) progressed to severe COVID-19 with a median (interquartile range) time of 6 (2.5-9.5) days, while 87 (87.0%) were discharged after 11 (8-16) days. Kaplan-Meier analysis showed that fully vaccinated patients had a significantly lower rate of progression to severe COVID-19 (p = 0.001, log-rank test). Cox proportional hazard analysis also indicated that full COVID-19 vaccination was significantly associated with reduced instances of progression to severe COVID-19 (hazard ratio 0.104, 95% confidence interval 0.022 to 0.483; p = 0.004) after balancing patient background characteristics using an inverse probability of treatment weight method. These results suggest that full vaccination status contributes to reducing the risk of progression from non-severe to severe COVID-19 in dialysis patients.

Severity predictors of COVID-19 in SARS-CoV-2 variant, delta and omicron period; single center study.

The outcomes of coronavirus disease 2019 (COVID-19) treatment have improved due to vaccination and the establishment of better treatment regimens. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, and the corresponding changes in the characteristics of the disease present new challenges in patient management. This study aimed to analyze predictors of COVID-19 severity caused by the delta and omicron variants of SARS-CoV-2. We retrospectively analyzed the data of patients who were admitted for COVID-19 at Yokohama City University Hospital from August 2021 to March 2022. A total of 141 patients were included in this study. Of these, 91 had moderate COVID-19, whereas 50 had severe COVID-19. There were significant differences in sex, vaccination status, dyspnea, sore throat symptoms, and body mass index (BMI) (p <0.0001, p <0.001, p <0.001, p = 0.02, p< 0.0001, respectively) between the moderate and severe COVID-19 groups. Regarding comorbidities, smoking habit and renal dysfunction were significantly different between the two groups (p = 0.007 and p = 0.01, respectively). Regarding laboratory data, only LDH level on the first day of hospitalization was significantly different between the two groups (p<0.001). Multiple logistic regression analysis revealed that time from the onset of COVID-19 to hospitalization, BMI, smoking habit, and LDH level were significantly different between the two groups (p<0.03, p = 0.039, p = 0.008, p<0.001, respectively). The cut-off value for the time from onset of COVID-19 to hospitalization was four days (sensitivity, 0.73; specificity, 0.70). Time from the onset of COVID-19 to hospitalization is the most important factor in the prevention of the aggravation of COVID-19 caused by the delta and omicron SARS-CoV-2 variants. Appropriate medical management within four days after the onset of COVID-19 is essential for preventing the progression of COVID-19, especially in patients with smoking habits.

Medications for early treatment of COVID-19 in Australia.

Early treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can prevent hospitalisation and death in patients with coronavirus disease 2019 (COVID-19) who have one or more risk factors for serious COVID-19 progression. While early treatment presents a range of logistical challenges, clinicians are nevertheless aided by a growing number of approved medications for early treatment of COVID-19. Medications include drugs that inhibit SARS-CoV-2 viral replication, anti-SARS-CoV-2 monoclonal antibody formulations that provide passive immunisation, and immunomodulatory drugs that suppress the body's inflammatory response. Several drugs with different modes of action are approved in Australia for early treatment of COVID-19, including nirmatrelvir plus ritonavir, molnupiravir, and monoclonal antibody formulations. Although these drugs are recommended, clinicians are encouraged to remain up to date on current indications, contraindications and the clinical efficacy of these drugs against SARS-CoV-2 variants currently circulating in communities. Other treatments, including hydroxychloroquine, ivermectin and dietary supplements, have been popularised but are not recommended for early treatment of COVID-19. As new drugs and new data on use of existing approved drugs become available, clinicians face a growing challenge in determining the optimal treatments from the array of options. As it stands, early treatment of COVID-19 needs to be individualised depending on age, pregnancy status, existing medications, and renal and liver disease status. Future treatments in development might have roles in patients with lower risk profiles and in reducing transmission as we learn to live with SARS-CoV-2.

Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19.

The recent outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China has spread rapidly around the world, leading to a widespread and urgent effort to develop and use comprehensive approaches in the treatment of COVID-19. While oral therapy is accepted as an effective and simple method, since the primary site of infection and disease progression of COVID-19 is mainly through the lungs, inhaled drug delivery directly to the lungs may be the most appropriate route of administration. To prevent or treat primary SARS-CoV-2 infections, it is essential to target the virus port of entry in the respiratory tract and airway epithelium, which requires rapid and high-intensity inhibition or control of viral entry or replication. To achieve success in this field, inhalation therapy is the most attractive treatment approach due to efficacy/safety profiles. In this review article, pulmonary drug delivery as a unique treatment option in lung diseases will be briefly reviewed. Then, possible inhalation therapies for the treatment of symptoms of COVID-19 will be discussed and the results of clinical trials will be presented. By pulmonary delivery of the currently approved drugs for COVID-19, efficacy of the treatment would be improved along with reducing systemic side effects.Graphical abstract

Early Outpatient Treatment With Remdesivir in Patients at High Risk for Severe COVID-19: A Prospective Cohort Study.

