Clinical significance of serum interleukin 6 in elderly patients infected with severe acute respiratory syndrome coronavirus 2 omicron variant and its correlation with underlying diseases

Objective To investigate the clinical significance of serum interleukin 6 (IL-6) in elderly patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant and its correlation with underlying diseases. Methods A total of 22 elderly patients (>80 years old) infected with omicron variant, who were admitted to Department of Infectious Diseases, The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Apr. to Jun. 2022 and tested positive for SARS-CoV-2 RNA, were included. The level of serum IL-6 was measured by flow cytometry, and the level of serum C reactive protein (CRP) was measured by immunonephelometry. Patients were divided into pneumonia group (16 cases) and non-pneumonia group (6 cases) according to the imaging examination results, and were divided into severe group (severe and critical type, 5 cases) and non-severe group (mild and normal type, 17 cases) according to the condition. Binary logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the correlation between serum IL-6 and CRP levels and the severity of the disease and whether it would progress to pneumonia. Meanwhile, the relationships between underlying diseases and serum IL-6 level were explored. Results Among the 22 patients, 6 were mild, 11 were normal, 3 were severe, and 2 were critical. The baseline serum IL-6 level in the pneumonia group was significantly higher than that in the non-pneumonia group ([20.16+/-12.36]pg/mL vs [5.42+/-1.57] pg/mL, P=0.009), and there was no significant difference in baseline serum CRP level between the 2 groups (P>0.05). There were no significant differences in baseline serum IL-6 or CRP levels between the severe group and the non-severe group (both P>0.05). Logistic regression analysis showed that the baseline serum IL-6 and CRP might be related to pneumonia after infection with omicron variant (odds ratio [OR]=2.407, 95% confidence interval [CI]0.915-6.328;OR=1.030, 95% CI 0.952-1.114). ROC curve analysis showed that the area under curve values of serum IL-6 and CRP in predicting the progression to pneumonia were 0.969 (95% CI 0.900-1.000) and 0.656 (95% CI 0.380-0.932), respectively, with statistical significance (Z=2.154, P=0.030). There were no significant differences in the baseline serum IL-6 level or proportions of severe patients or pneumonia patients among patients with or without hypertension, diabetes mellitus, coronary heart disease, chronic kidney disease or chronic obstructive pulmonary disease (all P>0.05). The baseline serum IL-6 levels of the omicron variant infected elderly patients with 1, 2, and 3 or more underlying diseases were 12.50 (9.15, 21.75), 23.55 (9.63, 50.10), and 10.90 (5.20, 18.88) pg/mL, respectively, with no statistical significance (P>0.05). Conclusion For omicron variant infected patients, serum IL-6 level is significantly increased in patients with pneumonia manifestations and is correlated with disease progression. Serum IL-6 level is of great guiding significance to judge disease progression and evaluate efficacy and prognosis of elderly coronavirus disease 2019 patients.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Hiv Outcomes after Extended 12-Month Scripts for Art during Covid-19 in South Africa

Background: There is an urgent need for more efficient models of differentiated anti-retroviral therapy (ART) delivery, with the World Health Organization and PEPFAR calling for evidence to guide whether 12-monthly ART prescriptions and clinic review (12M scripts) should be recommended in global guidelines. We assessed the association between 12M scripts (allowed temporarily during the COVID-19 pandemic) and clinical outcomes in South Africa. Method(s): We performed a retrospective cohort study using routine, deidentified data from 59 public clinics in KwaZulu-Natal. We included PLHIV aged >18 years with a recent suppressed viral load (VL), and who had been referred from their clinic into a community ART delivery programme with a standard 6-month prescription and clinic review (6M script) or a 12M script. In the community ART programme, PLHIV collected ART every two months at external pick-up points, before returning to the clinic after 6 or 12 months for a new script. We used multivariable modified Poisson regression, accounting for clinic clustering, to compare 12-month retention-in-care (not >90 days late for any visit) and viral suppression (< 50 copies/mL) between 6M and 12M script groups. Result(s): Among 27,148 PLHIV referred for community ART between Jun-Dec 2020, 42.6% received 6M scripts and 57.4% 12M scripts. The median age was 39 years (interquartile range [IQR] 33-46) and 69.4% were women. Age, gender, prior community ART use and time on ART were similar in the two groups (Table). However, a larger proportion of the 12M script group had a dolutegravirbased regimen (60.0% versus 46.3%). The median (IQR) number of clinic visits in the 12 months of follow-up was 1(1-1) in the 12M group and 2(2-3) in the 6M group. Retention at 12 months was 94.6% (95% confidence interval [CI] 94.2%- 94.9%) among those receiving 12M scripts and 91.8% (95% CI 91.3%-92.3%) among those with 6M scripts. 16.8% and 16.7% of clients in the 12M and 6M groups were missing follow-up VL data, respectively. Among those with VLs, 90.4% (95% CI 89.9%-91.0%) in the 12M group and 88.9% (95% CI 88.3%- 89.5%) in the 6M group were suppressed. After adjusting for age, gender, ART regimen, time on ART and prior community ART use, retention (adjusted risk ratio [aRR]: 1.03, 95% CI 1.01-1.04) and suppression (aRR: 1.02(1.01-1.03) were higher with 12M scripts. Conclusion(s): COVID-19 led to temporary introduction of 12M scripts in South Africa. Wider use could reduce clinic visits without negative impacts on shortterm clinical outcomes.

