Disease Severity In COVID-19 Patients Research Articles

Levels of soluble complement regulators predict severity of COVID-19 symptoms.

The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p<0.0001; FHR5: 2.4-fold, p<0.0001). Furthermore, for a subset of 77 SARS-CoV-2 +ve patients we also analysed time course samples taken approximately 28 days post-diagnosis. Here, we see complement regulator levels drop in all individuals with asymptomatic or mild disease, but regulators remain high in those with more severe outcomes, with elevations in FHR2 over baseline levels in this group. These data support the hypothesis that elevation of circulating levels of the FHR family of proteins could predict disease severity in COVID-19 patients, and that the duration of elevation (or lack of immune activation resolution) may be partly responsible for driving poor outcomes in COVID-19.

Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients.

Ectonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients’ cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease.

Procalcitonin as a predictive marker in COVID-19: A systematic review and meta-analysis.

BackgroundCoronavirus disease 2019 has emerged as a global pandemic causing millions of critical cases and deaths. Early identification of at-risk patients is crucial for planning triage and treatment strategies.Methods and findingsWe performed this systematic review and meta-analysis to determine the pooled prognostic significance of procalcitonin in predicting mortality and severity in patients with COVID-19 using a robust methodology and clear clinical implications.DesignWe used Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Handbook for Systematic Reviews of Interventions guidelines. We included thirty-two prospective and retrospective cohort studies involving 13,154 patients.ResultsThe diagnostic odds ratio of procalcitonin for predicting mortality were estimated to be 11 (95% CI: 7 to 17) with sensitivity, specificity, and summary area under the curveof 0.83 (95% CI: 0.70 to 0.91), 0.69 (95% CI: 0.58 to 0.79), and 0.83 (95% CI: 0.79 to 0.86) respectively. While for identifying severe cases of COVID-19, the odds ratio was 8.0 (95% CI 5.0 to 12.0) with sensitivity, specificity, and summary area under the curve of 0.73 (95% CI 0.67 to 0.78), 0.74 (0.66 to 0.81), and 0.78 (95% CI 0.74 to 0.82) respectively.ConclusionProcalcitonin has good discriminatory power for predicting mortality and disease severity in COVID-19 patients. Therefore, procalcitonin measurement may help identify potentially severe cases and thus decrease mortality by offering early aggressive treatment.

SARS-CoV-2 viral load in the upper respiratory tract and disease severity in COVID-19 patients

SARS-CoV-2 viral load in the upper respiratory tract and disease severity in COVID-19 patients

Role of prognostic factors in understanding disease severity in COVID-19 patients: Pakistan ordinance factories Hospital experience

BACKGROUND & OBJECTIVE: Coronavirus disease (COVID-19) is an emerging public health challenge. Study was conducted to determine the association of prognostic factors with disease severity in COVID-19 patients at POF Hospital, Wah Cantt. We conductedadescriptivecross-sectional study at a department of Medicine, POF Hospital, Wah Medical College (affiliated with National University of Medical Sciences) Wah Cantt.
 METHODOLOGY: We calculateda sample size of 158 patients (WHO Calculator). The study duration was 6 months (November 2020-April 2021).The selection of COVID patients was done through non probability sampling (consecutive). Respiratory sample for all participating patients were collected (from throat or sputum). These samples were tested for SARS-CoV-2 using WHO standard. SPSS version 24 was utilized for data analysis purpose. Chi square test and independent t-test were applied. Logistic regression was applied.
 RESULTS:Total data consist of 158 patients with COVID-19. Mean age of patients was52.3±3.26 years. Total leukocytes count (p=0.02), absolute neutrophil count (p=0.000), C reactive protein (p=0.000), NLR (p=0.03) were comparatively greater in patients with Severe COVID-19. While absolute lymphocyte were significantly lower in severe COVID-19 patients as compared to non-severe (p=0.03). Age[OR, 1.06 ;95% CI (1.027-1.114);p=0.01], diabetes mellitus[OR, 0.281 ;95% CI (0.100-0.788) p=0.016 and Hypertension [OR, 3.045 ;(1.044-8.878)95% CI p=0.04] are significant predictors of COVID-19 severity
 CONCLUSION:Prognostic factors of COVID-19 increased the likelihood of disease progression. C reactive protein andALC were significant predictors of COVID-19.

Association between inflammatory cytokines/chemokines, clinical laboratory parameters, disease severity and in-hospital mortality in critical and mild COVID-19 patients without comorbidities or immune-mediated diseases

ABSTRACT There are limited data on inflammatory cytokines and chemokines; the humoral immune response; and main clinical laboratory parameters as indicators for disease severity and mortality in patients with critical and mild COVID-19 without comorbidities or immune-mediated diseases in Saudi Arabia. We determined the expression levels of major proinflammatory cytokines and chemokines; C-reactive protein (CRP); procalcitonin; SARS-CoV-2 IgM antibody and twenty-two clinical laboratory parameters and assessed their usefulness as indicators of disease severity and in-hospital death. Our results showed a significant increase in the expression levels of SARS-CoV-2 IgM antibody; IL1-β; IL-6; IL-8; TNF-α and CRP in critical COVID-19 patients; neutrophil count; urea; creatinine and troponin were also increased. The elevation of these biomarkers was significantly associated and positively correlated with in-hospital death in critical COVID-19 patients. Our results suggest that the levels of IL1-β; IL-6; IL-8; TNF-α; and CRP; neutrophil count; urea; creatinine; and troponin could be used to predict disease severity in COVID-19 patients without comorbidities or immune-mediated diseases. These inflammatory mediators could be used as predictive early biomarkers of COVID-19 disease deterioration; shock and death among COVID-19 patients without comorbidities or immune-mediated diseases.

Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients.

COVID‐19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID‐19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID‐19, we characterized the EV composition of 20 mild and 26 severe COVID‐19 patients along with 16 sex and age‐matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients’ sera contained increased amounts of CD13+ and CD82+ EVs, which positively correlated with IL‐6‐producing and circulating myeloid‐derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID‐19 patients contained more HLA‐ABC+ EVs than sera of the healthy donors and more CD24+ EVs than severe COVID‐19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID‐19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID‐19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID‐19 progression.

When Outcomes Diverge: Age and Cardiovascular Risk as Determinants of Mortality and ICU Admission in COVID-19.

Background: Hospital mortality and admission to the Intensive Care Unit (ICU) are markers of disease severity in COVID-19 patients. Cardiovascular co-morbidities are one of the main determinants of negative outcomes. In this study we investigated the impact of cardiovascular co-morbidities on mortality and admission to the ICU in first-wave COVID-19 patients. Methods: A multicenter, retrospective, cohort study. A total of 1077 patients were analyzed for mortality and ICU admission. Cardiovascular risk factors were explored as determinants of the outcomes after correction for other confounders. Results: In the multivariable model, after correction for age, only a history of heart failure remained independently associated (p = 0.0013) with mortality (hazard ratio 2.22, 95% confidence interval 1.37 to 3.62). Age showed a mortality risk increase of 8% per year (hazard ratio 1.08, 95% confidence interval 1.05 to 1.10, p = 0.001). The transition from ward to the ICU had, as a single determinant, the age, but in a reversed fashion (hazard ratio 0.96, 95% confidence interval 0.94 to 0.98, p = 0.0002). Conclusions: Once adjusted for the main determinant of mortality (age) heart failure only remained independently associated with mortality. Admission to the ICU was less likely for elderly patients. This may reflect the catastrophic impact of the first wave of COVID-19 pandemic in terms of ICU bed availability in Lombardy, leading to a selection process for ICU admission.

