Non-severe Coronavirus Disease 2019 Research Articles

Efficacy of Azvudine Therapy in Patients with Severe and Non-Severe COVID-19: A Propensity Score-Matched Analysis.

Azvudine is used to treat patients with the coronavirus disease 2019 (COVID-19). This study evaluated the clinical efficacy of azvudine in hospitalized patients with different severities of COVID-19 because few studies have described this in patients with severe and non-severe COVID-19. This retrospective study included hospitalized patients with COVID-19 in Guizhou Provincial People's Hospital between December 2022 and January 2023. Azvudine-treated patients and controls were matched for sex, age, and disease severity at admission. Laboratory results and outcomes, including all-cause mortality, invasive mechanical ventilation, intensive care unit admission, and hospital stay length, were evaluated. Stratified analysis was used to explore the difference in the efficacy of azvudine in severe and non-severe COVID-19 patients. No significant differences in all-cause mortality were observed between the 303 azvudine recipients and 303 matched controls. However, azvudine-treated patients had shorter hospital stays (8.34±4.79 vs 9.17±6.25 days, P=0.046) and higher lymphocyte improvement rates (21.5% vs 13.9%, P=0.019), with a more pronounced effect in patients with non-severe COVID-19 (length of hospital stay, 8.07±4.35 vs 10.00±6.29 days, P=0.001; lymphocyte improvement rate, 23.8% vs 12.8%, P=0.015). Azvudine treatment shortens hospital stay length and increases the rate of lymphocyte count improvement in patients with non-severe COVID-19, suggesting that azvudine may be a treatment option for these patients.

Outcomes of COVID-19 in 24 hospitalized liver transplant recipients: an observational study

BackgroundAlthough liver transplant (LT) recipients are considered a population at risk of severe features of coronavirus disease 2019 (COVID-19), data in this regard are scarce and controversial. In this study, we reported the outcome of 24 cases of LT recipients who were hospitalized due to COVID-19 and investigated the role-playing factors in the severity of the disease.MethodsIn this single-center, analytic case-series study, eligible patients were among LT recipients who were hospitalized due to the diagnosis of COVID-19 based on positive results of polymerase chain reaction. Participants were categorized as severe COVID-19 if they were admitted to the intensive care unit, experienced respiratory failure demanding mechanical ventilation, or eventually died. Demographic and clinical data, COVID-19 symptoms and specific treatments, laboratory biomarkers, and immunosuppressive regimens and their alteration during the admission were recorded. Analysis was done using SPSS software.ResultsTwenty-four hospitalized LT patients were included, of which nine had severe and fifteen had non-severe COVID-19. Out of 9 patients with severe COVID-19, four sadly died. The analysis and comparison between the two groups revealed longer hospital stays (P = 0.02), lower lymphocyte counts (P = 0.002), and higher levels of C-reactive protein (CRP) (P = 0.006) in patients with severe COVID-19. Patients with non-severe COVID-19 had higher doses of tacrolimus and mycophenolate in their baseline immunosuppressive regimen (both P = 0.02).ConclusionLymphopenia and high CRP levels are associated with more severe forms of COVID-19 in LT patients. Mycophenolate may have protective properties against severe COVID-19. The role of severity indicators in LT patients with COVID-19 needs to be systematically recognized.

