Severe Coronavirus Disease 2019 Patients Research Articles

The Association Between Alveolar-Arterial Oxygen Tension Difference and the Severity of COVID-19 in Patients.

Coronavirus disease 2019 (COVID-19) emerged as a global pandemic and resulted in a significantly high death toll. Therefore, there is an urgent need to find a potential biomarker related to the disease severity that can facilitate early-stage intervention. In the present study, we collected 242 laboratory-confirmed COVID-19-infected patients. The patients were grouped according to the alveolar to arterial oxygen tension difference (PA-aO2) value of COVID-19 infection after admission. Among the 242 laboratory-confirmed COVID-19- infected patients, 155 (64.05%) had an abnormal PA-aO2 value on admission. Compared with the normal PA-aO2 group, the median age of the abnormal PA-aO2 group was significantly older (p=0.032). Symptoms such as fever, cough, and shortness of breath were more obvious in the abnormal PA-aO2 group. The proportion of severe events in the abnormal PA-aO2 group was higher than the normal PA-aO2 group (10.34% vs. 23.23%, p=0.013). The abnormal PA-aO2 group had a higher possibility of developing severe events compared with the normal PA-aO2 group (HR 2.622, 95% CI 1.197-5.744, p=0.016). After adjusting for age and common comorbidities (hypertension and cardiovascular disease), the abnormal PA-aO2 group still exhibited significantly elevated risks of developing severe events than the normal PA-aO2 group (HR 2.986, 95% CI 1.220-7.309, p=0.017). Additionally, the abnormal PA-aO2 group had more serious inflammation/coagulopathy/fibrinolysis parameters than the normal PA-aO2 group. Abnormal PA-aO2 value was found to be common in COVID-19 patients, was strongly related to severe event development, and could be a potential biomarker for the prognosis of COVID-19 patients.

Dynamic Changes in Circulatory Cytokines and Chemokines Levels in Mild to Severe COVID-19 Patients.

The online version contains supplementary material available at 10.1007/s12291-022-01108-x.

Intestinal Alkaline Phosphatase Activity and Efficiency Are Altered in Severe COVID-19 Patients.

Although gut inflammation and dysbiosis have been implicated in the pathophysiology of severe cases of coronavirus disease 2019 (COVID-19), the role of intestinal anti-inflammatory enzymes, such as alkaline phosphatase, is still underexplored. Therefore, the aim of this study was to compare intestinal alkaline phosphatase (iALP) activity and its proinflammatory substrate - bacterial lipopolysaccharide (LPS) - concentration between mild-to-moderate and severe COVID-19 patients. Stool samples collected from 53 mild-to-moderate and 57 severe adult COVID-19 patients, previously enrolled in a national multicentre cross-sectional study (NCT04355741), were analysed for iALP activity and LPS concentration. iALP activity decreased by 40% in severe compared to mild-to-moderate COVID-19 patients (median [interquartile range] of 120.6 [25.2-593.1] nmol pNP/min/g of protein vs 202.8 [102.1-676.1] nmol pNP/min/g of protein; P= .04) after adjustment for clinical and gut microbiota parameters. Regarding fecal LPS, its concentration was found to be decreased in severe patients (mean ± standard error of mean of 18,118 ± 1225 EU/g of feces vs 22,508 ± 1203 EU/g of feces; P= .01), although this parameter did not correlate with plasma levels of C-reactive protein (P= .08), a sensitive biomarker of systemic inflammation. In contrast, fecal ALP activity / LPS concentration ratio, an indicator of iALP efficiency, was found to be increased in severe compared to mild-to-moderate COVID-19 patients (P= .04). Changes in iALP kinetic parameters found in severe COVID-19 patients may represent a potential mechanism to counterbalance alterations in gut homeostasis (eg inflammation and dysbiosis) associated with COVID-19 severity.