Surfactant Protein B Reduces Respiratory Viral Infectivity in Human Lungs

Purpose of Study: COVID pneumonia caused by SARS-CoV-2 can result in a depletion of surfactant & lung injury, which resembles neonatal respiratory distress syndrome. Exogenous surfactant has shown promise as a therapeutic option in intubated hospitalized patients. Our preliminary data in human lung organoids (LOs) with a deficiency of surfactant protein B (SP-B) showed an increased viral load compared to normal LOs. Single cell RNA sequencing (scRNAseq) revealed that SP-B-deficient cells showed increased viral entry genes (ACE2 receptor) & dysregulated inflammatory markers emanating from the lung cells themselves. Our objective was to determine: (1) cell-specific transcriptional differences between normal & SP-B deficient human lung cells after infection with SARS-CoV-2 and (2) a therapeutic role of SP-B protein & surfactant in COVID-19 pneumonia. Methods Used: We used normal and SP-B mutant (homozygous, frameshift, loss of function mutation p.Pro133GlnfsTer95, previously known as 121ins2) human induced pluripotent stem cells (hiPSC) and differentiated them into 3D proximal lung organoids. The organoids were infected with the delta variant of SARS-CoV-2 for 24 hours at an MOI of 1. Infected and uninfected organoids were fixed in trizol in triplicate and underwent processing for bulk RNA sequencing. We tested for differentially expressed genes using the program DEseq. We also plated normal iPSC derived lung organoids as a monolayer and pre-treated them with 1mg/ml of Poractant alfa or 5 uM of recombinant SP-B protein. The delta strain of SARS-CoV-2 was added to the 96 wells at an MOI of 0.1 for one hour with shaking, then an overlay with DMEM/CMC/FBS was added and left on for 23 hours. The plate was fixed and stained for nucleocapsid (NC) protein. Summary of Results: Bioinformatic analysis of the bulk RNA sequencing data showed an increase in the multiple cytokines and chemokines in the SP-B mutant LOs compared to control. We also saw differential gene expression patterns in the SP-B mutant LOs including a reduction in SFTPC, FOXA2, and NKX2-1 and an increase in IL1A, VEGFA, PPARG and SMAD3. In the exogenous surfactant experiments, there was a decrease in total expression of viral NC in the Poractant alfa & rSP-B-treated cells compared to SARS-CoV-2 infection alone (p<0.001). Conclusion(s): Surfactant modulates the viral load of SARS-CoV-2 infection in the human lung. Deficiency in SP-B results in the dysregulation of the lung epithelial inflammatory signaling pathways resulting in worsening infections.

Awareness and Practices Regarding 'Long COVID' among Employees of Selected Smart Phone Manufacturing Industries in South India

Introduction: Long COVID is a term coined for long term post COVID-19 disease complications. Touted as the 'pandemic after the pandemic' it has significant implications for employment especially on productivity and quality of worker output. Objective(s): 1. To assess the baseline knowledge among employees working in selected smart phone manufacturing companies regarding COVID-19 disease, COVID vaccination and long COVID complications. 2. To assess the prevalence of long COVID complications among the study subjects. Methodology: We followed a quantitative cross-sectional study design between May-Jun 2022 in 6 factories across South India. A semi-structured, face-validated interview schedule was administered to the employees via Google Forms. Data was analyzed using SPSS v.21. Result(s): A total of 118 employees were included in the study. Most employees were male (89.2%), between 25-30 years of age (46.3%) and had completed their Bachelor's degree (71.29%). Most had at least 1-5 years of current work experience (80.5%). Almost 55.1% of the employees had suffered from COVID-19 in the past of which 33.8% had been hospitalised. Only 42.8% of employees knew about long COVID complications and 33.1% knew of only one symptom. None of the employees had taken the booster dose of the vaccine despite 67.8% knowing that the vaccine protected against severe disease. Almost 75% of employees reported to suffer from one or more post COVID complications. Long standing fatigue (16.9%), cough and breathing difficulty (6.1%) were the most common complaints. Conclusion and recommendations: Low awareness regarding long COVID will impact health seeking behavior and increase presenteeism at the workplace. Increasing awareness regarding COVID-19 disease, vaccinations and the post COVID complications through training programmes and health education sessions will bridge the key knowledge gaps identified. Promotion of booster dose vaccination against COVID-19 for all employees will help in reducing the burden of long COVID at the workplace.

Protein S Deficiency with Favourable Foetomaternal Outcome: A Case Report

Protein S is a multifunctional plasma protein, whose deficiency, results in a rare congenital thrombophilia, inherited in an autosomal dominant pattern. It can aggravate the hypercoagulable state of pregnancy, when it presents in parallel with the condition, leading to adverse maternal outcomes and foetal loss. A 35-year-old female third gravida having previous 2 deliveries by Lower Segment Caesarean Section (LSCS) presented to emergency at 10 weeks pregnancy with chief complaints of pain and swelling in left thigh since 4-5 days. After thorough investigations and work-up, the patient was diagnosed with Protein S deficiency. She was managed conservatively and was delivered by elective LSCS with bilateral tubal ligation at 38 weeks of gestation with good foetal and maternal outcomes.The rarity of Protein S deficiency along with the successful outcome of the pregnancy makes this a unique case.Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.

Real-World Experience on the Use of COVID-19 Vaccination in Multiple Sclerosis Patients Treated with Cladribine Tablets Participating in the ADVEVA Patient Support Program within the Gulf and Latin American Regions

Background: National Multiple Sclerosis Society and other international guidelines suggest that full COVID-19 vaccination status should be completed two to four weeks before starting Year 2 of treatment with cladribine tablets (CladT). CladT is administered twice over two years, Year 1 and Year 2. There is a special interest in real-world evidence on whether vaccination status may affect initiation of CladT treatment in Year 2. The objective of this analysis was to describe the proportion of patients treated with CladT who received COVID-19 vaccination, and whether this influenced the timing of initiating treatment with CladT in Year 2. Material(s) and Method(s): A vaccination questionnaire-based survey was sent to patients treated with CladT who were enrolled in the ADVEVA patient support program (PSP), upon their consent. The survey was carried out in the Gulf region (GULF) from Jun 2021 to Sept 2021, and in the Latin American region (LATAM) from Jan 2022 to Mar 2022. Demographics, COVID-19 vaccination status, type of vaccine(s), number of doses received, and dates of vaccination were collected. In each region, patient data from the survey were linked to data routinely collected by the PSP, with cut-off dates as mentioned. Fully vaccinated status was defined as having received 2 doses of mRNA vaccine, 1 dose of Johnson & Johnson vaccine or other vaccines approved by the World Health Organization, plus 14 days. Descriptive analyses were performed and time to Year 2 treatment initiation among those with at least 18 months' follow-up was estimated by vaccination status. Result(s): The survey participation rate in GULF was 87% (91 out of 105) and 19% in LATAM (152 out of 789). In total, 62 (68%) patients in GULF and 144 (95%) in LATAM were fully vaccinated against COVID-19. In both regions, among those with at least 18 months' follow-up (GULF, n=59;LATAM, n=81), all patients initiated Year 2 of treatment with CladT, regardless of vaccination status. In GULF, the mean (standard deviation) time to treatment initiation in Year 2 was 13.8(1.6) months among fully vaccinated patients (44%) and 13.3(3.5) months among those not fully vaccinated (21%). In LATAM, the mean time was 12.8(1.4) months among those fully vaccinated (52%) and 12.4(0.02) months among those not fully vaccinated (1.3%). In each region, only 1 patient initiated Year 2 treatment after at least 18 months from the start of Year 1. Conclusion(s): Most patients were fully vaccinated against COVID-19 in GULF and in LATAM, which was consistent with vaccination coverage and guidelines in both regions. In LATAM, low participation rates might lead to selection bias which limits interpretation of results. In these regions, with limited data, COVID-19 vaccination status did not appear to alter the time of treatment initiation with CladT in Year 2. Almost all patients followed the label recommendations in terms of timing of Year 2 treatment initiation.Copyright © 2022

Myocardial infarction with non-obstructive coronary arteries (MINOCA) complicating myocarditis

Myocarditis can lead to myocardial infarction in the absence of coronary artery obstruction. We report a case of probable myocarditis, complicated by myocardial infarction with non-obstructive coronary arteries. A 19-year-old man presented with chest pain typical of myocarditis. He was a smoker but was otherwise well. Electrocardiogram revealed diffuse ST-elevation and echocardiography revealed a thin, akinetic apex. Troponin-T levels on admission were raised leading to an initial diagnosis of myocarditis being made. However, late gadolinium enhancement study on cardiac magnetic resonance imaging demonstrated transmural enhancement typical of ischaemia. Coronary angiogram was normal, leading to a likely diagnosis of myocardial infarction with non-obstructive coronary arteries. It is important to highlight that coronary assessment remains important when working up for myocarditis, as myocardial infarction with non-obstructive coronary arteries can often complicate myocarditis in cases of normal angiography. Another important lesson was on how cardiac magnetic resonance imaging provided vital evidence to support underlying ischaemia despite normal coronary angiogram, leading to a diagnosis of myocardial infarction with non-obstructive coronary arteries. Myocardial infarction with non-obstructive coronary arteries remains a broad 'umbrella' term and cardiac magnetic resonance imaging, as well as more invasive coronary imaging techniques during angiography, can further assist in its diagnosis. Our case provides a reminder that myocardial infarction with non-obstructive coronary arteries, although increasingly recognised, remains under-diagnosed and can often overlap with peri-myocarditis, highlighting the need to employ multi-modality imaging in guiding management.Copyright © The Author(s) 2021.