Elevation in Liver Enzymes as a Predictor for COVID-19 Severity

Abstract Background The coronavirus disease 2019 (COVID-19) started in December of 2019 as a cluster of pneumonia cases of unclear etiology in Wuhan city of Hubei province in China. Later, it was found to be caused by a coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease rapidly spread throughout the world, becoming a pandemic, and as of April, 2022, there were more than 500 million cases worldwide with more than 6 million deaths. It is postulated that the virus enters the human body by binding to the angiotensin-converting enzyme receptor-2 (ACE-2) with the help of spike protein on its cell membrane. Aim of the Work To compare the serum liver chemistries such as hepatic transaminases to evaluate whether they can predict severity and mortality in COVID-19. Patients and Methods A comparative cross-sectional study for 6 months in Ain-Shams University hospitals, we studied 100 hospitalized patients with confirmed COVID-19 by RT- PCR for SARS- CoV-2. They included 70 patients with non-severe COVID-19 and 30 patients with severe COVID- 19 on hospital admission. This classification was based on the quick COVID-19 severity index (qCSI) and CT- severity index. Results The results of our study showed that levels of inflammatory markers such as CRP, serum ferritin, d-dimer, and procalcitonin were significantly higher in the severe group when compared to the non-severe group. This could be an indicator of a more intense inflammatory state in patients with severe COVID- 19 admitted to ICU. Our study showed that 40% of the severe group admitted to the ICU passed away. In our study, the median levels for ALT, AST at admission were 51 and 46 U/L, respectively, which are considered higher than the upper limit of normal levels. Our study showed that during hospitalization, the group of patients with severe COVID-19 who were admitted to ICU had significantly higher prevalence of abnormal ALT levels when compared to the non- severe group (86% versus 32%, respectively). Conclusion Our study showed that patients with severe COVID-19 have significantly higher levels of AST and ALT and that, on admission, patients with abnormal ALT and AST levels have significantly higher odds for developing severe COVID-19 compared to patients with normal levels. We confirm the importance of monitoring liver enzymes in hospitalized patients with COVID-19 as patients with abnormally elevated AST and ALT are more expected to progress to severe COVID- 19 which have prognostic implications in the COVID-19 disease course.

Characteristics of COVID-19 comorbidities and severity profiles among pregnant women from a single-center cross-sectional study.

The study aimed to determine the characteristics of comorbidities, association between comorbidities and coronavirus disease 2019 (COVID-19), as well as characteristics of COVID-19 severity among pregnant women at a tertiary hospital in Bandung. We conducted a cross-sectional study by taking secondary data between January 2020 and December 2021 involving 278 pregnant women aged 16 to 45 years that confirmedly diagnosed with COVID-19 via RT-PCR. We collected information from the medical record on severity and comorbidities. The admission C-reactive protein (CRP) profiles were compared between the severe and nonsevere COVID-19 patients. This study employed bivariate analysis, t test, and multivariate analysis with logistic regression models. Of the 278 data included in this study, 120 cases had comorbidities. Most patients were asymptomatic (82%). Obesity was the most common comorbid proportion. Only hypertension as comorbid showed a significant association with symptomatic or asymptomatic COVID-19 (<0.05). Pregnant women with hypertension were 6 times more likely to show symptoms than those without hypertension (OR = 6.092; 95% CI 3.103-11.962). Pregnant women with comorbidities were at higher risk of cesarean sections and stillbirth. The CRP levels which were found to have statistically significant association with COVID-19 severity (<0.05). The domination of asymptomatic COVID-19 in pregnant women was found in this study. Hypertension comorbid has a significant association with COVID-19 symptoms. Maternal and neonatal outcomes appear to be influenced by maternal comorbidities. Moreover, the CRP levels were found to be significant risk factors for COVID-19 severity in pregnant women that might have association with comorbidities.

The relationship between comprehensive geriatric assessment on the pneumonia prognosis of older adults: a cross-sectional study

BackgroundThe mortality of pneumonia in older adults surpasses that of other populations, especially with the prevalence of coronavirus disease 2019 (COVID-19). Under the influence of multiple factors, a series of geriatric syndromes brought on by age is one of the main reasons for the poor prognosis of pneumonia. This study attempts to analyze the impact of geriatric syndrome on the prognosis of pneumonia.MethodsThis is a prospective cross-sectional study. Patients over 65 years old with COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) were included in the research. General characteristics, laboratory tests, length of stay (LOS), and comprehensive geriatric assessment (CGA) were collected. Multivariate regression analysis to determine the independent predictors of the severity, mortality, and LOS of COVID-19. At the same time, the enrolled subjects were divided into three categories by clustering analysis of 10 CGA indicators, and their clinical characteristics and prognoses were analyzed.ResultsA total of 792 subjects were included in the study, including 204 subjects of SN-CAP (25.8%) and 588 subjects (74.2%) of COVID-19. There was no significant difference between non-severe COVID-19 and SN-CAP regarding mortality, LOS, and CGA (P > 0.05), while severe COVID-19 is significantly higher than both (P < 0.05). The Barthel Index used to assess the activities of daily living was an independent risk factor for the severity and mortality of COVID-19 and linearly correlated with the LOS (P < 0.05). The cluster analysis based on the CGA indicators divided the geriatric pneumonia patients into three groups: Cluster 1 (n = 276), named low ability group, with the worst CGA, laboratory tests, severity, mortality, and LOS; Cluster 3 (n = 228), called high ability group with the best above indicators; Cluster 2 (n = 288), named medium ability group, falls between the two.ConclusionThe Barthel Index indicates that decreased activities of daily living are an independent risk factor for the severity, mortality, and LOS of geriatric COVID-19. Geriatric syndrome can help judge the prognosis of pneumonia in older adults.

