Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis
Journal of Internal Medicine. 2022;289(1):97-115
Background: SARS-CoV-2 coronavirus infection ranges from asymptomatic through to fatal COVID-19 characterized by a 'cytokine storm' and lung failure Vitamin D deficiency has been postulated as a determinant of severity Objectives: To review the evidence relevant to vitamin D and COVID-19
Performance of a Point of Care Test for Detecting IgM and IgG Antibodies Against SARS-CoV-2 and Seroprevalence in Blood Donors and Health Care Workers in Panama
Frontiers in Medicine. 2021;8:616106
Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in 1 year. The serological detection of antibodies against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing, vaccine efficacy testing, and seroprevalence surveillance. Here, we aimed first to evaluate a lateral flow assay's ability to identify specific IgM and IgG antibodies against SARS-CoV-2 and second, to report the seroprevalence estimates of these antibodies among health care workers and healthy volunteer blood donors in Panama. We recruited study participants between April 30th and July 7th, 2020. For the test validation and performance evaluation, we analyzed serum samples from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, and a set of pre-pandemic serum samples. We used two by two table analysis to determine the test positive and negative percentage agreement as well as the Kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence among serum samples from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed a Kappa of 0.898 (95%CI 0.811-0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples from hospitalized COVID-19 patients indicates a correlation between test sensitivity and the number of days since symptom onset; the highest positive percent agreement [87% (95% CI 67.0-96.3%)] was observed at ≥15 days post-symptom onset (PSO). We found an overall antibody seroprevalence of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence testing in locations with active community transmission of SARS-CoV-2.
Imaging approach to COVID-19 Associated Pulmonary Embolism
International journal of clinical practice. 2021;:e14340
The novel coronavirus disease-2019 (COVID-19) illness and deaths, caused by the severe acute respiratory syndrome coronavirus-2, continue to increase. Multiple reports highlight the thromboembolic complications, such as pulmonary embolism (PE), in COVID-19. Imaging plays an essential role in the diagnosis and management of COVID-19 patients with PE. There continues to be a rapid evolution of knowledge related to COVID-19 associated PE. This review summarizes the current understanding of prevalence, pathophysiology, role of diagnostic imaging modalities, and management, including catheter-directed therapy for COVID-19 associated PE. It also describes infection control considerations for the radiology department while providing care for patients with COVID-19 associated PE.
Understanding COVID-19-associated coagulopathy: From PIC to SIC or DIC
Journal of Intensive Medicine. 2021
Coagulopathy, characterized by a high D-dimer level, is a common pathological occurrence in coronavirus disease 2019 (COVID-19) and is associated with poor prognosis Severe cases with COVID-19 is associated with a significantly higher risk of deep vein thrombosis and acute pulmonary embolism Pulmonary intravascular coagulopathy is the characteristic coagulopathy in COVID-19 Unlike sepsis-induced coagulopathy and disseminated intravascular coagulation, which are manifestations of systemic coagulopathy, pulmonary intravascular coagulopathy is a manifestation of a local coagulation disorder in the lung The progression from pulmonary intravascular coagulopathy to sepsis-induced coagulopathy or disseminated intravascular coagulation in the context of COVID-19 may indicate that the patient's coagulation dysfunction has progressed from local to systemic Exploring the associated coagulation disease will aid in the understanding of the pathophysiological mechanisms underlying severe COVID-19
Nonadministration of pharmacologic venous thromboembolism prophylaxis is less common in hospitalized patients with COVID-19
Journal of Thrombosis and Thrombolysis. 2021
INTRODUCTION The incidence of venous thromboembolism (VTE) in patients hospitalized with COVID-19 is higher than most other hospitalized patients. Nonadministration of pharmacologic VTE prophylaxis is common and is associated with VTE events. Our objective was to determine whether nonadministration of pharmacologic VTE prophylaxis is more common in patients with COVID-19 versus other hospitalized patients. MATERIALS AND METHODS In this retrospective cohort analysis of all adult patients discharged from the Johns hopkins hospital between Mar 1 and May 12, 2020, we compared demographic, clinical characteristics, VTE outcomes, prescription and administration of VTE prophylaxis between COVID-19 positive, negative, and not tested groups. RESULTS Patients tested positive for COVID-19 were significantly older, and more likely to be Hispanic, have a higher median body mass index, have longer hospital length of stay, require mechanical ventilation, develop pulmonary embolism and die (all p < 0.001). COVID-19 patients were more likely to be prescribed (aOR 1.51, 95% CI 1.38-1.66) and receive all doses of prescribed pharmacologic VTE prophylaxis (aOR 1.48, 95% CI 1.36-1.62). The number of patients who missed at least one dose of VTE prophylaxis and developed VTE was similar between the three groups (p = 0.31). CONCLUSIONS It is unlikely that high rates of VTE in COVID-19 are due to nonadministration of doses of pharmacologic prophylaxis. Hence, we should prioritize research into alternative approaches to optimizing VTE prevention in patients with COVID-19.
Does COVID-19 Provide a Clue for Thrombosis in ITP?
Seminars in Thrombosis and Hemostasis. 2021
Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: a multi-center, open-label, randomized controlled trial
Journal of Thrombosis and Haemostasis : JTH. 2021
BACKGROUND Coronavirus disease 2019 (COVID-19) is associated with coagulopathy but the optimal prophylactic anticoagulation therapy remains uncertain and may depend on COVID-19 severity. OBJECTIVE To compare outcomes in hospitalized adults with severe COVID-19 treated with standard prophylactic versus intermediate dose enoxaparin. METHODS We conducted a multi-center, open-label, randomized controlled trial comparing standard prophylactic dose versus intermediate dose enoxaparin in adults who were hospitalized with COVID-19 and admitted to an intensive care unit (ICU) and/or had laboratory evidence of coagulopathy. Patients were randomly assigned in a 1:1 ratio to receive standard prophylactic dose enoxaparin or intermediate weight-adjusted dose enoxaparin. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included arterial or venous thromboembolism and major bleeding. RESULTS A total of 176 patients (99 males and 77 females) underwent randomization. In the intention-to-treat population, all-cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin (odds ratio, 0.66; 95% confidence interval, 0.30-1.45; P=0.31 by chi-square test). Unadjusted Cox proportional hazards modeling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin (hazard ratio, 0.67; 95% confidence interval, 0.33 to 1.37; P=0.28). Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin. Major bleeding occurred in 2% of patients in each arm. CONCLUSION In hospitalized adults with severe COVID-19, standard prophylactic dose and intermediate dose enoxaparin did not differ significantly in preventing death or thrombosis at 30 days.
Adults hospitalized with COVID-19 admitted to an intensive care unit (n= 176).
Enoxaparin intermediate dose (n= 88).
Enoxaparin standard dose (n= 88).
In the intention-to-treat population, all-cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin. Unadjusted Cox proportional hazards modelling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin. Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin. Major bleeding occurred in 2% of patients in each arm.
The original and modified Caprini score equally predicts venous thromboembolism in COVID-19 patients
Journal of Vascular Surgery. Venous and Lymphatic Disorders. 2021
OBJECTIVE The study aimed to validate the original Caprini score and its modifications considering coronavirus disease (COVID-19) as a severe prothrombotic condition in patients admitted to the hospital. METHODS The relevant data were extracted from the electronic medical records with an implemented Caprini score and were retrospectively evaluated. The score was calculated twice: by the physician upon admission and by the investigator at discharge (death). The final assessment considered additional risk factors that occurred during inpatient treatment. Besides the original Caprini score (a version of 2005), the modified version added the elevation of D-dimer and specific scores for COVID-19 as follows: 2 points for asymptomatic, 3 points for symptomatic, and 5 points for symptomatic infection with positive D-dimer. Cases were evaluated retrospectively. The primary endpoint was symptomatic venous thromboembolism (VTE) detected during inpatient treatment and confirmed by appropriate imaging testing or autopsy. The secondary endpoints included those observed during hospitalization (admission to the intensive care unit (ICU), a requirement for invasive mechanical ventilation (IMV), death, bleeding), and those assessed at 6-month follow-up (symptomatic VTE, bleeding, death). The association of eight different versions of the Caprini score with VTE events was evaluated. RESULTS A total of 168 patients (83 males and 85 females at the age of 58.3±12.7 years old) were admitted to the hospital between 30 April and 29 May, 2020, and were discharged or died to the time of data analysis. The original Caprini score varied between 2-12 (5.4±1.8) at the admission and between 2-15 (5.9±2.5) at discharge or death. The maximal score was observed with modification including specific COVID-19 points of 5-20 (10.0±3.0). Patients received prophylactic (enoxaparin 40 mg once daily: 2.4%), intermediate (enoxaparin 80 mg once daily: 76.8%), or therapeutic (enoxaparin 1 mg/kg twice daily: 20.8%) anticoagulation. Despite this, symptomatic VTE was detected in 11 (6.5%) inpatients. Out of the 168 individuals, 28 (16.7%) admitted to the ICU, 8 (4.8%) required IMV, and 8 (4.8%) died. Clinically relevant non-major bleeding was detected in two (1.2%) cases. The Caprini score of all eight versions demonstrated a significant association with inpatient VTE frequency. The highest predictability was observed for the original scale when assessed at discharge (death). Only symptomatic VTE was reported after discharge with a cumulative incidence of 7.1%. This did not affect the predictability of the Caprini score. Extended antithrombotic treatment was prescribed to 49 (29%) patients with a cumulative incidence of bleeding of 1.8% at 6 months. CONCLUSION The study identified a significant correlation between the Caprini score and the risk of VTE in COVID-19 patients. All models including specific COVID-19 scores showed equally high predictability, and use of the original Caprini score is appropriate for COVID-19 patients.
Detection of SARS-CoV-2 virus using an alternative molecular method and evaluation of biochemical, hematological, inflammatory, and oxidative stress in healthcare professionals
Microbial Pathogenesis. 2021;:104975
In early December 2019, an outbreak of coronavirus disease 2019 caused by a new strain of coronavirus (SARS-CoV-2), occurred in the city of Wuhan, Hubei Province, China. On January 30, 2020, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern. Since then, frontline healthcare professionals have been experiencing extremely stressful situations and damage to their physical and mental health. These adverse conditions cause stress and biochemical, hematological, and inflammatory changes, as well as oxidative damage, and could be potentially detrimental to the health of the individual. The study population consisted of frontline health professionals working in BHU in a city in southern Brazil. Among the 45 participants, two were infected with the SARS-CoV-2 virus and were diagnosed using immunochromatographic tests such as salivary RT-LAMP and qRT-PCR. We also evaluated biochemical, hematological, inflammatory, and oxidative stress markers in the participants. The infected professionals (CoV-2-Prof) showed a significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, lactic dehydrogenase, lymphocytes, and monocytes. In this group, the levels of uric acid, triglycerides, leukocytes, neutrophils, hemoglobin, hematocrit, and platelets decreased. In the group of uninfected professionals (NoCoV-2-Prof), significant increase in HDL levels and the percentages of eosinophils and monocytes, was observed. Further, in this group, uric acid, LDH, triglyceride, and cholesterol levels, and the hematocrit count and mean corpuscular volume were significantly reduced. Both groups showed significant inflammatory activity with changes in the levels of C-reactive protein and mucoprotein. The NoCoV-2-Prof group showed significantly elevated plasma cortisol levels. To our kowledge, this study is the first to report the use of the RT-LAMP method with the saliva samples of health professionals, to evalute of SARS-CoV-2.
Anti-phospholipid syndrome and COVID-19 thrombosis: connecting the dots
Rheumatology Advances in Practice. 2021;5(1):rkaa081
As the coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide, it has emerged as a leading cause of mortality, resulting in >1 million deaths over the past 10 months. The pathophysiology of COVID-19 remains unclear, posing a great challenge to the medical management of patients. Recent studies have reported an unusually high prevalence of thromboembolic events in COVID-19 patients, although the mechanism remains elusive. Several studies have reported the presence of aPLs in COVID-19 patients. We have noticed similarities between COVID-19 and APS, which is an autoimmune prothrombotic disease that is often associated with an infective aetiology. Molecular mimicry and endothelial dysfunction could plausibly explain the mechanism of thrombogenesis in acquired APS. In this review, we discuss the clinicopathological similarities between COVID-19 and APS, and the potential role of therapeutic targets based on the anti-phospholipid model for COVID-19 disease.