Gene Expression of TNF-α among Iraqi COVID-19 Patients with a Different Severity Status

Background: Coronavirus disease 2019 (COVID-19) individuals with varied severity group are affected by the cytokine storm brought on by SARS-CoV2 infection, which is a significant cause of acute respiratory distress syndrome. Objective: The goal of the current study was to examine tumor necrosis factor (TNF-α) gene expression in COVID-19 at various severity levels. Materials and Methods: The study includes 140 divided into 105 COVID-19-positive patients (35 for each mild, moderate, and severe group) and 35 COVID-19-negative healthy people as control. COVID-19 positive patients had 46 males and 59 females, while COVID-19-negative healthy people included 16 males and 19 females. The separation of peripheral blood mononuclear cells (PBMC) was achieved using Ficoll, and then Ribonucleic acid was extracted and converted to cDNA and the gene expression using glyceraldehyde-3-phosphate dehydrogenase as the housekeeping gene. Results: The results revealed non-significant differences at P < 0.05 in age among different COVID-19 groups and control (F-ratio value is 0.54257 and P-value is 0.65397). The results revealed over-expression of TNF-α gene among COVID-19 patients and the relative quantification (fold change) (mean ± standard deviation) values were 6.542 ± 7.29, 5.740 ± 6.41, 7.306 ± 8.85, and 6.580 ± 6.47 for all, mild, moderate, and severe COVID-19 patients, respectively. One-way analysis of variance test relative quantification (fold change) TNF-α (mean ± standard deviation) for mild, moderate, and severe groups revealed non-significant at P < 0.05, the F-ratio value is 0.39889 and the P-value is 0.672109. Conclusion: The present study concludes upregulation of TNF-α gene in PBMC of COVID-19-positive patients without significant differences among different severity groups.

Insights into COVID-19 in age-related macular degeneration

Studies have shown that age-related macular degeneration (AMD) patients present a poor prognosis in coronavirus disease 2019 (COVID-19). These diseases have completely different etiologies and clinical courses. COVID-19 is a systemic, fast-evolving, and lethal infectious disease. AMD, in turn, is a chronic disease triggered by oxidative stress and is considered the main cause of irreversible blindness in old age. Both COVID-19 and AMD have in common the participation of immunological and inflammatory components arising from the imbalance of the redox state, responsible for the most severe phases of these diseases. Therefore, this study aims to present the triggering pathways of these diseases, as well as analyze the possible molecular mechanisms that increase the severity of COVID-19 in patients with AMD.

Utilization of Therapeutic Interventions for Coronavirus Disease-2019 (COVID-19) Hospitalized Patients and Emerging Treatment Possibilities from Clinical Trials: A Systematic Review and Meta-Analysis

Background and Objective: Few small observational studies have described various therapeutic interventions utilized in coronavirus disease 2019 (COVID-19) patients based on single/multi-center experiences across the globe. Understanding the utilization of available and possible treatments to curb the COVID-19 pandemic is paramount. We aimed to identify the prevalence and disease-associated utilization of specific therapeutic reagents in hospitalized COVID-19 patients as a function of severity status. Methods: In systematic review and meta-analysis, extracted data on treatments utilized and severity of COVID-19 hospitalized patients from observational studies using PRISMA guidelines from December 1, 2019 to August 20, 2020. The pooled prevalence and odds of treatment utilization were obtained, and created forest plots using random‐effects models. Results: 29 studies with 8570 COVID-19-positive patients were included. Higher odds of the utilization of steroids (pooled OR:4.47; 95%CI:3.18–6.28; p<0.00001), antibiotics (3.1;1.81–5.30; p<0.0001), and IV Immunoglobulin (IVIG) (3.76;2.11–6.72; p<0.00001) was observed in patients with severe disease. No association of remdesivir (initially administered via clinical trials and subsequently FDA-approved during this study period), lopinavir/ritonavir, or hydroxychloroquine (HCQ) treatment with the severity of disease was observed. Conclusion: Higher utilization of steroids, lopinavir/ritonavir, antibiotics, hydroxychloroquine (HCQ), and IV Immunoglobulin (IVIG) was observed in severe COVID-19 patients. Due to limited studies on remdesivir, its accurate utilization could not be delineated. Currently, no Level A evidence favoring single-drug treatment for COVID-19 exists, and trials are needed of combination therapy to evaluate efficacy on the survival outcome.

