COVID-19 Disease Progression Research Articles

Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARS-CoV-2 viral proteins in metabolic dysregulation in COVID-19 patients

Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC–MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.

Multicenter, randomized controlled trial of traditional Japanese medicine, kakkonto with shosaikotokakikyosekko, for mild and moderate coronavirus disease patients.

The traditional Japanese (Kampo) medicine, kakkonto with shosaikotokakikyosekko, has antiviral and anti-inflammatory effects. In this randomized trial, patients with mild and moderate coronavirus disease (COVID-19) were randomly allocated to the control group receiving conventional treatment for symptom relief such as antipyretics and antitussives or the Kampo group receiving mixed extract granules of kakkonto (2.5g) and shosaikotokakikyosekko (2.5g) three times a day for 14days in addition to conventional treatment. The main outcome was the number of days until total symptom relief. The secondary outcome was the number of days until each symptom's relief and whether the disease progressed to respiratory failure. We enrolled a total of 161 patients (Kampo group, n = 81; control group, n = 80). The results from Kaplan-Meier estimates of symptom relief showed that there are no significant differences between the groups. However, covariate-adjusted cumulative incidence of fever relief considering competitive risk showed that the recovery was significantly faster in the Kampo group than in the control group (HR 1.76, 95% CI 1.03-3.01). Additionally, the risk of disease progression to moderate COVID-19 requiring oxygen inhalation was lower in the Kampo group than in the control group (Risk Difference -0.13, 95% CI -0.27-0.01). No significant drug-related side effects were observed. Kakkonto with shosaikotokakikyosekko is effective for fever relief with suppression of disease progression in COVID-19 patients. Clinical Trial Registration: https://jrct.niph.go.jp/en-latest-detail/jRCTs021200020, identifier [jRCTs021200020].

Predictors of disease severity, clinical course, and therapeutic outcome in COVID-19 patients: our experience with 1,700 patients.

Our study aimed at investigating the impacts of demographic, hematological, and biochemical factors on the clinical course and the prognostic outcome in adult COVID-19 patients. This retrospective study was performed in the internal medicine departments of two hospitals, and data were extracted from the medical files of 1,700 adult COVID-19 patients (836 females, 49.2%; 864 males, 50.8%) with an average age of 48.23 ± 16.68 (range: 18-93). Clinical data included baseline descriptives, prior medical history, admission date, treatment, and hematological and biochemical blood test results. The relationship between the survival, length of hospitalization, hematological, and biochemical parameters was investigated. Advanced age (p<0.001), presence of at least on comorbid disease (p=0.045), increased length of hospitalization (p=0.006), elevated white blood cell (p=0.001) and neutrophil (p=0.002) counts, increased serum levels of glucose (p=0.027), blood urea nitrogen (p<0.001), AST (p=0.006), LDH (p<0.001), CRP (p>0.001), and D-dimer (p=0.001). In contrast, diminution of serum levels of albumin (p<0.001), ALT (p=0.028), calcium (p=0.022), and platelet count (p=0.010) were associated with increased mortality. There was a positive and weak relationship between serum D-dimer levels and length of hospitalization. Our data imply that identifying and validating indicators that predict COVID-19 disease progression to improve health outcomes is crucial. Age, comorbidities, immunological response, radiographic abnormalities, laboratory markers, and signs of organ dysfunction may all predict poor outcomes individually or collectively. Identifying characteristics that predict COVID-19 problems is critical to guiding clinical management, improving patient outcomes, and allocating limited resources.

Vitamin D-A prominent immunomodulator to prevent COVID-19 infection.

COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID-19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID-19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID-19 infection.

Mortality of COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation During the Three Epidemic Waves.