BackgroundEarly treatment of coronavirus disease 2019 (COVID-19) with remdesivir in high-risk patients, including those with immunosuppression of different causes, has not been evaluated. The objective of this study was to assess the clinical effectiveness of early remdesivir treatment among patients with mild to moderate COVID-19 at high risk of progression.MethodsThis prospective cohort comparative study was conducted in a tertiary referral center in Mexico City. Patients with mild to moderate COVID-19 at high risk for progression were treated with an ambulatory 3-day course of remdesivir. The primary efficacy composite outcome was hospitalization or death at 28 days after symptom onset. A Cox proportional hazards regression model was used to identify associations with the primary outcome.ResultsFrom December 1, 2021, to April 30, 2022, a total of 196 high-risk patients were diagnosed with COVID-19, of whom 126 were included in this study (43%, 54/126, received remdesivir; 57%, 72/126, did not receive remdesivir). Baseline clinical characteristics were similar between groups; autoimmune diseases (39/126), solid organ transplant (31/126), and malignant neoplasms (24/126) were the most common immunocompromising conditions. Diabetes mellitus was strongly associated with the primary outcome in both groups. Prior severe acute respiratory syndrome coronavirus 2 infection or vaccination was not independently associated with COVID-19 progression. Treatment with remdesivir significantly reduced the odds of hospitalization or death (adjusted hazard ratio, 0.16; 95% CI, 0.06–0.44; P < .01).ConclusionsEarly outpatient treatment with remdesivir significantly reduces hospitalization or death by 84% in high-risk, majority immunosuppressed patients with Omicron variant COVID-19.

A Bioinformatic Approach Based on Systems Biology to Determine the Effects of SARS-CoV-2 Infection in Patients with Hypertrophic Cardiomyopathy.

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide. While COVID-19 generally affects the lungs, it also damages other organs, including those of the cardiovascular system. Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disorder. Studies have shown that HCM patients with COVID-19 have a higher mortality rate; however, the reason for this phenomenon is not yet elucidated. Herein, we conducted transcriptomic analyses to identify shared biomarkers between HCM and COVID-19 to bridge this knowledge gap. Differentially expressed genes (DEGs) were obtained using the Gene Expression Omnibus ribonucleic acid (RNA) sequencing datasets, GSE147507 and GSE89714, to identify shared pathways and potential drug candidates. We discovered 30 DEGs that were common between these two datasets. Using a combination of statistical and biological tools, protein-protein interactions were constructed in response to these findings to support hub genes and modules. We discovered that HCM is linked to COVID-19 progression based on a functional analysis under ontology terms. Based on the DEGs identified from the datasets, a coregulatory network of transcription factors, genes, proteins, and microRNAs was also discovered. Lastly, our research suggests that the potential drugs we identified might be helpful for COVID-19 therapy.

Obesity and Coronavirus Disease 2019.

The coronavirus disease 2019 (COVID-19) pandemic has brought severe challenges to global public health. Many studies have shown that obesity plays a vital role in the occurrence and development of COVID-19. Obesity exacerbates COVID-19, leading to increased intensive care unit hospitalization rate, high demand for invasive mechanical ventilation, and high mortality. The mechanisms of interaction between obesity and COVID-19 involve inflammation, immune response, changes in pulmonary dynamics, disruptions of receptor ligands, and dysfunction of endothelial cells. Therefore, for obese patients with COVID-19, the degree of obesity and related comorbidities should be evaluated. Treatment methods such as administration of anticoagulants and anti-inflammatory drugs like glucocorticoids and airway management should be actively initiated. We should also pay attention to long-term prognosis and vaccine immunity and actively address the physical and psychological problems caused by longterm staying-at-home during the pandemic. The present study summarized the research to investigate the role of obesity in the incidence and progression of COVID-19 and the psychosocial impact and treatment options for obese patients with COVID-19, to guide the understanding and management of the disease.

Dissecting the role of the human microbiome in COVID-19 via metagenome-assembled genomes

Coronavirus disease 2019 (COVID-19), primarily a respiratory disease caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is often accompanied by gastrointestinal symptoms. However, little is known about the relation between the human microbiome and COVID-19, largely due to the fact that most previous studies fail to provide high taxonomic resolution to identify microbes that likely interact with SARS-CoV-2 infection. Here we used whole-metagenome shotgun sequencing data together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from 514 COVID-19 related nasopharyngeal and fecal samples in six independent cohorts. We reconstructed a total of 11,584 medium-and high-quality microbial MAGs and obtained 5403 non-redundant MAGs (nrMAGs) with strain-level resolution. We found that there is a significant reduction of strain richness for many species in the gut microbiome of COVID-19 patients. The gut microbiome signatures can accurately distinguish COVID-19 cases from healthy controls and predict the progression of COVID-19. Moreover, we identified a set of nrMAGs with a putative causal role in the clinical manifestations of COVID-19 and revealed their functional pathways that potentially interact with SARS-CoV-2 infection. Finally, we demonstrated that the main findings of our study can be largely validated in three independent cohorts. The presented results highlight the importance of incorporating the human gut microbiome in our understanding of SARS-CoV-2 infection and disease progression.

Analyzing network diversity of cell-cell interactions in COVID-19 using single-cell transcriptomics.

Cell–cell interactions (CCI) play significant roles in manipulating biological functions of cells. Analyzing the differences in CCI between healthy and diseased conditions of a biological system yields greater insight than analyzing either conditions alone. There has been a recent and rapid growth of methods to infer CCI from single-cell RNA-sequencing (scRNA-seq), revealing complex CCI networks at a previously inaccessible scale. However, the majority of current CCI analyses from scRNA-seq data focus on direct comparisons between individual CCI networks of individual samples from patients, rather than “group-level” comparisons between sample groups of patients comprising different conditions. To illustrate new biological features among different disease statuses, we investigated the diversity of key network features on groups of CCI networks, as defined by different disease statuses. We considered three levels of network features: node level, as defined by cell type; node-to-node level; and network level. By applying these analysis to a large-scale single-cell RNA-sequencing dataset of coronavirus disease 2019 (COVID-19), we observe biologically meaningful patterns aligned with the progression and subsequent convalescence of COVID-19.

Clinical Impact of Monoclonal Antibodies in the Treatment of High-Risk Patients with SARS-CoV-2 Breakthrough Infections: The ORCHESTRA Prospective Cohort Study.

The clinical impact of anti-spike monoclonal antibodies (mAb) in Coronavirus Disease 2019 (COVID-19) breakthrough infections is unclear. We present the results of an observational prospective cohort study assessing and comparing COVID-19 progression in high-risk outpatients receiving mAb according to primary or breakthrough infection. Clinical, serological and virological predictors associated with 28-day COVID-19-related hospitalization were identified using multivariate logistic regression and summarized with odds ratio (aOR) and 95% confidence interval (CI). A total of 847 COVID-19 outpatients were included: 414 with primary and 433 with breakthrough infection. Hospitalization was observed in 42/414 (10.1%) patients with primary and 8/433 (1.8%) patients with breakthrough infection (p < 0.001). aOR for hospitalization was significantly lower for breakthrough infection (aOR 0.12, 95%CI: 0.05–0.27, p < 0.001) and higher for immunocompromised status (aOR:2.35, 95%CI:1.08–5.08, p = 0.003), advanced age (aOR:1.06, 95%CI: 1.03–1.08, p < 0.001), and male gender (aOR:1.97, 95%CI: 1.04–3.73, p = 0.037). Among the breakthrough infection group, the median SARS-CoV-2 anti-spike IgGs was lower (p < 0.001) in immunocompromised and elderly patients >75 years compared with that in the immunocompetent patients. Our findings suggest that, among mAb patients, those with breakthrough infection have significantly lower hospitalization risk compared with patients with primary infection. Prognostic algorithms combining clinical and immune-virological characteristics are needed to ensure appropriate and up-to-date clinical protocols targeting high-risk categories.

The Associations of Iron Related Biomarkers with Risk, Clinical Severity and Mortality in SARS-CoV-2 Patients: A Meta-Analysis.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly around the world and has led to millions of infections and deaths. Growing evidence indicates that iron metabolism is associated with COVID-19 progression, and iron-related biomarkers have great potential for detecting these diseases. However, the results of previous studies are conflicting, and there is not consistent numerical magnitude relationship between those biomarkers and COVID-19. Thereby, we aimed to integrate the results of current studies and to further explore their relationships through a meta-analysis. We searched peer-reviewed literature in PubMed, Scopus and Web of Science up to 31 May 2022. A random effects model was used for pooling standard mean difference (SMD) and the calculation of the corresponding 95% confidence interval (CI). I2 was used to evaluate heterogeneity among studies. A total of 72 eligible articles were included in the meta-analysis. It was found that the ferritin levels of patients increased with the severity of the disease, whereas their serum iron levels and hemoglobin levels showed opposite trends. In addition, non-survivors had higher ferritin levels (SMD (95%CI): 1.121 (0.854, 1.388); Z = 8.22 p for Z < 0.001; I2 = 95.7%, p for I2 < 0.001), lower serum iron levels (SMD (95%CI): −0.483 (−0.597, −0.368), Z = 8.27, p for Z < 0.001; I2 = 0.9%, p for I2 =0.423) and significantly lower TIBC levels (SMD (95%CI): −0.612 (−0.900, −0.324), Z = 4.16, p for Z < 0.001; I2 = 71%, p for I2 = 0.016) than survivors. This meta-analysis demonstrates that ferritin, serum iron, hemoglobin and total iron banding capacity (TIBC) levels are strongly associated with the risk, severity and mortality of COVID-19, providing strong evidence for their potential in predicting disease occurrence and progression.

A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019.

BackgroundWe evaluated clinical effectiveness of regdanvimab (CT-P59), a severe acute respiratory syndrome coronavirus 2 neutralizing monoclonal antibody, in reducing disease progression and clinical recovery time in patients with mild-to-moderate coronavirus disease 2019 (COVID-19), primarily Alpha variant.MethodsThis was phase 3 of a phase 2/3 parallel-group, double-blind, randomized clinical trial. Outpatients with mild-to-moderate COVID-19 were randomized to single-dose regdanvimab 40 mg/kg (n = 656) or placebo (n = 659), alongside standard of care. The primary endpoint was COVID-19 disease progression up to day 28 among “high-risk” patients. Key secondary endpoints were disease progression (all randomized patients) and time to recovery (high-risk and all randomized patients).ResultsOf 1315 randomized patients, 880 were high risk; the majority were infected with Alpha variant. The proportion with disease progression was lower (14/446, 3.1% [95% confidence interval {CI}, 1.9%–5.2%] vs 48/434, 11.1% [95% CI, 8.4%–14.4%]; P < .001) and time to recovery was shorter (median, 9.27 days [95% CI, 8.27–11.05 days] vs not reached [95% CI, 12.35–not calculable]; P < .001) with regdanvimab than placebo. Consistent improvements were seen in all randomized and non-high-risk patients who received regdanvimab. Viral load reductions were more rapid with regdanvimab. Infusion-related reactions occurred in 11 patients (4/652 [0.6%] regdanvimab, 7/650 [1.1%] placebo). Treatment-emergent serious adverse events were reported in 5 of (4/652 [0.6%] regdanvimab and 1/650 [0.2%] placebo).ConclusionsRegdanvimab was an effective treatment for patients with mild-to-moderate COVID-19, significantly reducing disease progression and clinical recovery time without notable safety concerns prior to the emergence of the Omicron variant.Clinical Trials RegistrationNCT04602000; 2020-003369-20 (EudraCT).

Promising use of immune cell-derived exosomes in the treatment of SARS-CoV-2 infections.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is persistently threatening the lives of thousands of individuals globally. It triggers pulmonary oedema, driving to dyspnoea and lung failure. Viral infectivity of coronavirus disease 2019 (COVID‐19) is a genuine challenge due to the mutagenic genome and mysterious immune‐pathophysiology. Early reports highlighted that extracellular vesicles (exosomes, Exos) work to enhance COVID‐19 progression by mediating viral transmission, replication and mutations. Furthermore, recent studies revealed that Exos derived from immune cells play an essential role in the promotion of immune cell exhaustion by transferring regulatory lncRNAs and miRNAs from exhausted cells to the active cells. Fortunately, there are great chances to modulate the immune functions of Exos towards a sustained repression of COVID‐19. Engineered Exos hold promising immunotherapeutic opportunities for remodelling cytotoxic T cells’ function. Immune cell‐derived Exos may trigger a stable epigenetic repression of viral infectivity, restore functional cytokine‐producing T cells and rebalance immune response in severe infections by inducing functional T regulatory cells (Tregs). This review introduces a view on the current outcomes of immunopathology, and immunotherapeutic applications of immune cell‐derived Exos in COVID‐19, besides new perspectives to develop novel patterns of engineered Exos triggering novel anti‐SARS‐CoV‐2 immune responses.

Antibody therapy reverses biological signatures of COVID-19 progression

SummaryUnderstanding who is at risk of progression to severe coronavirus disease 2019 (COVID-19) is key to clinical decision making and effective treatment. We study correlates of disease severity in the COMET-ICE clinical trial that randomized 1:1 to placebo or to sotrovimab, a monoclonal antibody for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (ClinicalTrials.gov04545060). Laboratory parameters identify study participants at greater risk of severe disease, including a high neutrophil-to-lymphocyte ratio (NLR), a negative SARS-CoV-2 serologic test, and whole-blood transcriptome profiles. Sotrovimab treatment is associated with normalization of NLR and the transcriptomic profile and with a decrease of viral RNA in nasopharyngeal samples. Transcriptomics provides the most sensitive detection of participants who would go on to be hospitalized or die. To facilitate timely measurement, we identify a 10-gene signature with similar predictive accuracy. We identify markers of risk for disease progression and demonstrate that normalization of these parameters occurs with antibody treatment of established infection.