Comprehensive analysis of immunogenic cell death-related gene and construction of prediction model based on WGCNA and multiple machine learning in severe COVID-19

The death of coronavirus disease 2019 (COVID-19) is primarily due to from critically ill patients, especially from ARDS complications caused by SARS-CoV-2. Therefore, it is essential to contribute an in-depth understanding of the pathogenesis of the disease and to identify biomarkers for predicting critically ill patients at the molecular level. Immunogenic cell death (ICD), as a specific variant of regulatory cell death driven by stress, can induce adaptive immune responses against cell death antigens in the host. Studies have confirmed that both innate and adaptive immune pathways are involved in the pathogenesis of SARS-CoV-2 infection. However, the role of ICD in the pathogenesis of severe COVID-19 has rarely been explored. In this study, we systematically evaluated the role of ICD-related genes in COVID-19. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis based on ICD differentially expressed genes. The results showed that immune infiltration characteristics were altered in severe and non-severe COVID-19. In addition, we used multiple machine learning methods to screen for five risk genes (KLF5, NSUN7, APH1B, GRB10 and CD4), which are used to predict COVID-19 severity. Finally, we constructed a nomogram to predict the risk of severe COVID-19 based on the classification and recognition model, and validated the model with external data sets. This study provides a valuable direction for the exploration of the pathogenesis and progress of COVID-19, and helps in the early identification of severe cases of COVID-19 to reduce mortality.

The role of C-reactive protein, procalcitonin, interleukin-6 and neutrophil / lymphocyte ratio as a laboratory biomarker in COVID-19

Biomarkers such as Interleukin-6 (IL-6), Procalcitonin (PCT), C-reactive protein (CRP) and Neutrophil-Lymphocyte Ratio (NLR) have a role in the pathogenesis of severe coronavirus disease 2019 (COVID-19). The aim of this study was to explore the differences between serum levels of such biomarkers in severe and non-severe COVID-19 cases and compare them with normal people and to evaluate the sociodemographic variables and chronic diseases effect on the severity of COVID-19. The study included 160 subjects, divided into two groups, a case group of 80 patients, and a control group of 80 normal persons. The case group was divided into two subgroups: 40 severe COVID-19 patients and 40 patients with non-severe disease. Blood IL-6 was assessed by an enzyme-linked immunosorbent assay (ELISA), PCT by an immunoassay, CRP by an immunoturbidimetric assay and NLR from CBC. The levels of IL-6, PCT, CRP, and NLR were significantly higher in the case group than in control group (p= 0.001, for all). However, there was no difference between these biomarkers level in the non-severe COVID-19 subgroup and the control group (p&gt;0.05 for all). The proportion of severe COVID-19 was significantly higher in patients aged &gt;50 years, and in patients with chronic diseases (p=0.046 and p=0.001, respectively). We also found a strong correlation between such biomarkers and old age, and chronic diseases with the disease severity. There was a significant difference in the level of the three biomarkers (IL-6, PCT, CRP, and NLR) between patients’ subgroups and the control group. In conclusion, since the levels of these biomarkers are correlated with the severity of the COVID-19 disease, and there was a difference in the levels between the groups with severe and non-severe symptoms, we suggest a role of these biomarkers in predicting the severity COVID-19 disease and its poor prognosis.