Clinical Outcomes of Remdesivir in Section Moderate and Severe Cases of COVID-19: A Retrospective Cohort Study

Introduction: Remdesivir is a nucleotide analogue prodrug that perturbs viral replication. Remdesivir has been used in various trials previously for the treatment of Coronavirus Disease 2019 (COVID-19). Some clinical trials found that remdesivir had a mortality benefit, while other studies did not. It was also seen that remdesivir shortened the duration of hospital stay among COVID-19 patients in some trials while in other trials remdesivir did not have any influence on the duration of hospital stay. Aim: To study the clinical outcomes of Remdesivir in moderate and severe cases of COVID-19. Materials and Methods: The present retrospective, cohort study was conducted in the Department of General Medicine, SDM Medical College and Hospital, Dharwad, Karnataka, India, from September 2021 to May 2022, in which 400 case records of patients admitted with moderate to severe COVID-19 were studied. Among these 314 patients received remdesivir and 86 patients did not receive remdesivir. Categorical variables, nominal variables were represented as proportions and frequencies and continuous variables were represented as mean±SD. Statistical analysis was done using Chi-square test. Results: A total of 400 COVID-19 patients were included in the study, among which 314 received remdesivir and 86 did not receive remedisivir. Those who received remdesivir had a mortality rate of 13.69% as compared to 11.63% among those who did not receive remdesivir (p-value=0.6170). In the remdesivir group, 36.62% had a hospital stay of >11 days, while it was 30.23% among the non remedisivir group (p-value=0.3060). Conclusion: In this study, remdesivir did not reduce mortality nor did it reduce the duration of hospital stay among moderate to severe COVID-19 patients.

Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19: A Systematic Review, Meta-Analysis, and Trial Sequence Analysis.

This systematic review and meta-analysis aimed to find the association between serum Krebs von den Lungen-6 (KL-6) and the severity of Coronavirus disease 2019 (COVID-19) infection. Databases of Embase, PubMed, Web of Science, Science Direct, and Google Scholar were searched for studies reporting KL-6 levels in COVID-19 patients, published between January 2020 and September 30 2022. For comparison between the groups, standard mean difference (SMD) and 95% confidence intervals (CI) were computed as the effect sizes. Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were measured to assess the diagnostic power of KL-6. In addition, the summary receiver operating characteristics curve (sROC) was constructed to summarize the true positive (TP), and false positive (FP) rates. To validate the findings of meta-analysis, Trial Sequential Analysis (TSA) was conducted. Altogether 497 severe COVID-19 patients and 934 non-severe (mild to moderate) COVID-19 patients were included. Pooling of 12 studies indicated that the serum KL-6 level had significant association with severity of COVID-19 infection: standard mean difference = 1.18 (95% CI: 0.93-1.43), p = 0.01; I2: 58.56%]. Pooled diagnostic parameters calculated from eight studies were: sensitivity 0.53 (95% CI: 0.47-0.59); specificity 0.90 (95% CI: 0.88-0.93); positive likelihood ratio 4.80 (95% CI: 3.53-6.53); negative likelihood ratio 0.46 (95% CI: 0.32-0.68); and area under curve: 0.8841. Additionally, TSA verified the adequacy of sample size and robustness of the meta-analysis. Serum KL-6 level has a moderate degree of correlation with the severity of COVID-19 infection but has low sensitivity. So, it is not recommended as a screening test for severe COVID-19 infection.

Prognosis of COVID-19 patients using lab tests: A data mining approach.

The rapid prevalence of coronavirus disease 2019 (COVID-19) has caused a pandemic worldwide and affected the lives of millions. The potential fatality of the disease has led to global public health concerns. Apart from clinical practice, artificial intelligence (AI) has provided a new model for the early diagnosis and prediction of disease based on machine learning (ML) algorithms. In this study, we aimed to make a prediction model for the prognosis of COVID-19 patients using data mining techniques. In this study, a data set was obtained from the intelligent management system repository of 19 hospitals at Shahid Beheshti University of Medical Sciences in Iran. All patients admitted had shown positive polymerase chain reaction (PCR) test results. They were hospitalized between February 19 and May 12 in 2020, which were investigated in this study. The extracted data set has 8621 data instances. The data include demographic information and results of 16 laboratory tests. In the first stage, preprocessing was performed on the data. Then, among 15 laboratory tests, four of them were selected. The models were created based on seven data mining algorithms, and finally, the performances of the models were compared with each other. Based on our results, the Random Forest (RF) and Gradient Boosted Trees models were known as the most efficient methods, with the highest accuracy percentage of 86.45% and 84.80%, respectively. In contrast, the Decision Tree exhibited the least accuracy (75.43%) among the seven models. Data mining methods have the potential to be used for predicting outcomes of COVID-19 patients with the use of lab tests and demographic features. After validating these methods, they could be implemented in clinical decision support systems for better management and providing care to severe COVID-19 patients.

