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1.
Nutrients ; 14(1)2021 Dec 31.
Article in English | MEDLINE | ID: covidwho-1613922

ABSTRACT

The article by D'Avolio and colleagues [...].


Subject(s)
COVID-19/blood , COVID-19/mortality , Vitamin D/blood , Vitamins/blood , Humans , Incidence , Patient Acuity , Risk Assessment , SARS-CoV-2 , United States/epidemiology
2.
Front Immunol ; 12: 784989, 2021.
Article in English | MEDLINE | ID: covidwho-1603282

ABSTRACT

Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies, the transient and stress-triggered release of a sphingomyelinase, SMPD1, into circulation and subsequent ceramide generation provides a promising target for FDA-approved drugs. Here, we report the activation of sphingomyelinase-ceramide pathway in 23 intensive care patients with severe COVID-19. We observed an increase of circulating activity of sphingomyelinase with subsequent derangement of sphingolipids in serum lipoproteins and from red blood cells (RBC). Consistent with increased ceramide levels derived from the inert membrane constituent sphingomyelin, increased activity of acid sphingomyelinase (ASM) accurately distinguished the patient cohort undergoing intensive care from healthy controls. Positive correlational analyses with biomarkers of severe clinical phenotype support the concept of an essential pathophysiological role of ASM in the course of SARS-CoV-2 infection as well as of a promising role for functional inhibition with anti-inflammatory agents in SARS-CoV-2 infection as also proposed in independent observational studies. We conclude that large-sized multicenter, interventional trials are now needed to evaluate the potential benefit of functional inhibition of this sphingomyelinase in critically ill patients with COVID-19.


Subject(s)
COVID-19/metabolism , Ceramides/metabolism , Signal Transduction , Sphingomyelin Phosphodiesterase/metabolism , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Ceramides/blood , Enzyme Activation , Erythrocyte Membrane/metabolism , Erythrocytes/metabolism , Fatty Acids/metabolism , Humans , Intensive Care Units , Patient Acuity , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Sphingomyelin Phosphodiesterase/blood , Sphingomyelins/metabolism
3.
BMC Anesthesiol ; 22(1): 12, 2022 01 05.
Article in English | MEDLINE | ID: covidwho-1608359

ABSTRACT

BACKGROUND: The COVID-19 pandemic has taken a toll on health care systems worldwide, which has led to increased mortality of different diseases like myocardial infarction. This is most likely due to three factors. First, an increased workload per nurse ratio, a factor associated with mortality. Second, patients presenting with COVID-19-like symptoms are isolated, which also decreases survival in cases of emergency. And third, patients hesitate to see a doctor or present themselves at a hospital. To assess if this is also true for sepsis patients, we asked whether non-COVID-19 sepsis patients had an increased 30-day mortality during the COVID-19 pandemic. METHODS: This is a post hoc analysis of the SepsisDataNet.NRW study, a multicentric, prospective study that includes septic patients fulfilling the SEPSIS-3 criteria. Within this study, we compared the 30-day mortality and disease severity of patients recruited pre-pandemic (recruited from March 2018 until February 2020) with non-COVID-19 septic patients recruited during the pandemic (recruited from March 2020 till December 2020). RESULTS: Comparing septic patients recruited before the pandemic to those recruited during the pandemic, we found an increased raw 30-day mortality in sepsis-patients recruited during the pandemic (33% vs. 52%, p = 0.004). We also found a significant difference in the severity of disease at recruitment (SOFA score pre-pandemic: 8 (5 - 11) vs. pandemic: 10 (8 - 13); p < 0.001). When adjusted for this, the 30-day mortality rates were not significantly different between the two groups (52% vs. 52% pre-pandemic and pandemic, p = 0.798). CONCLUSIONS: This led us to believe that the higher mortality of non-COVID19 sepsis patients during the pandemic might be attributed to a more severe septic disease at the time of recruitment. We note that patients may experience a delayed admission, as indicated by elevated SOFA scores. This could explain the higher mortality during the pandemic and we found no evidence for a diminished quality of care for critically ill sepsis patients in German intensive care units.


Subject(s)
COVID-19/prevention & control , Pandemics , Sepsis/mortality , Time-to-Treatment/statistics & numerical data , Aged , Female , Germany/epidemiology , Humans , Male , Middle Aged , Patient Acuity , Prospective Studies , SARS-CoV-2 , Survival Analysis
4.
Iran J Immunol ; 18(4): 331-337, 2021 12.
Article in English | MEDLINE | ID: covidwho-1594484

ABSTRACT

BACKGROUND: According to the World Health Organization, Mexico presents one of the highest mortality rates due to coronavirus disease 2019 (COVID-19). The "cytokine storm" phenomenon has been proposed as a pathological hallmark of severe COVID-19. OBJECTIVE: To determine the association of serum cytokine levels with COVID-19 severity. METHODS: We studied the cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and the IFN-γ serum levels through flow cytometry in 56 COVID-19 patients (24 critical and 32 non-critical) from Northwest Mexico. RESULTS: We observed a significant increase in the IL-6 and the IL-10 levels in the sera of critical patients. These cytokines were also associated with mechanical ventilation necessity and death, IL-6 showing AUC values above 0.7 for both variables; and correlated with Na+, creatinine, and platelet levels. On the other hand, no association was found between IL-2, IL-4, TNF-α, and IFN-γ with tested variables. CONCLUSION: Our results corroborate previous observations regarding IL-6 and IL-10 involvement in the severity of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/physiopathology , Interleukin-10/metabolism , Interleukin-6/metabolism , COVID-19/pathology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/pathology , Female , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Mexico , Patient Acuity
5.
Med Sci Monit ; 27: e935379, 2021 Dec 30.
Article in English | MEDLINE | ID: covidwho-1593238

ABSTRACT

BACKGROUND This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments. MATERIAL AND METHODS The medical records of a cohort of 158 Italian patients with early COVID-19 treated at home were analyzed. Treatments consisted of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed. The association of treatment timeliness and of clinical variables with the duration of symptoms and with the risk of hospitalization was evaluated by logistic regression. RESULTS Patients were divided into 2 groups: group 1 (n=85) was treated at the earliest possible time (<72 h from onset of symptoms), and group 2 (n=73) was treated >72 h after the onset of symptoms. Clinical severity at the beginning of treatment was similar in the 2 groups. In group 1, symptom duration was shorter than in group 2 (median 6.0 days vs 13.0 days, P<0.001) and no hospitalizations occurred, compared with 19.18% hospitalizations in group 2. One patient in group 1 developed chest X-ray alterations and 2 patients experienced an increase in D-dimer levels, compared with 30 and 22 patients, respectively, in group 2. The main factor determining the duration of symptoms and the risk of hospitalization was the delay in starting therapy (P<0.001). CONCLUSIONS This real-world study of patients in the community showed that early diagnosis and early supportive patient management reduced the severity of COVID-19 and reduced the rate of hospitalization.


Subject(s)
COVID-19/diagnosis , COVID-19/drug therapy , Hospitalization/statistics & numerical data , Time-to-Treatment/statistics & numerical data , Aged , Aged, 80 and over , Aspirin/therapeutic use , Betamethasone/therapeutic use , Cohort Studies , Dietary Supplements , Early Diagnosis , Female , Flavonoids/therapeutic use , Follow-Up Studies , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Indomethacin/therapeutic use , Italy , Male , Middle Aged , Omeprazole/therapeutic use , Patient Acuity , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Time , Treatment Outcome
6.
Respir Res ; 22(1): 317, 2021 Dec 22.
Article in English | MEDLINE | ID: covidwho-1582067

