Severe Cases Of Coronavirus Disease 2019 Research Articles

Exploring immune response and lab markers across COVID-19 severity levels

<p>This retrospective cohort study investigated antigen-specific antibody responses to SARS-CoV-2 and laboratory markers in coronavirus disease 2019 (COVID-19) patients of varying severities. Serum or plasma samples collected early in the pandemic were analyzed for the presence of IgG antibodies and IgG subclasses which target the recombinant spike (S) and nucleocapsid (N) proteins of SARS-CoV-2. Correlation analyses were conducted to assess the possible relationship between the IgG subclasses to SARS-CoV-2 proteins, inflammatory markers, and the severity of the disease. It was shown that the severity of the disease positively correlated with the C-reactive protein (CRP), but most of all with the neutrophil/lymphocyte ratio (NLR) levels. IgG titers against the S- and N-proteins decreased in the most severe COVID-19 cases, which potentially attributed to a delayed IgG formation compared to milder infections. The presence of anti-spike IgG displayed a medium negative correlation trend (not statistically significant, which might be due to the small sample size in our study) with laboratory markers (such as CRP, Fibrinogen, Degree) which are suggestive of infection severity. anti-S IgG correlated positively but weakly with the serum histamine levels. The presence of anti-N IgG at the time of hospitalization correlated with the subsequent outcome. At the same time, anti-N IgG1 correlated with the detection of the viral RNA in the blood. Thus, seroconversion may occur later in patients with a more severe pneumonia. The summary data suggests correlations between the expression of inflammatory markers and the antibody responses, which can also serve as early clinical markers.</p>

Анализ состояния микрососудистого русла и планирование реабилитационных мероприятий у детей после перенесенной новой коронавирусной инфекции

Aim: to analyze microcirculation in children who recovered from coronavirus disease 2019 (COVID-19) in order to identify microcirculatory disorders and their association with clinical symptoms and to design rehabilitation measures Patients and Methods: the study included 78 children aged 7–15 years who recovered from COVID-19. All children had negative SARS- CoV-2 RNA tests (oropharyngeal and naso-pharyngeal swabs) by PCR and positive blood SARS-CoV-2 immunoglobulin class G (IgG). The control group included 30 healthy age-matched children who did not experience COVID-19. Microcirculation was evaluated by slit lamp biomicroscopy for imaging bulbar conjunctival microvasculature with further morphometric processing of images. Exclusion criteria included inflammatory eye diseases, acute bronchopulmonary diseases or their exacerbation, arterial hy-pertension, and obesity grades 2 to 4. Results: a decrease in the count of capillaries, pre- and postcapillaries, and 1 st-order ar-terioles, as well as a decrease in the percentage of 1st-order arterioles were identified in indi-viduals who had been asymptomatic or had experienced mild COVID-19 symptoms 3 to 12 months prior. Additionally, an increase in the count of 1st-order venules and arteriolar venular anastomoses, 2nd-order arterioles and venules, and 1st-order arteries and veins was revealed. The coefficient of irregularity in venular caliber in severe cases of COVID-19 was 0.62±0.05, which was significantly (p<0.023) greater than that in asymptomatic cases of COVID-19 (0.43±0.03). This indicates a persistent reduction in venous tone Conclusions: our study demonstrated microvascular disorders in children in the long-term period following COVID-19, indicating a long-term maladaptation of microcirculation These children can be classified as belonging to the risk group for microcirculatory disorders in the post- COVID period. KEYWORDS: children, COVID-19, long COVID, microvasculature, capillaries, venules, arterioles, microcirculation. FOR CITATION: Mikheeva I.G., Kurasova O.B., Milekhina M.Yu., Moiseev A.B., Kuznetsova N.I., Kalinovskaya I.I., Zimina N.A., Vereshchagina T.G. Study of microcirculation and the scheduling of rehabilitation measures in children who have recovered from coronavirus disease 2019. Russian Journal of Woman and Child Health. 2024;7(2):171–176 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-13.

Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against SARS-COV-2 targeting main protease and papain-like protease.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be over, but its variants continue to emerge, and patients with mild symptoms having long COVID is still under investigation. SARS-CoV-2 infection leading to elevated cytokine levels and suppressed immune responses set off cytokine storm, fatal systemic inflammation, tissue damage, and multi-organ failure. Thus, drug molecules targeting the SARS-CoV-2 virus-specific proteins or capable of suppressing the host inflammatory responses to viral infection would provide an effective antiviral therapy against emerging variants of concern. Evolutionarily conserved papain-like protease (PLpro) and main protease (Mpro) play an indispensable role in the virus life cycle and immune evasion. Direct-acting antivirals targeting both these viral proteases represent an attractive antiviral strategy that is also expected to reduce viral inflammation. The present study has evaluated the antiviral and anti-inflammatory potential of natural triterpenoids: azadirachtin, withanolide_A, and isoginkgetin. These molecules inhibit the Mpro and PLpro proteolytic activities with half-maximal inhibitory concentrations (IC50) values ranging from 1.42 to 32.7 μM. Isothermal titration calorimetry (ITC) analysis validated the binding of these compounds to Mpro and PLpro. As expected, the two compounds, withanolide_A and azadirachtin, exhibit potent anti-SARS-CoV-2 activity in cell-based assays, with half-maximum effective concentration (EC50) values of 21.73 and 31.19 μM, respectively. The anti-inflammatory roles of azadirachtin and withanolide_A when assessed using HEK293T cells, were found to significantly reduce the levels of CXCL10, TNFα, IL6, and IL8 cytokines, which are elevated in severe cases of COVID-19. Interestingly, azadirachtin and withanolide_A were also found to rescue the decreased type-I interferon response (IFN-α1). The results of this study clearly highlight the role of triterpenoids as effective antiviral molecules that target SARS-CoV-2-specific enzymes and also host immune pathways involved in virus-mediated inflammation.

Motivasi Keluarga Berhubungan Dengan Persepsi Masyarakat Dalam Penggunaan Vaksin COVID-19

Introduction: COVID-19 (Corona Virus Disease 2019) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In severe cases of COVID-19, it can cause pneumonia, acute respiratory syndrome, kidney failure, and even death. Vaccines are one of the efforts to deal with COVID-19. The existence of a vaccine is expected to be good news in preventing the spread of the COVID-19 virus. There are many factors that can influence a person's perception of the use of the COVID-19 vaccine. These factors include family motivation having a significant relationship with perceptions of the use of the COVID-19 vaccine. Methods: This study aims to determine the relationship between family motivation and public perception of the use of the COVID-19 vaccine in Haurwangi Village in Haurwangi District, Cianjur in 2021. This type of research is a quantitative study in the form of correlation research with a cross-sectional design approach. The research sample amounted to 99 respondents with a sampling technique that is purposive sampling technique. Results: Based on the results of the study, it was found that most of the respondents had high family motivation in the use of the COVID-19 vaccine (57,6%) most of the respondents had a good perception of the use of the COVID-19 vaccine (53,5%) there was a significant relationship between family motivation and public perception in the use of the COVID-19 vaccine in Haurwangi Village in Haurwangi District, Cianjur in 2021 (p-value = 0,004). Discussion: That was a significant relationship between family motivation and public perception in the use of the COVID-19 vaccine.

Efficacy and Safety of Treatment with Plasma from COVID-19-Recovered Individuals.

Convalescent plasma therapy, which involves administering plasma from recovered coronavirus disease 2019 (COVID-19) patients to infected individuals, is being explored as a potential treatment for severe cases of COVID-19. This study aims to evaluate the efficacy and safety of convalescent plasma therapy in COVID-19 patients with moderate to severe illness. An open-label, single-arm intervention study was conducted without a control group. Plasma collected from recovered COVID-19 patients was administered to eligible participants. The primary endpoint was the proportion of patients who were placed on artificial ventilation or died within 14 days of transfusion. Secondary endpoints included clinical improvement, viral load measurements, and adverse event monitoring. A total of 59 cases were included in the study. The primary endpoint was evaluated by comparing the rate obtained in the study to an existing rate of 25%. The study also assessed clinical improvement, viral load changes, and safety endpoints through adverse event monitoring. Convalescent plasma therapy shows potential as a treatment option for COVID-19. This study aimed to provide evidence for the efficacy and safety of this therapy and may contribute to its future use in treating severe cases of COVID-19.