Correlation between Coagulation Tests Parameter with Padua Prediction Score in Covid-19 Patients at General Hospital of Prof. Dr. R. D. Kandou Manado

Coronavirus disease 2019 (COVID-19) was associated with hypercoagulability state, some changes in parameter of coagulation tests, and also cause venous thromboembolism (VTE), which can be predicted with Padua Prediction Score (PPS). In this study, we are going to seek correlation of PPS and some parameter of coagulation tests between mild and moderate - severe COVID-19 patients in isolation room for COVID-19 patients at General Hospital of Prof. dr. R. D. Kandou Manado.

CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID-19 therapy.

The immune response is crucial for coronavirus disease 19 (COVID-19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is able to induce neutrophil activation by CLEC5A and Toll-like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS-CoV-2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS-CoV-2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID-19 patients in comparison with mild COVID-19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID-19. In hamsters, we detected CLEC5A gene expression during 3-15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS-CoV-2, promoting inflammatory cytokine production, probably through an interaction with the receptor-binding domain in the N-acetylglucosamine binding site (NAG-601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID-19 progression; therapy with a monoclonal antibody could be a good strategy for COVID-19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.

Increased mTOR Signaling and Impaired Autophagic Flux Are Hallmarks of SARS-CoV-2 Infection.

The COVID-19 (Coronavirus Disease 2019), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), severely affects mainly individuals with pre-existing comorbidities. Here our aim was to correlate the mTOR (mammalian/mechanistic Target of Rapamycin) and autophagy pathways with the disease severity. Through western blotting and RNA analysis, we found increased mTOR signaling and suppression of genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2 as well as in transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients. Immunofluorescence co-localization assays also indicated that SARS-CoV-2 colocalizes within autophagosomes but not with a lysosomal marker. Our findings indicate that SARS-CoV-2 can benefit from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling.

HUBUNGAN KADAR C-REACTIVE PROTEIN DENGAN DERAJAT KEPARAHAN PASIEN COVID-19 YANG DIRAWAT INAP DI RUMAH SAKIT

Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) can appear with a varied clinical spectrum, ranging from no symptoms, mild illness, moderate illness, to severe illness. The high mortality rate is closely related to the severity of the disease. One of the laboratory parameters that is thought to be related to the severity of COVID-19 is C-Reactive Protein (CRP). This study aimed to determine the relationship between CRP values and the severity of COVID-19 patients. This research has an analytical observational design with a cross-sectional approach. The samples were COVID-19 patients with moderate and severe symptoms who were hospitalized at RSUD dr. Soedarso West Kalimantan in January - December 2021. The sampling technique was total sampling to obtain medical record data which included CRP values and patient severity levels so that 49 data were obtained. The results showed that 8 respondents (16.3%) had CRP levels of 0.8 mg/dL, 24 respondents (49%) had CRP levels of 1.6 mg/dL, 9 respondents (18.4%) had CRP levels of 3 .2 mg/dL and 8 respondents (16.3%) had CRP levels of 6.4 mg/dL. Based on Kendall's tau-b statistical test, a significance value of 0.001 <0.05 was obtained, which means there is a significant relationship between CRP levels and severity. The correlation coefficient value of 0.708 shows a strong correlation coefficient between CRP levels and severity. This proves that the higher the CRP levels of COVID-19 patients found, the more severe the degree of disease that may be suffered by these patients, so there is a close relationship between CRP levels and the degree of disease of COVID-19 patients.

Clinical characteristics of severe coronavirus disease 2019 patients with chronic obstructive pulmonary disease.