Evaluation of the protein C pathway in critically ill patients with severe COVID-19 as compared to bacterial sepsis

Introduction Endothelial dysfunction has been shown to play a role in severe COVID-19, the pathophysiology of which may be attributed to a myriad of factors including unmitigated immune and inflammatory response, viral-induced injury to the endothelium, end-stage organ failure, and coagulopathy. In addition, severe COVID-19 is most often seen in patients with multiple comorbidities, which themselves are often associated with endothelial dysfunction (such as myocardial and renal failure, as well as thrombotic disorders). However, the literature is still emerging on this topic and there appears to be no consensus on the extent to which endothelial dysfunction plays a role in severe COVID-19. Method The aim of this study was to assess the functionality of the endothelial protein C pathway in hospitalized patients > 18 years of age with severe COVID-19 as compared to those hospitalized with bacterial sepsis. COVID-19 (n = 31) and sepsis (n = 47) patients who were admitted to the ICU were assessed for rates of thrombin and activated protein C (APC) generation. Indirect markers of thrombin formation, including thrombin-antithrombin (TAT) complex, prothrombin fragment 1 + 2 (F1 + 2), as well as D-dimer, and protein C (PC) were measured additionally. Statistical analysis was performed via the Mann-Whitney test and a p value of < 0.05 was considered statistically significant. Results Plasma levels of free thrombin in COVID-19 and sepsis patients did not differ significantly, with (median, IQR) 0.59 (0.46-1.21) vs 0.57 (0.46-1.10) pmol/L, respectively. TAT was also increased at similar extent in both cohorts (192;111-325 pmol/L in COVID-19 patients, 148;73-213 pmol/L in sepsis patients), whereas F1 + 2 was higher in COVID-19 than in sepsis patients, with 850 (440-1940) vs 380 (130-620) pmol/L (p = 1.3 x 10-5). Interestingly, rates of APC formation did not significantly differ between the two groups, with 7.47 (1.99- 19.14) vs 9.87 (2.08-16.87) pmol/L ( Fig. 1). D-dimer and protein C were significantly higher in the COVID-19 patients than in those with sepsis (14.3 vs 8.1 mg/L, p = 0.01, and 92.9 % vs 58.5 %, p = 3x10-8, respectively). Conclusion We hypothesized that APC formation rates in response to thrombin formation would be significantly lower in patients with severe COVID-19 as compared to those with bacterial sepsis due to the well-known association between severe COVID-19 disease burden and endothelial dysfunction due to the downregulation of thrombomodulin expression. However, our results indicate that this may not be universally true in this patient population, as our observations suggest a largely intact functionality of the protein C pathway. Further studies are warranted to investigate the pathophysiology of severe COVID-19. (Figure Presented).

Differentially expressed FOXO1, NFE2L2 and NFKB1 mRNAs are associated with differentially regulated corona- and influenza viral receptor genes and Toll-like receptor pathway genes in human bronchial epithelial cells under hyperbaric oxygen exposure

As hyperbaric oxygen (HBO) has been shown to mitigate the COVID-19 symptoms, we were interested in studying whether HBO exposure affects expression of viral entry genes and innate immune genes in the air-liquid interface (ALI)-cultured human bronchial epithelial cells (HBECs) derived from normal individuals (NHBECs) and age-matched COPD patients (DHBECs), which were cultured under normoxia or daily exposure of 40-min hyperbaric oxygen (HBO) with 100% O2 at 2.5 ATA for 28 days in total. We found for the first time that HBO exposure differentially regulated mucociliary differentiation of HBECs by respectively decreasing and increasing expression of CGRP, MUC5AC, FOXJ1, NOTCH3 and HEYL in NHBECs and DHBECs, and respectively decreased and increased FOXO1 expression whereas increased and decreased NFE2L2 and NFKB1 expression in NHBECs and DHBECs, in association with respectively decreased and increased expression the SARS-CoV-2 entry genes ACE2 and 2 TMPRSS2 and the tight junction protein genes TJP1 and TJP2, and in association with respectively increased and decreased expression of the cell growth and inflammatory transcription factors SRF, c-FOS and TP63, as well as the TLR pathway genes TLR3, AKT1, IL-1B, IL-5, IL-6, IL-33, IRAK4 and NFKBIA in NHBECs and DHBECs. (Figure Presented).