Assessing the gene expression of the adenosine 5'-monophosphate-activated protein kinase (AMPK) and its relation with the IL-6 and IL-10 plasma levels in COVID-19 patients.

Metabolic dysregulation and excessive inflammation are implicated in the pathogenesis of the highly infectious disease of coronavirus disease 2019 (COVID-19), which is caused by a newly emerging coronavirus (i.e., severe acute respiratory syndrome-coronavirus 2; SARS-CoV-2). The adenosine 5'-monophosphate-activated protein kinase (AMPK), an energy sensor regulating the metabolic pathways in diverse cells, exerts a regulatory role in the immune system. This study aims to examine the mRNA expression level of AMPK and the plasma levels of interleukin-6 (IL-6) and IL-10 cytokines in patients with different grades of COVID-19. Peripheral blood was collected from 60 patients with COVID-19 (Moderate, severe, and critical). The plasma levels of IL-6 and IL-10 were quantified by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression level of AMPK was determined using real-time PCR. The results showed that the plasma levels of IL-6 increased significantly in critical and severe patients compared to moderate cases of COVID-19 (P < 0.001). Moreover, IL-10 plasma concentrations were significantly higher in critical and severe cases than in moderate cases of COVID-19 (P < 0.01 and P < 0.05, respectively). Also, the gene expression of AMPK was meaningfully enhanced in critical patients relative to moderate and severe cases of COVID-19, in order (P < 0.001 and P < 0.01, respectively). There was a positive association between AMPK gene expression and plasma levels of IL-6 and IL-10 (P = 0.006, r = 0.348, P = 0.028, r = 0.283, respectively). Increasing AMPK gene expression is likely a necessary effort of the immune system to inhibit inflammation in critical COVID-19. However, this effort seems to be inadequate, probably due to factors that induce inflammation, like erythrocyte sedimentation rate (ESR) and IL-6.

Single-cell RNA-seq public data reveal the gene regulatory network landscape of respiratory epithelial and peripheral immune cells in COVID-19 patients.

Infection with SARS-CoV-2 leads to coronavirus disease 2019 (COVID-19), which can result in acute respiratory distress syndrome and multiple organ failure. However, its comprehensive influence on pathological immune responses in the respiratory epithelium and peripheral immune cells is not yet fully understood. In this study, we analyzed multiple public scRNA-seq datasets of nasopharyngeal swabs and peripheral blood to investigate the gene regulatory networks (GRNs) of healthy individuals and COVID-19 patients with mild/moderate and severe disease, respectively. Cell-cell communication networks among cell types were also inferred. Finally, validations were conducted using bulk RNA-seq and proteome data. Similar and dissimilar regulons were identified within or between epithelial and immune cells during COVID-19 severity progression. The relative transcription factors (TFs) and their targets were used to construct GRNs among different infection sites and conditions. Between respiratory epithelial and peripheral immune cells, different TFs tended to be used to regulate the activity of a cell between healthy individuals and COVID-19 patients, although they had some TFs in common. For example, XBP1, FOS, STAT1, and STAT2 were activated in both the epithelial and immune cells of virus-infected individuals. In contrast, severe COVID-19 cases exhibited activation of CEBPD in peripheral immune cells, while CEBPB was exclusively activated in respiratory epithelial cells. Moreover, in patients with severe COVID-19, although some inflammatory genes, such as S100A8/A9, were found to be upregulated in both respiratory epithelial and peripheral immune cells, their relative regulators can differ in terms of cell types. The cell-cell communication analysis suggested that epidermal growth factor receptor signaling among epithelia contributes to mild/moderate disease, and chemokine signaling among immune cells contributes to severe disease. This study identified cell type- and condition-specific regulons in a wide range of cell types from the initial infection site to the peripheral blood, and clarified the diverse mechanisms of maladaptive responses to SARS-CoV-2 infection.

Evaluation of the Relationship Between Serum miR-200b-3p and miR-214-3p Expression Levels with Soluble ACE2 and TMPRSS2 in COVID-19 Patients.

The emergence and rapid global spread of the coronavirus disease 2019 (COVID-19) has presented a significant global health challenge. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human host cells through the interaction of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), which serve as main regulators for viral entry. Specifically, ACE2 and TMPRSS2 genes are influenced by two microRNAs: miR-200b-3p and miR-214-3p, respectively. The objective of this study was to explore the association between the serum levels of miR-200b-3p and miR-214-3p and the presence of circulating ACE2 and TMPRSS2 in severe and non-severe cases of COVID-19. This study sought to examine the potential utility of microRNAs as biomarkers for assessing disease severity and progression. Additionally, the study aimed to elucidate the interplay between microRNAs and the ACE2 and TMPRSS2 proteins, which play crucial roles in facilitating SARS-CoV-2 viral entry and infection. This practical-foundational study involved the collection of samples from 61 hospitalized patients with confirmed COVID-19 and 31 healthy individuals. Subsequently, the enzyme-linked immunosorbent assay (ELISA) technique was utilized to measure the concentrations of ACE2 and TMPRSS2 in the blood samples. Additionally, the expression levels of serum miR-200b-3p and miR-214-3p were analyzed using real-time polymerase chain reaction (PCR). The statistical analysis of the data was conducted using GraphPad Prism software (version 8.02) and SPSS software (version 19.0), ensuring the accurate interpretation of results. The findings revealed significant increases in the peripheral blood concentrations of ACE2 and TMPRSS2 in patients with non-severe COVID-19, compared to healthy individuals (P < 0.001 and P < 0.01, respectively). Similarly, patients with severe COVID-19 exhibited higher serum levels of ACE2 and TMPRSS2 than healthy subjects (P < 0.0001). Additionally, the serum levels of miR-200b-3p and miR-214-3p were decreased in both non-severe and severe COVID-19 patients, compared to healthy individuals (P < 0.01 and P < 0.0001, respectively). Moreover, a decrease in the serum levels of both miR-200b-3p and miR-214-3p was observed in patients with severe COVID-19, compared to those with non-severe cases (P < 0.001). Furthermore, this study identified a negative correlation between miR-200b-3p and ACE2 serum levels and between miR-214-3p and TMPRSS2 peripheral blood levels. The above-mentioned findings suggest that miR-200b-3p and miR-214-3p might be potential biomarkers for disease severity and prognosis in COVID-19 patients.

SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels

Patients with coronavirus disease 2019 (COVID-19) present increased risk for ischemic cardiovascular complications up to 1 year after infection. Although the systemic inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques remains unknown. Here we report that SARS-CoV-2 viral RNA is detectable and replicates in coronary lesions taken at autopsy from severe COVID-19 cases. SARS-CoV-2 targeted plaque macrophages and exhibited a stronger tropism for arterial lesions than adjacent perivascular fat, correlating with macrophage infiltration levels. SARS-CoV-2 entry was increased in cholesterol-loaded primary macrophages and dependent, in part, on neuropilin-1. SARS-CoV-2 induced a robust inflammatory response in cultured macrophages and human atherosclerotic vascular explants with secretion of cytokines known to trigger cardiovascular events. Our data establish that SARS-CoV-2 infects coronary vessels, inducing plaque inflammation that could trigger acute cardiovascular complications and increase the long-term cardiovascular risk.

Long-term Cardiovascular, Cerebrovascular, and Other Thrombotic Complications in COVID-19 Survivors: A Retrospective Cohort Study.

Growing evidence suggests that some coronavirus disease 2019 (COVID-19) survivors experience a wide range of long-term postacute sequelae. We examined the postacute risk and burden of new-incident cardiovascular, cerebrovascular, and other thrombotic complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a highly vaccinated multiethnic Southeast Asian population, during Delta predominance. This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals who had a positive SARS-CoV-2 test between 1 September and 30 November 2021 when Delta predominated community transmission. Concurrently, we constructed a test-negative control group by enrolling individuals between 13 April 2020 and 31 December 2022 with no evidence of SARS-CoV-2 infection. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular, cerebrovascular, and other thrombotic complications using doubly robust competing-risks survival analysis. Risks were reported using 2 measures: hazard ratio (HR) and excess burden (EB) with 95% confidence intervals. We included 106 012 infected cases and 1 684 085 test-negative controls. Compared with the control group, individuals with COVID-19 exhibited increased risk (HR, 1.157 [1.069-1.252]) and excess burden (EB, 0.70 [.53-.88]) of new-incident cardiovascular and cerebrovascular complications. Risks decreased in a graded fashion for fully vaccinated (HR, 1.11 [1.02-1.22]) and boosted (HR, 1.10 [.92-1.32]) individuals. Conversely, risks and burdens of subsequent cardiovascular/cerebrovascular complications increased for hospitalized and severe COVID-19 cases (compared to nonhospitalized cases). Increased risks and excess burdens of new-incident cardiovascular/cerebrovascular complications were reported among infected individuals; risks can be attenuated with vaccination and boosting.

Association between cyclin-dependent kinase inhibitor 2B antisense RNA 1 and zinc finger homeobox 3 gene polymorphisms and COVID-19 severity

BackgroundThere is no doubt about the cardiovascular complications of coronavirus disease 2019 (COVID-19). Several genetic studies have demonstrated an association between genetic variants in a region on chromosome 9p21 and in a region on chromosome 16q22 with myocardial infarction (MI) and atrial fibrillation (AF) accompanied by cerebral infarction (CI), respectively.ObjectivesMI and CI susceptibility in patients with CDKN2B-AS1 and ZFHX3 polymorphisms, respectively, may have an effect on COVID-19 severity. We aimed to investigate whether there is an association between the cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) rs1333049 and zinc finger homeobox 3 (ZFHX3) rs2106261 single nucleotide polymorphisms (SNPs) and the degree of COVID-19 severity.Subjects and methodsThis current work was carried out on 360 subjects. They were classified into three groups: 90 severe COVID-19 cases, 90 moderate COVID-19 cases and 180 age- and gender-matched healthy controls. All subjects underwent genotyping of CDKN2B-AS1 (rs1333049) and ZFHX3 (rs2106261) by real-time PCR.ResultsThe frequency of G/C in CDKN2B-AS1 (rs1333049) was higher in severe and moderate COVID-19 patients than in controls (71.1% and 53.3% vs. 37.8%). The frequency of the C/C of CDKN2B-AS1 (rs1333049) was higher in moderate COVID-19 patients than in controls (26.7% vs. 13.3%). There were no significant differences regarding genotype frequency and allelic distribution of ZFHX3 (rs2106261) between COVID-19 patients and healthy controls.ConclusionCDKN2B-AS1 (rs1333049) gene polymorphism may play a role in determining the degree of COVID-19 severity. Further studies on its effect on cyclins and cyclin-dependent kinases (CDKs) [not measured in our study] may shed light on new treatment options for COVID-19.

Brain Renin-Angiotensin System: From Physiology to Pathology in Neuronal Complications Induced by SARS-CoV-2.

Angiotensin-converting enzyme 2 (ACE2), a key enzyme in the renin-angiotensin system (RAS), is expressed in various tissues and organs, including the central nervous system (CNS). The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease-2019 (COVID-19), binds to ACE2, which raises concerns about the potential for viral infection in the CNS. There are numerous reports suggesting a link between SARS-CoV-2 infection and neurological manifestations. This study aimed to present an updated review of the role of brain RAS components, especially ACE2, in neurological complications induced by SARS-CoV-2 infection. Several routes of SARS-CoV-2 entry into the brain have been proposed. Because an anosmia condition appeared broadly in COVID-19 patients, the olfactory nerve route was suggested as an early pathway for SARS-CoV-2 entry into the brain. In addition, a hematogenous route via disintegrations in the blood-brain barrier following an increase in systemic cytokine and chemokine levels and retrograde axonal transport, especially via the vagus nerve innervating lungs, have been described. Common nonspecific neurological symptoms in COVID-19 patients are myalgia, headache, anosmia, and dysgeusia. However, more severe outcomes include cerebrovascular diseases, cognitive impairment, anxiety, encephalopathy, and stroke. Alterations in brain RAS components such as angiotensin II (Ang II) and ACE2 mediate neurological manifestations of SARS-CoV-2 infection, at least in part. Downregulation of ACE2 due to SARS-CoV-2 infection, followed by an increase in Ang II levels, leads to hyperinflammation and oxidative stress, which in turn accelerates neurodegeneration in the brain. Furthermore, ACE2 downregulation in the hypothalamus induces stress and anxiety responses by increasing corticotropin-releasing hormone. SARS-CoV-2 infection may also dysregulate the CNS neurotransmission, leading to neurological complications observed in severe cases of COVID-19. It can be concluded that the neurological manifestations of COVID-19 may be partially associated with changes in brain RAS components.

Pediatric COVID-19 and Diabetes: An Investigation into the Intersection of Two Pandemics.

Coronavirus disease 2019 (COVID-19) is a complex infectious disease caused by the SARS-CoV-2 virus, and it currently represents a worldwide public health emergency. The pediatric population is less prone to develop severe COVID-19 infection, but children presenting underlying medical conditions, such as diabetes mellitus, are thought to be at increased risk of developing more severe forms of COVID-19. Diabetic children face new challenges when infected with SARS-CoV-2. On one hand, the glycemic values become substantially more difficult to manage as COVID-19 is a predisposing factor for hyperglycemia. On the other hand, alongside other risk factors, high glycemic values are incriminated in modulating immune and inflammatory responses, leading to potentially severe COVID-19 cases in the pediatric population. Also, there are hypotheses of SARS-CoV-2 being diabetogenic itself, but this information is still to be confirmed. Furthermore, it is reported that there was a noticeable increase in the number of cases of new-onset type 2 diabetes among the pediatric population, and the complications in these patients with COVID-19 include the risk of developing autoimmune diseases under the influence of stress. Additionally, children with diabetes mellitus are confronted with lifestyle changes dictated by the pandemic, which can potentially lead to the onset or exacerbation of a potential underlying anxiety disorder or depression. Since the literature contains a series of unknowns related to the impact of COVID-19 in both types of diabetes in children, the purpose of our work is to bring together the data obtained so far and to identify potential knowledge gaps and areas for future investigation regarding COVID-19 and the onset of diabetes type 1 or type 2 among the pediatric population.

Harnessing the Antiviral and Anti-inflammatory Properties of Copper and Zinc Chlorophyllins: A Potential Therapeutic for COVID-19 Patients with Acute Respiratory Distress Syndrome

Chlorophyllins are highly soluble non-toxic derivatives of chlorophyll α, containing a centralised metal at their core, known to target and treat cancer and immune-based diseases. The antiviral and anti-inflammatory effects of sodium copper chlorophyllin (SCC) and sodium zinc chlorophyllin (SZC), though documented, are rarely considered in treatment of viral respiratory diseases. Moreover, the use of chlorophyllins to potentially treat acute respiratory distress syndrome (ARDS), triggered by infection with respiratory viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has yet to be studied. The published literature suggests antiviral and anti-inflammatory effects against SARS-CoV-2 and other enveloped respiratory viruses. Treatment with chlorophyllins inhibits virus entry, as well as replication and budding of viral progeny from the host cell in cell lines infected with enveloped respiratory viruses. Furthermore, treatments with SCC in vivo show diminished viral loads in animals infected with respiratory viruses, suggesting clinical antiviral capacity in treating viruses that cause ARDS-like manifestations, notably coronavirus disease 2019 (COVID-19). Similarly, SZC reduces inflammatory responses, while SCC may block key pro-inflammatory markers in vitro and in vivo, producing an anti-inflammatory effect against interleukin-6 and tumour necrosis factor α, two of the main antagonists associated with poorer outcomes in viral respiratory diseases, particularly among COVID-19 patients. This indicates a possible application in treating cytokine storm and hyperinflammation. Both SCC and SZC could act as a novel therapeutic in the treatment and prevention of ARDS and related respiratory complications, especially relevant to severe COVID-19 cases.

The role of chest X-ray in coronavirus disease 2019 (COVID-19) infection: findings and correlation with clinical outcome.

It is possible to diagnose coronavirus disease 2019 (COVID-19) faster and more accurately with chest X-ray (CXR) and chest computed tomography (CT) than with reverse transcriptase PCR (RT-PCR) tests. The aim of this study was to verify the possibility of reducing the use of CT in diagnosis and follow-up of COVID-19 infection by using CXR. A total of 326 COVID-19 patients who were hospitalized in Ankara City Hospital were included in this retrospective study. A total of 326 patients were RT-PCR positive for COVID-19 infection; 178 were male (54.6%) and 148 were female (45.4%), with a median age of 45. Considering the results, the baseline CXR sensitivity in our experience was approximately 72%. The CXRs of 113 patients with abnormal CT were divided into 2 groups, the CXR normal and abnormal groups, and were then compared. In the 1st group with abnormal CXR, the mean age, the number of patients over 65 years old, and the comorbidity rate were higher. Additionally, it was determined that the number of patients requiring respiratory support and intensive care unit (ICU) admission in this 1st group was higher than in the 2nd group (with normal CXR). Most of the patients who died (91%, 10/11) were in Group 1. In the group with normal CXR, no patients in the critically ill category needed invasive or non-invasive mechanical ventilators. CXR can help in detecting clinically moderate and severe cases of COVID-19. CXR can assist clinicians in patient management and treatment planning regarding the clinical course, respiratory support, ICU need, and mortality and can help them prepare for potential negative outcomes.

The triangle relationship between human genome, gut microbiome, and COVID-19: opening of a Pandora's box.

Since the pandemic started, the coronavirus disease 2019 (COVID-19) has spread worldwide. In patients with COVID-19, the gut microbiome (GM) has been supposed to be closely related to the progress of the disease. The gut microbiota composition and human genetic variation are also connected in COVID-19 patients, assuming a triangular relationship between the genome, GM, and COVID-19. Here, we reviewed the recent developments in the study of the relationship between gut microbiota and COVID-19. The keywords "COVID-19," "microbiome," and "genome" were used to search the literature in the PubMed database. We first found that the composition of the GM in COVID-19 patients varies according to the severity of the illness. Most obviously, Candida albicans abnormally increased while the probiotic Bifidobacterium decreased in severe cases of COVID-19. Interestingly, clinical studies have consistently emphasized that the family Lachnospiraceae plays a critical role in patients with COVID-19. Additionally, we have demonstrated the impact of microbiome-related genes on COVID-19. Specially, we focused on angiotensin-converting enzyme 2's dual functions in SARS-CoV-2 infection and gut microbiota alternation. In summary, these studies showed that the diversity of GMs is closely connected to COVID-19. A triangular relationship exists between COVID-19, the human genome, and the gut flora, suggesting that human genetic variations may offer a chance for a precise diagnosis of COVID-19, and the important relationships between genetic makeup and microbiome regulation may affect the therapy of COVID-19.

Estimating the number of severe COVID-19 cases and COVID-19-related deaths averted by a nationwide vaccination campaign in Republic of Korea.

The Korea Disease Control and Prevention Agency promotes vaccination by regularly providing information on its benefits for reducing the severity of coronavirus disease 2019 (COVID-19). This study aimed to analyze the number of averted severe COVID-19 cases and COVID-19-related deaths by age group and quantify the impact of Republic of Korea's nationwide vaccination campaign. We analyzed an integrated database from the beginning of the vaccination campaign on February 26, 2021 to October 15, 2022. We estimated the cumulative number of severe cases and COVID-19-related deaths over time by comparing observed and estimated cases among unvaccinated and vaccinated groups using statistical modeling. We compared daily age-adjusted rates of severe cases and deaths in the unvaccinated group to those in the vaccinated group and calculated the susceptible population and proportion of vaccinated people by age. There were 23,793 severe cases and 25,441 deaths related to COVID-19. We estimated that 119,579 (95% confidence interval [CI], 118,901-120,257) severe COVID-19 cases and 137,636 (95% CI, 136,909-138,363) COVID-19-related deaths would have occurred if vaccination had not been performed. Therefore, 95,786 (95% CI, 94,659-96,913) severe cases and 112,195 (95% CI, 110,870-113,520) deaths were prevented as a result of the vaccination campaign. We found that, if the nationwide COVID-19 vaccination campaign had not been implemented, the number of severe cases and deaths would have been at least 4 times higher. These findings suggest that Republic of Korea's nationwide vaccination campaign reduced the number of severe cases and COVID-19 deaths.

Hypoxia-altered cholesterol homeostasis enhances the expression of interferon-stimulated genes upon SARS-CoV-2 infections in monocytes.

Hypoxia contributes to numerous pathophysiological conditions including inflammation-associated diseases. We characterized the impact of hypoxia on the immunometabolic cross-talk between cholesterol and interferon (IFN) responses. Specifically, hypoxia reduced cholesterol biosynthesis flux and provoked a compensatory activation of sterol regulatory element-binding protein 2 (SREBP2) in monocytes. Concomitantly, a broad range of interferon-stimulated genes (ISGs) increased under hypoxia in the absence of an inflammatory stimulus. While changes in cholesterol biosynthesis intermediates and SREBP2 activity did not contribute to hypoxic ISG induction, intracellular cholesterol distribution appeared critical to enhance hypoxic expression of chemokine ISGs. Importantly, hypoxia further boosted chemokine ISG expression in monocytes upon infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Mechanistically, hypoxia sensitized toll-like receptor 4 (TLR4) signaling to activation by SARS-CoV-2 spike protein, which emerged as a major signaling hub to enhance chemokine ISG induction following SARS-CoV-2 infection of hypoxic monocytes. These data depict a hypoxia-regulated immunometabolic mechanism with implications for the development of systemic inflammatory responses in severe cases of coronavirus disease-2019 (COVID-19).

How Can We Predict Disease Severity in Viral Infections?

How Can We Predict Disease Severity in Viral Infections?

The impact of bariatric and metabolic surgery on the morbidity and mortality of patients infected during the COVID-19 pandemic: a retrospective cohort study.

Since the impact of the coronavirus disease 2019 (COVID-19) pandemic in March 2020, several studies have shown a strong relationship between obesity and severe cases of COVID-19. It is imperative to assess whether bariatric surgery exerts a protective effect in such cases. This study aimed to assess the impact of bariatric surgery on the morbidity and mortality in obese patients during the COVID-19 pandemic. A comprehensive search was performed using the PubMed and Cochrane Library databases. Retrospective cohort studies conducted in the Faculdade de Medicina da Universidade Cidade de São Paulo, São Paulo (SP), Brazil. The search comprised the following descriptors: "bariatric, surgery, COVID-19". Current retrospective cohort studies that examined the influence of bariatric surgery on the morbidity and mortality of obese patients during the COVID-19 pandemic were considered eligible. After removing duplicates, 184 studies were obtained from the databases. Of these, 181 were excluded from the analysis as they did not meet the eligibility criteria. Patients undergoing postoperative follow-up of bariatric surgery had a similar probability of SARS-CoV-2 infection compared to the general population, and persistent comorbidities were associated with an increased risk and severity of infection. Bariatric surgery has a protective effect against severe COVID-19 in the obese population, bringing the prevalence of severe disease cases to levels equivalent to those of the nonobese general population, with a positive impact on morbidity and mortality.