Severe Forms Of Coronavirus Disease 2019 Research Articles

A rare case series of bilateral pneumothorax among adult COVID-19 patients reported at a tertiary care hospital in Mizoram, India

Apart from routine symptoms such as fever, cough, sore throat, myalgia, and dyspnea in severe form of Coronavirus Disease-2019 (COVID-19) infection, very rarely patients can develop worsening of dyspnea due to bilateral pneumothorax. The present case series is about five adult patients, of age ranging from 39 to 57 years, who developed bilateral pneumothorax during their stay in the hospital. All the cases were reported between May 2021 and October 2021 and were tested positive for COVID-19 by reverse transcriptase polymerase chain reaction. Out of five adults, three patients were males and were two females. All the patients were assessed with quick sequential organ failure assessment (q SOFA) score on admission and then monitored by SOFA Score. On admission, baseline contrast enhanced computer tomography chest was done for three patients, and chest radiography for one patient all showing features of moderate to severe COVID-19 pneumoniae. One patient with q SOFA Score of 3 on admission required immediate invasive mechanical ventilatory support with ultrasonogram chest immediately performed showing bilateral pneumothorax. Patients were started on remdesivir, dexamethasone, low molecular weight heparin or unfractionated heparin, tocilizumab, and antibiotics. Subsequently, during the course of stay in the hospital, rest of the four patients developed symptoms of pneumothorax and emergency bedside chest ultrasonography showed the typical barcode or stratosphere sign confirming bilateral pneumothorax. All the patients were managed with bilateral chest intercostal water seal drainage intercostal drain tube and invasive mechanical ventilation. Fraction of Inspired Oxygen (FIO2), and other ventilatory settings were adjusted depending on daily arterial blood gas findings. Attempts to wean off from ventilatory support and extubation were successful for two patients, whereas three patients did not survive. In this case series, we will be presenting about those five cases of bilateral pneumothorax in COVID-19 patients reported at a tertiary care hospital in Mizoram, India.

Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

Hematological ratios in coronavirus disease 2019 patients with and without invasive mechanical ventilation.

Patients with the most severe form of coronavirus disease 2019 (COVID-19) often require invasive ventilation. Determining the best moment to intubate a COVID-19 patient is complex decision and can result in important consequences for the patient. Therefore, markers that could aid in clinical decision-making such as hematological indices are highly useful. These markers are easy to calculate, do not generate extra costs for the laboratory, and are readily implemented in routine practice. Thus, this study aimed to investigate differences in the ratios calculated from the hemogram between patients with and without the need for invasive mechanical ventilation (IMV) and a control group. This was an observational retrospective analysis of 212 patients with COVID-19 that were hospitalized between April 1, 2020 and March 31, 2021 who were stratified as IMV (n = 129) or did not require invasive mechanical ventilation (NIMV) (n = 83). A control group of 198 healthy individuals was also included. From the first hemogram of each patient performed after admission, the neutrophil-to-lymphocyte ratio (NLR), the derived NLR (d-NLR), the lymphocyte-to-monocyte ratio, the platelet-to-lymphocyte ratio, the neutrophil-to-platelet ratio (NPR), and the systemic immune-inflammation index (SII) were calculated. All hematological ratios exhibited significant differences between the control group and COVID-19 patients. NLR, d-NLR, SII, and NPR were higher in the IMV group than they were in the NIMV group. The hematological indices addressed in this study demonstrated high potential for use as auxiliaries in clinical decision-making regarding the need for IMV.

Crowdsourcing temporal transcriptomic coronavirus host infection data: Resources, guide, and novel insights.

The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) reawakened the need to rapidly understand the molecular etiologies, pandemic potential, and prospective treatments of infectious agents. The lack of existing data on SARS-CoV-2 hampered early attempts to treat severe forms of coronavirus disease-2019 (COVID-19) during the pandemic. This study coupled existing transcriptomic data from severe acute respiratory syndrome-related coronavirus 1 (SARS-CoV-1) lung infection animal studies with crowdsourcing statistical approaches to derive temporal meta-signatures of host responses during early viral accumulation and subsequent clearance stages. Unsupervised and supervised machine learning approaches identified top dysregulated genes and potential biomarkers (e.g. CXCL10, BEX2, and ADM). Temporal meta-signatures revealed distinct gene expression programs with biological implications to a series of host responses underlying sustained Cxcl10 expression and Stat signaling. Cell cycle switched from G1/G0 phase genes, early in infection, to a G2/M gene signature during late infection that correlated with the enrichment of DNA damage response and repair genes. The SARS-CoV-1 meta-signatures were shown to closely emulate human SARS-CoV-2 host responses from emerging RNAseq, single cell, and proteomics data with early monocyte-macrophage activation followed by lymphocyte proliferation. The circulatory hormone adrenomedullin was observed as maximally elevated in elderly patients who died from COVID-19. Stage-specific correlations to compounds with potential to treat COVID-19 and future coronavirus infections were in part validated by a subset of twenty-four that are in clinical trials to treat COVID-19. This study represents a roadmap to leverage existing data in the public domain to derive novel molecular and biological insights and potential treatments to emerging human pathogens.

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.

Investigation of Serum Ferritin for the Prediction of COVID-19 Severity and Mortality: A Cross-Sectional Study.

Acute respiratory failure develops quickly in patients with a severe form of coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome Coronavirus 2 (SARS‑CoV‑2). Despite being commonly acknowledged as a measure of the body's overall iron storage, ferritin's predictive value is associated with COVID-19. This study aimed to evaluate the relationship between COVID-19 and serum ferritin levels as the biochemical markers of SARS-CoV-2 infection in Sulaymaniyah, Iraq. A biochemical test was performed at Baxshin Hospital in the period from February 2022 to April 2022. It was performed on a total of 85 patients (63.53% males and 36.47% females), ranging in age from 25 to 79 years old, with an average age of 48.4 years old. The patient's blood samples were taken to screen for ferritin levels. The resulting outcome of this work is high serum ferritin levels for the majority of infected patients. Overall, there is a significant difference between male and female serum ferritin observed with a p-value < 0.05. The median interquartile range (IQR) of serum ferritin was 896 ng/mL for males, while it was only 611 ng/mL for females. The current study showed that age level has a great effect on elevated ferritin levels. It has been discovered that gender impacts increasing ferritin levels; 62% were found to be men and 38% were found to be women, with average ferritin levels of 1111 ng/mL and 712.8 ng/mL, respectively. SARS-CoV-2 infection causes significant laboratory abnormalities, including a high level of serum ferritin.

Therapeutic Efficacy and Outcomes of Remdesivir versus Remdesivir with Tocilizumab in Severe SARS-CoV-2 Infection.

The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated many challenges to find an effective drug combination for hospitalized patients with severe forms of coronavirus disease 2019 (COVID-19) pneumonia. We conducted a retrospective cohort study, including 182 patients with severe COVID-19 pneumonia hospitalized between March and October 2021 in a Pneumology Hospital from Cluj-Napoca, Romania. Among patients treated with standard of care, 100 patients received remdesivir (R group) and 82 patients received the combination of remdesivir plus tocilizumab (RT group). We compared the clinical outcomes, the inflammatory markers, superinfections, oxygen requirement, intensive care unit (ICU) admission and mortality rate before drug administration and 7 days after in R group and RT group. Borg score and oxygen support showed an improvement in the R group (p &lt; 0.005). Neutrophiles, C-reactive protein (CRP) and serum ferritin levels decreased significantly in RT group but with a higher rate of superinfection in this group. ICU admission and death did not differ significantly between groups. The combination of remdesivir plus tocilizumab led to a significantly improvement in the inflammatory markers and a decrease in the oxygen requirement. Although the superinfection rate was higher in RT group than in R group, no significant difference was found in the ICU admission and mortality rate between the groups.

Comparative Study of Vaccinated and Unvaccinated Hospitalised Patients: A Retrospective Population Study of 500 Hospitalised Patients with SARS-CoV-2 Infection in a Spanish Population of 220,000 Inhabitants.

Objectives. This study aimed to compare the characteristics of fully and partially vaccinated or unvaccinated coronavirus disease 2019 (COVID-19) patients who were hospitalised in a population of 220,000 habitants. Methods: Retrospective, observational, and population studies were conducted on patients who were hospitalised due to COVID-19 from March to October 2021. We assessed the impact of vaccination and other risk factors through Cox multivariate analysis. Results: A total of 500 patients were hospitalised, among whom 77 (15.4%) were fully vaccinated, 86 (17.2%) were partially vaccinated, and 337 (67.4%) were unvaccinated. Fully vaccinated (FV) patients were older and had a higher Charlson index than those of partially vaccinated and unvaccinated patients (NFV). Bilateral pneumonia was more frequent among NFV (259/376 (68.9%)) than among FV patients (32/75 (42.7%)). The former had more intensive care unit admissions (63/423) than the latter (4/77); OR: 2.80; CI (1.07–9.47). Increasing age HZ: 1.1 (1.06–1.14)) and haematological disease at admission HZ: 2.99 (1.26–7.11)) were independent risk factors for higher mortality during the first 30 days of hospitalisation. The probability of an earlier discharge in the subgroup of 440 patients who did not die during the first 30 days of hospitalisation was related to age (older to younger: HZ: 0.98 (0.97–0.99)) and vaccination status. Conclusions: Among the patients hospitalised because of COVID-19, complete vaccination was associated with less severe forms of COVID-19, with an earlier discharge date. Age and haematological disease were related to a higher mortality rate during the first 30 days of hospitalisation.

Risk Factors Associated with Severe Disease and Intensive Care Unit Admission of Pregnant Patients with COVID-19 Infection-A Retrospective Study.

(1) Background: Pregnant patients with severe forms of coronavirus disease 2019 (COVID-19) can experience adverse pregnancy outcomes. The aim of this study was to retrospectively assess the risk factors associated with admission to the intensive care unit (ICU) of pregnant patients with COVID-19, as well as the pregnancy outcomes of these patients; (2) Methods: Medical records of 31 pregnant patients with COVID-19 admitted to three clinical hospitals from Romania, between October 2020 and November 2021 were examined. The patients were segregated into two groups depending on their clinical evolution: non-ICU admission (n = 19) or ICU admission (n = 12). Clinical and paraclinical findings were evaluated using univariate analysis, and the association of significant risk factors with maternal ICU admission was assessed using a multivariate analysis. Pregnancy outcomes of these patients were also recorded; (3) Results: Pulmonary disease, cough, dyspnea, leukocytosis, thrombocytosis, high serum values of transaminases, serum ferritin, and increased duration of hospital admission were identified as significant risk factors associated with maternal admission to the ICU. No significant differences regarding pregnancy outcomes were noted between the evaluated patients; (4) Conclusions: Specific risk factor identification in pregnant patients with severe forms of COVID-19 could improve the patient’s management.

CLL-224 Coronavirus Disease Mortality and Outcome in Macedonian Patients With Chronic Lymphocytic Leukemia: Single-Center Experience

Context: Patients with chronic lymphocytic leukemia (CLL) may be more predisposed to coronavirus disease 2019 (COVID-19) due to age, the nature of the disease, and treatment-related immunosuppression. Objective: The aim of the study was to assess risk factors of the outcome and course of COVID-19 for CLL patients in Macedonia. Design: Retrospective study of patients with CLL and COVID-19 infection in the period of time from the beginning of the pandemic to March 2022. Setting: Individual patient data from 55 CLL patients with COVID-19 infection were analyzed. The risk factors of COVID-19 disease severity and outcomes were investigated. Interventions: The outcome was the analysis of patients with COVID-19 infection in line with host risk factors and biological heterogeneity of the disease with previous therapy for CLL. Results: Our evaluation has shown that 80% of patients were male and 20% were female. The average age was 65 years. The average CIRS score was 2 and BMI was 23.6. Most of the patients (67.2%) have unmutated Ig genes. Ninety-one percent (91%) from that subgroup of patients have a severe form of COVID-19, 82% of patients were treated with chemotherapy, and 48% had a fatal outcome. Conclusions: CLL-directed treatment and unmutated Ig genes were significant risk factors for survival. Untreated patients and patients with mutated IGHV had a better chance of survival than those on treatment or who were recently treated.

Remdesivir Administration in COVID-19 Patients With Renal Impairment: A Systematic Review.

Remdesivir (RDV) is the main antiviral for the treatment of moderate to severe forms of Coronavirus disease 2019 (COVID-19). Several studies revealed a shortening time to clinical improvement of COVID-19 and mortality benefits in patients receiving RDV. The patients with renal disease were excluded from large clinical trials of RDV, and the probable nephrotoxicity of the drug, its metabolites, and the vehicle (sulfobutylether-β-cyclodextrin) have led to the recommendation against using RDV in patients with an estimated glomerular filtration rate of <30 mL/min. This systematic review aimed to collect data about the necessity and safety administration of RDV in the setting of renal impairment. Search through databases including MEDLINE, ScienceDirect, Cochrane Library, and PubMed was performed. The studies were carried out in adults and enrolled patients with different types of renal impairment (ie, acute kidney injury, chronic kidney disease, kidney transplant, and renal replacement therapy) were included. Eligible studies were assessed, and required data were extracted. Twenty-two cross-sectional studies, cohorts, case reports, and case series were included in this review. The mortality rate was between 7.3% and 50%, and various severity of COVID-19 was included in the studies. None of them reported an increase in adverse effects attributed to RDV administration. A decrease in inflammatory mediators and other benefits were obvious. Although the manufacturer's labeling does not recommend RDV administration in patients with severe renal impairment, it seems that nephrotoxicity is less concerning in the population of these patients. Moreover, RDV may be helpful in acute kidney injury induced by the viral invasion of COVID-19. To the best of our knowledge, this is the first systematic review of the use of RDV in kidney failure. Larger, well-designed, and pharmacokinetic studies are required to have a safe and logical recommendation about the use of RDV in patients with renal disorders.

Body mass index and comorbidities are associated with the duration of COVID-19 symptoms in non-hospitalized patients.

ObjectiveEvidence indicates that people with a high body mass index (BMI) tend to develop more severe forms of coronavirus disease 2019 (COVID-19). In this study, we aimed to determine the association between the duration of COVID-19 symptoms and variables such as BMI, age, presence of comorbidities, and smoking in non-hospitalized patients.MethodsIn this observational cross-sectional analytical study, we analyzed the data of patients with COVID-19 but without severe manifestations. We conducted descriptive statistics, non-parametric tests, and multivariate quasi-Poisson regression in the analysis. The quasi-Poisson regression model was configured with the duration of COVID-19 symptoms as the response variable, and BMI and the presence of comorbidities as the explanatory variables.ResultsAmong 302 non-hospitalized patients, we found a significant difference in COVID-19 symptom duration between the overweight group and the group with normal weight. Multivariate quasi-Poisson regression analysis showed that BMI and the presence of comorbidities were associated with the duration of COVID-19 symptoms. On the contrary, sex, age, and smoking status were not related to COVID-19 symptom duration.ConclusionsBMI and comorbidities were associated with the duration of COVID-19 symptoms in non-hospitalized patients.

The Mutual Relationship among Cardiovascular Diseases and COVID-19: Focus on Micronutrients Imbalance.

Micronutrients are ions and vitamins humbly required by the human body. They play a main role in several physiological mechanisms and their imbalance is strongly associated with potentially-fatal complications. Micronutrient imbalance is associated with many cardiovascular diseases, such as arrythmias, heart failure, and ischemic heart disease. It has been also observed in coronavirus disease 2019 (COVID-19), particularly in most severe patients. The relationship between cardiovascular diseases and COVID-19 is mutual: the latter triggers cardiovascular disease onset and worsening while patients with previous cardiovascular disease may develop a more severe form of COVID-19. In addition to the well-known pathophysiological mechanisms binding COVID-19 and cardiovascular diseases together, increasing importance is being given to the impact of micronutrient alterations, often present during COVID-19 and able to affect the balance responsible for a good functioning of the cardiovascular system. In particular, hypokalemia, hypomagnesemia, hyponatremia, and hypocalcemia are strongly associated with worse outcome, while vitamin A and D deficiency are associated with thromboembolic events in COVID-19. Thus, considering how frequent the cardiovascular involvement is in patients with COVID-19, and how it majorly affects their prognosis, this manuscript provides a comprehensive review on the role of micronutrient imbalance in the interconnection between COVID-19 and cardiovascular diseases.

Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters

ABSTRACT Obese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota’s composition might have a critical role in disease severity. Here, we investigated the consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the gut microbiota in the context of obesity and NASH. To this end, we set up a nutritional model of obesity with dyslipidemia and NASH in the golden hamster, a relevant preclinical model of COVID-19. Relative to lean non-NASH controls, obese NASH hamsters develop severe inflammation of the lungs and liver. 16S rRNA gene profiling showed that depending on the diet, SARS-CoV-2 infection induced various changes in the gut microbiota’s composition. Changes were more prominent and transient at day 4 post-infection in lean animals, alterations still persisted at day 10 in obese NASH animals. A targeted, quantitative metabolomic analysis revealed changes in the gut microbiota’s metabolic output, some of which were diet-specific and regulated over time. Our results showed that specifically diet-associated taxa are correlated with disease parameters. Correlations between infection variables and diet-associated taxa highlighted a number of potentially protective or harmful bacteria in SARS-CoV-2-infected hamsters. In particular, some taxa in obese NASH hamsters (e.g. Blautia and Peptococcus) were associated with pro-inflammatory parameters in both the lungs and the liver. These taxon profiles and their association with specific disease markers suggest that microbial patterns might influence COVID-19 outcomes.

COVID-19, dyslipidemia and familial hypercholesterolemia: an up-date

COVID-19 (coronavirus disease 2019) is an infection caused by the SARS-CoV-2 coronavirus, which can evolve into a severe respiratory condition, affecting the world population in a pandemic manner. In this study, we aimed to update the findings of the mechanisms that associate dyslipidemia with COVID-19 infection, the evolution of severe form and the influence of lipid-lowering treatment on outcomes. The search was performed in the PubMed and Embase databases and the selection was based on dyslipidemia and COVID-19 studies, which resulted in 31 articles. In results, the evidence in changes in cholesterol metabolism was found in SARS-CoV-2 virus infection with variations in high-density lipoprotein (HDL) levels. In addition, it provided an increase in triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDLc). Patients with familial hypercholesterolemia (FH) with COVID-19 representing a group of individuals who develop early atherosclerotic disease with a higher risk of cardiovascular event, which should intensify the lipid-lowering treatment due to the potential risk of coronary endothelial dysfunction caused by viral infection. Cholesterol modifying drugs have a potential to change the life cycle of the virus, resulting in a range of pleiotropic effect on infectivity, immunity and inflammation, such as statins, fibrates, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (iPCSK9), omega-3 fatty acids, bile acids sequestrants and nicotinic acid. As dyslipidemia is one of the main risk factors for the severe form of COVID-19, causing endothelial dysfunction previously installed in dyslipidemic patients, the use of lipid-lowering drugs can reduce the risk factors for the unfavorable outcome in these patients.

Vitamin D 25OH Deficiency and Mortality in Moderate to Severe COVID-19: A Multi-Center Prospective Observational Study.

IntroductionSeveral studies and meta-analyses suggested the role of vitamin D 25OH in preventing severe forms of coronavirus disease 2019 (COVID-19). However, the evidence on the clinical benefits of vitamin D 25OH adequacy in patients hospitalized for COVID-19 remain conflicting and speculative. We aimed to investigate the association between vitamin D 25OH serum levels and mortality in hospitalized patients with moderate to severe COVID-19.MethodThis prospective observational multicentre study included 361 consecutive patients with moderate to severe COVID-19 admitted to the Italian hospitals involved in the NUTRI-COVID19 trial from March to August 2020. For each patient, serum vitamin D 25OH levels were assessed 48 h since admission and classified as deficient (<20 ng/mL) or adequate (≥20 ng/mL). We built a propensity score for low/adequate vitamin D 25OH levels to balance the clinical and demographic properties of the cohort, which resulted in 261 patients with good common support used for the survival analysis.ResultsTwo Hundred-seventy-seven (77%) of the 361 enrolled patients (207 [57%] males, median age 73 ± 15.6 years) had vitamin D 25OH deficiency. Fifty-two (20%) of the 261 matched patients died during the hospital stay, corresponding to a hazard ratio of 1.18 for vitamin D 25OH deficiency (95% confidence interval: 0.86–1.62; p = 0.29).DiscussionThe prevalence of vitamin D 25OH deficiency was confirmed to be very high in hospitalized patients with COVID-19. The use of a propensity score demonstrate an absence of significant association between vitamin D deficiency and mortality in hospitalized patients.

Chasing the Ghost: Hyperinflammation Does Not Cause Sepsis.

Sepsis is infection sufficient to cause illness in the infected host, and more severe forms of sepsis can result in organ malfunction or death. Severe forms of Coronavirus disease-2019 (COVID-19), or disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are examples of sepsis. Following infection, sepsis is thought to result from excessive inflammation generated in the infected host, also referred to as a cytokine storm. Sepsis can result in organ malfunction or death. Since COVID-19 is an example of sepsis, the hyperinflammation concept has influenced scientific investigation and treatment approaches to COVID-19. However, decades of laboratory study and more than 100 clinical trials designed to quell inflammation have failed to reduce sepsis mortality. We examine theoretical support underlying widespread belief that hyperinflammation or cytokine storm causes sepsis. Our analysis shows substantial weakness of the hyperinflammation approach to sepsis that includes conceptual confusion and failure to establish a cause-and-effect relationship between hyperinflammation and sepsis. We conclude that anti-inflammation approaches to sepsis therapy have little chance of future success. Therefore, anti-inflammation approaches to treat COVID-19 are likewise at high risk for failure. We find persistence of the cytokine storm concept in sepsis perplexing. Although treatment approaches based on the hyperinflammation concept of pathogenesis have failed, the concept has shown remarkable resilience and appears to be unfalsifiable. An approach to understanding this resilience is to consider the hyperinflammation or cytokine storm concept an example of a scientific paradigm. Thomas Kuhn developed the idea that paradigms generate rules of investigation that both shape and restrict scientific progress. Intrinsic features of scientific paradigms include resistance to falsification in the face of contradictory data and inability of experimentation to generate alternatives to a failing paradigm. We call for rejection of the concept that hyperinflammation or cytokine storm causes sepsis. Using the hyperinflammation or cytokine storm paradigm to guide COVID-19 treatments is likewise unlikely to provide progress. Resources should be redirected to more promising avenues of investigation and treatment.

Durable functional limitation in patients with coronavirus disease-2019 admitted to intensive care and the effect of intermediate-dose vs standard-dose anticoagulation on functional outcomes

IntroductionPatients affected with severe forms of coronavirus disease 2019 (COVID-19) suffer from a wide range of sequelae, from limited airway diseases to multiple organ failure. These sequelae may create exercise limitation, impair the daily activity and thus impact the mental health and the social life. However, the extent of functional limitations and depressive symptoms are understudied especially in patients with COVID-19 after intensive care unit (ICU) hospitalization. MethodsThe Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) was a clinical trial that randomized ICU patients with COVID-19 to intermediate-dose vs standard-dose anticoagulation. In the current study, we assessed the interval change in 30-day and 90-day functional limitations based on the post-COVID-19 functional status scale (PCFS) and depressive symptoms based on the Patient Health Questionnaire-2 (PHQ-2) in the trial participants. We also assessed the effect of intermediate-dose vs standard-dose prophylactic anticoagulation on the functional outcomes and depressive symptoms. ResultsOf 600 randomized patients in INSPIRATION, 375 (age: 62 years; 42% women) participated in the functional status study. 195 patients died during the 90-day follow up (191 by day 30). Among survivors, between day 30 and day 90, the proportion of patients with moderate-to-severe functional limitation (PCSF grade 3-or-4) decreased from 20.0% to 4.8% (P <0.001) and PHQ-2 ≥ 3 decreased from 25.5% to 16.6% (P = 0.05). The proportion of patients with no functional limitations (PCFS grade 0) increased (4.2% to 15.4%, P<0.001). Intermediate-dose compared with standard-dose prophylactic anticoagulation did not impact the 90-day proportion of patients with PCFS grade 3-or-4 (5.3% vs 4.2%; odds ratio (OR), 1.20, [95% CI, 0.46–3.11]; P = 0.80) or PHQ-2 ≥ 3 (17.9% vs 15.3%; OR, 1.14, [95% CI, 0.79–1.65]; P = 0.14), with similar results when accounting for study center. ConclusionIn patients with COVID-19 admitted to the ICU, functional limitations and depressive symptoms were common at 30-day follow-up and had some improvement by 90-day follow-up among survivors. Intermediate-dose compared to standard-dose prophylactic anticoagulation did not improve functional outcomes.

Pre-existing humoral immune comebacks control the development of the severe form of coronavirus disease 2019 in Gaucher patients.

Coronavirus disease 2019 (COVID‐19) and the Gaucher disease (GD) exhibit lot of resemblances in induction of innate and adaptive immune inflammation that include the immune cells activation and the massive generation of pro‐inflammatory cytokines, chemokines, and growth factors, which are all critical for propagation of the disease process and the multiple organ damage. However, majority of the GD patients have not revealed the expansion of severe form of the COVID‐19. This study suggests that the pre‐existing humoral immunity influence the devlopment of strong network of antibodies to different structural proteins of SARS‐CoV2 in GD patients with COVID‐19. Such antibodies and virus proteins interaction cause the comprehensive neutralization of SARS‐CoV2 and provides protection from the development of severe form of COVID‐19 in GD patients. This information could be helpful for better understanding of the disease mechanism as well as the development of additional potential therapy that could stop the growth of the severe symptoms and/or death in GD patients with COVID‐19.

Diversified nutritional support of patients in severe forms of COVID-19

The Coronavirus Disease 2019 (COVID-19) pandemic, declared by the World Health Organization on March 11, 2020, has made significant adjustments to the principles of organizing medical care, including treatment, nutrition, and care of patients in infectious hospitals. The disease has different clinical courses: from mild asymptomatic to extremely severe, requiring aggressive medical interventions, such as organ replacement therapy to replace vital body functions.&#x0D; The spread of viral infection was global, but the pathophysiological aspects of the course of COVID-19 have not been studied comprehensively. The development of acute respiratory distress syndrome and systemic inflammatory response syndrome as part of the severe course of the disease is accompanied by severe metabolic disorders that require close attention. It is necessary to correct the clinical manifestations of organ dysfunction under severe hypercatabolism. Considerable importance is given to the peculiarities of providing nutritional support to patients using specialized nutritional mixtures to prevent conditions that worsen the prognosis of recovery and survival of patients.&#x0D; The target cells of the virus are angiotensin-converting enzyme receptors of the respiratory, nervous, urinary, and cardiovascular systems and organs of the gastrointestinal tract. Consequently, the site of the infection at different organs and systems gives rise to the phenomena of respiratory failure and several heterogeneous clinical manifestations of the disease, which can affect all ties in the pathogenesis of nutritional deficiency. Malnutrition is usually due to the mismatch between the intake and consumption of nutrients, micro- and macroelements.&#x0D; The causes for the imbalance of the intake-expenditure system can be divided into three groups: reduced nutrient intake, increased consumption due to hypercatabolism or hypermetabolism, and malabsorption and increased nutritional losses due to direct and indirect damages to the gastrointestinal tract. The division is traditional because, in the case of severe forms of coronavirus infection, there is always the presence of two or more factors leading to nutritional deficiencies.&#x0D; In this study, we systematized the ways in which we provide nutritional support based on the prevalent causes of protein-energy malnutrition, taking into account the patients individual needs and the extent of respiratory support. Several articles published by foreign colleagues and our own experience in the Department of Anesthesiology and Intensive Care for Patients with a New Coronavirus Infection COVID-19 at the Russian Academy of Sciences Central Clinical Hospital in Moscow in 2020 were analyzed.&#x0D; This study discusses in detail the problems and characteristics of clinical nutrition that a practicing intensive care specialist faces when enduring all possible measures to maintain the stable homeostasis of the patient.