Long-Term Impacts of COVID-19 on Severe Exacerbation and Mortality in Adult Asthma: A Nationwide Population-Based Cohort Study

BackgroundIn adults with asthma, the long-term impact of previous coronavirus disease 2019 (COVID-19) on severe exacerbations and mortality is unclear. ObjectiveWe evaluated the long-term risk of severe exacerbation and mortality in adults with asthma who recovered from COVID-19. MethodsUsing the Korean National Health Insurance claim-based database, we compared the risk of severe exacerbations (emergency room visits or hospitalization) and mortality in adults with asthma aged >20 years recovered from COVID-19 between October 8, 2020, and December 16, 2021 (COVID-19 cohort, n=10,739) with 1:1 propensity score-matched controls (n=10,739). ResultsDuring a median follow-up of 87 (range, 15–448) days, the incidence rate of severe exacerbation in the COVID-19 cohort and matched cohort was 187.3 and 119.3 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of severe exacerbation compared to the matched cohort (hazard ratio=1.57; 95% confidence interval [CI]=1.06–2.32). During a median follow-up of 360 (range, 15–721) days, the incidence rate of death in the COVID-19 and matched cohort was 128.3 and 73.5 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of death (hazard ratio=1.76; 95% CI=1.33–2.30) compared to the matched cohort. When further analyzed by COVID-19 severity, severe COVID-19 was associated with a 5.12-fold (95% CI=3.27–8.01) and 7.31-fold (95% CI=5.41–9.88) increased risk of severe exacerbation and death, respectively, but non-severe COVID-19 was not. ConclusionOur study heightens that severe COVID-19 is associated with increased long-term risk of severe exacerbation and mortality among individuals with asthma.

Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: a bicenter observational cohort study

BackgroundCadmium and nickel exposure can cause oxidative stress, induce inflammation, inhibit immune function, and therefore has significant impacts on the pathogenesis and severity of many diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also provoke oxidative stress and the dysregulation of inflammatory and immune responses. This study aimed to assess the potential associations of cadmium and nickel exposure with the severity and clinical outcomes of patients with coronavirus disease 2019 (COVID-19).MethodsWe performed a retrospective, observational, bicenter cohort analysis of patients with SARS-CoV-2 infection in Taiwan between June 2022 and July 2023. Cadmium and nickel concentrations in blood and urine were measured within 3 days of the diagnosis of acute SARS-CoV-2 infection, and the severity and clinical outcomes of patients with COVID-19 were analyzed.ResultsA total of 574 patients were analyzed and divided into a severe COVID-19 group (hospitalized patients) (n = 252; 43.9%), and non-severe COVID-19 group (n = 322; 56.1%). The overall in-hospital mortality rate was 11.8% (n = 68). The severe COVID-19 patients were older, had significantly more comorbidities, and significantly higher neutrophil/lymphocyte ratio, C-reactive protein, and interleukin-6 than the non-severe COVID-19 patients (all p < 0.05). Blood and urine cadmium and urine nickel concentrations were significantly higher in the severe COVID-19 patients than in the non-severe COVID-19 patients. Among the severe COVID-19 patients, those in higher urine cadmium/creatinine quartiles had a significantly higher risk of organ failure (i.e., higher APACHE II and SOFA scores), higher neutrophil/lymphocyte ratio, lower PaO2/FiO2 requiring higher invasive mechanical ventilation support, higher risk of acute respiratory distress syndrome, and higher 60-, 90-day, and all-cause hospital mortality (all p < 0.05). Multivariable logistic regression models revealed that urine cadmium/creatinine was independently associated with severe COVID-19 (adjusted OR 1.643 [95% CI 1.060–2.547], p = 0.026), and that a urine cadmium/creatinine value > 2.05 μg/g had the highest predictive value (adjusted OR 5.349, [95% CI 1.118–25.580], p = 0.036).ConclusionsUrine cadmium concentration in the early course of COVID-19 could predict the severity and clinical outcomes of patients and was independently associated with the risk of severe COVID-19.

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID-19.

