Severe COVID-19 Cases Research Articles

Abstract P129: Risk of COVID-19 Hospitalization or Death by the AHA's Life’s Essential 8: The Collaborative Cohort of Cohorts for COVID-19 Research (C4R)

Background: It is unknown how cardiovascular health (CVH) relates to severe Covid-19 illness in adults without clinical cardiovascular disease (CVD). We hypothesized that more optimal Life’s Essential 8 (LE8)-quantified CVH is associated with lower risk of severe Covid-19 among US adults without clinical CVD. Methods: C4R is ascertaining Covid-19 events in 14 NIH cohorts via questionnaires, serosurvey, and medical record adjudication. We included cohorts with pre-pandemic LE8 measures of body mass index (BMI), blood pressure (BP), lipids, diet, glucose, physical activity, smoking, and sleep in participants without clinical CVD. Covid-19 was defined as severe (hospitalization, death) or non-severe (all other events). Fine-Gray sub-distribution hazard models compared incident Covid-19 by LE8 quartiles, with non-severe and severe Covid-19 as competing risks. Models were censored at first event, stratified by cohort, and adjusted for sociodemographics and vaccinations at time of Covid-19. Results: Among 21,300 participants in 7 cohorts (mean [SD] age 67 years [14], 61% female, 2% American Indian, 4% Asian, 16% Black, 33% White, 43% Hispanic), mean (SD) LE8 was 65 (14). In 3/2020-9/2022, there were 3,034 non-severe and 488 severe Covid-19 cases. The best CVH quartile (Q) 4 had more non-severe and fewer severe Covid-19 events. The Q4 vs. Q1 aHR was 1.08 (95% CI 0.98, 1.20) for non-severe Covid-19 and 0.59 (0.45, 0.77) for severe Covid-19. Examining LE8 components separately, better status on 5 LE8 components (BMI, BP, glucose, physical activity, smoking) was associated with significantly lower risk of severe Covid-19, whereas 3 were not associated (cholesterol, diet, sleep; data not shown). Conclusions: Better LE8-quantified CVH was associated with 41% lower risk of severe Covid-19 events in adults without clinical CVD. Further research is needed to elucidate mechanisms of Covid-19 resilience and the role of CVH-directed interventions to reduce risks of severe Covid-19.

Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022

The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020-2022). The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Not applicable.

Simultaneous HPLC determination of remdesivir and dexamethasone in the presence of metformin, sitagliptin, and glimepiride in a synthetic mixture and spiked human plasma

The COVID-19 pandemic has raised many questions regarding the control and therapy of type 2 diabetes and the higher risk of severe disease progression. One of the therapeutic regimens used in moderate and severe cases of COVID-19, endorsed by the World Health Organization, involves the administration of an antiviral medicinal product and a corticosteroid. The present study describes the development of a liquid chromatographic method for the simultaneous separation and quantification of Remdesivir and Dexamethasone in the presence of Metformin, Sitagliptin, and Glimepiride in a synthetic mixture. The developed method also allows determination of Remdesivir, Dexamethasone, and Glimepiride in spiked plasma samples, using Sitagliptin as internal standard. A mixture of acetonitrile and potassium dihydrogen phosphate buffer (pH 3) in a ratio of 45:55 v/v was used as а mobile phase on a C18 column. The recovery percentages from plasma ranged from 85.1 to 108.5%. The developed method can serve in routine quality control and clinical laboratory practice.

Risk factors for critical COVID-19 illness during Delta- and Omicron-predominant period in Korea; using K-COV-N cohort in the National health insurance service.

This study evaluated the clinical characteristics of patients with COVID-19 in Korea, and examined the relationship between severe COVID-19 cases and underlying health conditions during the Delta (September 20, 2021 to December 4, 2021) and the Omicron (February 20, 2022 to March 31, 2022) predominant period. This study assessed the association between critical COVID-19 illness and various risk factors, including a variety of underlying health conditions, using multiple logistic regression models based on the K-COV-N cohort, a nationwide data of confirmed COVID-19 cases linked with COVID-19 vaccination status and the National Health Insurance claim information. We analyzed 137,532 and 8,294,249 cases of COVID-19 infection during the Delta and the Omicron variant dominant periods, respectively. During the Delta as well as the Omicron period, old age (≥80 years) showed the largest effect size among risk factors for critical COVID-19 illness (aOR = 18.08; 95% confidence interval [CI] = 14.71-22.23 for the Delta; aOR = 24.07; 95% CI = 19.03-30.44 for the Omicron period). We found that patients with solid organ transplant (SOT) recipients, unvaccinated, and interstitial lung disease had more than a two-fold increased risk of critical COVID-19 outcomes between the Delta and Omicron periods. However, risk factors such as urban residence, underweight, and underlying medical conditions, including chronic cardiac diseases, immunodeficiency, and mental disorders, had different effects on the development of critical COVID-19 illness between the Delta and Omicron periods. We found that the severity of COVID-19 infection was much higher for the Delta variant than for the Omicron. Although the Delta and the Omicron variant shared many risk factors for critical illness, several risk factors were found to have different effects on the development of critical COVID-19 illness between those two variants. Close monitoring of a wide range of risk factors for critical illness is warranted as new variants continue to emerge during the pandemic.

Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease

BackgroundThrombo-inflammation and neutrophil extracellular traps (NETs) are exacerbated in severe cases of COVID-19, potentially contributing to disease exacerbation. However, the mechanisms underpinning this dysregulation remain elusive. We hypothesised that lower DNase activity may be associated with higher NETosis and clinical worsening in patients with COVID-19.MethodsBiological samples were obtained from hospitalized patients (15 severe, 37 critical at sampling) and 93 non-severe ambulatory cases. Our aims were to compare NET biomarkers, functional DNase levels, and explore mechanisms driving any imbalance concerning disease severity.ResultsFunctional DNase levels were diminished in the most severe patients, paralleling an imbalance between NET markers and DNase activity. DNase1 antigen levels were higher in ambulatory cases but lower in severe patients. DNase1L3 antigen levels remained consistent across subgroups, not rising alongside NET markers. DNASE1 polymorphisms correlated with reduced DNase1 antigen levels. Moreover, a quantitative deficiency in plasmacytoid dendritic cells (pDCs), which primarily express DNase1L3, was observed in critical patients. Analysis of public single-cell RNAseq data revealed reduced DNase1L3 expression in pDCs from severe COVID-19 patient.ConclusionSevere and critical COVID-19 cases exhibited an imbalance between NET and DNase functional activity and quantity. Early identification of NETosis imbalance could guide targeted therapies against thrombo-inflammation in COVID-19-related sepsis, such as DNase administration, to avert clinical deterioration.Trial registration: COVERAGE trial (NCT04356495) and COLCOV19-BX study (NCT04332016).Graphical

Tackling Post-COVID-19 Rehabilitation Challenges: A Pilot Clinical Trial Investigating the Role of Robotic-Assisted Hand Rehabilitation.

Background: Prolonged hospitalization in severe COVID-19 cases can lead to substantial muscle loss and functional deterioration. While rehabilitation is essential, conventional approaches face capacity challenges. Therefore, evaluating the effectiveness of robotic-assisted rehabilitation for patients with post-COVID-19 fatigue syndrome to enhance both motor function and overall recovery holds paramount significance. Our objective is to assess the effectiveness of rehabilitation in post-COVID-19 patients with upper extremity impairment through the utilization of a hand exoskeleton-based robotic system. Methods: A total of 13 participants experiencing acute or limited functional or strength impairment in an upper extremity due to COVID-19 were enrolled in the study. A structured intervention consisted of 45 min therapy sessions, conducted four times per week over a six-week period, utilizing a hand exoskeleton. The research employed standardized health assessments, motion analysis, and semi-structured interviews for pre-intervention and follow-up evaluations. Paired sample t-tests were employed to statistically analyze the outcomes. Results: The outcomes showed a reduction in overall dependence levels across participants, positive changes in various quality of life-related measurements, and an average increase of 60.4 ± 25.7% and 28.7 ± 11.2% for passive and active flexion, respectively. Conclusions: Our data suggest that hand exoskeleton-based robotic systems hold promise to optimize the rehabilitation outcomes following severe COVID-19. Trial registration: ID NCT06137716 at ClinicalTrials.gov.

Estimating the Burden of Severe Cases of COVID-19 in Iran (North Khorasan Province) since the Beginning of the Pandemic: 2019-2021

Background: The death and fear of the COVID-19 pandemic has been a major concern in all countries. Estimating the burden of the disease is one of the indicators that estimates the severity of the damage caused by the disease. This study was performed to estimate the burden of years of life lost due to COVID-19 infection and premature death in North Khorasan.Methods: In this study, all cases of definitive infection (PCR test positive) with COVID-19 from the beginning of the epidemic to April 2021 were included in the study. Disability-Adjusted Life -Years index (DALYs) was used to estimate the burden of the disease.Results: Since the beginning of the epidemic, 63697 definite cases of the disease have been identified (prevalence equal to 7%) and the total number of years of life lost due to disability and premature death was estimated at 24769 years. This number represents 28.7 years per 100,000 populations, which in women and men, this number was equal to 26.6 and 30.8, respectively.Conclusion: According to the results of the study, COVID-19 has caused significant loss of years of life, which due to age and concomitant diseases, deaths are more common in the elderly.

The Impact of lncRNA-GAS5/miRNA-200/ACE2 Molecular Pathway on the Severity of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2), which is responsible for coronavirus disease (COVID-19), potentially has severe adverse effects, leading to public health crises worldwide. In COVID-19, deficiency of ACE-2 is linked to increased inflammation and cytokine storms via increased angiotensin II levels and decreased ACE-2/Mas receptor axis activity. MiRNAs are small sequences of noncoding RNAs that regulate gene expression by binding to the targeted mRNAs. MiR-200 dysfunction has been linked to the development of ARDS following acute lung injury and has been proposed as a key regulator of ACE2 expression. LncRNA growth arrest-specific transcript 5 (GAS5) has been recently studied for its modulatory effect on the miRNA-200/ACE2 axis. The current study aims to investigate the role of lncRNA GAS5, miRNA-200, and ACE2 as new COVID-19 diagnostic markers capable of predicting the severity of SARS-CoV-2 complications. A total of 280 subjects were classified into three groups: COVID-19-negative controls (n = 80), and COVID-19 patients (n=200) who required hospitalization were classified into two groups: group (2) moderate cases (n = 112) and group (3) severe cases (n = 88). The results showed that the serum GAS5 expression was significantly down-expressed in COVID-19 patients; as a consequence, the expression of miR-200 was reported to be overexpressed and its targeted ACE2 was down-regulated. The ROC curve was drawn to examine the diagnostic abilities of GAS5, miR-200, and ACE2, yielding high diagnostic accuracy with high sensitivity and specificity. lncRNA-GAS5, miRNA-200, and ACE2 panels presented great diagnostic potential as they demonstrated the highest diagnostic accuracy for discriminating moderate COVID-19 and severe COVID-19 cases.

Prevalence of Neutralizing Autoantibodies Against Type I Interferon in a Multicenter Cohort of Severe or Critical COVID-19 Cases in Shanghai

ObjectiveWe sought to explore the prevalence of type I interferon-neutralizing antibodies in a Chinese cohort and its clinical implications during the Omicron variant wave of SARS-CoV-2.MethodsType I interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity of the autoantibodies for in vitro interference with antiviral activity of IFN was assessed by using a SARS-CoV-2 replicon system. An analysis of the demographic and clinical profiles of patients exhibiting neutralizing antibodies was also conducted.ResultsIn this cohort, 11.8% of severe/critical cases exhibited the existence of type I IFN-neutralizing antibodies, specifically targeting IFN-α2, IFN-ω, or both, with an elderly male patient tendency. Notably, these antibodies exerted a pronounced inhibitory effect on the antiviral activity of IFN against SARS-CoV-2 under controlled in vitro conditions. Furthermore, a noteworthy correlation was discerned between the presence of these neutralizing antibodies and critical clinical parameters, including C-reactive protein (CRP) levels, D-dimer levels, and lymphocyte counts.ConclusionThe presence of type I IFN-neutralizing antibodies is a pervasive risk factor for severe/critical COVID-19 in the Chinese population.

Immunomodulatory and clinical effects of receptor-interacting protein kinase 1 (RIPK1) inhibitor eclitasertib (SAR443122) in patients with severe COVID-19: a phase 1b, randomized, double-blinded, placebo-controlled study

BackgroundTargeting receptor-interacting serine/threonine protein kinase 1 could mitigate the devastating sequelae of the hyperinflammatory state observed in severe cases of COVID-19. This study explored the immunomodulatory and clinical effects of the receptor-interacting serine/threonine protein kinase 1 inhibitor SAR443122 (eclitasertib) in patients with severe COVID-19.MethodsIn this Phase 1b, double-blinded, placebo-controlled study (NCT04469621) a total of 82 patients were screened, of whom 68 patients were eligible and randomized (2:1) to receive eclitasertib 600 mg (300 mg twice daily) or placebo up to 14 days. Primary outcome was relative change in C-reactive protein from baseline to Day 7. Time to clinical improvement using 7-point ordinal scale, ventilator/respiratory failure-free days, change in SpO2/FiO2 ratio, and biomarkers of severe COVID-19 were explored.ResultsGeometric mean ratio (point estimate [90% confidence interval]) of the relative change from baseline in C-reactive protein with eclitasertib vs. placebo on Day 7 was 0.85 (0.49–1.45; p = 0.30). Median time to 50% decrease in C-reactive protein from baseline was 3 days vs. 5 days (p = 0.056) with eclitasertib vs. placebo. Median time to ≥ 2-point improvement on 7-point clinical symptoms scale was 8 days vs. 10 days with eclitasertib vs. placebo (p = 0.38). Mean ventilator/respiratory failure-free days, change in baseline-adjusted SpO2/FiO2 ratio, and clinical biomarkers showed consistent numerical improvements with eclitasertib vs. placebo. The most frequently reported treatment-emergent adverse events were gastrointestinal disorders and condition aggravated/worsened COVID-19 pneumonia.ConclusionsEclitasertib was well tolerated with consistent trends toward more rapid resolution of inflammatory biomarkers and clinical improvement in severe COVID-19 patients than placebo.ClinicalTrials.gov identifierNCT04469621, first posted on clinicaltrials.gov on July 14, 2020.

Valsalva Manoeuvre-Induced Pneumothorax and Pneumomediastinum in a Covid-19 Patient with ARDS: An Unusual Mechanism for this Complication.

Until now, only a few cases of Valsalva-induced barotraumas (pneumothorax, pneumomediastinum and subcutaneous emphysema) have been described, and none of them among COVID-19 patients. A man in his 50s was admitted for SARS-CoV-2-related acute respiratory distress syndrome (ARDS). Initial evolution was favourable with non-invasive ventilatory support, high-flow oxygen nasal cannula and the best supportive drugs available at the time. During the Valsalva manoeuvre while defecating, the patient reported sudden chest pain and showed a new acute hypoxemic respiratory failure due to a pneumothorax. It led to multiple complications (pulmonary embolism, haemoptysis, and cardiac arrest), and despite the best supportive care, led to the patient's death. The Valsalva manoeuvre can be an overlooked cause of pneumothorax in patients with COVID-19. Predisposition to barotrauma in COVID-19 patients could be explained by several factors, including the extensive use of non-invasive and invasive ventilation during the pandemic, and the histological changes observed in the lungs of those infected with COVID-19. We report the first description of a Valsalva-induced barotrauma in a COVID-19 infection. We emphasise the importance of treating constipation particularly in severe COVID-19 cases, to prevent complications such as barotrauma. Pneumothorax is a common complication of severe COVID-19 infection, but Valsalva manoeuvre-induced pneumothorax in COVID-19 patients has never been reported previously.Particular care should be taken to prevent and treat constipation in hospitalised patients as it may cause a wide range of complications, including barotraumatism.The extensive use of non-invasive and invasive ventilation may play a role in barotrauma, but causal association has not been proven.

Epidemiological and Clinical Characteristics Associated with COVID-19 Severity Among Hospitalized Patients in the United Arab Emirates: A Retrospective Multicentre Study

ObjectivesTo investigate the clinical and epidemiological factors associated with severe COVID-19 cases in hospitalized patients across two emirates within the United Arab Emirates (UAE).MethodsA retrospective observational analytical study analysed data from 738 medical records and conducted 573 in-depth interviews with patients hospitalized across multiple healthcare centers in the UAE, between 29 January 2020 and 14 October 2021. Regression analysis predicted risk factors for COVID-19 severity.ResultsMain risk factors identified were crowding (aOR 1.919; 95%CI 1.144, 3.221), obesity (aOR 2.383; 95%CI 1.332, 4.263), diabetes (aOR 11.14; 95%CI 2.653–46.797), severe dehydration (aOR 3.219; 95%CI 2.161, 4.795), cough or sore throat (aOR 1.607; 95%CI 1.032, 2.502), shortness of breath (aOR 1.921; 95%CI 1.294, 2.853), increased days from symptom onset to admission (aOR 1.055; 95%CI 1.006, 1.105), elevated ANC (aOR 1.263, 95%CI 1.121, 1.424), and AST/SGOT (aOR 1.055, 95% CI 1.016, 1.095). Protective factors included smoking (aOR 0.367; 95%CI 0.182, 0.740), first dose of COVID-19 vaccination (aOR 0.595; 95%CI 0.377, 0.93), higher oxygen saturation (aOR 0.853; 95%CI: 0.801, 0.907) and elevated ALC (aOR 0.540; 95%CI 0.323, 0.905).ConclusionIdentifying risk factors is crucial for high-risk individuals who may require closer monitoring to improve their outcomes. This can provide guidance for surveillance systems and early detection strategies to mitigate the impact of future outbreaks.

Intubation Decision Based on Illness Severity and Mortality in COVID-19: An International Study.

To evaluate the impact of intubation timing, guided by severity criteria, on mortality in critically ill COVID-19 patients, amidst existing uncertainties regarding optimal intubation practices. Prospective, multicenter, observational study conducted from February 1, 2020, to November 1, 2022. Ten academic institutions in the United States and Europe. Adults (≥ 18 yr old) confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalized specifically for COVID-19, requiring intubation postadmission. Exclusion criteria included patients hospitalized for non-COVID-19 reasons despite a positive SARS-CoV-2 test. Early invasive mechanical ventilation (EIMV) was defined as intubation in patients with less severe organ dysfunction (Sequential Organ Failure Assessment [SOFA] < 7 or Pa o2 /F io2 ratio > 250), whereas late invasive mechanical ventilation (LIMV) was defined as intubation in patients with SOFA greater than or equal to 7 and Pa o2 /F io2 ratio less than or equal to 250. The primary outcome was mortality within 30 days of hospital admission. Among 4464 patients, 854 (19.1%) required mechanical ventilation (mean age 60 yr, 61.7% male, 19.3% Black). Of those, 621 (72.7%) were categorized in the EIMV group and 233 (27.3%) in the LIMV group. Death within 30 days after admission occurred in 278 patients (42.2%) in the EIMV and 88 patients (46.6%) in the LIMV group ( p = 0.28). An inverse probability-of-treatment weighting analysis revealed a statistically significant association with mortality, with patients in the EIMV group being 32% less likely to die either within 30 days of admission (adjusted hazard ratio [HR] 0.68; 95% CI, 0.52-0.90; p = 0.008) or within 30 days after intubation irrespective of its timing from admission (adjusted HR 0.70; 95% CI, 0.51-0.90; p = 0.006). In severe COVID-19 cases, an early intubation strategy, guided by specific severity criteria, is associated with a reduced risk of death. These findings underscore the importance of timely intervention based on objective severity assessments.

Role of Neutrophil-Lymphocyte Ratio in Predicting Severity of COVID-19

Background: Higher neutrophil-lymphocyte ratio (NLR) is considered as cardinal findings with prognostic potentials in identification of severe COVID-19 cases. However, whether baseline NLR could be a predictor of disease severity and outcome remained to be investigated. Hence, this study was conducted with an aim to evaluate the relation of NLR (on admission) with disease severity. Objective: The objective of the study was to estimate the neutrophil-lymphocyte ratio among COVID-19 patients and its role in predicting disease severity. Method: This cross-sectional study was conducted in Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2020 to June 2021. Ninety-four COVID-19 admitted patients were enrolled following inclusion &amp; exclusion criteria. Informed consent was taken from the subjects. Ethical clearance was obtained from institutional review board (IRB) of BSMMU. Complete blood count for N-L ratio was done by standard procedure on admission by SYSMEX XN-2000 haematology analyser. Clinical and laboratory information were recorded with a semi-structured questionnaire. After collection of all the required data, analysis was done by SPSS 24.0. Results: Mean age of the patients was 56.59±12.25 years, wherein maximum patients were male (67%), non-smoker (80.9%), and retired/current service holder (51.1%). Maximum patients were hypertensive (61.7%) and diabetic (56.4%). Besides, maximum study patients (64.9%) were in severe category of COVID-19, followed by moderate (20.2%) and mild (14.9%) category according to National Guidelines on Clinical Management of COVID-19 criteria. Mean NLR was 5.40±4.35 (SD), wherein on admission NLR was significantly higher among severe COVID-19 patients compared to mild/moderate category (6.90±4.64 vs 2.61±1.53, p &lt;0.05). 28-days hospital mortality was found to be significantly associated with NLR (p&lt;0.05). Receiver operator curve analysis found highly significant cut-off value for NLR (3.42) with 75.4% sensitivity and 75.8% specificity in predicting severe COVID-19 patients (AUC= 0.841, p value &lt;0.001). Multivariate logistic regression analysis found NLR as an independent predictor for severe COVID-19 (OR=4.68, 95% CI: 1.29-16.81, P=0.019). Pearson correlation analysis showed that NLR had significant positive correlation with CRP and D-dimer as p value &lt;0.05. Conclusion: NLR can predict the disease severity and outcome of hospitalized COVID-19 patients. However, further larger study is recommended.

Genomic and Phylogenetic Characterisation of SARS-CoV-2 Genomes Isolated in Patients from Lambayeque Region, Peru.

this study aims to identify and characterise genomic and phylogenetically isolated SARS-CoV-2 viral isolates in patients from Lambayeque, Peru. Nasopharyngeal swabs were taken from patients from the Almanzor Aguinaga Asenjo Hospital, Chiclayo, Lambayeque, Peru, which had been considered mild, moderate, and severe cases of COVID-19. Patients had to have tested positive for COVID-19, using a positive RT-PCR for SARS-CoV-2. Subsequently, the SARS-CoV-2 complete viral genome sequencing was carried out using Illumina MiSeq®. The sequences obtained from the sequence were analysed in Nextclade V1.10.0 to assign the corresponding clades, identify mutations in the SARS-CoV-2 genes and perform quality control of the sequences obtained. All sequences were aligned using MAFFT v7.471. The SARS-CoV-2 isolate Wuhan NC 045512.2 was used as a reference sequence to analyse mutations at the amino acid level. The construction of the phylogenetic tree model was achieved with IQ-TREE v1.6.12. It was determined that during the period from December 2020 to January 2021, the lineages s C.14, C.33, B.1.1.485, B.1.1, B.1.1.1, and B.1.111 circulated, with lineage C.14 being the most predominant at 76.7% (n = 23/30). These lineages were classified in clade 20D mainly and also within clades 20B and 20A. On the contrary, the variants found in the second batch of samples of the period from September to October 2021 were Delta (72.7%), Gamma (13.6%), Mu (4.6%), and Lambda (9.1%), distributed between clades 20J, 21G, 21H, 21J, and 21I. This study reveals updated information on the viral genomics of SARS-CoV-2 in the Lambayeque region, Peru, which is crucial to understanding the origins and dispersion of the virus and provides information on viral pathogenicity, transmission and epidemiology.