ABSTRACT

BACKGROUND: Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched. METHODS: In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2 < 200 receiving tocilizumab plus usual care versus usual care alone. Tocilizumab was administered at the time point that PaO2/FiO2 < 200 was observed. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10. FINDINGS: Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95% CI: 1.21-9.30), (p = 0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28 day period for patients receiving tocilizumab compared to usual care [11.0 days (95% CI: 9.0 to 16.0) vs 14.0 days (95% CI: 10.0-24.0), HR: 1.32 (95% CI: 0.84-2.08), p = 0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95% CI: 23.0-84.7) vs 15.8 (95% CI: - 19.4-50.3), p = 0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5 ± 2.1 vs 0.6 ± 2.6, p = 0.005). CONCLUSION: Administration of tocilizumab, at the time point that PaO2/FiO2 < 200 was observed, improved survival and other clinical outcomes in hospitalized patients with severe COVID-19 irrespective of systemic inflammatory markers levels.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/drug therapy , COVID-19/mortality , Hospitalization/trends , Patient Acuity , Administration, Intravenous , Aged , COVID-19/diagnosis , Female , Humans , Male , Middle Aged , Prospective Studies , Survival Rate/trends
7.
Acta Neuropathol Commun ; 9(1): 199, 2021 12 23.
Article in English | MEDLINE | ID: covidwho-1581995

ABSTRACT

Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.


Subject(s)
Apolipoprotein E4/genetics , COVID-19/complications , COVID-19/genetics , Cerebral Hemorrhage/genetics , Mental Fatigue/genetics , Patient Acuity , Adult , Aged , Autopsy , Biological Specimen Banks , COVID-19/diagnosis , COVID-19/epidemiology , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/epidemiology , Cohort Studies , Female , Finland/epidemiology , Genetic Association Studies/methods , Heterozygote , Humans , Male , Mental Fatigue/diagnosis , Mental Fatigue/epidemiology , Microvessels/pathology , Middle Aged , Prospective Studies , Risk Factors , Young Adult
8.
Front Immunol ; 12: 707159, 2021.
Article in English | MEDLINE | ID: covidwho-1581347

ABSTRACT

Coronavirus disease-2019 (COVID-19) was declared as a pandemic by WHO in March 2020. SARS-CoV-2 causes a wide range of illness from asymptomatic to life-threatening. There is an essential need to identify biomarkers to predict disease severity and mortality during the earlier stages of the disease, aiding treatment and allocation of resources to improve survival. The aim of this study was to identify at the time of SARS-COV-2 infection patients at high risk of developing severe disease associated with low survival using blood parameters, including inflammation and coagulation mediators, vital signs, and pre-existing comorbidities. This cohort included 89 multi-ethnic COVID-19 patients recruited between July 14th and October 20th 2020 in Doha, Qatar. According to clinical severity, patients were grouped into severe (n=33), mild (n=33) and asymptomatic (n=23). Common routine tests such as complete blood count (CBC), glucose, electrolytes, liver and kidney function parameters and markers of inflammation, thrombosis and endothelial dysfunction including complement component split product C5a, Interleukin-6, ferritin and C-reactive protein were measured at the time COVID-19 infection was confirmed. Correlation tests suggest that C5a is a predictive marker of disease severity and mortality, in addition to 40 biological and physiological parameters that were found statistically significant between survivors and non-survivors. Survival analysis showed that high C5a levels, hypoalbuminemia, lymphopenia, elevated procalcitonin, neutrophilic leukocytosis, acute anemia along with increased acute kidney and hepatocellular injury markers were associated with a higher risk of death in COVID-19 patients. Altogether, we created a prognostic classification model, the CAL model (C5a, Albumin, and Lymphocyte count) to predict severity with significant accuracy. Stratification of patients using the CAL model could help in the identification of patients likely to develop severe symptoms in advance so that treatments can be targeted accordingly.


Subject(s)
Biomarkers/blood , COVID-19/blood , COVID-19/mortality , Complement C5a/analysis , Patient Acuity , Adult , Aged , COVID-19/complications , Cohort Studies , Female , Humans , Hypoalbuminemia/mortality , Hypoalbuminemia/virology , Lymphocyte Count , Lymphopenia/mortality , Lymphopenia/virology , Male , Middle Aged , Prognosis , Prospective Studies , Qatar , SARS-CoV-2
9.
Nutrients ; 14(1)2021 Dec 31.
Article in English | MEDLINE | ID: covidwho-1580544

ABSTRACT

There are many ways to regulate emotions. People use both adaptive (e.g., regulation by music) and maladaptive (e.g., regulation by food) strategies to do this. We hypothesized that participants with a high level of food-based regulatory strategies and a low level of music-based regulatory strategies (a group with the least adaptive form of emotion regulation) would have significantly greater levels of unhealthy eating behaviours, depression, anxiety and stress, as well as a significantly lower level of healthy eating behaviours than those with a low level of food-based regulatory strategies and a high level of music-based regulatory strategies (a group with the greatest adaptive form of emotion regulation). Participants (N = 410; Mage = 31.77, SD = 13.53) completed: the Brief Music in Mood Regulation Scale, the Emotional Overeating Questionnaire, the Healthy and Unhealthy Eating Behavior Scale, the Depression, Anxiety and Stress Scale and a socio-demographic survey. The four clusters were identified: (a) Cluster 1 (N = 148): low food-based regulatory strategies and high music-based regulatory strategies; (b) Cluster 2 (N = 42): high food-based regulatory strategies and high music-based regulatory strategies; (c) Cluster 3 (N = 70): high food-based regulatory strategies and low music-based regulatory strategies; (d) Cluster 4 (N = 150): low food-based regulatory strategies and low music-based regulatory strategies. Overall, our outcomes partially support our hypothesis, as higher levels of unhealthy eating behaviours, depression, anxiety and stress were observed in participants with high food-based and low music-based regulatory strategies as compared with adults with low food-based and high music-based regulatory strategies. To sum up, the results obtained indicate that during the COVID-19 pandemic the group of people regulating their emotional state and unhealthy eating predominantly with food is potentially characterized by worse functioning than the group of people regulating with music. Therefore, it can be concluded that people who regulate their functioning using food should be included in preventive measures by specialists. During the visit, psychologists and primary care physicians can ask patients about their daily strategies and based on this information specialists can estimate the potential risk of developing high levels of stress and anxiety, depressive disorders and unhealthy eating habits and provide specific (match) intervention.


Subject(s)
Anxiety Disorders/therapy , COVID-19/psychology , Depressive Disorder/therapy , Diet, Healthy/statistics & numerical data , Feeding and Eating Disorders/therapy , Music/psychology , Stress, Psychological/therapy , Adolescent , Adult , Aged , Anxiety Disorders/complications , Anxiety Disorders/psychology , Cluster Analysis , Depressive Disorder/complications , Depressive Disorder/psychology , Emotional Regulation , Feeding and Eating Disorders/complications , Feeding and Eating Disorders/psychology , Female , Humans , Male , Middle Aged , Patient Acuity , SARS-CoV-2 , Stress, Psychological/complications , Stress, Psychological/psychology , Surveys and Questionnaires , Young Adult
10.
Drugs ; 82(1): 43-54, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1588657

ABSTRACT

OBJECTIVE: To determine the association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) use and coronavirus disease 2019 (COVID-19) severity and outcomes in US veterans. PATIENTS AND METHODS: We retrospectively examined 27,556 adult US veterans who tested positive for COVID-19 between March to November 2020. Logistic regression and Cox proportional hazards models using propensity score (PS) for weight, adjustment, and matching were used to examine the odds of an event within 60 days following a COVID-19-positive case date and time to death, respectively, according to ACEI and/or ARB prescription within 6 months prior to the COVID-19-positive case date. RESULTS: The overlap PS weighted logistic regression model showed lower odds of an intensive care unit (ICU) admission (odds ratio [OR] 95% CI 0.77, 0.61-0.98) and death within 60 days (0.87, 0.79-0.97) with an ACEI or ARB prescription. Veterans with an ARB-only prescription also had lower odds of an ICU admission (0.64, 0.44-0.92). The overlap PS weighted model similarly showed a lower risk of time to all-cause mortality in veterans with an ACEI or ARB prescription (HR [95% CI]: 0.87, 0.79-0.97) and an ARB only prescription (0.78, 0.67-0.91). Veterans with an ACEI prescription had higher odds of experiencing a septic event within 60 days after the COVID-19-positive case date (1.22, 1.02-1.46). CONCLUSION: In this study of a national cohort of US veterans, we found that the use of an ACEI/ARB in patients with COVID-19 was not associated with increased mortality and other worse outcomes. Future studies should examine underlying pathways and further confirm the relationship of ACEI prescription with sepsis.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/epidemiology , Hypertension/drug therapy , Hypertension/epidemiology , Adult , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , COVID-19/mortality , Female , Humans , Intensive Care Units/statistics & numerical data , Logistic Models , Male , Middle Aged , Patient Acuity , Proportional Hazards Models , Retrospective Studies , SARS-CoV-2 , Sepsis/epidemiology , Veterans
11.
Cells ; 10(12)2021 12 11.
Article in English | MEDLINE | ID: covidwho-1572377

ABSTRACT

The SARS-CoV-2 (COVID-19) pandemic has caused millions of deaths worldwide. Early risk assessment of COVID-19 cases can help direct early treatment measures that have been shown to improve the prognosis of severe cases. Currently, circulating miRNAs have not been evaluated as canonical COVID-19 biomarkers, and identifying biomarkers that have a causal relationship with COVID-19 is imperative. To bridge these gaps, we aim to examine the causal effects of miRNAs on COVID-19 severity in this study using two-sample Mendelian randomization approaches. Multiple studies with available GWAS summary statistics data were retrieved. Using circulating miRNA expression data as exposure, and severe COVID-19 cases as outcomes, we identified ten unique miRNAs that showed causality across three phenotype groups of COVID-19. Using expression data from an independent study, we validated and identified two high-confidence miRNAs, namely, hsa-miR-30a-3p and hsa-miR-139-5p, which have putative causal effects on developing cases of severe COVID-19. Using existing literature and publicly available databases, the potential causative roles of these miRNAs were investigated. This study provides a novel way of utilizing miRNA eQTL data to help us identify potential miRNA biomarkers to make better and early diagnoses and risk assessments of severe COVID-19 cases.


Subject(s)
COVID-19/genetics , Circulating MicroRNA/genetics , MicroRNAs/genetics , Patient Acuity , SARS-CoV-2/genetics , Biomarkers/blood , COVID-19/blood , Circulating MicroRNA/blood , Genome-Wide Association Study , Humans , Mendelian Randomization Analysis , MicroRNAs/blood , SARS-CoV-2/metabolism
12.
PLoS One ; 16(12): e0261432, 2021.
Article in English | MEDLINE | ID: covidwho-1571995

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is the ongoing pandemic with multitude of manifestations and association of ABO blood group in South-East Asian population needs to be explored. METHODS: It was a retrospective study of patients with COVID-19. Blood group A, B, O, and AB were identified in every participant, irrespective of their RH type and allotted groups 1, 2,3, and 4, respectively. Correlation between blood group and lab parameters was presented as histogram distributed among the four groups. Multivariate regression and logistic regression were used for inferential statistics. RESULTS: The cohort included 1067 patients: 521 (48.8%) participants had blood group O as the prevalent blood type. Overall, 10.6% COVID-19-related mortality was observed at our center. Mortality was 13.9% in blood group A, 9.5% in group B, 10% in group C, and 10.2% in AB blood group (p = 0.412). IL-6 was elevated in blood group A (median [IQR]: 23.6 [17.5,43.8]), Procalcitonin in blood group B (median [IQR]: 0.54 [0.3,0.7]), D-dimers and CRP in group AB (median [IQR]: 21.5 [9,34]; 24 [9,49], respectively). Regarding severity of COVID-19 disease, no statistical difference was seen between the blood groups. Alteration of the acute phase reactants was not positively associated with any specific blood type. CONCLUSION: In conclusion, this investigation did not show significant association of blood groups with severity and of COVID-19 disease and COVID-19-associated mortality.


Subject(s)
ABO Blood-Group System , COVID-19/blood , COVID-19/mortality , Adult , Aged , Humans , Interleukin-6/blood , Middle Aged , Multivariate Analysis , Patient Acuity , Procalcitonin/blood , Retrospective Studies
13.
Crit Care ; 25(1): 423, 2021 12 13.
Article in English | MEDLINE | ID: covidwho-1571913

ABSTRACT

BACKGROUND: Autoptic pulmonary findings have been described in severe COVID-19 patients, but evidence regarding the correlation between clinical picture and lung histopathologic patterns is still weak. METHODS: This was a retrospective cohort observational study conducted at the referral center for infectious diseases in northern Italy. Full lung autoptic findings and clinical data of patients who died from COVID-19 were analyzed. Lung histopathologic patterns were scored according to the extent of tissue damage. To consider coexisting histopathologic patterns, hierarchical clustering of histopathologic findings was applied. RESULTS: Whole pulmonary examination was available in 75 out of 92 full autopsies. Forty-eight hospitalized patients (64%), 44 from ICU and four from the medical ward, had complete clinical data. The histopathologic patterns had a time-dependent distribution with considerable overlap among patterns. Duration of positive-pressure ventilation (p < 0.0001), mean positive end-expiratory pressure (PEEP) (p = 0.007), worst serum albumin (p = 0.017), interleukin 6 (p = 0.047), and kidney SOFA (p = 0.001) differed among histopathologic clusters. The amount of PEEP for long-lasting ventilatory treatment was associated with the cluster showing the largest areas of early and late proliferative diffuse alveolar damage. No pharmacologic interventions or comorbidities affected the lung histopathology. CONCLUSIONS: Our study draws a comprehensive link between the clinical and pulmonary histopathologic findings in a large cohort of COVID-19 patients. These results highlight that the positive end-expiratory pressures and the duration of the ventilatory treatment correlate with lung histopathologic patterns, providing new clues to the knowledge of the pathophysiology of severe SARS-CoV-2 pneumonia.


Subject(s)
COVID-19 , Lung , Autopsy , Humans , Lung/pathology , Patient Acuity , Retrospective Studies
14.
Lipids Health Dis ; 20(1): 179, 2021 Dec 13.
Article in English | MEDLINE | ID: covidwho-1571759

ABSTRACT

Lipids have a wide variety and vital functions. Lipids play roles in energy metabolism, intracellular and extracellular signal traffic, and transport of fat-soluble vitamins. Also, they form the structure of the cell membrane. SARS-CoV-2 interacts with lipids since its genetic material contains lipid-enveloped ribonucleic acid (RNA). Previous studies have shown that total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) levels are lower in patients with severe novel coronavirus disease 2019 (COVID-19) compared to patients with non-severe COVID-19.Na+/H+ Exchanger (NHE) is an important antiport that keeps the intracellular pH value within physiological limits. When the intracellular pH falls, NHE is activated and pumps H+ ions outward. However, prolonged NHE activation causes cell damage and atherosclerosis. Prolonged NHE activation may increase susceptibility to SARS-CoV-2 infection and severity of COVID-19.In COVID-19, increased angiotensin II (Ang II) due to angiotensin-converting enzyme-2 (ACE2) dysfunction stimulates NHE. Lipids are in close association with the NHE pump. Prolonged NHE activity increases the influx of H+ ions and free fatty acid (FFA) inward. Ang II also causes increased low-density lipoprotein receptor (LDLR) levels by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9). Thus, intracellular atheroma plaque formation is accelerated.Besides, SARS-CoV-2 may replicate more rapidly as intracellular cholesterol increases. SARS-CoV-2 swiftly infects the cell whose intracellular pH decreases with NHE activation and FFA movement. Novel treatment regimens based on NHE and lipids should be explored for the treatment of COVID-19.


Subject(s)
COVID-19/pathology , Cholesterol/metabolism , Receptors, LDL/metabolism , SARS-CoV-2 , Sodium-Hydrogen Exchangers/metabolism , COVID-19/metabolism , COVID-19/mortality , Cause of Death , Humans , Lipid Metabolism , Patient Acuity , SARS-CoV-2/metabolism
15.
Cell Rep ; 37(12): 110126, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1556413

ABSTRACT

Previous studies have shown that the high mortality caused by viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus primarily results from complications of a cytokine storm. Therefore, it is critical to identify the key factors participating in the cytokine storm. Here we demonstrate that interferon-induced protein 35 (IFP35) plays an important role in the cytokine storm induced by SARS-CoV-2 and influenza virus infection. We find that the levels of serum IFP35 in individuals with SARS-CoV-2 correlates with severity of the syndrome. Using mouse model and cell assays, we show that IFP35 is released by lung epithelial cells and macrophages after SARS-CoV-2 or influenza virus infection. In addition, we show that administration of neutralizing antibodies against IFP35 considerably reduces lung injury and, thus, the mortality rate of mice exposed to viral infection. Our findings suggest that IFP35 serves as a biomarker and as a therapeutic target in virus-induced syndromes.


Subject(s)
COVID-19/blood , COVID-19/drug therapy , Influenza, Human/blood , Influenza, Human/drug therapy , Intracellular Signaling Peptides and Proteins/blood , Animals , Antibodies, Neutralizing/administration & dosage , Biomarkers/blood , COVID-19/pathology , COVID-19/physiopathology , Disease Models, Animal , Humans , Inflammation/metabolism , Influenza, Human/pathology , Lung/metabolism , Lung/pathology , Macrophages/metabolism , Macrophages/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Patient Acuity , SARS-CoV-2/physiology
16.
Clin Lab ; 67(12)2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1538779

ABSTRACT

BACKGROUND: Coronavirus disease, which initially appeared in Wuhan, China during the month of December 2019, very quickly spread and became a worldwide pandemic. The African continent was not spared. The poor health system and low socioeconomic status in some regions has raised concern on the risk of an epidemic disaster due to the rapid transmission of the virus. This study therefore aims to determine the relationship between the modifications of complete blood count parameters, CRP, and the severity and outcome of SARS-CoV2 infection in the first patients hospitalized at the Centre Hospitalier Universitaire de Libreville (Libreville University Hospital Center) in Gabon. METHODS: This is a prospective study led from April to July 2020 in the COVID infectious department (SICov) of the Centre Hospitalier Universitaire de Libreville (CHUL). RESULTS: In total, 184 patients participated in the study. The median age was 47 (37 - 54) years. Male subjects predominated. The median number of leucocytes was 5.6 (4.4 - 7.45) x 109/L. It was significantly higher in patients with acute respiratory distress syndrome (ARDS) and in intensive care units (ICU) compared to pauci-symptomatic cases (p < 0.01). Factors associated with death were leukocytosis (crude OR 37.1 (8.3 - 98.4) p < 0.01), neutrophilia (OR 20.1 (4.6 - 89.0) p < 0.01), NRL ≥ 9 (OR 13.5 (2.7 - 67.4); p < 0.01) and CRP > 100 mg/L (OR 17.8 (2.0 - 154.0) p = 0.02). CONCLUSIONS: The hematological profile of patients with COVID-19 varies according to the severity of the disease. Leukocytosis, neutrophilia, a NLR above 6 and a CRP higher than 100 mg/L were associated with the severity of the infection and death in Gabonese patients.


Subject(s)
C-Reactive Protein , COVID-19 , Receptors, Immunologic , Blood Cell Count , Humans , Male , Middle Aged , Patient Acuity , Prospective Studies , RNA, Viral , Receptors, Immunologic/analysis , SARS-CoV-2
17.
S Afr Med J ; 111(11): 1092-1097, 2021 11 05.
Article in English | MEDLINE | ID: covidwho-1534501

ABSTRACT

BACKGROUND: The availability of well and functional healthcare workers (HCWs) and support staff is pivotal to a country's ability to manage the COVID-19 pandemic effectively. While HCWs have been identified as being at increased risk for acquisition of SARS-CoV-2 infection, there is a paucity of data pertaining to South African (SA) HCW-related infection rates. Global and provincial disparities in these numbers necessitate local data in order to mitigate risks. OBJECTIVES: To ascertain the overall SARS-CoV-2 infection rates and outcomes among all hospital staff at three hospitals in the Tshwane district of Gauteng Province, SA, and further determine associations with the development of severe COVID-19 disease. METHODS: This retrospective audit was conducted across three academic hospitals in the Tshwane district for the period 1 June - 31 August 2020. Deidentified data from occupational health and safety departments at each hospital were used to calculate infection rates. A more detailed analysis at one of the three hospitals included evaluation of demographics, work description, possible source of SARS-CoV-2 exposure (community or hospital), comorbidities and outcomes. RESULTS: The period prevalence of SARS-CoV-2 infections ranged from 6.1% to 15.4% between the three hospitals, with the average period prevalence being 11.1%. The highest incidence of SARS-CoV-2 infections was observed among administrative staff (2.8 cases per 1 000 staff days), followed by nursing staff (2.7 cases per 1 000 staff days). Medical doctors had the lowest incidence of 1.1 cases per 1 000 staff days. SARS-CoV-2 infections were categorised as either possibly community or possibly healthcare facility acquired for 26.6% and 73.4% of the infections, respectively. The administrative group had the highest proportion of possible community-acquired infections (41.8%), while doctors had the lowest (6.1%). The mean age of individuals with mild and severe disease was 41 years and 46.1 years, respectively (p=0.004). The presence of comorbidities was significantly associated with severity of disease (p=0.002). CONCLUSIONS: This study highlights that hospital staff, including administrative staff, are clearly at high risk for acquisition of SARS-CoV-2 infection during a surge.


Subject(s)
Academic Medical Centers , COVID-19/epidemiology , Personnel, Hospital/statistics & numerical data , Adult , Age Distribution , COVID-19/physiopathology , Female , Humans , Incidence , Male , Middle Aged , Patient Acuity , Prevalence , Retrospective Studies , Risk Factors , South Africa/epidemiology
18.
BMC Nephrol ; 22(1): 381, 2021 11 13.
Article in English | MEDLINE | ID: covidwho-1515439

ABSTRACT

BACKGROUND: Kidney dysfunction occurs in severe COVID-19, and is a predictor of COVID-19 mortality. Whether kidney dysfunction causes severe COVID-19, and hence is a target of intervention, or whether it is a symptom, is unclear because conventional observational studies are open to confounding. To obtain unconfounded estimates, we used Mendelian randomization to examine the role of kidney function in severe COVID-19. METHODS: We used genome-wide significant, uncorrelated genetic variants to predict kidney function, in terms of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), and then assessed whether people with genetically instrumented higher eGFR or lower UACR, an indication of better kidney function, had a lower risk of severe COVID-19 (8779 cases, 1,001,875 controls), using the largest available cohorts with extensive genotyping. For comprehensiveness, we also examined their role in COVID-19 hospitalization (24,274 cases, 2,061,529 controls) and all COVID-19 (1,12,612 cases, 2,474,079 controls). RESULTS: Genetically instrumented higher eGFR was associated with lower risk of severe COVID-19 (odds ratio (OR) 0.90, 95% confidence interval (CI) 0.83, 0.98) but not related to COVID-19 hospitalization or infection. Genetically instrumented UACR was not related to COVID-19. CONCLUSIONS: Kidney function appears to be one of the key targets for severe COVID-19 treatment. Use of available medications to improve kidney function, such as antihypertensives, might be beneficial for COVID-19 treatment, with relevance to drug repositioning.


Subject(s)
COVID-19/complications , COVID-19/genetics , Glomerular Filtration Rate/genetics , Kidney/physiopathology , Patient Acuity , Albuminuria/urine , Case-Control Studies , Creatinine/urine , Genetic Variation , Genome-Wide Association Study , Hospitalization , Humans , Mendelian Randomization Analysis , Risk Factors , SARS-CoV-2 , /genetics
20.
Am J Nurs ; 121(11): 10, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1506395
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