Coronavirus disease 2019 (COVID-19) in elderly and patients with chronic respiratory diseases (COPD) had a poor prognosis. COPD is one of the most common chronic respiratory diseases. We explore the epidemiological characteristics of patients with severe COVID-19 with COPD patients in order to provide medical evidence for the prevention and treatment of severe COVID-19. We retrospectively analyzed the clinical baseline characteristics, treatment strategies, disease progression and prognosis of 557 severe COVID-19 patients admitted to the West Court of Union Hospital of Huazhong University of Science and Technology from January 29, 2020 to April 8, 2020. A total of 465 patients with severe COVID-19 were enrolled in the study, including 248 (53.3%) males and 217 (46.7%) females. The median age of severe COVID-19 patients was 62.0 years, and 53 patients were complicated with COPD. Common symptoms at the onset included fever (78.5%), dry cough (67.1%), shortness of breath (47.3%) and fatigue (40.9%). Compared with non-COPD patients, patients with COPD had significantly lower levels of SpO2 in admission (90.0% vs 92.0%, P=0.014). In terms of laboratory examinations, patients with COPD had higher levels of C-reactive protein, interleukin-6, procalcitonin, total bilirubin, blood urea nitrogen, serum creatinine, lipoprotein (a), high-sensitivity troponin I, and D-dimer, while had lower levels of platelet counts, albumin and apolipoprotein AI. Severe COVID-19 patients with COPD had higher Sequential Organ Failure Assessment scores [3.0(2.0, 3.0) vs 2.0(2.0, 3.0), P=0.038] and CURB-65 score [1.0(1.0, 2.0) vs1.0(0.0, 1.0), P<0.001], and a higher proportion of progressing to critical illness (28.3% vs 10.0%, P<0.001) with more complications [e.g. septic shock (15.1% vs 6.1%, P=0.034)], had higher incidence rates of antibiotic therapies (90.6% vs 77.2%, P=0.025), non-invasive (11.3% vs 1.7%, P<0.001) and invasive mechanical ventilation (17.0% vs 8.3%, P=0.039), ICU admission (17.0% vs 7.5%, P=0.021) and death (15.1% vs 6.1%, P=0.016). Cox proportion hazard model was carried out, and the results showed that comorbid COPD was an independent risk factor for severe COVID-19 patients progressing to critical type, after adjusting for age and gender [adjusted hazard ratio (AHR)=2.38(1.30-4.37), P=0.005] and additionally adjusting for chronic kidney diseases, hypertension, coronary heart disease [AHR=2.63(1.45-4.77), P<0.001], or additionally adjusting for some statistically significant laboratory findings [AHR=2.10(1.13-3.89), P=0.018]. Severe COVID-19 patients with COPD have higher levels of disease severity, proportion of progression to critical illness and mortality rate. Individualized treatment strategies should be adopted to improve the prognosis of severe COVID-19 patients.

Association between Vitamin D Status and Secondary Infections in Patients with Severe COVID-19 Admitted in the Intensive Care Unit of a Tertiary-Level Hospital in Turkey.

There are several studies showing that the vitamin D status can determine risk of COVID-19 infections, severity and mortality from coronavirus disease 2019 (COVID-19). However, the association between vitamin D (25(OH)D) and secondary infections in the prognosis of COVID-19 patients has not been reported yet. The aim was to investigate whether the vitamin D status affects the rates of secondary infections in patients with severe COVID-19 hospitalized in the intensive care unit (ICU) of a tertiary-level hospital in Turkey. The data of 194 patients with diagnosis of severe COVID-19 who were admitted to the ICU from March 2020 to June 2021 and older than 18 years were evaluated in this retrospective study. The patients were divided into two groups according to total serum 25(OH)D level as normal group (≥20 ng/mL) and low group (<20 ng/mL). The 25(OH)D level was low in 118 (60.8%) and normal in 76 (39.2%) patients. The mean age of the low group was significantly higher than that of the normal group (67.02 ± 14.47 vs. 61.70 ± 14.38; p = 0.013). The systolic and diastolic blood pressure as well as the Glasgow coma scale score of the low group were significantly lower than that of the normal group (p = 0.004, 0.002 and 0.001, respectively). The intubation rate and APACHE (Acute Physiology and Chronic Health Evaluation) score of the low group was significantly higher than that of the normal group (p = 0.001). The platelets number and blood pH decreased, and the neutrophil/lymphocyte ratio, procalcitonin, lactate, urea, creatinine and lactate dehydrogenase concentrations increased significantly in the low group (p < 0.05). The mortality rate was 79.7% in the low group and 22.4% in the normal group (p < 0.001). Microbiological growth was observed in 68.6% of the normal group and 52.6% of the normal group (p = 0.025). The number of cultures with resistant bacteria was significantly higher in the low group (25.9%) than that in the normal group (17.5%) (p = 0.035). The severe COVID-19 patients hospitalized with vitamin D deficiency may have increased risks of poor prognosis and mortality due to secondary infections in the ICU.