The association between vitamin D deficiency and the clinical outcomes of hospitalized COVID-19 patients

Background Vitamin D deficiency is an emerging public health problem that affects more than one billion people worldwide. Vitamin D has been shown to be effective in preventing and reducing the severity of viral respiratory diseases, including influenza. However, the role of vitamin D in COVID-19 infection remains controversial. This study aimed to analyze the association of vitamin D deficiency on the clinical outcome of hospitalized COVID-19 patients. Methods A prospective cohort study was conducted among hospitalized COVID-19 patients at two COVID-19 referral hospitals in Indonesia from October 2021 until February 2022. Results The median serum 25(OH)D level in 191 hospitalized COVID-19 patients was 13.6 [IQR=10.98] ng/mL. The serum 25(OH)D levels were significantly lower among COVID-19 patients with vitamin D deficiency who had cardiovascular disease (p-value=0.04), the use of a ventilator (p-value=0.004), more severe COVID-19 cases (p-value=0.047), and mortality (p-value=0.002). Furthermore, serum 25(OH)D levels were significantly different between patients with mild and severe COVID-19 cases (p-value=0.019). Serum 25(OH)D levels in moderate and severe COVID-19 cases were significantly different (p-value=0.031). Lower serum 25(OH)D levels were significantly associated with an increased number of comorbidities (p-value=0.03), the severity of COVID-19 (p-value=0.002), and the use of mechanical ventilation (p-value=0.032). Mortality was found in 7.3% of patients with deficient vitamin D levels. However, patients with either sufficient or insufficient vitamin D levels did not develop mortality. Conclusions COVID-19 patients with vitamin D deficiency were significantly associated with having cardiovascular disease, mortality, more severe COVID-19 cases, and the used of mechanical ventilation. Lower serum 25(OH)D levels were associated with an increased number of comorbidities, COVID-19 severity, and the use of mechanical-ventilation. Thus, we suggest hospitalized COVID-19 patients to reach a sufficient vitamin D status to improve the clinical outcome of the disease.

HB-EGF Plasmatic Level Contributes to the Development of Early Risk Prediction Nomogram for Severe COVID-19 Cases.

(1) Background: Heparin-Binding Epidermal Growth Factor-like Growth Factor (HB-EGF) is involved in wound healing, cardiac hypertrophy, and heart development processes. Recently, circulant HB-EGF was reported upregulated in severely hospitalized COVID-19 patients. However, the clinical correlations of HB-EGF plasma levels with COVID-19 patients' characteristics have not been defined yet. In this study, we assessed the plasma HB-EGF correlations with the clinical and paraclinical patients' data, evaluated its predictive clinical value, and built a risk prediction model for severe COVID-19 cases based on the resulting significant prognostic markers. (2) Methods: Our retrospective study enrolled 75 COVID-19 patients and 17 control cases from May 2020 to September 2020. We quantified plasma HB-EGF levels using the sandwich ELISA technique. Correlations between HB-EGF plasma levels with clinical and paraclinical patients' data were calculated using two-tailed Spearman and Point-Biserial tests. Significantly upregulated parameters for severe COVID-19 cases were identified and selected to build a multivariate logistic regression prediction model. The clinical significance of the prediction model was assessed by risk prediction nomogram and decision curve analyses. (3) Results: HB-EGF plasma levels were significantly higher in the severe COVID-19 subgroup compared to the controls (p = 0.004) and moderate cases (p = 0.037). In the severe COVID-19 group, HB-EGF correlated with age (p = 0.028), pulse (p = 0.016), dyspnea (p = 0.014) and prothrombin time (PT) (p = 0.04). The multivariate risk prediction model built on seven identified risk parameters (age p = 0.043, HB-EGF p = 0.0374, Fibrinogen p = 0.009, PT p = 0.008, Creatinine p = 0.026, D-Dimers p = 0.024 and delta miR-195 p < 0.0001) identifies severe COVID-19 with AUC = 0.9556 (p < 0.0001). The decision curve analysis revealed that the nomogram model is clinically relevant throughout a wide threshold probability range. (4) Conclusions: Upregulated HB-EGF plasma levels might serve as a prognostic factor for severe COVID-19 and help build a reliable risk prediction nomogram that improves the identification of high-risk patients at an early stage of COVID-19.

Bioinformatic-based Study to Investigate the Structure and Function of Pro-inflammatory Cytokines TNFα and IL-6 Involved in the Pathogenesis of COVID-19.

Besides the clinical and laboratory research on the COVID-19 virus, the bioinformatics study in the field of genetics of immunity to COVID-19 is of particular importance. In this account, studies show that in patients with COVID-19, the level of tumor necrosis alpha (TNFα) and interleukin-6 (IL-6) is high and in severe cases of COVID-19, the production of IL-6, TNF-α, and other cytokines increases profoundly. On the other hand, investigating the molecular structure and receptors of IL-6 and TNFα and the structural analysis of the receptor proteins may potentially help to develop new therapeutic plans for COVID-19 infection. To identify genes with significant and different expressions in patients with COVID-19 in a microarray data set containing transcriptional profiles from GEO as a functional genomic database the GEO query package version 2.64.2 in a programming language R version 4.2.1 was downloaded. In this way, functional enrichment analysis for DEGs, WikiPathways, REGO, gene ontology, and STRING database was also investigated and employed. The structure and function of pro-inflammatory cytokines TNFα and IL-6 involved in the pathogenesis of COVID-19 were investigated, and in general, after performing various analyses in this study and extracting A series of genes with different expressions from the KEGG database, the final 5 DEGs include CXCL14, CXCL6, CCL8, CXCR1, TNFRSF10, and the relationship and expression effects of them were observed in different pathways. IL-6 and TNFα were involved in immunological processes that had a direct and indirect relationship with the activation of cytokines, including IL6 and TNF-a, and cytokine storm, and this indicates their role in the formation of problems and complications, including ARDS, in COVID-19 patients. Of course, determining the effectiveness of each of these genes requires more specialized and clinical studies.

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review

The potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in the management of COVID-19 and other medical conditions has emerged as an intriguing area of research. PCSK9 is primarily known for its impact on cholesterol metabolism, but recent studies have unveiled its involvement in various physiological processes, including inflammation, immune regulation, and thrombosis. In this abstract, the authors review the rationale and potential implications of PCSK9 inhibition during the inflammatory stage of SARS-CoV-2 infection. Severe cases of COVID-19 are characterized by an uncontrolled inflammatory response, often referred to as the cytokine storm, which can lead to widespread tissue damage and organ failure. Preclinical studies suggest that PCSK9 inhibition could dampen this inflammatory cascade by reducing the production of pro-inflammatory cytokines. Additionally, PCSK9 inhibition may protect against acute respiratory distress syndrome (ARDS) through its effects on lung injury and inflammation. COVID-19 has been linked to an increased risk of cardiovascular complications, especially in patients with pre-existing cardiovascular conditions or dyslipidemia. PCSK9 inhibitors are known for their ability to lower low-density lipoprotein (LDL) cholesterol levels by enhancing the recycling of LDL receptors in the liver. By reducing LDL cholesterol, PCSK9 inhibition might protect blood vessels from further damage and lower the risk of atherosclerotic plaque formation. Moreover, PCSK9 inhibitors have shown potential antithrombotic effects in preclinical studies, making them a potential avenue to mitigate the increased risk of coagulation disorders and thrombotic events observed in COVID-19. While the potential implications of PCSK9 inhibition are promising, safety considerations and possible risks need careful evaluation. Hypocholesterolemia, drug interactions, and long-term safety are some of the key concerns that should be addressed. Clinical trials are needed to establish the efficacy and safety of PCSK9 inhibitors in COVID-19 patients and to determine the optimal timing and dosing for treatment. Future research opportunities encompass investigating the immune response, evaluating long-term safety, exploring combination therapy possibilities, and advancing personalized medicine approaches. Collaborative efforts from researchers, clinicians, and policymakers are essential to fully harness the therapeutic potential of PCSK9 inhibition and translate these findings into meaningful clinical outcomes.

Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters

IntroductionThe emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination...