Severe Coronavirus Disease 2019 Disease Research Articles

Clinical characteristics and treatments of multi-system inflammatory syndrome in children: a systematic review.

Multisystem inflammatory syndrome in children (MIS-C) can occur in association with coronavirus disease 2019 (COVID-19). It is not easy to differentiate MIS-C from severe COVID-19 or Kawasaki disease based on symptoms. The aim of this study was to describe the clinical and laboratory characteristics of MIS-C. We searched PubMed/Medline for case series and reports of MIS-C published until June 20, 2020. From a total of nine articles involving 45 cases, various clinical and laboratory data were extracted. Each target case was evaluated by using different diagnostic criteria. The average age at onset of MIS-C was 8.6 years. In 80% of cases, the age of patients ranged from 5 to 15 years. Fever (100%) and shock (82%) were the most common presenting symptoms. Sixty percent of cases met the diagnostic criteria for typical or atypical Kawasaki disease. Biomarkers indicative of inflammation, coagulopathy, or cardiac injury were characteristically elevated as follows: ferritin (mean: 1,061 ng/mL), CRP (217 mg/L), ESR (69 mm/hr), IL-6 (214.8 pg/mL), TNFα (63.4 pg/mL), D-dimer (3,220 ng/mL), PT (15.5 s), troponin I (1,006 ng/L), and BNP (12,150 pg/mL). Intravenous immunoglobulin was administered in all target cases, and inotropic agents were commonly used as well. No case of death was observed. This study demonstrated that MIS-C is a serious condition that presents with fever, rash, as well as cardiovascular and gastrointestinal symptoms. Although it is challenging to differentiate MIS-C from Kawasaki disease or severe COVID-19, initiation of appropriate treatments through early diagnosis is warranted.

Associations between Serum Interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10) and Disease Severity of COVID-19: A Systematic Review and Meta-Analysis

Background To investigate the association between interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10) and the disease severity of coronavirus disease 2019 (COVID-19). Materials and Methods We systematically searched records investigating the role of interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10) in COVID-19 patients in Web of Science, Pubmed, and Embase through December 2020. Data were extracted and pooled, and the weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated. The funnel plot and the nonparametric trim and fill method were used to visualize and adjust the publication bias. Results In total, 61 studies enrolled 14,136 subjects (14,041 patients and 95 healthy subjects) were enrolled in this meta-analysis. Our results showed that serum IL-2, IL-4, IL-6, and IL-10 levels were elevated in COVID-19 patients compared to healthy controls, and IL-6, IL-8, and IL-10 levels were increased in severe COVID-19 cases compared to nonsevere patients. Additionally, the levels of IL-1β, IL-6, and IL-8 were elevated in nonsurvivor patients compared to survivors. For patients in the intensive care unit (ICU), IL-6 and IL-8 levels were increased than that in non-ICU patients. Conclusions Elevated levels of IL-6, IL-8, and IL-10 were associated with the disease severity of COVID-19, and elevated levels of IL-1β, IL-6, and IL-8 were related to the prognosis of COVID-19 patients, which could be used to evaluate COVID-19 patients' disease severity and prognosis.

Prevalence of Micronutrient Deficiencies in Patients Hospitalized with COVID-19: An Observational Cohort Study.

Background: A higher risk for severe clinical courses of coronavirus disease 2019 (COVID-19) has been linked to deficiencies of several micronutrients. We therefore studied the prevalence of deficiencies of eight different micronutrients in a cohort of hospitalized COVID-19-patients. Methods: We measured admission serum/plasma levels of vitamins A, B12, D, and E, as well as folic acid, zinc, selenium, and copper in 57 consecutively admitted adult patients with confirmed COVID-19 and analyzed prevalence of micronutrient deficiencies and correlations among micronutrient levels. Further, we studied associations of micronutrient levels with severe disease progression, a composite endpoint consisting of in-hospital mortality and/or need for intensive care unit (ICU) treatment with logistic regression. Results: Median age was 67.0 years (IQR 60.0, 74.2) and 60% (n = 34) were male. Overall, 79% (n = 45) of patients had at least one deficient micronutrient level and 33% (n = 19) had ≥3 deficiencies. Most prevalent deficiencies were found for selenium, vitamin D, vitamin A, and zinc (51%, 40%, 39%, and 39%, respectively). We found several correlations among micronutrients with correlation coefficients ranging from r = 0.27 to r = 0.42. The strongest associations with lower risk for severe COVID-19 disease progression (adjusted odds ratios) were found for higher levels of vitamin A (0.18, 95% CI 0.05–0.69, p = 0.01), zinc (0.73, 95% CI 0.55–0.98, p = 0.03), and folic acid (0.88, 95% CI 0.78–0.98, p = 0.02). Conclusions: We found a high prevalence of micronutrient deficiencies in mostly older patients hospitalized for COVID-19, particularly regarding selenium, vitamin D, vitamin A, and zinc. Several deficiencies were associated with a higher risk for more severe COVID-19 courses. Whether supplementation of micronutrients is useful for prevention of severe clinical courses or treatment of COVID-19 warrants further research.

Evaluating The Utility of Interleukin-6, C -Reactive Protein (CRP) and Procalcitonin in Predicting Disease Severity and Prognosis in Hospitalized SARS-CoV-2 Patients: A North Indian Retrospective Study

Background: Coronavirus disease 2019 (COVID-19) associated inflammatory cytokine storm that worsens COVID-19, relies heavily on the inflammatory response. IL-6, a TH1 cytokine, PCT and CRP have been linked to serious illness and a higher mortality rate. We further tried to evaluate the role of these indicators and their association with clinical severity in COVID-19 patients. Material and Methods: Eighty-three consecutive patients with age ≥18 years with RT-PCR test positive for SARS-CoV-2 were included in the study. Demographic characteristics (age and sex), underlying co-morbidities, symptoms, physical findings, and laboratory tests of the patients were recorded. All patients were categorized as having mild, moderate, and severe COVID-19 disease, according to the Indian Council of Medical Research (ICMR). The levels of IL-6 and PCT were estimated by electrochemiluminescence immunoassay (ECLIA) using Cobas-e411 Immunoassay System, and Quantitative CRP was done by Unicorn-230 automated biochemistry analyzer to find out their correlation with disease severity and outcome. Multiple Regression was performed to find out factors associated with the adverse outcome of the disease. Result: Mean age of patients was 51 years. IL-6, CRP, and PCT levels increased in 73 %, 68.0 %, and 8.2 % patients on admission, respectively. The most common co-morbidity associated with the disease was hypertension (25%), followed by diabetes (24%) and respiratory disease (15%). Increased IL-6, CRP, and PCT levels were found in 77 percent, 79 percent, and 20 percent of patients, respectively. We found that IL-6 (P≤0.05), CRP (P≤0.05), and PCT (P≤0.05) were significantly raised in COVID-19 patients with increasing severity of the disease. The Area under the receiver operating characteristic (AUROC) of these parameters ranged between 0.65 and 0.8 (IL-6, 0.828; CRP, 0.809; and PCT, 0.658), indicating a reliable biomarker to assess clinical severity. Conclusion: Sequential measurement of blood levels of IL-6, CRP, and PCT levels is useful in determining the severity and predicting the outcome of the patients with severe disease. IL-6 and CRP have an independent prognostic value. On the other hand, the importance of normal PCT concentrations in patients with viral pneumonia needs to be studied further.

Management of patients with SARS-CoV-2 infections with focus on patients with chronic lung diseases (as of 10 January 2022) : Updated statement of the Austrian Society of Pneumology (ASP).

The Austrian Society of Pneumology (ASP) launched a first statement on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, at a time when in Austria 285 people had died from this disease and vaccinations were not available. Lockdown and social distancing were the only available measures to prevent more infections and the breakdown of the health system. Meanwhile, in Austria over 13,000 patients have died in association with a SARS-CoV‑2 infection and coronavirus disease 2019 (COVID-19) was among the most common causes of death; however, SARS-CoV‑2 has been mutating all the time and currently, most patients have been affected by the delta variant where the vaccination is very effective but the omicron variant is rapidly rising and becoming predominant. Particularly in children and young adults, where the vaccination rate is low, the omicron variant is expected to spread very fast. This poses a particular threat to unvaccinated people who are at elevated risk of severe COVID-19 disease but also to people with an active vaccination. There are few publications that comprehensively addressed the special issues with SARS-CoV‑2 infection in patients with chronic lung diseases. These were the reasons for this updated statement. Pulmonologists care for many patients with an elevated risk of death in case of COVID-19 but also for patients that might be at an elevated risk of vaccination reactions or vaccination failure. In addition, lung function tests, bronchoscopy, respiratory physiotherapy and training therapy may put both patients and health professionals at an increased risk of infection. The working circles of the ASP have provided statements concerning these risks and how to avoid risks for the patients.

SARS-CoV-2 Employ BSG/CD147 and ACE2 Receptors to Directly Infect Human Induced Pluripotent Stem Cell-Derived Kidney Podocytes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the Coronavirus disease 2019 (COVID-19), which has resulted in over 5.9 million deaths worldwide. While cells in the respiratory system are the initial target of SARS-CoV-2, there is mounting evidence that COVID-19 is a multi-organ disease. Still, the direct affinity of SARS-CoV-2 for cells in other organs such as the kidneys, which are often targeted in severe COVID-19, remains poorly understood. We employed a human induced pluripotent stem (iPS) cell-derived model to investigate the affinity of SARS-CoV-2 for kidney glomerular podocytes, and examined the expression of host factors for binding and processing of the virus. We studied cellular uptake of the live SARS-CoV-2 virus as well as a pseudotyped virus. Infection of podocytes with live SARS-CoV-2 or spike-pseudotyped lentiviral particles revealed cellular uptake even at low multiplicity of infection (MOI) of 0.01. We found that direct infection of human iPS cell-derived podocytes by SARS-CoV-2 virus can cause cell death and podocyte foot process retraction, a hallmark of podocytopathies and progressive glomerular diseases including collapsing glomerulopathy observed in patients with severe COVID-19 disease. We identified BSG/CD147 and ACE2 receptors as key mediators of spike binding activity in human iPS cell-derived podocytes. These results show that SARS-CoV-2 can infect kidney glomerular podocytes in vitro via multiple binding interactions and partners, which may underlie the high affinity of SARS-CoV-2 for kidney tissues. This stem cell-derived model is potentially useful for kidney-specific antiviral drug screening and mechanistic studies of COVID-19 organotropism.

Is Fatty Liver Associated with Increased Mortality and Morbidity in Coronavirus Disease 2019 (COVID-19) Pneumonia?

BackgroundFatty liver has been shown to be associated with severe COVID-19 disease without any impact on mortality. This is based on heterogenous criteria for defining both fatty liver as well as the severity parameters. This study aimed to study the impact of fatty liver on the mortality and severity of disease in patients with COVID-19 pneumonia.MethodsIn a case control study design, patients with COVID-19 pneumonia (COVID-19 computed tomography severity index [CTSI] on high-resolution computed tomography chest of ≥1) with fatty liver (defined as liver to spleen attenuation index ≤5 on noncontrast computed tomography cuts of upper abdomen) were compared with those without fatty liver. The primary outcome measure was in-hospital mortality, and the secondary outcome measures were CTSI score, need for intensive care unit (ICU) care, need for ventilatory support, duration of ICU stay, and duration of hospital stay.ResultsOf 446 patients with COVID-19 pneumonia, 289 (64.7%)admitted to Max Hospital, Saket, India, between January 1, 2021, and October 30, 2021, had fatty liver. Fifty-nine of 446 patients died during the index admission. In-hospital mortality was not different between patients with fatty liver (38 [13.24%]) or without fatty liver (21 [13.81%]). COVID-19 CTSI score was found to be significantly higher among patients who had fatty liver (13.40 [5.16] vs 11.81 [5.50]; P = 0.003). There was no difference in the requirement of ICU (94 [32%] vs 62 [39.49%]; P = 0.752), requirement of ventilatory support (27 [9.34%] vs 14 [8.91%]; P = 0.385), duration of ICU stay (8.29 [6.87] vs 7.07 [5.71] days; P = 0.208), and duration of hospital stay (10.10 [7.14] vs 10.69 [8.13] days; P = 0.430) between the groups with fatty liver or no fatty liver. Similarly, no difference was found in primary or secondary outcomes measure between the group with severe fatty liver vs mild/moderate or no fatty liver. High total leucocyte count and Fibrosis-4 (FIB-4) index were independently associated with mortality.ConclusionsFatty liver may not be associated with increased mortality or clinical morbidity in patients who have COVID-19 pneumonia.

Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19), with macrophages as one of the main cell types involved. It is urgent to understand the interactions among permissive cells, macrophages, and the SARS-CoV-2 virus, thereby offering important insights into effective therapeutic strategies. Here, we establish a lung and macrophage co-culture system derived from human pluripotent stem cells (hPSCs), modeling the host-pathogen interaction in SARS-CoV-2 infection. We find that both classically polarized macrophages (M1) and alternatively polarized macrophages (M2) have inhibitory effects on SARS-CoV-2 infection. However, M1 and non-activated (M0) macrophages, but not M2 macrophages, significantly up-regulate inflammatory factors upon viral infection. Moreover, M1 macrophages suppress the growth and enhance apoptosis of lung cells. Inhibition of viral entry using an ACE2 blocking antibody substantially enhances the activity of M2 macrophages. Our studies indicate differential immune response patterns in distinct macrophage phenotypes, which could lead to a range of COVID-19 disease severity.

Hematological findings in adult patients with SARS CoV‐2 infection at Tygerberg Hospital Cape Town South Africa

BackgroundCoronavirus disease 2019 (COVID‐19) is associated with hematological abnormalities of variable severity. The full blood count (FBC) and leukocyte differential count (DIFF) could facilitate the prediction of disease severity and outcome in COVID‐19. This study aimed to assess the hematological parameters in early severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and their correlation with disease outcome.MethodsA retrospective cross‐sectional descriptive study was performed. Adults with a FBC and positive SARS‐CoV‐2 polymerase chain reaction results between March 1, and June 31, 2020 were reviewed. Basic hematological parameters (FBC, DIFF) and human immunodeficiency virus (HIV) status were recorded. Outcome measures were admission to a general ward or intensive care unit (ICU), recovery or death.ResultsSix hundred and eighty‐five cases median age 51 years, were analyzed. Forty‐four percent were males and fourteen percent were HIV‐positive with no association between death and/or ICU admission (p = 0.522 and p = 0.830, respectively). Leucocytosis was predictive of ICU admission (odds ratio [OR]: 2.4, confidence interval [CI]: 1.77–3.8186) and neutrophilia, of both mortality (OR: 1.5, CI: 1.0440–2.0899) and ICU admission (OR: 4, CI: 2.5933–6.475). Median lymphocyte count was decreased and d‐dimer raised, showing no significant association with outcome. Raised neutrophil‐to‐lymphocyte‐ratio (NLR) was associated with increased odds of mortality (OR: 2.5, CI: 1.3556–3.2503) and ICU admission (OR: 4.8, CI: 2.4307–9.5430) as was monocyte‐to‐lymphocyte‐ratio (MLR) (OR: 2, CI: 1.3132–2.9064) and (OR: 2.3, CI: 1.0608–1.9935), respectively. Hospital admission and older age were significantly associated with mortality (p = 0.0008 and p < 0.0001), respectively.ConclusionEvidence‐based interpretation of routine laboratory parameters, readily available in resource‐constrained settings, may identify patients at increased risk of mortality. The FBC, DIFF, NLR, and MLR should form part of the early COVID‐19 investigation.

Penggunaan High Flow Nasal Cannula sebagai Terapi Oksigen pada Kasus Covid-19 Berat dengan Obesitas: Laporan Kasus

Coronavirus Disease 2019 (COVID-19) is a disease which caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In December 2019, this disease was encountered in Wuhan, China. Covid-19 is still a global pandemic to this day. Obesity is one of the comorbidities which has been shown to increase the severity of COVID-19 cases. There is research which stated that invasive mechanical ventilation may contribute to mortality rate in severe case of COVID-19. Other than that, the increase rate of severe COVID-19 cases and the limited availability of facilities and infrastructure makes the usage of high flow nasal cannula (HFNC) begins to be considered. Aim of this case report is to represent the outcome of obese COVID-19 patient whom treated with HFNC, furthermore could evoke readers to take further research of the effectiveness of HFC usage as an oxygen therapy in severe COVID-19 cases. Case summary: 21 years old woman came to Emergency Department in Wangaya Regional Hospital with shortness of breath, unproductive cough, sore throat, and inability to smell. Patient was treated and diagnosed with confirmed severe COVID-19. She got obesity as comorbidity (weight 105 kg; height 160 cm; Body Mass Index (BMI) 41.02 kg/m2). Patient was treated for 15 days, which include 10 days of treatment in negative pressure ward in Intensive Care Unit Department (ICU). During the treatment course, patient received pharmacologic and non-pharmacologic treatment, including the administration of HFNC. After five days of HFNC usage, oxygen supplementation was downgraded to conventional oxygen supplementation (non-rebreather mask and nasal cannula). Patient then discharge without any complain and proceed self-quarantine at home. HFNC could be considered as one of non-invasive oxygen supplementation treatment in patient with severe COVID-19 disease. The initiation of usage of HFNC could be started with 30 L/minute flow, with 40% fraction of inspired oxygen (FiO2) in accordance to patient comfort with Sp02 target 92-96%. If there is an increased breathing effort, high respiratory rate, and unachieved Sp02 target, flow and inspiration fraction titrated gradually. ROX index could be used as a treatment failure indication and the need of invasive ventilation.

ABO Blood Groups Are Not Associated With COVID-19 Disease Incidence and Severity When Correcting for Ethnicity Differences in Blood Type.

ObjectivesTo determine if blood type is a risk factor for coronavirus disease 2019 (COVID-19) disease incidence and severity after correcting for ethnicity differences between novel infections and known ABO blood type frequency differences.MethodsWe performed a retrospective analysis on all severe acute respiratory system coronavirus 2 (SARS-CoV-2) infections and disease severity across two major testing sites in Colorado. We evaluated all individuals with a SARS-CoV-2 nucleic acid test (NAT) and a known blood type between March 1, 2020, and June 1, 2020. We then created a prediction algorithm based on the corrected blood types by ethnicity using data from the Colorado Department of Health and established blood types by ethnicity. We applied this prediction algorithm to all patients in our sample.ResultsOf 8,676 patients, 485 (5.6%) had a positive SARS-CoV-2 NAT test and 8,191 (94.4%) had a negative test. All patients had ABO blood types that mirrored the expected blood type distribution within the state of Colorado (P = .15, χ 2 statistic = 5.31). No differences in expected blood groups were present between ethnicity-adjusted SARS-CoV-2–negative and SARS-CoV-2–positive patients (χ 2 = 3.416313, P = .332).ConclusionsBlood type is not associated with COVID-19 disease incidence or severity after correcting for ethnicity differences in expected blood type frequencies.

Weight excess association with severity in children and adolescents with COVID-19: A systematic review.

Background & aimsConcomitantly to the coronavirus disease 2019 (COVID-19), in the child population there was already another pandemic wave in progress: childhood obesity. Numerous studies in adults have been carried out and describe obesity as an independent risk and prognostic factor for the severity of COVID-19. This study aims to systematically review the literature on the relation between weight excess and the severity of COVID-19 in children and adolescents.MethodsThis systematic review was developed following the PRISMA standards (Preferred Reporting Items for Systematic Review and Meta-Analysis). The literature search was performed in September 2020, in the following databases: MEDLINE (via PubMed), Embase, Scopus, The Cochrane Library (Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials (CENTRAL)), Web of Science, BVS/LILACS and SciELO. Registration on the PROSPERO platform (International Prospective Registry of Systematic Reviews) can be found under the registration number: CRD42021230686.ResultsOf the 667 selected articles, 11 were included according to all agreed criteria, most of them being unicentric and American. In assessing the risk of bias and quality, following the criteria of the Newcastle–Ottawa Scale, eight studies achieved scores higher than 7. Only 5 studies sought to assess obesity and its relation with worse outcomes (such as need for pediatric intensive care unit (PICU), mechanical ventilation (MV), tracheostomy, hospital readmission and mortality), and out of these, only one article demonstrated this comorbidity as a prognostic factor for worse evolution of the COVID picture.ConclusionsFew studies in the literature seek to assess excess weight and its relation with worse outcomes of COVID-19 in children and adolescents. Taking into account that there is already scientific evidence on this subject in adult patients, it is necessary to carry out more research in the pediatric age group.

Inflammatory biomarkers and severity of COVID-19: Cross sectional study among Egyptian patients

The newly emerging coronavirus disease 2019 (COVID-19) is characterized by multisystem inflammatory syndrome. The development of SARS-CoV-2 complications usually starts within few days following infection, and the severity of the disease determines its outcome. Vitamin D insufficiency is associated with risk of lung infections, also cell-based studies reported the ability of vitamin D to control enveloped virus growth. We aimed to investigate the relationship between the most eminent inflammatory biomarkers and the level of vitamin D aiming to provide a tool for early diagnosis and prediction of disease progression. The current study was approved by Research Ethics Committee (REC), Kasr Al-Ainy. After confirmation of being COVID-19 by PCR, the admitted patients were categorized as mild-moderate, and severe-critically ill based on clinical and radiologic data. The total levels of serum 25(OH)D, as well as other pro-inflammatory biomarkers were measured and were analyzed by receiver operating characteristic curve (ROC) analysis for detection of their association with COVID-19 disease severity and to determine their sensitivity and specificity at optimum cutoff points. The area under the curve (AUC) ROC for predicting COVID-19 disease severity was the highest (of 0.97) for vitamin D, inflammatory cytokines, liver enzymes, ferritin, and D-Dimer. In addition, high serum levels of creatinine, and elevated liver enzymes associated with severe-critical COVID-19. The low 25(OH)D was associated with the disease severity.

Neutrophil-to-Lymphocyte Ratio as a Predictor of Disease Severity and Mortality in Coronavirus Disease 2019: Prospective Study From Central India.

Background: Clinical presentation of coronavirus disease 2019 (COVID-19) varies from an asymptomatic state to severe disease characterized by acute respiratory distress syndrome, respiratory failure, thrombosis, and multi-organ dysfunction syndrome. The neutrophil-to-lymphocyte ratio (NLR) has been reviewed as one of the laboratory factors that have been proposed to predict the severity of disease and mortality in COVID-19 pandemic.Aim and objectives: To evaluate the association between NLR and the disease severity and mortality in COVID-19.Materials and methods: After approval from Institutional Ethics Committee, this prospective cohort study was carried out in a tertiary-care teaching medical institute of Central India. COVID-19 patients of the age group 18 years and above admitted during the study period were included. Cases were categorized into four groups as asymptomatic (Group A), mild (Group B), moderate (Group C), and severe (Group D) based on clinical symptoms, respiratory rate, oxygen saturation, and chest imaging. NLR was calculated by doing a complete blood count at the time of hospitalization by the Mindray BC-6000 auto hematology analyzer. The outcome of the disease was classified as recovery and death during hospitalization. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of NLR at admission to predict severe COVID-19 or mortality. Ordinal regression analysis was used to assess the impact of NLR on disease severity and mortality.Results: Mean NLR was significantly higher in the severe COVID-19 group as compared to the mild/moderate group and in deceased as compared to discharged cases. ROC curve analysis revealed NLR to be an excellent predictor of disease severity as well as a prognostic parameter for risk of death. NLR was found to be a significant independent positive predictor for contracting the severe disease (Odd’s ratio 1.396, 95% CI=1.112-1.753, p=0.004) and mortality (Odd’s ratio 1.276, 95% CI=1.085-1.499, p=0.003).Conclusion: High NLR was significantly associated with the disease severity and mortality in COVID-19.

Do Admitted COVID-19-Positive Patients on Anticoagulation Therapy Have a Reduced Hospital Stay and Disease Severity?

BackgroundAs of December 2021, the coronavirus disease 2019 (COVID-19) pandemic has resulted in the deaths of over 5 million people. It is known that infection with this virus causes a state of hypercoagulability. Because of this, there has been considerable debate on whether or not patients should be placed on anticoagulation prophylaxis/therapy. The goal of our project was to shed light on this topic by examining the effects of preexisting anticoagulation therapy in COVID-19 patients on disease severity (measured by blood clot readmissions, transfusion counts, and length of hospital stay). In this retrospective cohort study, we conducted an analysis based on data from 30,076 COVID-19-positive patients’ electronic medical records.Materials and methodsThis is a retrospective cohort study. Patients included in this study were identified from the HCA Healthcare corporate database. Registry data was sourced from HCA East Florida hospitals. All patients included in this study were COVID-19 positive via polymerase chain reaction (PCR) or rapid antigen testing on admission and over age 18. A total of 30,076 patients were included in this study with hospital admission dates from March 1, 2020 to June 30, 2021. The analysis examined the relationship between age, sex, blood clot history, and most importantly current anticoagulation status on COVID-19 disease severity (through blood clot readmissions, length of stay, and transfusion count). Blood clot readmissions were analyzed with a logistic regression model while the length of hospital stay and transfusion count were analyzed with a linear regression model.ResultsOur analysis revealed that the odds of experiencing a blood clot readmission is 2.017 times more likely in patients already on anticoagulation therapy compared to those who were not (p = 0.0024). We also found that patients on anticoagulation therapy had a hospital stay of 6.90 days longer on average than patients not on anticoagulation therapy (p < 0.0001). Finally, patients on anticoagulation therapy had, on average, 0.20 more blood transfusions than patients not on anticoagulation therapy (p < 0.001). ConclusionWhile these findings may be affected by the underlying conditions of those on preexisting anticoagulation therapy, they provide valuable insight into the debate on whether COVID-19-positive patients should be anticoagulated on admission to a hospital.

Transcriptome Analysis of Lungs in a Mouse Model of Severe COVID-19

Severe manifestations of coronavirus disease 2019 (COVID-19) are mostly restricted to distinct groups of people who have preexisting morbidities. Most COVID-19 animal models develop a mild pathology that resolves within a relatively short period of time, reflecting the more prevalent asymptomatic-to-mild performance of the disease observed in humans. Mice are normally unaffected by SARS coronavirus-2 infection, because of the inability of the virus to bind effectively to the murine angiotensin-converting enzyme 2 (ACE2) receptor. We have previously demonstrated that induction of mild and transient pulmonary morbidity, by application of low doses of ricin, rendered CD1 mice to be susceptible to this virus, which was displayed by sustained body weight loss and mortality rates &amp;gt;50%. In the present study, we performed transcriptomic analyses charting the major alterations in gene expression of mice that were pre-exposed to low doses of ricin and then subjected to SARS-CoV-2 infection compared to mice that were solely exposed to ricin or infected with SARS-CoV-2. Mice intoxicated and infected with ricin and SARS-CoV-2 demonstrated a marked stimulation of essential immunity genes and biological pathways involved in the activation of natural-killer response, cell death receptors, cytotoxic T-cells, Toll-like receptor signaling and the NLRP3 inflammasome pathway. At the protein level, an induced early and transient interferon response was recorded which was subsequently suppressed. The activation of this array of genes predicts clinical manifestations that are consistent with severe COVID-19 in humans, thereby establishing the suitability of this unique animal model for the study of severe COVID-19 disease.

SARS-CoV-2 in inflammatory bowel disease population: Antibodies, disease and correlation with therapy.

BACKGROUNDGuidelines recommend to cease inflammatory bowel disease (IBD) biologic therapy during coronavirus disease 2019 (COVID-19).AIMTo investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody positivity in an IBD cohort, COVID-19 disease severity and to evaluate the correlation with clinical/therapeutic variables.METHODSProspective observational cohort study. IBD patients were tested for SARS-CoV-2 IgG. Data on COVID-19 disease, demographics/therapeutics and clinical features of the IBD population were collected. IgG ≥ 7 was set for SARS-CoV-2 antibody positivity. Throat swab was performed in cases of IgG positivity. Correlations between antibody positivity or COVID-19 symptoms and therapeutic/clinical data were assessed.RESULTSIn total, 103 IBD patients were enrolled. Among them, 18.4% had IgG ≥ 7. Multivariate analysis of antibody positivity correlated only with IBD treatment. For IgG ≥ 7, the odds ratio was 1.44 and 0.16 for azathioprine and mesalazine, respectively, vs biologic drugs (P = 0.0157 between them). COVID-19 related symptoms were reported in 63% of patients with IgG positivity. All but one patient with COVID-19 symptoms did not require ceasing IBD treatment or hospitalization. IBD treatment and body mass index correlated with COVID-19 disease development with symptoms.CONCLUSIONThe IBD population does not have a higher risk of severe COVID-19. The relative risk of having SARS-CoV-2 antibodies and symptoms was higher for patients taking azathioprine, then biologic therapy and lastly mesalazine. None of the patients under biologic therapy developed severe COVID-19.

Current evidence on efficacy of COVID-19 booster dose vaccination against the Omicron variant: A systematic review.

Coronavirus disease 2019 (COVID‐19) is an ongoing pandemic, which affected around 45 million confirmed cases of COVID‐19, including more than 6 million deaths. However, on November 24, 2021, the World Health Organization announced a new severe acute respiratory syndrome coronavirus 2 variant designated as the B.1.1.529, a variant of concern (VOC), and the variant has been named as “Omicron.” Available preliminary evidence suggests that, as compared with previous VOCs, it has an increased risk of infectivity. Studies have shown that protection from various vaccines effectiveness against hospitalization and death from severe COVID‐19 disease is decreasing slowly after a two‐dose schedule of COVID‐19 vaccines. In response to experiencing a new COVID‐19 variant and ongoing resurgence of cases, the importance of COVID‐19 vaccine booster dose and durability of the effect of the third dose of vaccine against COVID‐19 Omicron variant is controversial yet. To address this, we conducted a systematic literature survey on effectiveness of the third or booster dose of COVID‐19 vaccine against the Omicron variant. We have performed a systematic search in PubMed (Medline), Google Scholar, and MedRXiv database, from inception to January 2022 using the MeSH terms and keywords “Corona Virus Disease‐2019 OR COVID‐19 AND Omicron AND COVID‐19 Booster Vaccine.” We have identified a total of 27 published studies. We have reviewed all the eligible available studies on the effectiveness of the COVID‐19 vaccine booster shots against the Omicron variant. This review may be helpful in accelerating the COVID‐19 booster dose vaccination.

Co-infections in COVID-19 patients and correlation with mortality rate. Minireview.

The goal of our review was to gather information on the most important community-acquired and hospital-acquired co-infections among coronavirus disease 2019 (COVID-19) patients, and to examine not only the effect of these co-infections on disease outcomes but also to identify the possible risk factors that predispose COVID-19 patients to co-infections. Medline (PubMed) and Google Scholar were searched for relevant articles published between January 1st, 2020, and September 31st, 2021, on the topic of co-infections among COVID-19 patients. Among community-acquired and hospital-acquired co-infections, bacterial and fungal co-infections are equally frequent, followed by viral co-infections that affected a relatively smaller portion of patients. Overall, co-infections were more frequent in the hospital than at the community level. Risk factors for acquiring co-infections include male gender, longer length of hospital stay, presence of supportive treatment, such as ventilation, the admission to intensive care units, the administration of medications, such as steroids or antibiotics, and certain blood parameters, such as high C-reactive protein or lymphopenia. The presence of co-infections could aggravate the COVID-19 disease severity, prolong the healing time of patients, and lead to worse disease outcomes overall. Co-infections may increase the mortality of COVID-19 patients, especially in the hospital setting. Paying closer attention to hygiene, adhering to diagnostic and therapeutic protocols, implementing antimicrobial stewardship programs could decrease the occurrence of co-infections and lead to improved outcomes for COVID-19 patients.

Activation of the Carboxypeptidase U (CPU, TAFIa, CPB2) System in Patients with SARS-CoV-2 Infection Could Contribute to COVID-19 Hypofibrinolytic State and Disease Severity Prognosis.

Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic complications are frequent in COVID-19 patients and suggested to be the result of a dysregulation of the hemostatic balance. Although several markers of coagulation and fibrinolysis have been studied extensively, little is known about the effect of SARS-CoV-2 infection on the potent antifibrinolytic enzyme carboxypeptidase U (CPU). Blood was collected longitudinally from 56 hospitalized COVID-19 patients and 32 healthy controls. Procarboxypeptidase U (proCPU) levels and total active and inactivated CPU (CPU+CPUi) antigen levels were measured. At study inclusion (shortly after hospital admission), proCPU levels were significantly lower and CPU+CPUi antigen levels significantly higher in COVID-19 patients compared to controls. Both proCPU and CPU+CPUi antigen levels showed a subsequent progressive increase in these patients. Hereafter, proCPU levels decreased and patients were, at discharge, comparable to the controls. CPU+CPUi antigen levels at discharge were still higher compared to controls. Baseline CPU+CPUi antigen levels (shortly after hospital admission) correlated with disease severity and the duration of hospitalization. In conclusion, CPU generation with concomitant proCPU consumption during early SARS-CoV-2 infection will (at least partly) contribute to the hypofibrinolytic state observed in COVID-19 patients, thus enlarging their risk for thrombosis. Moreover, given the association between CPU+CPUi antigen levels and both disease severity and duration of hospitalization, this parameter may be a potential biomarker with prognostic value in SARS-CoV-2 infection.