Clinical presentation and mortality of patients treated with extracorporeal membrane oxygenation (ECMO) for COVID-19 acute respiratory distress syndrome (CARDS) were different during the French epidemic waves. The management of COVID-19 patients evolved through waves as much as knowledge on that new viral disease progressed. We aimed to compare the mortality rate through the first three waves of CARDS patients on ECMO and identify associated risk factors. Fifty-four consecutive ECMO for CARDS hospitalized at Amiens University Hospital during the three waves were included. Patients were divided into three groups according to their hospitalization date. Clinical characteristics and outcomes were compared between groups. Pre-ECMO risk factors predicting 90 day mortality were evaluated using multivariate Cox regression. Among 54 ECMO (median age of 61[48-65] years), 26% were hospitalized during the first wave (n = 14/54), 26% (n = 14/54) during the second wave, and 48% (n = 26/54) during the third wave. Time from first symptoms to ECMO was higher during the second wave than the first wave. (17 [12-23] days vs. 11 [9-15]; p < 0.05). Ninety day mortality was higher during the second wave (85% vs. 43%; p < 0.05) but less during the third wave (38% vs. 85%; P < 0.05). Respiratory ECMO survival prediction score and time from symptoms onset to ECMO (HR 1.12; 95% confidence interval [CI]: 1.05-1.20; p < 0.001) were independent factors of mortality. After adjustment, time from symptoms onset to ECMO was an independent factor of 90 day mortality. Changes in CARDS management from first to second wave-induced a later ECMO cannulation from symptoms onset with higher mortality during that wave. The duration of COVID-19 disease progression could be selection criteria for initiating ECMO.

Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and Omicron BA.1.1.529 but not with Omicron BA.1.1 and BA.2 variants.

The rapid spread of SARS-CoV-2 variants in the global population is indicative of the development of selective advantages in emerging virus strains. Here, we performed a case-control investigation of the clinical and demographic characteristics, clinical history, and virological markers to predict disease progression in hospitalized adults for COVID-19 between December 2021 and January 2022 in Chennai, India. COVID-19 diagnosis was made by a commercial TaqPath COVID-19 RT-PCR, and WGS was performed with the Ion Torrent Next Generation Sequencing System. High-quality (<5% of N) complete sequences of 73 Omicron B.1.1.529 variants were randomly selected for phylogenetic analysis. SARS-CoV-2 viral load, number of comorbidities, and severe disease presentation were independently associated with a shorter time-to-death. Strikingly, this was observed among individuals infected with Omicron BA.2 but not among those with the BA.1.1.529, BA.1.1, or the Delta B.1.617.2 variants. Phylogenetic analysis revealed severe cases predominantly clustering under the BA.2 lineage. Sequence analyses showed 30 mutation sites in BA.1.1.529 and 33 in BA.1.1. The mutations unique to BA.2 were T19I, L24S, P25del, P26del, A27S, V213G, T376A, D405N and R408S. Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and the Omicron BA.1.1.529 variant but not with Omicron BA.1.1 or BA.2 suggests that the newer strains are largely immune escape variants. The number of vaccine doses received was independently associated with increased odds of developing asymptomatic disease or recovery. We propose that the novel mutations reported herein could likely bear a significant impact on the clinical characteristics, disease progression, and epidemiological aspects of COVID-19. Surging rates of mutations and the emergence of eclectic variants of SARS-CoV-2 appear to impact disease dynamics.

Immunomodulatory role of Nanocurcumin in COVID-19 patients with dropped natural killer cells frequency and function

The ongoing COVID-19 pandemic is still a challenging problem in the case of infection treatment. The immunomodulatory effect of Nanocurcumin was investigated in the present study in an attempt to counterbalance the immune response and improve the patients' clinical symptoms. 60 confirmed COVID-19 patients and 60 healthy controls enrolled in the study. COVID-19 patients were divided into Nanocurcumin and placebo received groups. Due to the importance of the role of NK cells in this disease, the frequency, cytotoxicity, receptor gene expression of NK cells, and serum secretion levels of inflammatory cytokines IL-1β, IL-6, TNF-α, as well as circulating C5a as a chemotactic factor an inflammatory mediator was evaluated by flow cytometry, real-time PCR and enzyme-linked immunosorbent assay in both experimental groups before and after the intervention. Given the role of measured factors in the progression and pathogenesis of COVID-19 disease, the results can help find appropriate treatments. The results of this study indicated that the Nanocurcumin could significantly increase the frequency and function of NK cells compared to the placebo-treated group. As an immunomodulatory agent, Nanocurcumin may be a helpful choice to improve NK cell function in COVID-19 patients and improve the clinical outcome of patients.

