Disease Severity In COVID-19 Patients Research Articles

Enhancement of NETosis by ACE2-cross-reactive anti-SARS-CoV-2 RBD antibodies in patients with COVID-19.

High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown. In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied. An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection. Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients.

Serum ACE2 and S19P gene polymorphism in Egyptian patients with COVID-19 infection: correlation with disease severity

The expression of ACE2 is linked to disease severity in COVID-19 patients. The ACE2 receptor gene polymorphisms are considered determinants for SARS-CoV-2 infection and its outcome. In our study, serum ACE2 and its genetic variant S19P rs73635825 polymorphism were investigated in 114 SARS-CoV-2 patients. The results were compared with 120 control subjects. ELISA technique and allele discrimination assay were used for measuring serum ACE2 and genotype analysis of ACE2 rs73635825. Our results revealed that serum ACE2 was significantly lower in SARS-CoV-2 patients (p = 0.0001), particularly in cases with hypertension or diabetes mellitus. There was a significant difference in the genotype distributions of ACE2 rs73635825 A > G between COVID-19 patients and controls (p-value = 0.001). A higher frequency of the heterozygous AG genotype (65.8%) was reported in COVID-19 patients. The G allele was significantly more common in COVID-19 patients (p < 0.0001). The AG and GG genotypes were associated with COVID-19 severity as they were correlated with abnormal laboratory findings, GGO, CXR, and total severity scores with p < 0.05. Our results revealed that the ACE2 S19P gene variant is correlated with the incidence of infection and its severity, suggesting the usefulness of this work in identifying the susceptible population groups for better disease control.

Association of Altered Plasma Lipidome with Disease Severity in COVID-19 Patients.

The severity of COVID-19 is linked to an imbalanced immune response. The dysregulated metabolism of small molecules and bioactive lipids has also been associated with disease severity. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyze over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). This is the third publication in a series, and it reports the results of comprehensive lipidome profiling using targeted LC-MS/MS. We identified 1076 lipid features across 25 subclasses, including glycerophospholipids, sterols, glycerolipids, and sphingolipids, among which 531 lipid features were dramatically changed in the plasma of intensive care unit (ICU) patients compared to patients in the ward. Patients in the ICU showed 1.3-57-fold increases in ceramides, (lyso-)glycerophospholipids, diglycerides, triglycerides, and plasmagen phosphoethanolamines, and 1.3-2-fold lower levels of a cyclic lysophosphatidic acid, sphingosine-1-phosphates, sphingomyelins, arachidonic acid-containing phospholipids, lactosylceramide, and cholesterol esters compared to patients in the ward. Specifically, phosphatidylinositols (PIs) showed strong fatty acid saturation-dependent behavior, with saturated fatty acid (SFA)- and monosaturated fatty acid (MUFA)-derived PI decreasing and polystaturated (PUFA)-derived PI increasing. We also found ~4000 significant Spearman correlations between lipids and multiple clinical markers of immune response with |R| ≥ 0.35 and FDR corrected Q < 0.05. Except for lysophosphatidic acid, lysophospholipids were positively associated with the CD4 fraction of T cells, and the cytokines IL-8 and IL-18. In contrast, sphingosine-1-phosphates were negatively correlated with innate immune markers such as CRP and IL-6. Further indications of metabolic changes in moderate COVID-19 disease were demonstrated in recovering ward patients compared to those at the start of hospitalization, where 99 lipid species were altered (6 increased by 30-62%; 93 decreased by 1.3-2.8-fold). Overall, these findings support and expand on early reports that dysregulated lipid metabolism is involved in COVID-19.

Comparison of DASH diet score and total antioxidant capacity of diet on serum levels of TMPRSS-2, inflammatory biomarkers, and disease severity in COVID-19 patients: A case-control study.

There is evidence that healthy diets improve the immune system and lessen the severity of infectious diseases such as COVID-19. We have investigated whether the dietary total antioxidant capacity (TAC) and dietary approach to stop hypertension (DASH) score could be associated with the occurrence and clinical outcomes of COVID-19. This case-control study included 120 adults who were admitted to the hospital. Dietary TAC and DASH diet scores were determined by a 138-item semi-quantitative food frequency questionnaire (FFQ). Inflammation-related markers including C-reactive protein (CRP) and transmembrane protease serine 2 (TMPRSS-2) differential were measured. Also, using chest radiology criteria, the severity of the disease was evaluated. The mean CRP values in the lowest and highest tertiles of either dietary TAC or DASH diet scores were 9.44 ± 11.26 and 3.52 ± 4.83 mg/dL (p = .003) or 9.04 ± 11.23 and 4.40 ± 6.23 mg/dL (p = .013), respectively. Individuals with higher dietary TAC were at a lower risk of COVID-19 (OR: 0.06, p < ·0001). Individuals with greater DASH diet scores were also at decreased odds of COVID-19 (OR: 0.12, p < ·0001). No significant associations were found between dietary TAC and DASH diet scores with severity of COVID-19 disease, CRP, or TMPRSS-2 (p > 0.05). The study found that adherence to a diet with higher dietary TAC and DASH diet scores may be protective against COVID-19 and improve outcomes of the disease. More research is needed to corroborate these findings.

Relationship between body mass index and disease severity in COVID-19 patients admitted from April to September 2020 at Imam Khomeini Hospital Complex, Tehran, Iran

Relationship between body mass index and disease severity in COVID-19 patients admitted from April to September 2020 at Imam Khomeini Hospital Complex, Tehran, Iran

Relationship between Serum Cobalamin Levels and Disease Severity in COVID-19 Patients

Background and Objective: Vitamins play a crucial role in cellular growth, function, and evolution. Additionally, they contribute significantly to pathogen defense through cellular responses and immune enhancement. Cobalamin has been identified to play a role in suppressing virus replication, generating anti-inflammatory responses, and boosting immunity in infected patients with COVID-19. Therefore, we hypothesized that the low cobalamin levels are associated with a predisposition to severe COVID-19 infection. The present study aimed to investigate the relationship between cobalamin levels and disease severity and prognosis in COVID-19 patients. Materials and Methods: This cross-sectional study included 117 COVID-19 patients hospitalized at Sina Hospital and categorized them into three groups based on their disease severity: mild to moderate, severe, and critical. Demographic information and clinical findings of the patients were recorded. Serum cobalamin levels were assessed using biochemical methods. Logistic regression and Receiver Operating Characteristic (ROC) analyses were employed for mortality prediction based on serum cobalamin levels. Results: The results revealed that patients with low cobalamin levels are more susceptible to severe COVID-19 infections. Furthermore, with each additional day of hospitalization, the mortality rate due to COVID-19 increased by 24%. The high area under the ROC curve (0.837) indicated that mortality in COVID-19 patients can be effectively predicted based on cobalamin levels. Conclusion: It appears that cobalamin supplementation may have positive effects on COVID-19 patients’ outcomes. Additionally, serum cobalamin levels serve as a valuable indicator for predicting the mortality rate in COVID-19 patients. However, comprehensive, longer-term studies with a larger number of patients are required.

Serum Insulin-like Growth Factor-Binding Protein-2 as a Prognostic Factor for COVID-19 Severity.

Insulin-like growth factor-binding protein (IGFBP)-2 is a regulator of anabolic pathways, which become inactivated in severe illness. Here, we measured the serum IGFBP-2 levels of COVID-19 patients with moderate and severe disease as well as healthy controls to identify the associations of serum IGFBP-2 levels with disease severity. Patients with severe COVID-19 had higher serum IGFBP-2 levels than those with moderate disease and healthy controls, who had similar levels. Non-survivors of COVID-19 tended to have elevated serum IGFBP-2 levels compared to survivors. Increased serum IGFBP-2 levels were observed in patients requiring dialysis and vasopressor therapy. Serum IGFBP-2 was positively correlated with procalcitonin in both patient groups. Bacterial co-infection in severe COVID-19 patients did not influence serum IGFBP-2 levels. Patients with liver cirrhosis and obesity, showing increased and decreased serum IGFBP-2 levels, respectively, were excluded from the study. The present analysis showed that higher serum IGFBP-2 levels are associated with increased disease severity in COVID-19 patients. The similarity in serum IGFBP-2 levels between patients with moderate COVID-19 and healthy controls suggests that elevated IGFBP-2 is associated with critical illness rather than SARS-CoV-2 infection itself.

Changes in chemokine and growth factor levels may be useful biomarkers for monitoring disease severity in COVID-19 patients; a pilot study.

The aim of the present study was to assess differences in the serum levels of chemokines and growth factors (GFs) between COVID-19 patients and healthy controls. The diagnostic utility of the analyzed proteins for monitoring the severity of the SARS-CoV- 2 infection based on the patients' MEWS scores was also assessed. The serum levels of chemokines and growth factors were analyzed in hospitalized COVID-19 patients (50 women, 50 men) with the use of the Bio-Plex Pro™ Human Cytokine Screening Panel (Biorad) and the Bio-Plex Multiplex system. The study demonstrated that serum levels of MIP-1α, RANTES, Eotaxin, CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, SCGF-β, G-CSF, M-CSF, SCF, MIF, LIF, and TRAIL were significant higher in COVID-19 patients than in the control group. The concentrations of CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, PDGF- BB, GM-CSF, SCF, LIF, and TRAIL were higher in asymptomatic/mildly symptomatic COVID-19 patients (stage 1) and COVID-19 patients with pneumonia without respiratory failure (stage 2). The receiver operating characteristic (ROC) analysis revealed that IP-10, MIF, MIG, and basic-FGF differentiated patients with COVID-19 from healthy controls with the highest sensitivity and specificity, whereas GM-CSF, basic-FGF, and MIG differentiated asymptomatic/mildly symptomatic COVID-19 patients (stage 1) from COVID-19 patients with pneumonia without respiratory failure (stage 2) with the highest sensitivity and specificity. MIG, basic-FGF, and GM-CSF can be useful biomarkers for monitoring disease severity in patients with COVID-19.

The Role of Platelet Parameters in Predicting the Disease Severity of COVID-19 Patients: A Hospital-Based Study.

Background and objective Globally, a large number of people have been impacted by the extremely contagious coronavirus disease 2019 (COVID-19) infection, and several pieces of literature were published on hematological parameter changes in this infection, particularly focusing on leucocytes. In this study, we have analyzed the platelet parameters and platelet-leucocyte ratios in COVID-19 patients and correlated them with the disease severity. Methods The COVID-19 patients who were hospitalized during the second peak of the pandemic were assessed. The platelet count and indices, platelet to lymphocyte ratio (PLR), neutrophil to platelet ratio (NPR), and clinical severity of each patient were analyzed. The significance of parameters and clinical severity was evaluated using analysis of variance (ANOVA) and the Kruskal Wallis test. A bivariate analysis was performed to assess the strength of the association. Receiver operating characteristic (ROC) curves were plotted to detect the predictive value of parameters for disease severity. Results The data of 132 COVID-19 patientshas been evaluated. The average mean age was 45.60 ± 15.76 years with slight female predominance. Thrombocytopenia was found in 33% of cases with the majority of them being mild. Age, platelet distribution width (PDW), and PLR and NPR parameters were significantly (p-value <0.05) associated with disease severity. ROC curves showed age, PDW, PLR, NPR, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) had significant prediction values for clinical severity. Conclusions Platelet parameters may not accurately reflect the severity of the disease, but when combined with leucocyte parameters and their ratios (PLR and NPR), they offer important information about disease severity.

D-Dimer a biomarker for disease severity in COVID-19 patients

D-Dimer a biomarker for disease severity in COVID-19 patients

Correlation of lymphocyte subsets and inflammatory biomarkers with disease severity in COVID-19 patients.

To determine the correlation of lymphocyte subsets and soluble serum inflammatory biomarkers with disease severity in coronavirus disease-2019 infection. The retrospective study was conducted at the Department of Immunology, Sindh Institute of Urology and Transplantation (SIUI), Karachi, Pakistan from September 1 to November 30, 2021, and comprised data of patients admitted from June to July 2021 who tested positive for coronavirus disease-2019 on the basis of reverse transcription-polymerase chain reaction of nasopharyngeal swab specimens. The patients were categorised into severe group A and non-severe group B. Initial investigations included complete blood count, neutrophil-to-lymphocytes ratio, C-reactive protein, D-Dimers and serum ferritin levels. Lymphocyte subsets included cluster of differentiation-3+, cluster of differentiation-4+/ cluster of differentiation-3+, cluster of differentiation-8+ T lymphocytes, cluster of differentiation-19+B lymphocytes, cluster of differentiation-16+ cluster of differentiation-56+ Natural Killer cells and serum cytokine levels of interleukin-2, interleukin- 4, interleukin-6, interleukin-10, tumour necrosis factor-alpha and interferon gamma. They were correlated with disease severity. Data was analysed using SPSS 20. Of the 54 patients, 33(61.1%) were males and 21(38.9%) were females. There were 29(53.70%) patients in group A with median age 52 years (interquartile range: 43.5-65 years), and 25(46.29%) in group B with median age 50 years (interquartile range: 36.5-59 years) (p=0.241). Disease was significantly more severe in male patients compared to female (p=0.002). In group A, cluster of differentiation-3+ T cells were reduced in 21(72.4%) patients, cluster of differentiation-8+ T cells in 16(55.2%), cluster of differentiation-4+ T cells in 23(79.3%) and cluster of differentiation-19+ B cells in 8(27.6%). In group B, cluster of differentiation-3+ T cells were reduced in 10(40%) subjects, cluster of differentiation-8+ T cells in 7(28%), cluster of differentiation-4+ T cells in 12(48%) and cluster of differentiation-19+ B cells in 4(16%) patients. Serum cytokine levels were not significantly different between the groups (p>0.05). In group A, 7(24.13%) patients died, and in such cases, the neutrophil-to-lymphocytes ratio was significantly higher (p=0.037). Pro-inflammatory markers and cytokine levels increased, while lymphocyte subsets decreased with increasing severity of the disease.

An umbrella review on treatments and therapeutic options for COVID-19

Introduction. As the COVID-19 pandemic continues to pose a significant challenge to global health, effective therapeutic options for preventing and treating the disease have become increasingly important. We aimed to provide an update on current treatments and therapeutic options for COVID-19 patients.Materials and methods. The purpose of this umbrella review is to explore the current treatments and therapeutic options for COVID-19 patients. Keywords and their combinations were searched across online databases in Embase, PubMed/MEDLINE, Web of Science, and Scopus spanning from July 1, 2020, through March 3, 2023. Publications were selected for data extraction in two steps based on the study inclusion/exclusion criteria. The study adheres to the PRISMA checklist as well as NIH bias risk and quality assessment tool.Results. In this review, 28 relevant articles were selected for the final qualitative synthesis. The majority of included studies had reported on the efficacy of Lopinavir/Ritonavir (n = 4), Ivermectin (n = 3), Baricitinib (n = 2), Tocilizumab (n = 2), Remdesivir (n = 2), ACEI/ARB (n = 2), Vitamin D (n = 2), Molnupiravir (n = 2), Traditional Chinese medicine (TCM) (n = 2), Convalescent plasma transfusion (CPT) (n = 2) and hydroxychloroquine (n = 2) in treating COVID-19. It appeared that Baricitinib, Remdesivir, ACEI/ARB, TCM, and CPT may have beneficial effects on reducing mortality, hospitalization duration, and disease severity in COVID-19 patients. Other interventions, such as Lopinavir/Ritonavir, Ivermectin, Vitamin D, and Hydroxychloroquine did not show clear benefits or had inconclusive results.Conclusion. This umbrella review provides a comprehensive overview of the current evidence on the effectiveness and safety of various pharmacological and non-pharmacological interventions for COVID-19. These results provide an updated overview of the current landscape for COVID-19 treatments, highlighting potential avenues for further research and clinical practice. It is crucial to continue monitoring emerging evidence and conducting rigorous studies to guide the development and optimization of therapeutic strategies against COVID-19.

High sera levels of SARS-CoV-2 N antigen are associated with death in hospitalized COVID-19 patients.

The presence of free severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid-antigen in sera (N-antigenemia) has been shown in COVID-19 patients. However, the link between the quantitative levels of N-antigenemia and COVID-19 disease severity is not entirely understood. To assess the dynamics and clinical association of N-antigen sera levels with disease severity in COVID-19 patients, we analyzed data from patients included in the French COVID cohort, with at least one sera sample between January and September 2020. We assessed N-antigenemia levels and anti-N IgG titers, and patient outcomes was classified in two groups, survival or death. In samples collected within 8 days since symptom onset, we observed that deceased patients had a higher positivity rate (93% vs. 81%; p < 0.001) and higher median levels of predicted N-antigenemia (2500 vs. 1200 pg/mL; p < 0.001) than surviving patients. Predicted time to N-antigen clearance in sera was prolonged in deceased patients compared to survivors (23.3 vs 19.3 days; p < 0.0001). In a subset of patients with both sera and nasopharyngeal (NP) swabs, predicted time to N-antigen clearance in sera was prolonged in deceased patients (p < 0.001), whereas NP viral load clearance did not differ between the groups (p = 0.07). Our results demonstrate a strong relationship between N-antigenemia levels and COVID-19 severity on a prospective cohort.

Evaluation of serum procalcitonin level as a biomarker for disease severity in Covid-19 patients: The experience of Mohammed VI University Hospital in Oujda.

The pandemic of coronavirus disease (Covid-19) has infected millions of individuals around the globe. The current study was aimed to evaluate the serum procalcitonin (PCT) level as a biomarker for bacterial co-infection and disease severity in Covid-19 patients. A total of 319 Covid-19 positive patients were examined in this study. Among the total individuals, 169 (53%) were male while 150 (47%) were female. Among the examined samples, 142 (44.5%) were hospitalized in Covid services, and 177(55.5%) were admitted in the intensive care unit (ICU). The mean PCT level for Covid-19 services patients was 0.58 ng/mL and for ICU patients was 7.84 ng/mL. The statistical analysis revealed that there was a significant association of PCT value and age (P&lt;0,0001) while there was no association of gender and PCT value in COVID-19 patients (P=0.2745). Most Covid-19 patients have low PCT levels but elevated markers of inflammation such as C-reactive protein (CRP) on admission. It can be concluded that the serial PCT measurement could determine the prognosis of disease and presence of bacterial co-infection in Covid-19 patients. The main objective of our study is to determine the role of serum procalcitonin in the diagnosis and clinical management of patients with COVID-19 from Oriental Region of Morocco, also we evaluate the correlation between Procalcitonin and disease severity in COVID-19. We report the experience of the Moroccan Mohammed VI University Hospital of Oujda.

Distinct laboratory parameters as strict prognostic values in the setting of COVID-19 severity

Introduction: To the best of our knowledge, a new emerging viral infection induced by SARS-CoV-2 was named COVID-19 with high morbidity and mortality on a global scale. To date, COVID-19 is implied as a respiratory disease with varied manifestations from asymptomatic to long-standing complications. In this regard, discerning a potential prognostic value of critical outcomes in the early stages would be more appreciable to stratify the risk of disease severity and 28-day mortality. In this clinical study, we aimed to evaluate distinct laboratory biomarkers, including neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP), and lactate dehydrogenase (LDH), as reliable indicators to predict disease severity in COVID-19 patients admitted in a medical referral center. Methods: Following the COVID-19 diagnosis, all consecutive patients (n=685) with confirmed SARS-CoV-2 infection were included since September 2020 for one year. Data were collected using electronic medical records. Results: Based on obtained results, NLR and serum level of LDH showed a positive correlation with length of hospital stay. Moreover, the mortality rate and MV required in patients with either positive CRP or the high levels of LDH were remarkably greater than that of the non-severe group (P=0.01). Finally, we could not find significant differences between female and male patients regarding the evaluated parameters. Conclusion: Our findings highlighted those high values of NLR, CRP, and LDH can be considered valuable clinical prognostic aids for risk stratification, identification of disease severity, and triage of patients at the time of admission.

Genetically determined thymic function affects strength and duration of immune response in COVID patients with pneumonia.

Thymic activation improves the outcome of COVID-19 patients with severe pneumonia. The rs2204985 genetic polymorphism within the TCRA-TCRD locus, which affects thymic output in healthy individuals, was found here to modify SARS-CoV-2-specific immunity and disease severity in COVID-19 patients with severe pneumonia. Forty patients with severe COVID-19 pneumonia were investigated. The GG genotype at the rs2204985 locus was associated, independently of age and sex, with stronger and long-lasting anti-SARS-CoV-2 helper and cytotoxic T cell responses 6 months after recovery. The GG genotype was also associated with less severe lung involvement, higher thymic production, and higher counts of blood naïve T lymphocytes, including recent thymic emigrants, and a larger population of activated stem cell memory CD4+ T cells. Overall, GG patients developed a more robust and sustained immunity to SARS-CoV-2. Polymorphism at rs2204985 locus should be considered as an additional predictive marker of anti-SARS-CoV-2 immune response.

Rare peptide anchors of HLA class I alleles contribute to the COVID-19 disease severity and T cell memory

Understanding how human leukocyte antigen (HLA) polymorphism affects both the susceptibility and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will help to identify individuals at higher risk to better manage and prioritize vaccination at the clinical level and explain the differences in epidemic trends in different regions at the epidemiological level. This study compared the frequencies of HLA class I alleles (HLA-A, B) in 214 coronavirus disease 2019 (COVID-19) patients with different disease severity and 35 healthy controls and analyzed the correlations between specific HLA alleles and disease severity and T cell memory. The results showed no significant difference in HLA allele frequencies between COVID-19 patients and healthy controls (P > 0.05). The allele HLA-B*13:02 was significantly correlated with the disease severity of COVID-19 patients (P = 0.006). After adjustment for age and disease severity, the T cell responses of COVID-19 convalescents with the allele HLA-B*40:01 may be lower at six months (P = 0.044) and 12 months (P = 0.069). Moreover, these results may be due to their rare peptide anchors by analyzing the binding peptide motifs of these HLA alleles. The study may be valuable for investigating the potential association of specific HLA alleles with SARS-CoV-2 infection.

Clinical Characteristics of Hospitalized Patients With COVID-19: A Retrospective Cohort Study in Pakistan.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of severe upper respiratory tract infections known as COVID-19. This single-center study aimed to investigate the demographics, comorbidities, symptoms, and disease severity of COVID-19 patients in Pakistan. A retrospective descriptive study was conducted at the Pakistan Kidney and Liver Institute and Research Center from April 2020 to August 2020. A total of 430 PCR-positive COVID-19 patients were categorized into symptomatic and asymptomatic groups. The symptomatic group was further classified into severe and non-severe subgroups. Patients' demographics, comorbid conditions, presenting symptoms, laboratory parameters, and clinical outcomes were assessed in these two subgroups. Statistical tests were applied to determine significant differences. A total of 430 patients with COVID-19 presented in our center, of whom 334 (78%) were symptomatic and included in the study. Severe disease was observed in 83 (24.8%) symptomatic patients, with a male predominance (75.9%) and higher mean age (61.7 ± 13.2). Travel to high-risk destinations (p < 0.002) and close contact with COVID-19 patients (p < 0.001) were significant risk factors. Major comorbid conditions included diabetes mellitus (30.5%) and hypertension (39.8%). Frequent symptoms included fever (71.8%), cough (68.8%), dyspnea (53.8%), and myalgias (35.9%). Higher C-reactive protein (median = 12.76 vs. 1.45, p = 0.001), ferritin (median = 996.70 vs. 628, p = 0.004), and D-dimers (median = 1121 vs. 439.50, p = 0.009) were noted in severe vs non-severe disease. Lymphopenia was more prevalent in severe vs. non-severe disease (83.1% vs. 14.3% p-value = 0.033). More deaths (28.9%) and ICU admissions (53%) with a prolonged hospital stay (median = 25 days, IQR = 16.0-31.0) were noted in the severe group. This retrospective study provides insights into the clinical characteristics and outcomes of COVID-19 patients. Age, male gender, comorbidities, and specific symptoms were associated with disease severity. Inflammatory markers, including D-dimers, ferritin, and CRP, were elevated in severe cases. These findings contribute to a better understanding of COVID-19 and may aid in clinical management and decision-making for patients affected by the disease.

Plasma metabolomics profiling identifies new predictive biomarkers for disease severity in COVID-19 patients.

Recently, numerous studies have reported on different predictive models of disease severity in COVID-19 patients. Herein, we propose a highly predictive model of disease severity by integrating routine laboratory findings and plasma metabolites including cytosine as a potential biomarker of COVID-19 disease severity. One model was developed and internally validated on the basis of ROC-AUC values. The predictive accuracy of the model was 0.996 (95% CI: 0.989 to 1.000) with an optimal cut-off risk score of 3 from among 6 biomarkers including five lab findings (D-dimer, ferritin, neutrophil counts, Hp, and sTfR) and one metabolite (cytosine). The model is of high predictive power, needs a small number of variables that can be acquired at minimal cost and effort, and can be applied independent of non-empirical clinical data. The metabolomics profiling data and the modeling work stemming from it, as presented here, could further explain the cause of COVID-19 disease prognosis and patient management.

Impact of the SARS-CoV-2 nucleocapsid 203K/204R mutations on the inflammatory immune response in COVID-19 severity

BackgroundThe excessive inflammatory responses provoked by SARS-CoV-2 infection are critical factors affecting the severity and mortality of COVID-19. Previous work found that two adjacent co-occurring mutations R203K and G204R (KR) on the nucleocapsid (N) protein correlate with increased disease severity in COVID-19 patients. However, links with the host immune response remain unclear.MethodsHere, we grouped nasopharyngeal swab samples of COVID-19 patients into two cohorts based on the presence and absence of SARS-CoV-2 nucleocapsid KR mutations. We performed nasopharyngeal transcriptome analysis of age, gender, and ethnicity-matched COVID-19 patients infected with either SARS-CoV-2 with KR mutations in the N protein (KR patients n = 39) or with the wild-type N protein (RG patients n = 39) and compared to healthy controls (n = 34). The impact of KR mutation on immune response was further characterized experimentally by transcriptomic and proteomic profiling of virus-like-particle (VLP) incubated cells.ResultsWe observed markedly elevated expression of proinflammatory cytokines, chemokines, and interferon-stimulated (ISGs) genes in the KR patients compared to RG patients. Using nasopharyngeal transcriptome data, we found significantly higher levels of neutrophils and neutrophil-to-lymphocyte (NLR) ratio in KR patients than in the RG patients. Furthermore, transcriptomic and proteomic profiling of VLP incubated cells confirmed a similar hyper-inflammatory response mediated by the KR variant.ConclusionsOur data demonstrate an unforeseen connection between nucleocapsid KR mutations and augmented inflammatory immune response in severe COVID-19 patients. These findings provide insights into how mutations in SARS-CoV-2 modulate host immune output and pathogenesis and may contribute to more efficient therapeutics and vaccine development.