Disease Severity In COVID-19 Patients Research Articles

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.

GASTROINTESTINAL SYMPTOMS ARE ASSOCIATED WITH SEVERITY OF CORONAVIRUS DISEASE 2019: A SYSTEMATIC REVIEW

Background:
 Aim: This study aims to summarize and evaluate the association between GI symptoms in COVID-19 and disease severity.
 Methods: A systematic search strategy was conducted across several electronic reference databases (PubMed, Cochrane Library, Google Scholar) and included articles published between 2019–2023. Duplicate publications, review articles, and incomplete articles were excluded.
 Results: Database searches identified a total of 17632 articles. Of these, 100 articles passed the screening process, resulting in 15 articles for full-text assessment. Among them, 6 articles did not evaluate the outcome of interest. Hence, we found 9 appropriate studies included.
 Conclusion: Current findings are insufficient to establish a association between GI symptoms and disease severity in COVID-19 patients.

Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium

Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells (AECs) is a quick way to find novel treatments for COVID-19. Computational screening has found dicoumarol (DCM), a natural anticoagulant, to be a potential SARS-CoV-2 inhibitor, but its inhibitory effects and possible working mechanisms remain unknown. Using air-liquid interface culture of primary human AECs, we demonstrated that DCM has potent antiviral activity against the infection of multiple Omicron variants (including BA.1, BQ.1 and XBB.1). Time-of-addition and drug withdrawal assays revealed that early treatment (continuously incubated after viral absorption) of DCM could markedly inhibit Omicron replication in AECs, but DCM did not affect the absorption, exocytosis and spread of viruses or directly eliminate viruses. Mechanistically, we performed single-cell sequencing analysis (a database of 77,969 cells from different airway locations from 10 healthy volunteers) and immunofluorescence staining, and showed that the expression of NAD(P)H quinone oxidoreductase 1 (NQO1), one of the known DCM targets, was predominantly localised in ciliated AECs. We further found that the NQO1 expression level was positively correlated with both the disease severity of COVID-19 patients and virus copy levels in cultured AECs. In addition, DCM treatment downregulated NQO1 expression and disrupted signalling pathways associated with SARS-CoV-2 disease outcomes (e.g., Endocytosis and COVID-19 signalling pathways) in cultured AECs. Collectively, we demonstrated that DCM is an effective post-exposure prophylactic for SARS-CoV-2 infection in the human AECs, and these findings could help physicians formulate novel treatment strategies for COVID-19.

SARS-CoV-2 ORF8 Mediates Signals in Macrophages and Monocytes through MyD88 Independently of the IL-17 Receptor.

SARS-CoV-2 has caused an estimated 7 million deaths worldwide to date. A secreted SARS-CoV-2 accessory protein, known as open reading frame 8 (ORF8), elicits inflammatory pulmonary cytokine responses and is associated with disease severity in COVID-19 patients. Recent reports proposed that ORF8 mediates downstream signals in macrophages and monocytes through the IL-17 receptor complex (IL-17RA, IL-17RC). However, generally IL-17 signals are found to be restricted to the nonhematopoietic compartment, thought to be due to rate-limiting expression of IL-17RC. Accordingly, we revisited the capacity of IL-17 and ORF8 to induce cytokine gene expression in mouse and human macrophages and monocytes. In SARS-CoV-2-infected human and mouse lungs, IL17RC mRNA was undetectable in monocyte/macrophage populations. In cultured mouse and human monocytes and macrophages, ORF8 but not IL-17 led to elevated expression of target cytokines. ORF8-induced signaling was fully preserved in the presence of anti-IL-17RA/RC neutralizing Abs and in Il17ra-/- cells. ORF8 signaling was also operative in Il1r1-/- bone marrow-derived macrophages. However, the TLR/IL-1R family adaptor MyD88, which is dispensable for IL-17R signaling, was required for ORF8 activity yet MyD88 is not required for IL-17 signaling. Thus, we conclude that ORF8 transduces inflammatory signaling in monocytes and macrophages via MyD88 independently of the IL-17R.

Immunity due to COVID-19 vaccination and its correlation with lung involvement severity as an indicator of disease severity

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a worldwide challenge; regarding the lack of an effective and efficient drug. It seems that the vaccine is the only modality to save the world from this pandemic. Objectives: This study was conducted to assess the effect of vaccination on preventing pulmonary involvement and the disease severity of COVID-19 patients. Patients and Methods: This descriptive-analytical study was conducted on 247 people with coronavirus disease 2019 infection. Demographic characteristics and vaccination status information were collected. Patients’ lung computed tomography scan findings were scored based on the pulmonary involvement percentage, and then according to this score, they were graded into severe, moderate, mild, and without lung involvement. The association between pulmonary involvement and vaccination status were evaluated by Fisher’s exact test and logistic regression. Results: Most participants were male, with a mean age of 53.74 ± 10.96 years. Most people (42.9%) were partial-vaccinated. Lungs in 53.3% were with lung involvement and in 46.6% were without. The correlation between pulmonary involvement and vaccination was significant (P<0.001). Conclusion: Vaccination is an effective and efficient method in preventing coronavirus disease 2019 severity.

Evaluation of NLR, d-NLR, and PLR in terms of disease severity in COVID-19 patients

İnflamasyonu ve bağışıklık durumunu temsil edebilen dolaşımdaki bazı biyobelirteçler, COVID-19 hastalarının prognozu için potansiyel öngörücü olabilmektedir. Periferik beyaz kan hücresi (WBC) sayısı, nötrofil-lenfosit oranı (NLR), türetilmiş NLR oranı [d-NLR, nötrofil sayısı/ (WBC sayısı- nötrofil sayısı)] ve trombosit-lenfosit oranı (PLR) viral pnömonili hastaların prognozu için yararlı prediktör olarak sistematik inflamatuar cevabın göstergeleridir. Bu çalışmada COVID-19 hastalarında NLR, d-NLR ve PLR biyobelirteçleri kullanılarak hastalık ciddiyetinin değerlendirilmesi amaçlanmıştır. COVID-19 tanısıyla 2020 yılı Nisan ayından itibaren bir yıllık süreçte takip ve tedavileri yapılan hastalar çalışmaya alınmıştır. SARS-COV-2 PCR testi pozitif olan veya PCR sonuçları negatif olan ancak periferik, bilateral veya multifokal yuvarlak buzlu cam opasitesi gibi tipik Akciğer BT bulguları olan hastalar, klinik tablo başka bir nedenle açıklanamıyorsa çalışmaya dahil edilmiştir. Dünya Sağlık Örgütü (DSÖ) ve T.C. Sağlık Bakanlığı COVID-19 tanı ve tedavi kılavuzları rehberliğine göre hastalar ciddi ve ciddi olmayan COVID-19 olarak gruplanmıştır. Çalışmaya alınan 395 hastanın ortanca yaşı 66.5 idi ve %52.7’si kadındı. İleri yaş (<.001), yüksek d-NLR (0.027) ve CRP (<0.001) düzeyleri COVID-19 hastalık ciddiyeti ile önemli ölçüde ilişkiliydi. Komorbidite, diyabet, kalp hastalığı ve KOAH ciddi hastalık tablosu olan COVID-19 hastalarında istatistiksel olarak anlamlı derecede yüksek oranda izlendi (Sırasıyla <0.001, 0.022, 0.004 ve 0.027). Ciddi COVID-19 hastalarında, ciddi olmayan hasta grubuna göre NLR, d-NLR ve PLR değerleri daha yüksek seyretmiştir. Bulgularımız klinik pratikte d-NLR düzeylerinin kullanımını desteklemekle birlikte, kesin bir konsensüs eşik değeri elde etmek için daha ileri çalışmalar geliştirilmelidir.

Dysnatremia in COVID-19 Patients-An Analysis of the COLOS Study.

Sodium imbalance is one of the most common electrolyte disturbances encountered in the medical practice, and it may present with either hyponatremia or hypernatremia. Both sodium abnormalities are related with unfavorable outcomes. Elucidation of the prevalence of dysnatremia among COVID-19 patients and its impact on 30- and 90-day mortality and need for ICU admission was the goal. A single-center, retrospective, observational study was conducted. A total of 2026 adult, SARS-CoV-2 positive patients, admitted to Wroclaw University Hospital between 02.2020 and 06.2021, were included. On admission, patients were divided into groups: normonatremic (N), hyponatremic (L), and hypernatremic (H). Acquired data was processed, and Cox hazards regression and logistic regression were implemented. Hyponatremia on admission occurred in 17.47% (n = 354) of patients and hypernatremia occurred in 5.03% (n = 102). Dysnatremic patients presented with more comorbidities, used more drugs, and were statistically more often admitted to the ICU. Level of consciousness was the strongest predictor of ICU admission (OR = 1.21, CI: 1.16-1.27, p < 0.001). Thirty-day mortality was significantly higher in both the L and H groups (28.52%, p = 0.0001 and 47.95%, p < 0.0001, respectively), in comparison to 17.67% in the N group. Ninety-day mortality showed a similar trend in all study groups: 34.37% in the L group (p = 0.0001), 60.27% (p < 0.0001) in the H group, and 23.32% in the N group. In multivariable analyses, hypo- and hypernatremia were found to be independent predictors of 30- and 90-day mortality. Both hypo- and hypernatremia are strong predictors of mortality and disease severity in COVID-19 patients. Extraordinary care should be taken when dealing with hypernatremic, COVID-positive patients, as this group exhibits the highest mortality rates.

ABO Blood System Associated with Susceptibility, and Rhesus (Rh) Status Associated with Disease Severity in COVID-19 Patients, (Southeast of Iran)

ABO Blood System Associated with Susceptibility, and Rhesus (Rh) Status Associated with Disease Severity in COVID-19 Patients, (Southeast of Iran)

Interleukin-28 as a Promising Marker for Predicting Invasive Mechanical Ventilation Requirement and Mortality in COVID-19 Patients.

The study aimed to evaluate serum interleukin-28 levels in COVID-19 patients and correlate the results with disease severity. This study included 90 patients who presented to the COVID-19 outpatient clinics, hospital wards, and intensive care units. Serum interleukin-28, C-reactive protein, lactate dehydrogenase, fibrinogen, d-dimer, and ferritin levels were measured. Patients were divided into 3 groups based on clinical severity to mild, moderate, and severe groups (each group consisted of 30 patients). There were significant differences in serum C-reactive protein, lactate dehydrogenase, fibrinogen, d-dimer, ferritin, and interleukin- 28 levels between all groups. The mean serum interleukin-28 levels of all patients were 383.74 ± 63.58 ng/L. The mean serum interleukin-28 levels were 335.52 ± 42.12 ng/L in the mild group, 366.88 ± 41.27 ng/L in the moderate group, and 453.46 ± 36.78 ng/L in the severe group. There were significant differences in comparisons of all pairs (P < .05). Interleukin-28 may be a promising biomarker for detecting disease severity in COVID-19 patients.

Baseline serum vitamin A and vitamin C levels and their association with disease severity in COVID-19 patients.

We aimed to investigate the association between the serum concentrations of Vitamin A and Vitamin C and the severity of the COVID-19. Methods:Fifty-three consecutive PCR (+) COVID-19 patients admitted to a dedicated ward were enrolled in this study. Blood samples for serum Vitamin A and C measurements were drawn from all participants upon admission. All subjects underwent thoracic CT imaging prior to hospitalization. CT severity score (CT-SS) was then calculated for determining the extent of pulmonary involvement. A group of healthy volunteers, in whom COVID-19 was ruled out, were assigned to the control group (n=26). These groups were compared by demographic features and serum vitamin A and C levels. The relationship between serum concentrations of these vitamins and pre-defined outcome measures, CT-SS and length of hospitalization (LOH), was also assessed. Results:In COVID-19 patients, serum Vitamin A (ng/ml, 494±96 vs. 698±93; p<0.001) and Vitamin C (ng/ml, 2961 [1991-31718] vs. 3953 [1385-8779]; p=0.007) levels were significantly lower with respect to healthy controls. According to the results of correlation analyses, there was a significant negative association between Vitamin A level and outcome measures (LOH, r=-0.293; p=0.009 and CT-SS, r=-0.289; p=0.010). The negative correlations between Vitamin C level and those measures were even more prominent (LOH, r=-0.478; p<0.001 and CT-SS, r=-0.734: p<0.001). COVID-19 patients had lower baseline serum Vitamin A and Vitamin C levels as compared to healthy controls. In subjects with COVID-19, Vitamin A and Vitamin C levels were negatively correlated with CT-SS and LOH.

C-reactive protein isoforms as prognostic markers of COVID-19 severity.

C-reactive protein (CRP), an active regulator of the innate immune system, has been related to COVID-19 severity. CRP is a dynamic protein undergoing conformational changes upon activation in inflammatory microenvironments between pentameric and monomeric isoforms. Although pentameric CRP is the circulating isoform routinely tested for clinical purposes, monomeric CRP shows more proinflammatory properties. Therefore, we aimed to determine the potential of monomeric CRP in serum as a biomarker of disease severity in COVID-19 patients (admission to intensive care unit [ICU] and/or in-hospital mortality). We retrospectively determined clinical and biological features as well as pentameric and monomeric CRP levels in a cohort of 97 COVID-19 patients within 72h of hospital admission. Patients with severe disease had higher levels of both pentameric and monomeric CRP. However, multivariate analysis showed increased mCRP but not pCRP to be independently associated to disease severity. Notably, mCRP levels higher than 4000 ng/mL (OR: 4.551, 95% CI: 1.329-15.58), together with number of co-morbidities, low lymphocyte count, and procalcitonin levels were independent predictors of disease severity in the multivariate model. Our results show the potential of mCRP levels as a marker of clinical severity in COVID-19 disease.

Remdesivir improves biomarkers associated with disease severity in COVID-19 patients treated in an outpatient setting

BackgroundRemdesivir (RDV) is an intravenous antiviral with activity against SARS-CoV-2 for treatment of hospitalized COVID-19 patients with moderate-to-severe disease. Biomarkers associated with clinical outcomes have been identified for COVID-19, but few evaluated in context of antiviral treatment. Here, we assessed baseline (day 1, prior to first RDV dose) biomarkers and the impact of RDV treatment on longitudinal biomarker readouts.MethodsRecently, RDV was evaluated in high-risk, non-hospitalized patients with confirmed SARS-CoV-2 infection and was highly effective at preventing disease progression. The randomized, double-blind, placebo-controlled Phase 3 study included 562 participants who received at least 1 dose of study drug, of which 312 consented for longitudinal biomarker assessments at baseline, day 3, and day 14. We assessed sixteen baseline biomarkers and the impact of RDV treatment on longitudinal biomarker readouts.ResultsSix well-known, inflammation-associated biomarkers are elevated at baseline in participants meeting the primary endpoint of hospitalization or death by day 28. Moreover, in comparison to placebo, biomarkers in RDV-treated participants show accelerated improvement, including reduction of soluble angiopoietin-2, D-dimer, and neutrophil-to-lymphocyte ratio, as well as an increase in lymphocyte counts.ConclusionsOverall, the findings in this study suggest that RDV treatment may accelerate the improvement of multiple biomarkers of COVID-19 severity, which are associated with better clinical outcomes during infection. These findings have implications for better understanding the activity of antiviral treatments in COVID-19.

The Role of Soluble ACE2 as a Prognostic Marker in Severe COVID-19: A Brief Meta-Analysis.

The recently emerged novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has posed a serious threat to public health, and there is an urgent need to establish tools that can aid the clinician in the evaluation and management of highrisk patients. This meta-analysis aimed to investigate the potential of sACE2 (soluble angiotensinconverting enzyme 2) as a prognostic biomarker in COVID-19. A comprehensive search of PubMed/MEDLINE, Cochrane, and Google Scholar, was performed until May 26, 2021. Data extraction and quality assessment of the study were independently conducted by the authors. Finally, 6 studies were included in this meta-analysis. ACE-2 serum or plasma levels were compared between COVID-19 patients and healthy controls. ACE-2 level was not significantly different between severe COVID-19 patients and healthy controls (SMD = 1.2; 95% CI: -1.3-1.5; P = 0.86), severe and non-severe COVID-19 patients (SMD = 0.3; 95% CI: -0.06-0.7; P = 0.1), and severe COVID-19 patients and healthy controls (SMD = 0.6; 95% CI: -1.1-2.3; P = 0.5). We cautiously propose that circulating levels of ACE2 cannot be used as a biomarker to assess disease severity in COVID-19 patients.

The relationship between ischemia-modified albumin/albumin ratio levels and disease severity in COVID-19 patients

The relationship between ischemia-modified albumin/albumin ratio levels and disease severity in COVID-19 patients

Analysis of differential gene expression of pro-inflammatory cytokines in the nasopharyngeal milieu of mild & severe COVID-19 cases.

A subset of individuals with COVID-19 can suffer from a severe form of the disease requiring breathing support for respiratory failure and even death due to disease complications. COVID-19 disease severity can be attributed to numerous factors, where several studies have associated changes in the expression of serum pro-inflammatory cytokines with disease severity. However, very few studies have associated the changes in expression of pro-inflammatory changes in the nasopharyngeal milieu with disease severity. Therefore, in the current study, we performed differential gene expression analysis of various pro-inflammatory cytokines in the nasopharyngeal milieu of mild & severe COVID-19 cases. For this retrospective, cross-sectional study, a total of 118 nasopharyngeal swab samples, previously collected from mild and severe (based on the WHO criteria) COVID-19 patients were used. A real-time qPCR was performed to determine the viral loads and also evaluate the mRNA expression of eight cytokines (IL-1, IL-2, IL-4, IL-6, IL-10, IFN-γ, TGF-β1, and TNF-α). Subsequently, an unpaired T-test was applied to compare the statistical difference in mean expression of viral loads and each cytokine between the mild and severe groups, while the Pearson correlation test was applied to establish a correlation between disease severity, viral load, and cytokines expression. Similarly, a multivariable logistic regression analysis was performed to assess the relationship between different variables from the data and disease severity. Out of 118 samples, 71 were mild, while 47 were severe. The mean viral load between the mild and severe groups was comparable (mild group: 27.07± 5.22; severe group: 26.37 ±7.89). The mRNA expression of cytokines IL-2, IL-6, IFN- γ, and TNF-α was significantly different in the two groups (p<0.05), where the Log2 normalized expression of IL-2, IL-6, IFN- γ, and TNF-α was found to be 2.2-, 16-, 2.3-, and 1.73-fold less in the severe group as compared to the mild group. Furthermore, we also observed a significant positive correlation between all the cytokines in the severe group. The multivariate analysis showed a significant relationship between age, IL-6, and disease severity. This decreased expression of certain cytokines (IL-2, IL-6, TNF-α, and IFN-γ) in the nasopharyngeal milieu may be considered early biomarkers for disease severity in COVID-19 patients.

Bioinformatics insights into the genes and pathways on severe COVID-19 pathology in patients with comorbidities.

Background: Coronavirus disease (COVID-19) infection is known for its severe clinical pathogenesis among individuals with pre-existing comorbidities. However, the molecular basis of this observation remains elusive. Thus, this study aimed to map key genes and pathway alterations in patients with COVID-19 and comorbidities using robust systems biology approaches. Methods: The publicly available genome-wide transcriptomic datasets from 120 COVID-19 patients, 281 patients suffering from different comorbidities (like cardiovascular diseases, atherosclerosis, diabetes, and obesity), and 252 patients with different infectious diseases of the lung (respiratory syncytial virus, influenza, and MERS) were studied using a range of systems biology approaches like differential gene expression, gene ontology (GO), pathway enrichment, functional similarity, mouse phenotypic analysis and drug target identification. Results: By cross-mapping the differentially expressed genes (DEGs) across different datasets, we mapped 274 shared genes to severe symptoms of COVID-19 patients or with comorbidities alone. GO terms and functional pathway analysis highlighted genes in dysregulated pathways of immune response, interleukin signaling, FCGR activation, regulation of cytokines, chemokines secretion, and leukocyte migration. Using network topology parameters, phenotype associations, and functional similarity analysis with ACE2 and TMPRSS2-two key receptors for this virus-we identified 17 genes with high connectivity (CXCL10, IDO1, LEPR, MME, PTAFR, PTGS2, MAOB, PDE4B, PLA2G2A, COL5A1, ICAM1, SERPINE1, ABCB1, IL1R1, ITGAL, NCAM1 and PRKD1) potentially contributing to the clinical severity of COVID-19 infection in patients with comorbidities. These genes are predicted to be tractable and/or with many existing approved inhibitors, modulators, and enzymes as drugs. Conclusion: By systemic implementation of computational methods, this study identified potential candidate genes and pathways likely to confer disease severity in COVID-19 patients with pre-existing comorbidities. Our findings pave the way to develop targeted repurposed therapies in COVID-19 patients.

STUDY OF HEMATOLOGICAL PARAMETERS IN PATIENTS WITH COVID-19 DISEASE IN KURDISTAN REGION-IRAQ

&nbsp; Background: Coronavirus disease 2019 is an infectious disease that was found at the end of 2019. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was recognized as the virus that leads to COVID-19. The study was directed to find out the hematological parameter changes in COVID-19 patients according to the severity of the disease. Methods: The study has been done in two centers Sulaymaniyah and Duhok Governorates for a period of six months between September 2021 to March 2022. A total of 201 enrolled patients were included. For each patient demographic characteristics and blood test results (total and differential WBC, Hb, platelet, ferritin, CRP, D-dimer, NLR, PLR) were collected, following the severity of the disease and the outcome of each one of the patients. SPSS software was used for statistical analysis. Results: The study revealed that female patients were more than males 60.2% and 39.8% respectively with an overall mean age of 54.65±17 years. The mean duration of hospitalization is 14.4 ± 7.7 days. Furthermore, the study showed that patients had 30.8% leukocytosis,17.4% lymphopenia, and 31.8% neutrophilia. Higher NLR and PLT are seen in severe cases with NLR ≥3.1and PLR ≥ 285. Also, high levels of CRP, D-dimer, and ferritin were seen in severe COVID-19 patients. Conclusions: Changes in hematological parameters can be useful in predicting of the disease severity of COVID-19 patients.

Evaluating the Relationship Between Antiphospholipid Antibodies and COVID-19 Severity.

Coronavirus 2 (COVID-19) has emerged as a new global pandemic, causing severe acute respiratory syndrome. Furthermore, the existence of antiphospholipid (APL) antibodies (Abs) and ultimately patient death may be linked to the occurrence of thrombotic events in patients with COVID-19. We aimed to investigate if there was a link between the presence of APL Abs and the severity of COVID-19 disease in patients at the Vali-Asr Hospital in Zanjan from June to July 2021. Real-time PCR was used to diagnose COVID-19 in 76 hospitalized patients. A total of 38 patients were hospitalized in the internal medicine ward and another 38 people were admitted to the intensive care unit of the Vali-Asr Educational Hospital in Iran's Zanjan region. Lupus anticoagulant (LAC) detection was done using the dilute Russell viper venom time method, and tests for anticardiolipin (ACL) Abs, IgG and IgM, and anti-beta2 glycoprotein 1 Abs, IgG and IgM, were done on blood and plasma samples of linked patients using the enzyme-linked immunosorbent assay technique. SPSS 24 was used to analyze data. Our findings showed that the presence of LAC was associated with disease severity in COVID-19 patients (p = 0.001). However, there was no significant relationship between APL Abs and mortality in patients affected with COVID-19. The evaluation of APL Abs, particularly LAC, in COVID-19 patients appears to be helpful in predicting the severity of the disease.

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&lt;0.0001; FHR5: 2.4-fold, p&lt;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.