Examining the Determinants of COVID-19 Severity: A Cohort Study in Morocco of 915 Patients.

Coronavirus disease 2019 (COVID-19) is unpredictable and it varies from mild to severe and critical forms that are associated with a higher mortality rate. Risk factors associated with severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been investigated worldwide. We aimed to evaluate the clinical course of severe COVID-19 patients and to compare them with the non-severe patients concerning clinical and epidemiological characteristics, biological parameters and outcomes and thus, highlight the factors associated with severe forms of COVID-19 in our country. This is a single-center, ambidirectional cohort study, conducted in Tangier's COVID-19 care premises. We included diagnosed COVID-19 patients between August 2020 and October 2021. Sampling was performed through stratification according to clinical forms. All patients were followed-up throughout disease evolution, until remission for mild to moderate forms and 30 days after discharge for hospitalized patient's group (severe to critical forms). Data were collected using the WHO International Severe Acute Respiratory and Emerging Infection (ISARIC) case report form (CRF) and extracted from medical records alongside with interviews with patients and their relatives. Among 915 included COVID-19 patients in Tangier, the non-severe group comprised 344 (37.6%) patients and the severe group comprised 571 (62.4%) patients. Some 514 were males (56.2%) and 401 were females (43.8%) and the mean age was 56.01 years (±16.76). The mean delay from onset of symptoms to diagnosis was 6.65 days ±4.68 in the severe group and 5.4 days ±4.57 in the non-severe group (p<0.001). Among the severe patient's group, 230 (40.3%) patients were admitted to the resuscitation unit, 258 (45.2%) patients were deceased during hospitalization, 313 (54.8%) were discharged alive, and 16 deaths occurred after discharge. Demographic, clinical, and biological characteristics showed significant differences between non-severe group and severe group. Multivariable logistic regression analysis showed increased odds of severity with male gender (adjusted odds ratio, aOR=2.91, p<0.003), age over 65 years old (aOR=2.68, p<0.001), diabetes (aOR=2.18, p<0.03), elevated D-dimers(>1 mg/mL) (aOR=6.09, p<0.001), superinfection (aOR=3.78, p<0.001), and baseline lymphopenia < 1000c/mm3 (aOR=8.66, p<0.001). The high-risk factors for developing severe COVID-19 are age > 65 years, male gender, diabetes, elevated D-dimers, baseline lymphopenia, and superinfection. To predict severe and fatal COVID-19, factors identified may be used in the development of prediction tools for COVID-19 prognosis and risk stratification. Recalling the importance of considering at-risk populations, the management of epidemics must be planned in conjunction with the specificity of each community. Findings from our study may serve for health economic analyses and research in order to assist public health decisions in the future and should be integrated into health emergency preparedness and response strategies ensuring a resilient health system.

Glycemic control using intermittently scanned continuous glucose monitoring in patients with diabetes requiring methylprednisolone therapy for severe COVID-19.

In patients with severe coronavirus disease 2019 (COVID-19) with diabetes, glycemic control is essential for a better outcome, however, we face difficulty controlling hyperglycemia induced by high-dose glucocorticoids. We report five cases of severe COVID-19 patients with diabetes, whose glycemic control was managed using an intermittently scanned continuous glucose monitoring (isCGM) system during methylprednisolone therapy. Patients using isCGM showed significantly lower average blood glucose levels and significantly higher total daily insulin dose during the methylprednisolone therapy, compared to patients under regular blood glucose monitoring. The use of isCGM enables remote glucose monitoring, and this can reduce the risks of healthcare workers who have frequent contact with the patients. Thus, we suggest that using isCGM should be considered in hospitalized patients with diabetes under the COVID-19 pandemic to achieve better glycemic control and to minimize the possible risks of healthcare workers.

Pulmonary Recovery 12 Months after Non-Severe and Severe COVID-19: The Prospective Swiss COVID-19 Lung Study

Background: Lung function impairment persists in some patients for months after acute coronavirus disease 2019 (COVID-19). Long-term lung function, radiological features, and their association remain to be clarified. Objectives: We aimed to prospectively investigate lung function and radiological abnormalities over 12 months after severe and non-severe COVID-19. Methods: 584 patients were included in the Swiss COVID-19 lung study. We assessed lung function at 3, 6, and 12 months after acute COVID-19 and compared chest computed tomography (CT) imaging to lung functional abnormalities. Results: At 12 months, diffusion capacity for carbon monoxide (DLCO_corr) was lower after severe COVID-19 compared to non-severe COVID-19 (74.9% vs. 85.2% predicted, p < 0.001). Similarly, minimal oxygen saturation on 6-min walk test and total lung capacity were lower after severe COVID-19 (89.6% vs. 92.2%, p = 0.004, respectively, 88.2% vs. 95.1% predicted, p = 0.011). The difference for forced vital capacity (91.6% vs. 96.3% predicted, p = 0.082) was not statistically significant. Between 3 and 12 months, lung function improved in both groups and differences in DLCO between non-severe and severe COVID-19 patients decreased. In patients with chest CT scans at 12 months, we observed a correlation between radiological abnormalities and reduced lung function. While the overall extent of radiological abnormalities diminished over time, the frequency of mosaic attenuation and curvilinear patterns increased. Conclusions: In this prospective cohort study, patients who had severe COVID-19 had diminished lung function over the first year compared to those after non-severe COVID-19, albeit with a greater extent of recovery in the severe disease group.

Comparison of the Effects of Plasmapheresis, Hemoperfusion, and Convalescent Plasma Therapy on Inflammatory Factors in COVID-19 Patients.

Background: Since the emergence of coronavirus disease 2019 (COVID-19), the treatment protocols are continuously updated, based on the evidence gathered all around the world and reported to the World Health Organization. Like many other emerging infectious diseases, using convalescent plasma from those recovered from the disease was a preliminary treatment approach that showed partial effectiveness for severe COVID-19 patients. Besides, blood filtration strategies, such as hemoperfusion and plasmapheresis, are employed to lessen the load of inflammatory molecules. However, few studies compared their effects to conclude which treatment might be more efficacious for COVID-19 patients. We compared the effects of plasmapheresis or plasma exchange, convalescent plasma therapy, and hemoperfusion on O2 saturation and inflammatory factors in COVID-19 patients. Methods: In this retrospective study, 50 COVID-19 patients received standard treatments based the international guidelines. Patients were divided into 4 groups: hemoperfusion, plasmapheresis, plasma therapy, and control. The control group received only the standard treatments. The mortality rate, O2 saturation, and laboratory factors were compared between the 4 groups. Results: We found a significant decrease in the C-reactive protein level following hemoperfusion (32.75 ± 23.76 vs 13 ± 7.54 mg/dL; p = 0.032) but not plasmapheresis and plasma therapy. Besides, serum levels of lactate dehydrogenase (p = 0.327, 0.136, 0.550, for hemoperfusion, plasmapheresis, and plasma therapy, respectively) and other inflammatory molecules did not significantly change following treatments. There is also no significant difference in the mortality rate between the treatment groups (p = 0.353). Conclusion: It seems that hemoperfusion, plasmapheresis, and plasma therapy did not have considerable effects on decreasing the inflammation and mortality rate compared with standard treatment.

Cross-talk between red blood cells and plasma influences blood flow and omics phenotypes in severe COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by using microfluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases.