VEGFR and DPP-IV as Markers of Severe COVID-19 and Predictors of ICU Admission.

The pathophysiology of the severe course of COVID-19 is multifactorial and not entirely elucidated. However, it is well known that the hyperinflammatory response and cytokine storm are paramount events leading to further complications. In this paper, we investigated the vascular response in the pathophysiology of severe COVID-19 and aimed to identify novel biomarkers predictive of ICU admission. The study group consisted of 210 patients diagnosed with COVID-19 (age range: 18-93; mean ± SD: 57.78 ± 14.16), while the control group consisted of 80 healthy individuals. We assessed the plasma concentrations of various vascular factors using the Luminex technique. Then, we isolated RNA from blood mononuclear cells and performed a bioinformatics analysis investigating various processes related to vascular response, inflammation and angiogenesis. Our results confirmed that severe COVID-19 is associated with vWF/ADAMTS 13 imbalance. High plasma concentrations of VEGFR and low DPP-IV may be potential predictors of ICU admission. SARS-CoV-2 infection impairs angiogenesis, hinders the generation of nitric oxide, and thus impedes vasodilation. The hypercoagulable state develops mainly in the early stages of the disease, which may contribute to the well-established complications of COVID-19.

CXCL8, CCL2, and CMV Seropositivity as New Prognostic Factors for a Severe COVID-19 Course.

The exact pathophysiology of severe COVID-19 is not entirely elucidated, but it has been established that hyperinflammatory responses and cytokine storms play important roles. The aim of this study was to examine CMV status, select chemokines, and complement components in COVID-19, and how concentrations of given molecules differ over time at both molecular and proteomic levels. A total of 210 COVID-19 patients (50 ICU and 160 non-ICU patients) and 80 healthy controls were enrolled in this study. Concentrations of select chemokines (CXCL8, CXCL10, CCL2, CCL3, CCR1) and complement factors (C2, C9, CFD, C4BPA, C5AR1, CR1) were examined at mRNA and protein levels with regard to a COVID-19 course (ICU vs. non-ICU group) and CMV status at different time intervals. We detected several significant differences in chemokines and complement profiles between ICU and non-ICU groups. Pro-inflammatory chemokines and the complement system appeared to greatly contribute to the pathogenesis and development of severe COVID-19. Higher concentrations of CXCL8 and CCL2 in the plasma, with reduced mRNA expression presumably through negative feedback mechanisms, as well as CMV-positive status, correlated with more severe courses of COVID-19. Therefore, CXCL8, CCL2, and CMV seropositivity should be considered as new prognostic factors for severe COVID-19 courses. However, more in-depth research is needed.

IgA-Based Secretory Response in Tears of COVID-19 Patients: A Potential Biomarker of Pro-Inflammatory State in Course of SARS-CoV-2 Infection.

Mucosal immunity, including secretory IgA (sIgA), plays an important role in the early defence against SARS-CoV-2 infection. However, a comprehensive evaluation of the local immune response in tears in relation to blood antibody reservoirs has not yet been conducted. A total of 179 symptomatic laboratory-confirmed COVID-19 patients were included in this single-centre study. Conjunctival swabs were analysed by a reverse transcription polymerase chain reaction for the detection of SARS-CoV-2 RNA. In parallel, tear samples collected by Schirmer test strips and plasma samples were analysed by ELISA to detect anti-S1 IgA levels. The concentrations of selected inflammatory cytokines in tears were determined by a magnetic bead assay. Anti-SARS-CoV-2 sIgA was present in the tears of 81 (45.25%) confirmed COVID-19 patients, and the tear IgA levels were correlated with the plasma IgA levels (Rs = +0.29, p = 0.0003). SARS-CoV-2 RNA in the conjunctival sac was identified in 18 COVID-19 patients (10%). Positive correlations between the tear IgA level and the concentrations of several cytokines TNF-α (Rs = +0.23, p = 0.002), IL-1ß (Rs = +0.25, p < 0.001), IL-2 (Rs = +0.20, p = 0.007), IL-4 (Rs = +0.16, p = 0.04), IL-5 (Rs = +0.36, p < 0.001), IL-6 (Rs = +0.32, p < 0.001), IL-8 (Rs = +0.31, p < 0.001), VEGF (Rs = +0.25, p < 0.001) and GM-CSF (Rs = +0.27, p < 0.001) were also found. Quantitative tear film-based sIgA could potentially serve as a rapid and easily accessible biomarker of external mucosal immunity to SARS-CoV-2. The concentration of sIgA is directly related to individual host immune responses to SARS-CoV-2 infection.

Epigenetic activation of antiviral sensors and effectors of interferon response pathways during SARS-CoV-2 infection.

Recent studies have shown that methylation changes identified in blood cells of COVID-19 patients have a potential to be used as biomarkers of SARS-CoV-2 infection outcomes. However, different studies have reported different subsets of epigenetic lesions that stratify patients according to the severity of infection symptoms, and more importantly, the significance of those epigenetic changes in the pathology of the infection is still not clear. We used methylomics and transcriptomics data from the largest so far cohort of COVID-19 patients from four geographically distant populations, to identify casual interactions of blood cells' methylome in pathology of the COVID-19 disease. We identified a subset of methylation changes that is uniformly present in all COVID-19 patients regardless of symptoms. Those changes are not present in patients suffering from upper respiratory tract infections with symptoms similar to COVID-19. Most importantly, the identified epigenetic changes affect the expression of genes involved in interferon response pathways and the expression of those genes differs between patients admitted to intensive care units and only hospitalized. In conclusion, the DNA methylation changes involved in pathophysiology of SARS-CoV-2 infection, which are specific to COVID-19 patients, can not only be utilized as biomarkers in the disease management but also present a potential treatment target.

Remdesivir Reduces Mortality in Hemato-Oncology Patients with COVID-19.

Introduction: Remdesivir is the first agent with proven clinical efficacy against coronavirus disease 2019 (COVID-19); however, its benefit is associated with early use, and its efficacy has been poorly studied in patients with hemato-oncological diseases, who have an increased risk of a severe course of infection. This study aimed to assess the effects of remdesivir on mortality, mechanical ventilation, and the duration of hospitalization in both the general population and in patients with hemato-oncological diseases. Materials and Methods: Longitudinal data for 4287 patients with confirmed COVID-19 were analyzed, including a subset of 200 individuals with hemato-oncological diseases. In total, 1285 (30.0%) patients received remdesivir, while the remaining patients were treated with other methods. Survival statistics for the 14- and 30-day observation time points were calculated using non-parametric and multivariate Cox models. Results: Mortality for the 14- and 30-day observation time points was notably lower among patients receiving remdesivir (7.2% vs 11.6%, p < 0.001 and 12.7% vs 16.0, p = 0.005, respectively); however, in multivariate models adjusted for age, sex, lung involvement, and lactate dehydrogenase and interleukin-6 levels, the administration of remdesivir did not reduce patient mortality at either the 14-day or 30-day time points. Among patients with haemato-oncological disease, significant survival benefit was observed at 14 and 30 days for patients treated with remdesivir (11.3% vs.16.7% and 24.2% vs 26.1%, respectively; p < 0.001). A favorable effect of remdesivir was also noted for the 14-day time point in multivariate survival analysis (HR:4.03 [95% confidence interval:1.37-11.88]; p = 0.01). Conclusion: Remdesivir significantly reduced the early mortality rate in COVID-19 patients with comorbid hemato-oncological disease, which emphasizes the need to administer this agent to immunosuppressed patients.

Evaluating Ocular Symptoms and Tear Film Cytokine Profiles in Symptomatic COVID-19 Patients.

Background: This study investigated the presence and duration of ophthalmic symptoms in the early phase of COVID-19 to assess the corresponding local immune response on the ocular surface. Methods: The study included data from 180 COVID-19 patients and 160 age-matched healthy controls. The main finding was the occurrence of ophthalmological manifestations at the time of admission to the hospital and during the preceding 7 days. Tear film concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay. Results: Among the COVID-19 patients, 12.64% had at least one ocular symptom at the time of admission, and 24.14% had symptoms within the preceding 7 days (p < 0.001 vs. controls). We found that the COVID-19 patients complained more frequently about eye tearing (p = 0.04) and eye pain (p = 0.01) than controls. A multivariate analysis of the patients and controls adjusted for age and sex revealed that COVID-19 was an independent factor associated with higher VEGF and IL-10 tear film concentrations (ß = +0.13, p = 0.047 and ß = +0.34, p < 0.001, respectively) and lower IL-1ß, IL-8, and GM-CSF levels (ß = −0.25, p < 0.001; ß = −0.18, p = 0.004; and ß = −0.82, p = 0.0 respectively). Conclusions: SARS-CoV-2 does not attract a strong local response of the conjunctival immune system; therefore, ophthalmic symptoms may not constitute a substantial element in the clinical picture of novel COVID-19 infection.

Increased proinflammatory cytokines in tears correspond with conjunctival SARS-CoV-2 positivity in symptomatic COVID-19 patients.

Tear fluid cytokine levels may serve as biomarkers of innate immune system response against SARS-CoV-2 infection. Therefore, our aim was to analyze panel of selected inflammatory cytokines in tears of COVID-19 patients in relation to presence of SARS-CoV-2 viral load in conjunctival secretions. In this study concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay in tear film collected from 232 symptomatic COVID-19 patients. SARS-CoV-2 ocular infection was confirmed based on positive conjunctival swab-based RT-PCR testing. Viral RNA in conjunctival sac was detected in 21 patients (9%). No relation between presence and the duration of ophthalmic symptoms and SARS-CoV-2 infection detected in conjunctival secretions was found. The tear film concentrations of IFN-γ, TNF-α, IL-5, IL-8 and GM-CSF were found to be significantly greater among patients with positive conjunctival swab results as compared to the group negative for SARS-CoV-2 in conjunctival sac. Our current data depict a group of inflammatory mediators in human tears, which may play a significant role in ocular pathology of SARS-CoV-2 conjunctival infection.

Renal and Inflammation Markers-Renalase, Cystatin C, and NGAL Levels in Asymptomatic and Symptomatic SARS-CoV-2 Infection in a One-Month Follow-Up Study.

The aim of our study was to evaluate the influence of asymptomatic infection and the occurrence of symptomatic COVID-19 on specific biochemical, renal, and immune parameters-renalase, neutrophil gelatinase-associated lipocalin (NGAL) cystatin C (CysC), and creatinine-and their weekly fluctuations during a one-month observation period in COVID-19 patients admitted to hospital. The study involved 86 individuals: 30 patients with diagnosed COVID-19, 28 people with asymptomatic infection confirmed with IgG antibodies-the IG(+) group-and 28 individuals without any (IgG, IgE) anti-SARS-CoV-2 antibodies-the IG(-) group. In the COVID-19 group, blood was drawn four times: (1) on day 0/1 after admission to hospital (C1 group), (2) 7 days later (C7 group), (3) 14 days later (C14 group), and (4) 28 days later (C28 group). In the IG(-) and IG(+) groups, blood was drawn once. There were no significant differences in creatinine, Cys C, and uric acid between any of the analyzed groups. NGAL levels were significantly higher in IG(+) and at all time-points in the COVID-19 groups than in controls. A similar observation was made for renalase at the C7, C14, and C28 time-points. Plasma renalase, NGAL, and CysC are unrelated to kidney function in non-critically ill COVID-19 patients and those with asymptomatic infection. Renalase and NGAL are most likely related to the activation of the immune system rather than kidney function. Asymptomatic SARS-CoV-2 infection causes a rise in plasma NGAL levels similar to those observed in symptomatic COVID-19 patients. Therefore, more attention should be paid to tracking and monitoring the health of these people.

Molecular Evolution and Epidemiological Characteristics of SARS COV-2 in (Northwestern) Poland.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) evolved into a worldwide outbreak, with the first Polish cases in February/March 2020. This study aimed to investigate the molecular epidemiology of the circulating virus lineages between March 2020 and February 2021. We performed variant identification, spike mutation pattern analysis, and phylogenetic and evolutionary analyses for 1106 high-coverage whole-genome sequences, implementing maximum likelihood, multiple continuous-time Markov chain, and Bayesian birth-death skyline models. For time trends, logistic regression was used. In the dataset, virus B.1.221 lineage was predominant (15.37%), followed by B.1.258 (15.01%) and B.1.1.29 (11.48%) strains. Three clades were identified, being responsible for 74.41% of infections over the analyzed period. Expansion in variant diversity was observed since September 2020 with increasing frequency of the number in spike substitutions, mainly H69V70 deletion, P681H, N439K, and S98F. In population dynamics inferences, three periods with exponential increase in infection were observed, beginning in March, July, and September 2020, respectively, and were driven by different virus clades. Additionally, a notable increase in infections caused by the B.1.1.7 lineage since February 2021 was noted. Over time, the virus accumulated mutations related to optimized transmissibility; therefore, faster dissemination is reflected by the second wave of epidemics in Poland.