P16.37: Outcomes of COVID-19 Vaccination Among Kidney Transplant Recipients Admitted for COVID-19 at the National Kidney And Transplant Institute: A Retrospective Study

Background: Kidney transplant recipients are immunocompromised hosts of COVID-19 with a higher risk of infection and severe disease due to underlying CKD and long-term immunosuppression, thus vaccination against COVID is strongly recommended. However, studies indicate that transplant recipients mount lower antibody responses following vaccination compared with healthy individuals. Due to limited information on the outcomes of COVID-19 vaccination on transplant recipients, this study will examine the efficacy of vaccination in preventing severe to critical COVID in this immunocompromised population. Objective: To determine the outcomes of kidney transplant recipients admitted for COVID-19 at the National Kidney and Transplant Institute and the impact of COVID-19 vaccination status on their survival. Methods and Materials: A retrospective study of 131 kidney transplant recipients admitted for COVID-19 from March 2020 to December 2021. Descriptive statistics were used to summarize the clinical characteristics and outcomes of the participants. Results: The median age was 51 years old with a male gender distribution of 54.5%. Chronic glomerulonephritis was the most common primary renal disease. Diabetes, hypertension, and cardiovascular disease were the most common co-morbidities. Patients belonging to the critical COVID group were observed to have older kidney allografts with a median age of 120 months. Among 131 kidney transplant recipients, 24.8% were fully vaccinated and 74.2% were either unvaccinated or partially vaccinated. Of the 32 patients in the vaccinated group, 3 were vaccinated with Astra Zeneca, 5 received Janssen, 7 from Moderna, 10 from Pfizer, 1 received Sputnik and 12 received Coronavac (Sinovac). Among the vaccinated group, those who received Moderna and Pfizer vaccines were observed to have moderate COVID-19 disease progression only with 57.1% from the Moderna group and 40% from the Pfizer group. Among patients who progressed to critical COVID-19, it was observed that a significant number of them came from the Coronavac group. The need for oxygenation was observed in 64% of patients, of which 65.5% were unvaccinated. Acute kidney injury was reported in 43.5% of the overall population, 63.2% of which were observed in the unvaccinated group. Of the 16% who had graft loss during COVID-19 admission, 57.1% were unvaccinated. The incidence of death was lower among fully vaccinated than those in the partial and unvaccinated groups. Likewise, the probability of survival is highest among fully vaccinated than those partially vaccinated and unvaccinated. Renal graft biopsy on patients with COVID-19 has not been practiced at NKTI thus rendering rates of biopsy-proven acute rejection a limitation of the study. Conclusion: Our experience shows that lack of COVID-19 vaccination among kidney transplant recipients demonstrates a higher rate of mortality associated with COVID-19. Key words: COVID-19, renal transplantation, survival, Philippines.

A meta-summary and bioinformatic analysis identified interleukin 6 as a master regulator of COVID-19 severity biomarkers.

With the rising demand for improved COVID-19 disease monitoring and prognostic markers, studies have aimed to identify biomarkers using a range of screening methods. However, the selection of biomarkers for validation from large datasets may result in potentially important biomarkers being overlooked when datasets are considered in isolation. Here, we have utilized a meta-summary approach to investigate COVID-19 biomarker datasets to identify conserved biomarkers of COVID-19 severity. This approach identified a panel of 17 proteins that showed a consistent direction of change across two or more datasets. Furthermore, bioinformatics analysis of these proteins highlighted a range of enriched biological processes that include inflammatory responses and compromised integrity of physiological systems including cardiovascular, neurological, and metabolic. A panel of upstream regulators of the COVID-19 severity biomarkers were identified, including chemical compounds currently under investigation for COVID-19 treatment. One of the upstream regulators, interleukin 6 (IL6), was identified as a “master regulator” of the severity biomarkers. COVID-19 disease severity is intensified due to the extreme viral immunological reaction that results in increased inflammatory biomarkers and cytokine storm. Since IL6 is the primary stimulator of cytokines, it could be used independently as a biomarker in determining COVID-19 disease progression, in addition to a potential therapeutic approach targeting IL6. The array of upstream regulators of the severity biomarkers identified here serve as attractive candidates for the development of new therapeutic approaches to treating COVID-19. In addition, the findings from this study highlight COVID-19 severity biomarkers which represent promising, robust biomarkers for future validation studies for their use in defining and monitoring disease severity and patient prognosis.

CellDrift: inferring perturbation responses in temporally sampled single-cell data.

Cells and tissues respond to perturbations in multiple ways that can be sensitively reflected in the alterations of gene expression. Current approaches to finding and quantifying the effects of perturbations on cell-level responses over time disregard the temporal consistency of identifiable gene programs. To leverage the occurrence of these patterns for perturbation analyses, we developed CellDrift (https://github.com/KANG-BIOINFO/CellDrift), a generalized linear model-based functional data analysis method that is capable of identifying covarying temporal patterns of various cell types in response to perturbations. As compared to several other approaches, CellDrift demonstrated superior performance in the identification of temporally varied perturbation patterns and the ability to impute missing time points. We applied CellDrift to multiple longitudinal datasets, including COVID-19 disease progression and gastrointestinal tract development, and demonstrated its ability to identify specific gene programs associated with sequential biological processes, trajectories and outcomes.

Examining the impact of trimester of diagnosis on COVID-19 disease progression in pregnancy

BackgroundCOVID-19 infection is associated with increased morbidity in pregnancy as well as adverse maternal and neonatal outcomes. Little is currently known about how the timing of infection during pregnancy affects these outcomes.ObjectiveTo evaluate the effect of trimester of COVID-19 infection on disease progression and severity in pregnant patients.Study DesignThis is a prospective cohort study of pregnant patients diagnosed with COVID-19 infection who delivered at a single urban hospital. Universal testing for SARS-CoV-2 was performed at hospital admission as well as for symptomatic patients in inpatient, emergency department, and outpatient settings. Disease severity was defined as asymptomatic, mild, moderate, severe, or critical based on National Institutes of Health (NIH) criteria. We evaluated disease progression from asymptomatic to symptomatic infection as well as asymptomatic or mild infection to moderate, severe, or critical illness, and stratified by trimester of COVID-19 diagnosis. Primary outcomes included progression of COVID-19 disease severity and a composite obstetric outcome, which included delivery < 37 weeks, preeclampsia with severe features, abruption, excess blood loss at delivery (> 500mL for vaginal or > 1000mL for cesarean,) and stillbirth.ResultsFrom March 18, 2020 to September 30, 2021, 1326 pregnant patients were diagnosed with COVID-19 and delivered at our institution, including 103(8%) first, 355(27%) second, and 868(65%) third trimester. First trimester patients were older and had more medical comorbidities; 86% of patients in all trimesters were Hispanic. Among patients admitted within 14 days of a positive test, 3/18(17%) first trimester, 20/47(43%) second trimester, and 34/574(6%) third trimester patients were admitted for the indication of COVID-19 illness. Across all trimesters, 1195(90%) of 1326 COVID-19 infections were asymptomatic or mild, and 45 (10%) of 436 initially asymptomatic patients developed symptoms. Of patients with asymptomatic or mild symptoms at diagnosis, 4 (4%) of 93 first, 18 (5%) of 337 second, and 49 (6%) of 836 third trimester patients developed moderate, severe, or critical illness (p=0.80). There was no significant difference in composite obstetric outcome with respect to trimester of COVID-19 diagnosis (24% 1st trimester, 28% second trimester, 28% third trimester, p=0.69).ConclusionsModerate, severe, or critical illness develops in almost 10 percent of pregnant patients. The frequency of COVID-19 disease progression in pregnancy does not differ by trimester of diagnosis.

Allelic Variations in the Human Genes TMPRSS2 and CCR5, and the Resistance to Viral Infection by SARS-CoV-2.

During the first wave of COVID-19 infection in Italy, the number of cases and the mortality rates were among the highest compared to the rest of Europe and the world. Several studies demonstrated a severe clinical course of COVID-19 associated with old age, comorbidities, and male gender. However, there are cases of virus infection resistance in subjects living in close contact with infected subjects. Thus, to explain the predisposition to virus infection and to COVID-19 disease progression, we must consider, in addition to the genetic variability of the virus and other environmental or comorbidity conditions, the allelic variants of specific human genes, directly or indirectly related to the life cycle of the virus. Here, we analyzed three human genetic polymorphisms belonging to the TMPRSS2 and CCR5 genes in a sample population from Sicily (Italy) to investigate possible correlations with the resistance to viral infection and/or to COVID-19 disease progression as recently described in other human populations. Our results did not show any correlations of the rs35074065, rs12329760, and rs333 polymorphisms with SARS-CoV-2 infection or with COVID-19 disease severity. Further studies on other human genetic polymorphisms should be performed to identify the major human determinants of SARS-CoV-2 viral resistance.

Host cell stress response as a predictor of COVID-19 infectivity and disease progression.

The coronavirus disease (COVID-19) caused by a coronavirus identified in December 2019 has caused a global pandemic. COVID-19 was declared a pandemic in March 2020 and has led to more than 6.3 million deaths. The pandemic has disrupted world travel, economies, and lifestyles worldwide. Although vaccination has been an effective tool to reduce the severity and spread of the disease there is a need for more concerted approaches to fighting the disease. COVID-19 is characterised as a severe acute respiratory syndrome . The severity of the disease is associated with a battery of comorbidities such as cardiovascular diseases, cancer, chronic lung disease, and renal disease. These underlying diseases are associated with general cellular stress. Thus, COVID-19 exacerbates outcomes of the underlying conditions. Consequently, coronavirus infection and the various underlying conditions converge to present a combined strain on the cellular response. While the host response to the stress is primarily intended to be of benefit, the outcomes are occasionally unpredictable because the cellular stress response is a function of complex factors. This review discusses the role of the host stress response as a convergent point for COVID-19 and several non-communicable diseases. We further discuss the merits of targeting the host stress response to manage the clinical outcomes of COVID-19.

Effect of SARS-CoV-2 Variants on the Progression of COVID-19 Disease: A Retrospective Analysis From a Pandemic Hospital

Effect of SARS-CoV-2 Variants on the Progression of COVID-19 Disease: A Retrospective Analysis From a Pandemic Hospital

Blood-based biomarkers for diagnosis, prognosis, and severity prediction of COVID-19: Opportunities and challenges.

The reasons for high morbidity and mortality with Corona virus disease (COVID-19) disease remain unanswered with extremes of manifestation and uncertainty of modes of transmission for which biomarkers are urgently needed for early prediction of severity and prompt treatment. We have reviewed publications from PubMed (years 2019-2021) analysing the biochemical, immune-inflammatory, nucleic acid, and cellular biomarkers that predict infection, disease progression in COVID-19 with emphasis on organ-specific damage. Our analysis of 65 biomarkers assessing the impact of SCoV-2 infection on five organs (lung, liver, cardiac, kidney, and neural) reported that increased levels of CRP, TNF-α, ferritin, IL-6, D-dimer, Procalcitonin, Fibrinogen to Albumin Ratio (FAR), and decrease platelet count (PC), lymphocyte count, leukocyte count, and CD4+/CD8 + ratio shows promising association in the early diagnosis, prediction of prognosis and severity disease and also correlates with cytokine storm a cardinal feature of COVID-19 progression. In the above scenario, this review has put forth the most promising biomarkers for COVID diagnosis and prognosis based on the reported literature. In recent year's chemically synthesized antibody-like biomolecules, aptamers were also used in the diagnosis of COVID-19 which could be preferably used for diagnosis over antibodies. Biomarkers including increase in free DNA and Fibrinogen-to-Albumin Ratio, CRP, PCT, and Ferritin along with a consequential decrease of CD3+ T, CD4+ T, CD8+ T, NK cells with corresponding increase in CD4+/CD8+ ratio following SARS CoV-2 infection has been consistently correlated with disease severity. Despite the two waves of COVID-19 pandemic, currently there is no standard clinical practice guideline for evaluating the severity of the devastating pandemic of COVID-19, hence these biomarkers will have immense relevance for the third and subsequent wave of COVID-19 and related pandemic.

The possible role of TyG index and TRG/HDL, CRP/HDL, NEUTROPHILS/HDL lymphocytes/HDL ratios in disease severity and outcomes in COVID-19 hospitalized patients with arterial hypertension

Background and Aims : The aim of this research was to determine the possible differences and associations of the TyG index and TRG/HDL-C, CRP/HDL-C, NEUTROPHILS/HDL-C, LYMPHOCYTES/HDL-C ratios with disease progression and outcomes in COVID-19 hospitalized patients with AH.

Prognostic significance of serum galectin-3 in hospitalized patients with COVID-19

BackgroundThere are no major tools that could predict disease severity in COVID-19. The aim of this study is to evaluate if serum galectin-3 levels can identify disease progression in COVID-19. MethodsPatients that were hospitalized due to COVID-19 between March and June 2020 were included in this cross-sectional prospective study. Baseline demographic and clinical data in addition to levels of serum parameters including galectin-3 were measured at the time of hospital admission. Patients with COVID-19 were categorized into two groups (non-severe and severe illness). The need for ICU during hospital stay, duration from hospital admission to the transfer to the ICU, and the total length of hospital stay were recorded. ResultsA total of 175 patients were included in the study and among these, 64 patients formed the severe illness group whereas 111 comprised the non-severe illness group. There was statistically significant difference in terms of galectin-3 levels between groups (1.07 ± 0.75 vs 0.484 ± 0.317, p < 0.0001, respectively). Our results showed that galectin-3, IL-6 and CRP levels at admission were independent risk factors associated with transfer to the ICU whereas only galectin-3 was an independent factor for the need for advanced ventilatory support. Also, galectin-3 and IL-6 were independent risk factors related to in-hospital mortality. ConclusionIn conclusion, our results indicated that galectin-3 had moderate power in outlining disease severity and the need for ICU transfer throughout the clinical course in COVID-19.

Pengaruh Pemberian Tiamin Intravena terhadap Kadar Tumor Necrosis Factor Alpha (TNF- α) pada Pasien COVID-19 di Ruang Isolasi

Introduction : Many cytokines and inflammatory mediators play a role in the progression of COVID-19 disease, including the interleukins, interferons, and tumor necrosis factor-α (TNF-α.) groups. An intervention is needed to reduce the levels of this cytokine. Thiamine has the potential to reduce levels of proinflammatory cytokines, especially TNF-α.&#x0D; Objective: To determine the effect of intravenous thiamine administration on TNF-α levels in COVID-19 patients in the isolation room of RSUP H Adam Malik.&#x0D; Methods: This study used an analytical design of one group pre test - post test in the isolation room of Haji Adam Malik General Hospital Medan with a sample size of 16 people. Samples were given thiamine IV 200 mg/12 hours and then the levels of TNF-α were measured by ELISA method.&#x0D; Results: Characteristics of the sample obtained were equal in number of males and females (1:1), the mean age was 43 ±14.78 years, the mean BMI was 23.31 ± 6.55, the mean systolic was 122.50 ± 5.77 mmHg and diastolic 88.88 ± 6.55 mmHg. The majority of the sample (50%) had no comorbidities. Before administration of thiamine, the median TNF-α was 186.5 pg/mL with a minimum and maximum value (171-420 pg/mL) and after administration of thiamine, the median TNF-α was 180.50 pg/mL with a minimum and maximum value (122-200 pg/mL) obtained a p value of 0.001 &lt; 0.05 (there is a significant effect).&#x0D; Conclusion: In this study, the mean TNF-α level was lower when given intravenous thiamine. This decrease in TNF-α levels was also found to be significant after intravenous thiamine administration.

Pulmonary lesions following inoculation with the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant in Syrian golden hamsters

ABSTRACT The Omicron BA.1 (B.1.1.529) SARS-CoV-2 variant is characterized by a high number of mutations in the viral genome, associated with immune escape and increased viral spread. It remains unclear whether milder COVID-19 disease progression observed after infection with Omicron BA.1 in humans is due to reduced pathogenicity of the virus or due to pre-existing immunity from vaccination or previous infection. Here, we inoculated hamsters with Omicron BA.1 to evaluate pathogenicity and kinetics of viral shedding, compared to Delta (B.1.617.2) and to animals re-challenged with Omicron BA.1 after previous SARS-CoV-2 614G infection. Omicron BA.1 infected animals showed reduced clinical signs, pathological changes, and viral shedding, compared to Delta-infected animals, but still showed gross- and histopathological evidence of pneumonia. Pre-existing immunity reduced viral shedding and protected against pneumonia. Our data indicate that the observed decrease of disease severity is in part due to intrinsic properties of the Omicron BA.1 variant.

Metabolite, protein, and tissue dysfunction associated with COVID-19 disease severity

Proteins are direct products of the genome and metabolites are functional products of interactions between the host and other factors such as environment, disease state, clinical information, etc. Omics data, including proteins and metabolites, are useful in characterizing biological processes underlying COVID-19 along with patient data and clinical information, yet few methods are available to effectively analyze such diverse and unstructured data. Using an integrated approach that combines proteomics and metabolomics data, we investigated the changes in metabolites and proteins in relation to patient characteristics (e.g., age, gender, and health outcome) and clinical information (e.g., metabolic panel and complete blood count test results). We found significant enrichment of biological indicators of lung, liver, and gastrointestinal dysfunction associated with disease severity using publicly available metabolite and protein profiles. Our analyses specifically identified enriched proteins that play a critical role in responses to injury or infection within these anatomical sites, but may contribute to excessive systemic inflammation within the context of COVID-19. Furthermore, we have used this information in conjunction with machine learning algorithms to predict the health status of patients presenting symptoms of COVID-19. This work provides a roadmap for understanding the biochemical pathways and molecular mechanisms that drive disease severity, progression, and treatment of COVID-19.