Patients with coronavirus disease-2019 (COVID-19) are characterized by hyperinflammation. Calprotectin (S100A8/S100A9) is a calcium- and zinc-binding protein mainly secreted by neutrophilic granulocytes or macrophages and has been suggested to be correlated with the severity and prognosis of COVID-19. To thoroughly evaluate the diagnostic and prognostic utility of calprotectin in patients with COVID-19 by analyzing relevant studies. PubMed, Web of Science, and Cochrane Library were comprehensively searched from inception to August 1, 2023 to retrieve studies about the application of calprotectin in COVID-19. Useful data such as the level of calprotectin in different groups and the diagnostic efficacy of this biomarker for severe COVID-19 were extracted and aggregated by using Stata 16.0 software. Fifteenstudies were brought into this meta-analysis. First, the pooled standardized mean differences (SMDs) were used to estimate the differences in the levels of circulating calprotectin between patients with severe and non-severe COVID-19. The results showed an overall estimate of 1.84 (95% confidence interval [CI]: 1.09-2.60). Diagnostic information was extracted from 11 studies, and the pooled sensitivity and specificity of calprotectin for diagnosing severe COVID-19 were 0.75 (95%CI: 0.64-0.84) and 0.88 (95%CI: 0.79-0.94), respectively. The AUC was 0.89 and the pooled DOR was 18.44 (95%CI: 9.07-37.51). Furthermore, there was a strong correlation between elevated levels of circulating calprotectin and a higher risk of mortality outcomes in COVID-19 patients (odds ratio: 8.60, 95%CI: 2.17-34.12; p < 0.1). This meta-analysis showed that calprotectin was elevated in patients with severe COVID-19, and this atypical inflammatory cytokine might serve as a useful biomarker to distinguish the severity of COVID-19 and predict the prognosis.

Correlation between Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio with the severity of Covid-19 patients in Dr. Hasan Sadikin Central Public Hospital

Coronavirus Disease 2019 (COVID-19) has a clinical spectrum that varies from asymptomatic to death. Cytokine storms cause neutrophilia, lymphopenia, and thrombocytopenia at various levels of COVID-19 severity. These three parameters can be studied as markers of inflammation in the form of ratios. This study aims to discover the correlation between NLR &amp; PLR inflammatory markers in determining the severity of COVID-19.An analytical cross-sectional study was carried out on secondary data from 274 subjects collected from the subject's hematological parameters from first day of admission to Hasan Sadikin Hospital from May-December 2020. The statistical analysis with Spearman test using the SPSS 17.0 program. There are 274 subjectswith non-severe and severe COVID-19 were NLR (3,44 vs 7,17), PLR (182,4 vs 254,4). The r coefficient of NLR and PLR reached 0.308 and 0.198, p-value of &lt; 0.001.In the next phase, days 7-14, lymphocytes decrease significantly. This study found a weak correlation because neutrophilia occurred on the third-seventh day of treatment, while the assessment was performed at first day of admission with clinical symptoms on day 1-3. PLR and NLR have a weak positive correlation with the severity of COVID-19. Therefore, it cannot be utilized independently in determining the severity of COVID-19.

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.

Analysis of Leukocyte Subpopulations by Flow Cytometry during Hospitalization Depending on the Severity of COVID-19 Course.

The mechanisms underlying the immune response to coronavirus disease 2019 (COVID-19) and the recovery process have not been fully elucidated. The aim of the study was to analyze leukocyte subpopulations in patients at significant time points (at diagnosis, and 3 and 6 months after infection) selected according to the analysis of changes in the lungs by the CT classification system, considering the severity of the disease. The study groups consisted of severe and non-severe COVID-19 patients. There was a significant decrease in CD8+ T cells, NK and eosinophils, with an increasing percentage of neutrophils during hospitalization. We noticed lower levels of CD4 and CD8 T lymphocytes, eosinophils, basophils, and CD16+ monocytes and elevated neutrophil levels in severe patients relative to non-severe patients. Three months after infection, we observed higher levels of basophils, and after 6 months, higher CD4/CD8 ratios and T cell levels in the severe compared to non-severe group. Non-severe patients showed significant changes in the leukocyte populations studied at time of hospitalization and both within 3 months and 6 months of onset. The CT CSS classification with parameters of the flow cytometry method used for COVID-19 patients determined changes that proved useful in the initial evaluation of patients.

The Comparison of Soluble P-selectin, Anti-platelet Factor 4, and Platelet Maximum Aggregation Levels among Coronavirus Disease 2019 Patients

Abstract INTRODUCTION: The coronavirus disease 2019 (COVID-19) continues to have an enormous and extensive effect on global health, causing widespread devastation. Patients who have recovered from COVID-19 have an increased risk of thromboembolic disease. We suggest that soluble P-selectin and anti-platelet factor 4 (anti-PF4) plays a significant role in platelet activation, ultimately resulting in thrombosis. The purpose of this study is to compare the role of soluble P-selectin, anti-PF4, and platelet maximal aggregation levels in COVID-19 patients. MATERIALS AND METHODS: A cross-sectional study was conducted among COVID-19 patients who were admitted to the hospital between October 2021 and January 2022. RESULTS: From 160 individuals, we found that a number of individuals with older age (P = 0.014) and lower hemoglobin levels (P = 0.042) were significantly higher in the severe COVID-19 group compared to the nonsevere COVID-19 group. Remarkably, soluble P-selectin levels in mild-to-moderate COVID-19 were found to be significantly higher than the severe group, with statistical significance (P = 0.02). However, there was no significant difference in anti-PF4 levels between severe and nonsevere COVID-19 groups. Furthermore, platelet maximum aggregation was also significantly higher in the severe COVID-19 group than in the mild-to-moderate COVID-19 group by using 2.5 μM (P = 0.024), 5 μM (P = 0.026), and 10 mM adenosine-diphosphate (P = 0.02). CONCLUSION: Soluble P-selectin, an indicator of platelet activation, was shown to be significantly higher in mild-to-moderate COVID-19 group than the severe COVID-19 group. The maximum aggregation of platelets was also observed to be significantly greater in the severe COVID-19 group.

Effects of renin-angiotensin system blockers on outcomes from COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Randomized controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This meta-analysis provides estimates of the safety and efficacy of treatment with (vs. without) RAS blockers from these trials. PubMed, Web of Science, and ClinicalTrials.gov were searched (1 March-12 April 2023). Event/patient numbers were extracted, comparing angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) treatment with no treatment, for the outcomes: intensive care unit (ICU) admission, mechanical ventilation, vasopressor use, acute kidney injury (AKI), renal replacement therapy (RRT), acute myocardial infarction, stroke/transient ischaemic attack, heart failure, thromboembolic events, and all-cause death. Fixed-effects meta-analysis estimates were pooled. Sixteen RCTs including 3492 patients were analysed. Compared with discontinuation of RAS blockers, continuation was not associated with increased risk of ICU [risk ratio (RR) 0.96, 0.66-1.41], ventilation (RR 0.77, 0.55-1.09), vasopressors (RR 0.92, 0.58-1.44), AKI (RR 1.01, 0.40-2.56), RRT (RR 1.01, 0.46-2.21), or thromboembolic events (RR 1.07, 0.36-3.19). RAS blocker initiation was not associated with increased risk of ICU (RR 0.71, 0.47-1.08), ventilation (RR 1.12, 0.91-1.38), AKI (RR 1.28, 0.89-1.86), RRT (RR 1.66, 0.89-3.12), or thromboembolic events (RR 1.20, 0.06-23.70), although vasopressor use increased (RR 1.27, 1.02-1.57). The RR for all-cause death in the continuation/discontinuation trials was 1.24 (0.80-1.92), and 1.22 (0.96-1.55) in the initiation trials. In patients with severe/critical COVID-19, RAS blocker initiation increased the risk of all-cause death (RR 1.31, 1.01-1.72). ACE inhibitors and ARBs may be continued in non-severe COVID-19 infection, where indicated. Conversely, initiation of RAS blockers may be harmful in critically ill patients.PROSPERO registration number: CRD42023408926.

Increased blood pressure after nonsevere COVID-19.

Various sequelae have been described after nonsevere coronavirus disease 2019 (COVID-19), but knowledge on postacute effects on blood pressure is limited. This is a cross-sectional analysis of blood pressure profiles in individuals after nonsevere COVID-19 compared with matched population-based individuals without prior COVID-19. Data were derived from the ongoing and prospective Hamburg City Health Study, a population-based study in Hamburg, Germany, and its associated COVID-19 program, which included individuals at least 4 months after COVID-19. Matching was performed by age, sex, education, and preexisting hypertension in a 1 : 4 ratio. Four hundred and thirty-two individuals after COVID-19 (mean age 56.1 years) were matched to 1728 controls without prior COVID-19 (56.2 years). About 92.8% of COVID-19 courses were mild or moderate, only 7.2% were hospitalized, and no individual had been treated on an intensive care unit. Even after adjustment for relevant competing risk factors, DBP [+4.7 mmHg, 95% confidence interval (95% CI) 3.97-5.7, P < 0.001] was significantly higher in individuals after COVID-19. For SBP, a trend towards increased values was observed (+1.4 mmHg, 95% CI -0.4 to 3.2, P = 0.120). Hypertensive blood pressures at least 130/80 mmHg (according to the ACC/AHA guideline) and at least 140/90 mmHg (ESC/ESH guideline) occurred significantly more often in individuals after COVID-19 than matched controls (odds ratio 2.0, 95% CI 1.5-2.7, P < 0.001 and odds ratio 1.6, 95% CI 1.3-2.0, P < 0.001, respectively), mainly driven by changes in DBP. Blood pressure is higher in individuals after nonsevere COVID-19 compared with uninfected individuals suggesting a significant hypertensive sequela.

Risk Factors for Severe-Critical COVID-19 in Pregnant Women.

Risk factors associated with severe-critical COVID-19 (coronavirus disease 2019) are based on findings in the general population. Pregnant women are at increased risk of severe-critical infection, and few reports are based on these women. A multicentric case-control study was conducted at the Mexican Institute of Social Security, State of Mexico, during the COVID-19 pandemic. We included pregnant women who were consecutively admitted to respiratory care units and were followed until 30 days after the resolution of pregnancy. A total of 758 pregnant women with a positive RT-PCR test for SARS-CoV-2 were enrolled from June 2020 to July 2021. We defined groups using the World Health Organization Severity Classification; cases were pregnant women with severe-critical COVID-19 (n = 123), and controls were subjects with non-severe COVID-19 (n = 635). Data was gathered from clinical files. A multivariate logistic regression analysis was used to adjust odds ratios and their 95% confidence intervals of factors associated with severe-critical COVID-19. Risk factors associated with severe-critical COVID-19 in pregnancy were non-vaccination (OR 10.18), blood type other than O (OR 6.29), maternal age > 35 years (OR 5.76), history of chronic hypertension (OR 5.12), gestational age at infection ≥ 31 weeks (OR 3.28), and multiparity (OR 2.80).

Clinical use of antiviral, antibiotic and immunomodulatory drugs in hospitalized COVID-19 patients: a retrospective study in Bandung, Indonesia

Background: Evidence of highly effective repurposed drugs for coronavirus disease 2019 (COVID-19) is insufficient. However, empirical therapy using antiviral, antibiotic and immunomodulatory drugs is massive. This study aimed to evaluate the clinical use of these drugs and the outcome of hospitalization in COVID-19 patients. Methods: We performed a retrospective study using medical records of hospitalized COVID-19 patients from July 2020 to March 2021 in Bandung, Indonesia. Data were collected at relevant timelines: age, sex, comorbid condition, peripheral oxygen saturation (SpO 2), and hematology at admission; antiviral, antibiotic, and immunomodulator treatment during hospitalization; length of stay hospitalization (LOS) and death at discharge. Clinical use of the drug regimens included dose, frequency, and duration of therapy. The main outcome of hospitalization was LOS and death. Results: Out of 249 patients, 43.3% had a comorbid condition, 74.7% had non-severe COVID-19 (SpO 2 ≥ 90%), and almost all received antiviral or antibiotic agents. Patients receiving a combination of remdesivir and favipiravir had lower SpO 2 compared to those receiving oseltamivir alone (p=0.01). Remdesivir alone and combination of favipiravir and oseltamivir had shorter LOS compared to the other antivirals (p=0.03 and p=0.01 respectively). Immunomodulatory drugs (methylprednisolone, dexamethasone, tocilizumab) were prescribed in patients with lower baseline SpO 2 (p=0.001) and resulted ini longer LOS (p=0.0043) compared to those with no immunomodulators. The increased risk of death in patients treated with the combination of remdesivir and favipiravir (OR 4.1;95%CI 1.4-12.2), and immunomodulatory drugs (OR 6.2; 95%CI 1.7-23.3) was confounded by the baseline characteristics of older age, comorbid condition, SpO 2 level, and low lymphocyte number. Conclusions: Some treatment regimens were associated with short LOS, but there were drug regimens which might increase the risk of death. Further study should control the clinical conditions of COVID-19 patients at admission to confirm the outcome of death following drug therapy.

Traditional Vietnamese Medicine Containing Garlic Extract for Patients With Non-severe COVID-19: A Phase-II, Double-Blind, Randomized Controlled Trial.

Background Coronavirus disease 2019 (COVID-19) is still ongoing with the omicron variant. Low-cost, effective treatments are still needed, particularly in low-to-middle-income countries. This study assessed the safety and efficacy of TD0068, an herbal medicine developed from mainly garlic, for patients with non-severe COVID-19. Methods This is a phase-II, double-blind, randomized controlled trial to compare oral capsule TD0068 and placebo in adults aged 18-65 years with non-severe COVID-19 between September and October 2021. The efficacy outcomes measured included daily cycle threshold (Ct) value from the time of the initial reverse transcription-polymerase chain reaction (RT-PCR) test, time to viral clearance, daily symptom severity score from 15 symptoms of interest, time to symptom resolution, and progression to severe/critical COVID-19. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Results Sixty patients were randomized (31 received TD0068, and 29 received a placebo). The two groups were balanced in baseline characteristics: mean age was 39 years, and female was predominant (66%). Daily Ct value (median on days 3, 5, 7, and 9 was 25.7, 30.8, 35.4, and 37.6 in the TD0068 group, and 26.4, 31.2, 36.0, and 37.4 in the placebo group, respectively) and time to viral clearance (median: 10 vs. 11 days in TD0068 and placebo groups) were similar between groups. Daily symptom severity score (median on days 3, 5, 7, and 9 was 2, 2, 1, and 0 in the TD0068 group, and 3, 2, 1, and 1 in the placebo group), and time to symptom resolution (median: seven vs. nine days, respectively) were also comparable between groups. No SAE occurred in the study. Conclusions TD0068 is safe but does not show an effect for non-severe COVID-19 patients. Further research is needed to explore the potential benefits of garlic in other forms or dosages for the treatment of COVID-19.

Implications of Inflammatory markers for disease management in patients with chronic kidney disease and COVID-19 infection: A cross-sectional study from North India

ABSTRACT Background: The world witnessed the emergence of a global pandemic. Individuals with chronic illnesses like chronic kidney disease (CKD), already known to be immunologically compromised, have the potential to develop a scenario of an acute-on-chronic condition on coronavirus disease 2019 (COVID-19) contraction. Measurement of serum inflammatory biomarkers like interleukin (IL-6), high-sensitivity C-reactive protein (hsCRP) and ferritin may foresee the prognosis despite the pre-existing low-grade inflammation in these patients. Aims: To determine the utility of serum IL-6, hsCRP and Ferritin levels to determine COVID-19 severity and probable prognosis in CKD patients with COVID-19. Materials and Methods: A cross-sectional study was performed on 100 adult known cases of stage 5 of CKD, recently diagnosed as COVID-19 positive by real-time reverse transcription-polymerase chain reaction. The study population was divided into two groups according to COVID-19 severity: A non-severe and a severe group based on guidelines given in the Clinical Management Protocol: COVID-19. Their clinical and laboratory data obtained on the day of admission were analysed. Results: The severe group (n = 17) had 65% of males and 35% of females. A significant difference was found with respect to the age, body mass index and serum IL-6, hsCRP and ferritin levels between the two groups (P &lt; 0.05). Among the three inflammatory biomarkers, hsCRP was found to have the maximum potential to categorise COVID-19 as severe or non-severe disease. Conclusion: Similar to patients with uncomplicated COVID-19 disease, higher serum levels of inflammatory biomarkers – IL-6, hsCRP and ferritin are seen in patients of CKD with severe COVID-19 illness in comparison to those with non-severe COVID-19, despite having a pre-existing background of low-grade chronic inflammation. The serum levels of IL-6, hsCRP and ferritin can be utilised to determine COVID-19 severity and probable prognosis in CKD patients with COVID-19.