The predictive value of coagulation parameters for the course of disease in COVID-19 patients

Introduction COVID-19 is a systemic disease associated with a high incidence of thrombotic complications. In this study we aimed to identify coagulation parameters as predictors of mortality in hospitalized patients with severe COVID- 19 infection. Method We conducted a non-interventional, national, monocentric observational study of patients treated for COVID infection at the ICU at Frankfurt University Hospital. A total of 410 patients were enrolled in the study between April 1, 2020 and December 31, 2021. Patients had to be 18 years or older and the diagnosis was confirmed by COVID real-time PCR. Coagulation parameters were analysed once on admission to the clinic and 5 to 8 days later. Variables studied included thromboplastin time, aPTT, fibrinogen, D-dimers, antithrombin, hs-troponin, all coagulation factors and vWF antigen, protein C and protein S. Data was also collected on age, sex, comorbidities, medication, and invasive ventilation, ECMO therapy and dialysis. In order to compare patients regarding their general disease status, the SAPS-II and the Horovitz index were determined at the beginning and end of the observation period. Univariate and multivariate logistic regression models were then used to screen coagulation parameters for association with mortality in critically ill COVID patients. Results The arithmetic mean age of patients was 60.9 ( +/- 14.7) years, with 76.1 % being male. Of 410 patients, 259 (63.2 %) received invasive ventilation, 95 (23.2 %) received ECMO therapy and 105 (25.6 %) received renal replacement therapy. The median inpatient length of stay was 16 (IQR: 10-29) days and ICU length of stay was 12 (IQR: 6-25) days. 176 patients (43 %) died because of their COVID disease, 234 (57 %) were discharged home or to other facilities for further treatment. In univariate logistic regression, increased age (OR = 1,029, 95 %-CI [1,013- 1,1,044]), higher SAPS-II (OR = 1,031, 95 %-CI [1,018-1,045]), fibrinogen (OR = 1,002, 95 %-CI [1,001-1,003]), FVIII (OR = 1,004, 95 %-CI [1,001-1,007]) and vWF antigen (OR = 1,005, 95 %-CI [1,003-1,007]) as well as lower antithrombin (OR = 0,981, 95 %-CI [0,971-0,991]), FII (OR = 0,983, 95 %-CI [0,972-0,993]), FXIII (OR = 0,992, 95 %-CI [0,986-0,999]), Horovitz index at admission (OR = 0,994, 95 %-CI [0,990-0,997]) and decreased protein C activity (OR = 0,989, 95 %-CI [0,982-0,996]) were associated with increased mortality. In the final multivariate regression analysis with backward elimination, low antithrombin activity (OR = 0.987, 95 %-CI [0.974-1.000]), high vWF antigen levels (OR = 1.004, 95 %-CI [1.002-1.007]) and a low Horovitz index (OR = 0.993, 95 %-CI [0.989-0.997]) were identified as independent predictive factors for increased mortality. Conclusion In the study of 410 COVID patients requiring intensive care, the Horovitz index, antithrombin activity and vWF antigen on hospital admission were identified as independent predictors of mortality.

A Persistent Nightmare: A Case of Recurrent Brachial Artery Thrombosis

Background Brachial artery thrombosis can be seen with thromboembolism, hypercoagulability, and arterial thoracic outlet syndrome. Case A 33-year-old healthy female construction worker presented with right hand discoloration and pain. She suffered a COVID-19 infection 8 weeks prior with hand symptoms developing shortly thereafter. She could no longer work due to the pain. Duplex ultrasound and CTA of the right upper extremity (Figure) demonstrated localized thrombosis of the right brachial artery. The workup yielded no aortic or intracardiac thrombus, and cardiac event monitor showed no atrial arrhythmia. She underwent thrombectomy with brachial artery stenting and was found, during surgery, to have distal ulnar artery occlusion. Two days post-op, she had recurrent pain and was found to have brachial artery recurrent thrombosis. She underwent urgent brachial-brachial bypass. Arm pain continued despite graft patency, so ulnarpalmar bypass was performed. Decision-making Hypercoagulability workup, including antiphospholipid antibody, protein C, protein S, homocysteine, and Lp(a), was negative. Neither central thrombus on TEE nor evidence of thoracic outlet syndrome was found. As a diagnosis of exclusion, brachial artery thrombosis was ascribed to COVID infection. Despite rivaroxaban, the patient developed gangrene (Panel C) requiring partial digit amputation. Conclusion We present a case of COVID-19-induced recurrent brachial artery thrombosis despite surgical intervention. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

Statistical Processing of Relationship Between Biomarkers and Disease Severity Caused by COVID-19 Infection-Delta Variant

Severe infectious disease caused by acute respiratory syndrome, COVID-19 (SARS-CoV-2), spread rapidly worldwide, infecting several million people. According to scientific data, the disease develops through several different stages. After 2–4 days of infection and disease development, the lower respiratory tract is attacked and in a relatively short time interstitial pneumonia develops in a certain number of patients (with genetic predisposition between 5 and 10% of cases). Patients infected with COVID-19 have symptoms such as very high temperatures, fever, persistent cough, joint and bone pain, in some cases diarrhea, and loss of appetite and taste. Disease monitoring should primarily include erythrocyte sedimentation rate, leukocyte count, leukocyte count formula, C-reactive protein (CRP), determination of troponin I (hsTnI) and T (cTnT) levels, N-terminal pro-B natriuretic peptide (NT-proBNP), fibrinogen, and D-dimer level. Previous studies have shown that in pneumonia developed from chronic and acute obstructive pulmonary infections, high levels of D-dimer are observed in patients, and it is suggested that this parameter can be used as a specific prognostic biomarker, and the values higher than > 1000 ng/ml represent increased risk factors for mortality in patients with COVID-19. Because vascular thrombosis affects the promotion of an unfavorable clinical progression for the patient, the identification of early and accurate predictors of the worst outcome seems to be essential for timely and appropriate anticoagulant treatment in patients with SARS-CoV-2 infection. Overall, these data suggest that acute myocardial damage, or heart failure, may be an important indicator of disease severity and adverse prognosis in patients with COVID-19. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Evaluation of protein C and S levels in patients with COVID-19 infection and their relation to disease severity.

Background: The COVID-19 pandemic has been associated with millions of deaths around the world. One of the important causes of death associated with COVID-19 was pulmonary thromboembolism. The risk for venous thromboembolism was markedly increased in patients with COVID-19 especially those admitted to the intensive care unit. The aims of our study were to measure the protein C and S levels in COVID-19-infected patients in comparison with the normal population and to assess the correlation of protein C and S levels in the plasma to the severity of infection. Methods: This was a case-control study measuring the protein C and S levels in patients infected with COVID-19 at the time of diagnosis compared to the normal population. The study included one hundred participants, sixty of them are patients with COVID-19, and forty of them are normal healthy adults. The patient group was subclassified into three subgroups according to disease severity: mild, moderate, and severe COVID-19 infections. Results: The activity of protein C in the patient group serum was significantly lower than that in the control group serum (79.35 ± 26.017 vs 97.43 ± 15.007; p < 0.001). Protein S is also significantly decreased in patients' serum when compared to the control group (70.233 ± 22.476 vs 91 ± 14.498; p < 0.001). There was a statistically significant decrease in the levels of protein C and S associated with the increase in disease severity (p < 0.05). However, protein S showed no statistically significant difference between the moderate and severe disease subgroups. Conclusion: The study concluded that the levels of protein C and S activities were both decreased in patients with COVID-19 when compared to the healthy population. It also concluded that the decrease in their levels is statistically significant in relation to the disease severity.

The peptide link between pathogens and human centromere proteins

This work tested the hypothesis that infection causes unexplained production of anti-centromere protein antibodies (ACA) via autoimmune cross-reactivity. To further examine the clinical origin of ACA, the overlapped peptides between human pathogens, including viruses, bacteria and fungi and centromere proteins (CENP-A, CENP-B and CENP-C) were assessed. We found a broad overlap of pathogenetic peptides with human centromere proteins. These data indicate potential immune cross-reactivity between pathogens and human centromere proteins. Additionally, the current findings corroborate a molecular and mechanistic framework for autoimmune disorders related to infection. Moreover, preliminary evidence for a potential role of infection in ACA-related autoimmune diseases was presented. © 2022 The Scandinavian Foundation for Immunology.

Increased risk of dialysis circuit clotting in hemodialysis patients with COVID-19 is associated with elevated FVIII, fibrinogen and D-dimers.

INTRODUCTION: Severe COVID-19 infections increase the risk of thrombotic events and Intensive Care Units reported increased extracorporeal circuit clotting (ECC) in COVID-19 patients with acute kidney injury. We wished to determine whether hemodialysis (HD) patients with COVID-19 also have increased risk of circuit clotting. METHODS: We reviewed coagulation studies and HD records, 4 weeks before and after COVID-19 polymerase chain reaction detection in HD patients between April 2020 and June 2021. FINDINGS: Sixty-eight (33.5%) of 203 HD patients with COVID-19, 65% male, mean age 64.9 ± 15.3 years, experienced some circuit clotting, and no clotting recorded prior to positive test results. In those who experienced ECC, prothrombin, activated partial thromboplastin or thrombin times were not different, whereas median factor VIII (273 [168-419] vs. 166 [139-225] IU/dl, p < 0.001), D-dimers (2654 [1381-6019] vs. 1351 [786-2334] ng/ml, p < 0.05), and fibrinogen (5.6 ± 1.4 vs. 4.9 ± 1.4 g/L, p < 0.05) were greater. Antithrombin (94 [83-112] vs. 89 [84-103] IU/dl), protein C (102 [80-130] vs. 86 [76-106] IU/dl), protein S (65 [61-75] vs. 65 [52-79] IU/dl) and platelet counts (193 [138-243] vs. 174 [138-229] × 109 /L) did not differ. On multivariable logistic analysis, circuit clotting was associated with log factor VIII (odds ratio [OR] 14.8 (95% confidence limits [95% CL] 1.12-19.6), p = 0.041), fibrinogen (OR 1.57 [95% CL 1.14-21.7], p = 0.006) and log D dimer (OR 4.8 [95% CL 1.16-12.5], p = 0.028). DISCUSSION: Extracorporeal circuit clotting was increased within 4 weeks of testing positive for COVID-19. Clotting was associated with increased factor VIII, fibrinogen and D-dimer, suggesting that the risk of circuit clotting was related to the inflammatory response to COVID-19.

Mineralizing angiopathy: an underrecognized clinicoradiologic entity

Case Report: Initial History/Presentation: A term vaccinated 7-month-old male with a history of eczema presents with two hours of right-sided hemiplegia and hemidystonia. Parents deny loss of consciousness, altered mental status, or facial symptoms. He has no known history of recent or remote head trauma. Patient may have had COVID two months prior when he had upper respiratory symptoms, with his mother testing COVID+ at that time. Of note, he received a Moderna COVID vaccination one day prior to onset of symptoms. Physical Exam: Pertinent exam findings include CN II-XII intact, right-sided upper and lower extremity strength 3/5, sensation intact, and truncal ataxia while seated. Physical exam is otherwise unremarkable. Diagnostic Evaluation: Initial lab work revealed leukocytosis (20.9), but otherwise a reassuring CMP, triglycerides, HDL, and LDL. PTT was elevated, but normal on recheck. Protein C antigen and activity were low, but deemed non-concerning by hematology. All other hypercoagulable labs were normal. On imaging, CT Brain showed linear calcifications in bilateral basal ganglia suggestive of mineralizing angiopathy. HisCTA head/neckwas negative.MRI Brain revealed an acute infarct of the body/tail of the left caudate nucleus, posterior limb of internal capsule, and posterior putamen. Clinical Course/Follow-up: Our patient was started on Aspirin 4 mg/kg daily. Throughout the course of his 3-day inpatient stay, he had mild improvement of right-sided strength and function, and continued improvement upon follow-up with his pediatrician. Given the short interval between receiving his COVID vaccination and onset of symptoms, his case was reported to the Vaccine Adverse Event Reporting System. Conclusion(s): From a radiological perspective, mineralizing angiopathy is an uncommon but familiar finding seen in up to 5% of all neonatal head ultrasounds and increasing to nearly 20% in preterm infants. It is most commonly associated with infection, hypoxia, and chromosomal abnormalities but is usually of minimal clinical significance. However, there are numerous reports of basal ganglia and thalamic strokes following minor head trauma in children with mineralizing angiopathy. For radiologists, this association is important to recognize and relay to the primary team so targeted history and MRI, if indicated, may be obtained to expedite definitive diagnosis and initiation of treatment to preserve precious brain tissue. Without a history of head trauma, in this case, stroke provocation is unclear, and other infectious or inflammatory disorders could appear similarly if they induced vasospasm or blood pressure lability. A short-interval timeframe between COVID vaccine administration and symptom onset is likely incidental, but research to exclude or illicit any link may be of benefit. Findings of mineralizing angiopathy on CT in the appropriate clinical setting should prompt further evaluation with emergent MRI to determine the presence of basal ganglia or thalamic stroke. Copyright © 2023 Southern Society for Clinical Investigation.

Decreased protein C activity, lower ADAMTS13 antigen and free protein S levels accompanied by unchanged thrombin generation potential in hospitalized COVID-19 patients.

INTRODUCTION: COVID-19 is associated with an increased thromboembolic risk. However, the mechanisms triggering clot formation in those patients remain unknown. PATIENTS AND METHODS: In 118 adult Caucasian severe but non-critically ill COVID-19 patients (median age 58 years; 73 % men) and 46 controls, we analyzed in vitro plasma thrombin generation profile (calibrated automated thrombogram [CAT assay]) and investigated thrombophilia-related factors, such as protein C and antithrombin activity, free protein S level, presence of antiphospholipid antibodies and factor V Leiden R506Q and prothrombin G20210A mutations. We also measured circulating von Willebrand factor (vWF) antigen and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) antigen and activity. In patients, blood samples were collected on admission to the hospital before starting any therapy, including heparin. Finally, we examined the relationship between observed alterations and disease follow-up, such as thromboembolic complications. RESULTS: COVID-19 patients showed 17 % lower protein C activity, 22 % decreased free protein S levels, and a higher prevalence of positive results for IgM anticardiolipin antibodies. They also had 151 % increased vWF, and 27 % decreased ADAMTS13 antigens compared with controls (p < 0.001, all). On the contrary, thrombin generation potential was similar to controls. In the follow-up, pulmonary embolism (PE) occurred in thirteen (11 %) patients. They were characterized by a 55 % elevated D-dimer (p = 0.04) and 2.7-fold higher troponin I (p = 0.002) during hospitalization and 29 % shorter time to thrombin peak in CAT assay (p = 0.009) compared to patients without PE. CONCLUSIONS: In COVID-19, we documented prothrombotic abnormalities of peripheral blood. PE was characterized by more dynamic thrombin generation growth in CAT assay performed on admittance to the hospital.

Is Undected Inherited Thrombophilia The Hades Of COVID-19?

Introduction: Thrombophilia is a co-morbidity in the general population with a prevalence of 5%. However, it is not known whether it affects severity of COVID-19. It may be possible that undiagnosed thrombophilia exaggerates an already prothrombotic state in COVID- 19 patients and hence, results in severe disease. Aims & Objectives: To study the association of underlying thrombophilia with severity of COVID-19 in post COVID patients after a minimum of 6 weeks of recovery. Material(s) and Method(s): Eighty RT-PCR confirmed adult covid patients (40 severe,40 non-severe) post 6 weeks of recovery were included. The venous blood in EDTA and citrate vials was tested for complete blood counts and coagulation parameters such as Prothrombin time, activated partial prothrombin time, Lupus anticoagulant by dRVVT, Antithrombin-III, Protein C and S). Result(s): 6/40 patients had Protein C deficiency in severe category and none in non severe. 7/40 patients had Protein S deficiency in severe category and 1 patient was deficiant in non-severe group. Conclusion(s): Thrombophilia was detected significantly in patients with severe COVID even after 6 weeks of recovery, indicating that undetected underlying thrombophilia could be a factor affecting disease severity. The common abnormalities detected were Protein C & S deficiency. This is a novel finding which needs to be explored further with extensive thrombophilia profiles. The influence of underlying thrombophilia in patients who succumbed to the disease is not known and cannot be known retrospectively. However, the extrapolation of this study suggests that thrombophilia may be an important influence on severity and mortality. (Table Presented).

Impact Of Covid-19 On The Linkages Between Indochina Metal Futures Markets

This paper attempts to test whether the Covid-19 pandemic has an impact on the linkages of the metal futures market of India and China. Taking Daily closing prices from 4 Jun 2016 to 23 Apr 2021 for the seven metals, including copper, aluminum, zinc, lead, nickel, gold, and silver, have been included in the study in the pre-announcement and post-announcement of covid-19 as a pandemic. The autoregressive distributed lag (ARDL) bound test and Johansen cointegration test report no cointegrating relationship between the markets for all the metal futures before the covid period. There is no change in the absence of cointegration in the post-announcement period of Covid-19. Similarly, Granger causality results report no change in the short-run relationship between the metal futures markets except for silver futures. The results have implications for portfolio managers and investors looking to reshuffle their portfolios in the light of changes in the market due to the covid-19 pandemic. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Haemostatic differences between SARS-CoV- 2 PCR-positive and -negative patients at the time of hospital admission

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) is associated with a prothrombotic phenotype with an increased risk for thrombosis. Aim(s): To investigate whether COVID-19 is associated with changes in coagulation parameters upon presentation at the emergency department and whether these changes are associated with the development of thrombotic complications in patients with SARS-CoV- 2 infection. Method(s): A single centre, cross-sectional cohort study: The MArkers in COVID-19 And Relations to Outcomes in the Netherlands (MACARON) study was conducted. All patients suspected of SARS-CoV- 2 infection referred to the emergency department of the Meander Medical Center between March-May 2020 were included. 519 patients (26% PCR positive, median age 66 (range 19-97 years), 52.2% male) were included from whom an oro-and nasopharyngeal swab was obtained for detection of SARS-CoV- 2 by polymerase chain reaction (PCR). Blood samples for laboratory analysis were obtained from all patients. Thrombosis was defined as a clinical diagnosis of venous thromboembolism or atherothrombotic event based upon radiology and laboratory results. Result(s): SARS-CoV- 2 PCR positive patients had increased fibrinogen levels (5.41 g/L vs. 4.21 g/L, p < 0.001) and decreased levels of protein C (85.1% vs. 96.1%, p < 0.001) and alpha2-macroglobulin (4.41 muM vs. 5.11 muM, p < 0.001) compared to the PCR negative patients. In addition, we found more acquired activated protein C resistance in PCR positive patients. Furthermore, we found that elevated levels of factor VIII (208% vs. 162%, p = 0.028) and von Willebrand Factor (208% vs. 186%, p = 0.038) and decreased ADAMTS-13 levels (597 ng/ml vs. 691 ng/ml, p < 0.001) were associated with increased occurrence of thrombosis in PCR positive patients (thrombosis vs. non-thrombosis). Conclusion(s): We found that PCR positive patients had a more pronounced prothrombotic phenotype with endothelial activation upon hospital admission showing that coagulation tests may be considered useful to discriminate severe cases of COVID-19 at risk for thrombosis.