The use of the ferritin/procalcitonin ratio as a marker for the prognosis of disease severity in COVID-19 patients

Aim: COVID-19 infection caused by the SARS-CoV-2 virus emerged in Wuhan, China, in December 2019 and rapidly became a global pandemic. There is still a need for markers to predict disease severity and prognosis. The aim of this retrospective study was to evaluate the relationship between the ferritin-procalcitonin ratio (FPR) and disease severity and prognosis in patients followed up with COVID-19 pneumonia. Materials and methods: The study included patients with COVID-19 pneumonia confirmed by real-time polymerase chain reaction test positivity on nasal and pharyngeal smear samples. Results: Evaluation was made of 2120 cases, comprising 1155 (54.5%) males and 965 (45.5%) females. FPR was determined to be statistically significantly lower in non-survivors, those admitted to the Intensive Care Unit, and those with diabetes, hypertension, chronic obstructive pulmonary disease, coronary artery disease, cancer, or chronic renal failure (p<0.01). It was found that FPR is significantly lower in critical cases compared to cases of moderate and severe disease. In this study, FPR was determined to be at a significantly lower level in cases with severe pneumonia than in cases with mild and moderate severity pneumonia. Conclusions: FPR, which is a simple analysis, can be of use to clinicians in predicting disease severity, the course, and prognosis of COVID-19 and can be easily used in clinical practice. With this ratio’s guidance, patients with a severe disease course and poor prognosis can be identified earlier. Thus healthcare resources can be assigned appropriately to suitable patients. Keywords: COVID-19, disease severity, ferritin/procalcitonin ratio

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort.

BackgroundInterleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort.MethodsSecondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata.ResultsA total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age.ConclusionIn those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

Antibodies targeting conserved non-canonical antigens and endemic coronaviruses associate with favorable outcomes in severe COVID-19.

While there have been extensive analyses characterizing cellular and humoral responses across the severity spectrum in COVID-19, outcome predictors within severe COVID-19 remain less comprehensively elucidated. Furthermore, properties of antibodies (Abs) directed against viral antigens beyond spike and their associations with disease outcomes remain poorly defined. We perform deep molecular profiling of Abs directed against a wide range of antigenic specificities in severe COVID-19 patients. The profiles included canonical (spike [S], receptor-binding domain [RBD], and nucleocapsid [N]) and non-canonical (orf3a, orf8, nsp3, nsp13, and membrane [M]) antigenic specificities. Notably, multivariate Ab profiles directed against canonical or non-canonical antigens are equally discriminative of survival in severe COVID-19. Intriguingly, pre-pandemic healthy controls have cross-reactive Abs directed against nsp13, a protein conserved across coronaviruses. Consistent with these findings, a model built on Ab profiles for endemic coronavirus antigens also predicts COVID-19 outcome. Our results suggest the importance of studying Abs targeting non-canonical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and endemic coronavirus antigens in COVID-19.

An ultrasensitive UHPLC-ESI-MS/MS method augmented with a controlled microwave derivatization reaction for quantitation of vitamin D3 and its major metabolites in COVID-19 patients

It is established that vitamin D deficiency is correlated with the disease severity in COVID-19 patients. However, the reliable and sensitive quantitation of vitamin D3 (D3) and its metabolites remains a difficult challenge. Herein, a novel ultrasensitive and reliable UHPLC-ESI-MS/MS method was developed and validated for the quantitation of D3 and its major metabolites in COVID-19 patients. The mass spectral sensitivity was augmented via controlled microwave-assisted derivatization reaction (CMDR) with 2-nitrosopyridine (Pyr-NO) at 65 °C for 2 min. CMDR hyphenation with UHPLC-MS/MS improves detection sensitivity while shortening separation and derivatization reaction times. The precursor to product ion transitions for D3, 25-hydroxy D3 (25(OH)D3), 1,25-dihydroxy D3 (1,25-(OH)2D3) and calcipotriol (CPT) as an internal standard were m/z 493.4 → 231.3, m/z 509.4 → 231.3, m/z 525.4 → 247.3, and m/z 521.4 → 247.3; respectively. The separation of the formed derivatives was conducted using a gradient elution mode with mobile phase A: formic acid (0.1%) in water and mobile phase B: formic acid (0.1%) in acetonitrile. The elution started with 40% (v/v) of B for 0.3 min then increased linearly to 90% (v/v) at 2 min on an Agilent EclipsePlus C18 (50 × 2.1 mm, 1.8 μm) column at a flow rate of 0.3 mL min−1. The method was validated using FDA standards for bioanalytical method validation over a concentration range of 0.02–50 ng mL−1 with correlation coefficient ≥0.9987 and the lower limit of quantitation (LLOQ) were 0.02–0.05 ng mL−1 in human plasma. The developed method has demonstrated excellent comparability to a well-established chemiluminescent immunoassay (CLIA) method for the analysis of D3 metabolites in human samples. The developed UHPLC-ESI-MS/MS method was implemented for routine and reliable quantitation of D3 and its major metabolites in COVID-19 patients.

Association of polymorphisms in genes encoding prothrombotic and cardiovascular risk factors with disease severity in COVID-19 patients: A pilot study.

The present study aimed to assess the association of 16 polymorphisms in genes encoding prothrombotic and cardiovascular risk factors with COVID‐19 disease severity: FV G1691A, FV H1299R, FII G20210A, MTHFR C677T, MTHFR A1298, factor XIII V34L, PAI‐1 4G/5G, EPCR haplotypes (A1/A2/A3), eNOS −786 T > C, eNOS G894T, LTA C804A, ACE I/D, ITGB3 PIA1/A2, ITGA2B Baka/b, β‐Fbg −455 G > A and ApoB R3500Q. The study included 30 patients with severe COVID‐19 and 49 non‐severe COVID‐19 patients. All studied polymorphisms except ITGA2B Baka/b were determined using multilocus genotyping assays CVD StripAssays (ViennaLab Diagnostics), while ITGA2B was genotyped using a real‐time PCR method based on TaqMan technology. A higher frequency of carriers of at least one ITGB3 PIA2 allele was found in severe COVID‐19 patients (p = 0.009). The distribution of genotypes was significantly different for ß‐Fbg −455 G > A (p = 0.042), with only three homozygous AA genotypes found among severe COVID‐19 patients. The association with an increased risk for severe COVID‐19 was found for ITGB3, with carriers of at least one ITGB3 PIA2 allele having a 3.5‐fold greater risk of severe COVID‐19 (p = 0.011). Genotype distribution differences were obtained for the combinations of FV H1299R and FXIII V34L (p = 0.026), ITGB3 PIA1/A2 and ITGA2B Baka/b (p = 0.024), and ACE I/D and PAI‐1 4G/5G (p = 0.046). ITGB3 polymorphism emerged as an independent risk factor for severe COVID‐19 and homozygosity for ß‐Fbg −455 G > A mutation could contribute to disease severity. The combined effect of polymorphisms in genes encoding prothrombotic and cardiovascular risk factors could further contribute to disease severity.

Early and strong antibody responses to SARS-CoV-2 predict disease severity in COVID-19 patients

BackgroundAntibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown.MethodsA novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls.ResultsAntibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation.ConclusionsThis is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.

Prevalence of vitamin D deficiency among patients attending Post COVID-19 follow-up clinic: a cross-sectional study.

Post-COVID-19 syndrome appears to be a multi-organ illness with a broad spectrum of manifestations, occurring after even mild acute illness. Limited data currently available has suggested that vitamin D deficiency may play a role in COVID-19 cases. However, to our knowledge, no study has examined the frequency of vitamin D deficiency in post-COVID-19 cases and its effect on the symptom severity. The aim of this study is to both screen the frequency of vitamin D deficiency in post-COVID-19 syndrome patients and to study its relation to persistent symptoms. A cross-sectional, single-center study was conducted involving all cases attending post-COVID-19 follow-up clinic from November 2020 to May 2021. Complete history, clinical examination, and laboratory analysis [kidney functions, serum calcium, C-reactive protein, serum ferritin, Serum 25-(OH) vitamin D] was done as well as HRCT chest. The study included 219 post-COVID-19 cases, 84% had deficient vitamin D levels (< 20 ng/dL); 11.4% had insufficient level (20-30 ng/dL) and only 4.9 % reported normal level. There was no link between levels of vitamin D with either the acute or post-COVID-19 symptoms in the studied groups. Despite the prevalence of vitamin D deficiency among the study population, no association was observed between the levels of vitamin D and post-COVID-19 symptoms. It appears that post-COVID-19 syndrome pathophysiology involves a more complex interaction with the immune system. Dedicated clinical trials are advised to better study vitamin D levels and the related disease severity in COVID-19 patients.

Can Maintaining Optimal Magnesium Balance Reduce the Disease Severity of COVID-19 Patients?

Can Maintaining Optimal Magnesium Balance Reduce the Disease Severity of COVID-19 Patients?

High Angiotensin-Converting Enzyme and Low Carboxypeptidase N Serum Activity Correlate with Disease Severity in COVID-19 Patients.

(1) Background: Angiotensin-converting enzyme 2 (ACE2) is a functional receptor of SARS-CoV-2 and counter-balances ACE in the renin–angiotensin system (RAS). An imbalance of the RAS could be associated with severe COVID-19 progression. (2) Methods: Activities of serum proteases angiotensin-converting enzyme (ACE) and carboxypeptidase N (CPN) for 45 hospitalized and 26 convalescent COVID-19 patients were investigated vs. healthy controls using labeled bradykinin (DBK) degradation with and without inhibition by captopril as a read-out. Data were correlated to clinical parameters. (3) Results: DBK degradation and CPN activity were significantly reduced gender-independently in COVID-19 and returned to normal during convalescence. ACE activity was over-active in severe disease progression; product DBK1-5 was significantly increased in critically ill patients and strongly correlated with clinical heart and liver parameters. ACE inhibitors seemed to be protective, as DBK1-5 levels were normal in moderately ill patients in contrast to critically ill patients. (4) Conclusions: CPN and ACE serum activity correlated with disease severity. The RAS is affected in COVID-19, and ACE could be a therapeutic target. Further proof from dedicated studies is needed.

Endocan as a potential marker in diagnosis and predicting disease severity in COVID-19 patients: a promising biomarker for patients with false-negative RT-PCR.

BackgroundEndothelial-specific molecule 1 (endocan) has emerged as an inflammatory biomarker in recent years. The purpose of this study was to investigate the diagnostic value of serum endocan levels in the prediction of COVID-19 disease among patients with a false-negative reverse transcription polymerase change reaction (RT-PCR) test, and also to determine its correlation with the clinical severity of the disease.MethodsThirty patients with positive RT-PCR results and 30 with false-negative RT-PCR results, both with suspected COVID-19 in terms of clinical, radiological, and laboratory findings, were included in the study. Thirty healthy controls were also enrolled.ResultsSerum endocan levels were estimated to be 821.8 ± 99.3 pg/mL in COVID-19 RT-PCR (+) patients, 803.9 ± 97.0 pg/mL in RT-PCR false (–) patients with suspected COVID-19, and 382.9 ± 37.5 pg/mL in the control group. No significant difference was observed between RT-PCR (+) and RT-PCR false (–) patients (P = 0.68). However, serum endocan levels differed significantly between patient groups and control group (P < 0.05). With a cut-off value of 444.2 pg/mL serum endocan levels differentiated COVID-19 cases from healthy individuals with 92% sensitivity and 80% specificity. Moreover, a significant positive correlation was observed between serum endocan levels and clinical severity (P < 0.01, r = 0.94).ConclusionsThere is a need for different laboratory markers capable of assisting diagnosis and showing COVID-19 infection in suspected COVID-19 RT-PCR false-negative patients. Endocan levels can be used as an assistant blood test for identifying COVID-19 patients with false-negative RT-PCR tests and in determining the clinical severity of the disease.

Epigenetic modifications associated with genes implicated in cytokine storm: The potential biotherapeutic effects of vitamins and minerals in COVID-19.

Cytokine storm is a phrase used to refer to an abrupt upsurge in the circulating levels of various pro-inflammatory cytokines, causing increased stimulation and activity of immune cells during disease conditions. The binding of pattern recognition receptors to pathogen-associated molecular patterns during COVID-19 infection recruits response machinery involving the activation of transcription factors and proteins required for a robust immune response by host cells. These immune responses could be influenced by epigenetic modifications as evidenced by significant variations in COVID-19 pathophysiology and response to therapy observed among patients across the globe. Considering that circulating levels of interleukin 1, tumor necrosis factor-α, and interleukin 6 are significantly elevated during cytokine storm in COVID-19 patients, genetic and epigenetic variations in the expression and function of these proteins could enhance our understanding of the disease pathogenesis. Treatment options that repress the transcription of specific cytokine genes during COVID-19 infection could serve as possible targets to counteract cytokine storm in COVID-19. Therefore, the present article reviews the roles of cytokines and associated genes in the COVID-19 cytokine storm, identifies epigenetic modifications associated with the disease progression, and possible ameliorative effects of some vitamins and minerals obtained as epigenetic modifiers for the control of cytokine storm and disease severity in COVID-19 patients. PRACTICAL APPLICATIONS: COVID-19 causes mortality and morbidity that adversely affect global economies. Despite a global vaccination campaign, side effects associated with vaccination, misconceptions, and a number of other factors have affected the expected successes. Cytokine storm in COVID-19 patients contributes to the disease pathogenesis and response to therapy. Epigenetic variations in the expression of various cytokines could be implicated in the different outcomes observed in COVID-19 patients. Certain vitamins and minerals have been shown to interfere with the expression and activity of cytokines implicated in cytokine storm, thereby counteracting observed pathologies. This review examines cytokines implicated in cytokine storm in COVID-19, epigenetic modifications that contribute to increased expression of identified cytokines, specific foods rich in the identified vitamins and minerals, and suggests their possible ameliorative benefits. The article will be beneficial to both scientists and the general public who are interested in the role of vitamins and minerals in ameliorating COVID-19.

Factors affecting the disease severity of COVID-19 patients in an emergency setting

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Bungaran Partahi Saud Manalu S, Leonard E, Paramita C, Tendean M. Factors affecting the disease severity of COVID-19 patients in an emergency setting. Family Medicine & Primary Care Review. 2022;24(1):56-60. doi:10.5114/fmpcr.2022.113014. APA Bungaran Partahi Saud Manalu, S., Leonard, E., Paramita, C., & Tendean, M. (2022). Factors affecting the disease severity of COVID-19 patients in an emergency setting. Family Medicine & Primary Care Review, 24(1), 56-60. https://doi.org/10.5114/fmpcr.2022.113014 Chicago Bungaran Partahi Saud Manalu, Samuel, Elcha Leonard, Carennia Paramita, and Marshell Tendean. 2022. "Factors affecting the disease severity of COVID-19 patients in an emergency setting". Family Medicine & Primary Care Review 24 (1): 56-60. doi:10.5114/fmpcr.2022.113014. Harvard Bungaran Partahi Saud Manalu, S., Leonard, E., Paramita, C., and Tendean, M. (2022). Factors affecting the disease severity of COVID-19 patients in an emergency setting. Family Medicine & Primary Care Review, 24(1), pp.56-60. https://doi.org/10.5114/fmpcr.2022.113014 MLA Bungaran Partahi Saud Manalu, Samuel et al. "Factors affecting the disease severity of COVID-19 patients in an emergency setting." Family Medicine & Primary Care Review, vol. 24, no. 1, 2022, pp. 56-60. doi:10.5114/fmpcr.2022.113014. Vancouver Bungaran Partahi Saud Manalu S, Leonard E, Paramita C, Tendean M. Factors affecting the disease severity of COVID-19 patients in an emergency setting. Family Medicine & Primary Care Review. 2022;24(1):56-60. doi:10.5114/fmpcr.2022.113014.