The use of combined hormonal contraception in the context of the COVID-19 pandemic

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was declared the cause of a global pandemic in early 2020. Patients with COVID-19 are at high risk for thrombotic occlusions of the arteries and veins. There are many ways that explain the high risk of thrombosis in COVID-19, they are conditionally divided into two main categories: mechanisms in which the renin-angiotensinaldosterone system is involved and mechanisms that affect the regulation of the immune response. It is assumed that the uncomplicated course of the disease is characterized by endothelial dysfunction, but if the process progresses with a pronounced immune response, plasma coagulation factors may also be involved, which significantly increases the risks of thromboembolic complications. The use of combined hormonal contraception (CHC) in the current conditions raises a number of concerns. According to some researchers, disorders of the hemostasis system observed in patients with COVID-19 may worsen while taking CHC and increase the risk of thromboembolic complications, which is especially important in severe disease with prolonged immobilization. However, with the use of CHC, the increase in thrombotic risks is explained primarily by changes in the plasma component of the hemostasis sys tem. At first glance, the recommendations to stop hormone therapy with confirmed COVID-19 seem logical, but they are based only on the procoagulant activity of estrogens, and not on real evidence. In patients with COVID-19, the increase in coagulation is associ ated with massive damage to the vascular endothelium (the so-called «external» coagulation pathway) and the immune response, and not with a primary increase in the level of coagulation factors per se. At the same time, stopping the intake of estrogens deprives the patient of their important protective effect. Thus, it became necessary to develop clinical guidelines for the management of women using contraception in the context of the COVID-19 pandemic.

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Haemostasis in coronavirus disease 2019 - lesson from viscoelastic methods: a systematic review

Thrombosis and Haemostasis ◽

10.1055/a-1346-3178 ◽

2021 ◽

Author(s):

Artur Slomka ◽

Mariusz Kowalewski ◽

Ewa Żekanowska

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

High Risk ◽

Clinical Studies ◽

Core Collection ◽

Web Of Science ◽

Severe Disease ◽

Thromboembolic Complications ◽

Fibrinolysis Shutdown ◽

Coagulation And Fibrinolysis

Haemostatic unbalance is often observed in patients with coronavirus disease 2019 (COVID-19), and patients with severe disease are at high risk of developing thromboembolic complications. Viscoelastic methods (VEMs), including thrombelastography (TEG) and thromboelastometry (TEM), provide data on the nature of haemostatic disturbance. In this systematic review, we assessed the performance of TEG and TEM in the assessment of blood coagulation and fibrinolysis in patients with COVID-19. PubMed, Scopus, Web of Science Core Collection, medRxiv and bioRxiv were systematically searched for clinical studies evaluating TEG and/or TEM variables in COVID-19 individuals. Ten studies, with a total of 389 COVID-19 patients, were included, and VEMs were performed in 292 of these patients. Most patients (90%) presented severe COVID-19 and required mechanical ventilation. TEG and TEM variables showed that these patients displayed hypercoagulability and fibrinolysis shutdown, despite the use of appropriate thromboprophylaxis. However, the mechanism underlying these phenomena and their clinical significance in COVID-19 patients who developed thrombosis, is still not clear. Further studies are warranted if VEMs might help to identify those at highest risk of thrombotic events and who therefore may derive the greatest benefit from antithrombotic therapy.

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Contraception and thrombophilia

Hämostaseologie ◽

10.1055/s-0037-1617024 ◽

2009 ◽

Vol 29 (02) ◽

pp. 193-196 ◽

Cited By ~ 3

Author(s):

H. Rott ◽

A. Kruempel ◽

G. Kappert ◽

U. Nowak-Göttl ◽

S. Halimeh

Keyword(s):

Chronic Illness ◽

High Risk ◽

Children And Adolescents ◽

Hormonal Contraception ◽

Hormonal Contraceptives ◽

Thromboembolic Events ◽

Contraceptive Methods ◽

Secondary Complications ◽

Increased Risk ◽

Coagulation Proteins

SummaryThe risk of thromboembolic events (TE) is increased by acquired or inherited thrombo -philias (IT). We know that some hormonal contraceptives also increase the risk of thrombosis, thus, the use of such contraceptives are discussed as contraindications in women with IT. TEs are infrequent events in children and adolescents and in the majority of cases are associated with secondary complications from underlying chronic illness. Although adolescents are not typically considered to be at high-risk for TE, this cohort is frequently using hormonal contraception, leading to an increased risk in cases with unknown IT. The risk of TE with pregnancy alone is higher than associated with combined hormonal contra -ception. Progestin-only methods have not been found to increase the risk of TE with only moderate changes of coagulation proteins compared to normal reference values. Conclusion: Thrombophilic women are good candidates for progestin-only contraceptive methods.

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Place of progestogenic oral contraceptives in gynecological practice

Medical alphabet ◽

10.33667/2078-5631-2019-1-1(376)-19-26 ◽

2019 ◽

Vol 1 (1) ◽

pp. 19-26

Author(s):

I. V. Kuznetsova

Keyword(s):

Venous Thrombosis ◽

Oral Contraceptives ◽

Hormonal Contraception ◽

Review Of The Literature ◽

Safety Issues ◽

Routes Of Administration ◽

Positive Effects ◽

Combined Hormonal Contraception

The review of the literature presents data on the possible risks of using combined hormonal contraception and the possibilities of prescribing purely progestogenic contraception as an alternative to the use of combined means. Progestogen contraceptives include a group of agents with different routes of administration, doses and characteristics of progestins, which have a number of differences in the ratio of benefits and risks, availability, reversibility and other properties of contraception. Particular attention is paid to purely progestogenic tablets containing desogestrel, as a means equivalent in effectiveness to combination contraceptives, but safer. Safety issues are considered in the context of the use of breastfeeding women, as well as from the standpoint of the risk of arterial and venous thrombosis. The issues of non-contraceptive positive effects of purely progestogenic contraceptives are covered.

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Personalized stratification of back to work risk amidst COVID-19: A machine learning approach (Preprint)

10.2196/preprints.22030 ◽

2020 ◽

Author(s):

Carson Lam ◽

Jacob Calvert ◽

Gina Barnes ◽

Emily Pellegrini ◽

Anna Lynn-Palevsky ◽

...

Keyword(s):

Machine Learning ◽

High Risk ◽

Learning Algorithm ◽

Severe Disease ◽

High Specificity ◽

Population Level ◽

The United States ◽

Health Condition ◽

Available P ◽

Severe Illness

BACKGROUND In the wake of COVID-19, the United States has developed a three stage plan to outline the parameters to determine when states may reopen businesses and ease travel restrictions. The guidelines also identify subpopulations of Americans that should continue to stay at home due to being at high risk for severe disease should they contract COVID-19. These guidelines were based on population level demographics, rather than individual-level risk factors. As such, they may misidentify individuals at high risk for severe illness and who should therefore not return to work until vaccination or widespread serological testing is available. OBJECTIVE This study evaluated a machine learning algorithm for the prediction of serious illness due to COVID-19 using inpatient data collected from electronic health records. METHODS The algorithm was trained to identify patients for whom a diagnosis of COVID-19 was likely to result in hospitalization, and compared against four U.S policy-based criteria: age over 65, having a serious underlying health condition, age over 65 or having a serious underlying health condition, and age over 65 and having a serious underlying health condition. RESULTS This algorithm identified 80% of patients at risk for hospitalization due to COVID-19, versus at most 62% that are identified by government guidelines. The algorithm also achieved a high specificity of 95%, outperforming government guidelines. CONCLUSIONS This algorithm may help to enable a broad reopening of the American economy while ensuring that patients at high risk for serious disease remain home until vaccination and testing become available.

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Human Coronaviruses: Counteracting the Damage by Storm

Viruses ◽

10.3390/v13081457 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1457

Author(s):

Dewald Schoeman ◽

Burtram C. Fielding

Keyword(s):

Immune Response ◽

Severe Disease ◽

Antiviral Agents ◽

The Elderly ◽

Highly Pathogenic ◽

Vaccine Responses ◽

Cell Mediated Immune Response ◽

Inhibition Antibody ◽

A Cell ◽

Human Coronaviruses

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

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H-Ras gene takes part to the host immune response to COVID-19

Cell Death Discovery ◽

10.1038/s41420-021-00541-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Salvatore Sciacchitano ◽

Andrea Sacconi ◽

Claudia De Vitis ◽

Giovanni Blandino ◽

Giulia Piaggio ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Severe Disease ◽

Host Immune Response ◽

Severe Form ◽

Ras Gene ◽

Peripheral Blood Mononuclear ◽

Ras Genes

AbstractRas gene family members play a relevant role in cancer, especially when they are mutated. However, they may play additional roles in other conditions beside cancer. We performed gene expression analysis using the NanoString PanCancer IO 360 panel in the peripheral blood mononuclear cell (PBMC) of six COVID-19 patients and we found that H-Ras gene was significantly upregulated, while both K-Ras and N-Ras genes were downregulated. In particular, H-Ras gene upregulation was more evident in COVID-19 patients with a more severe disease. We compared our results with those obtained by analyzing two different and independent datasets, including a total of 53 COVID-19 patients, in which the gene expression analysis was performed using the Immunology_V2 panel. Comparative analysis of the H-Ras gene expression in these patients confirmed our preliminary results. In both of them, in fact, we were able to confirm the upregulation of the expression of the H-Ras gene. The exact role of this specific upregulation of the H-Ras gene in response to SARS-CoV-2 infection and its possible role in cancer still remains to be elucidated. In conclusion, H-Ras gene participates to the host immune response to SARS-CoV-2 virus infection, especially in patients affected by the most severe form of the COVID-19.

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COVID-19 in a Cohort of Patients with Congenital Myasthenic Syndrome

Journal of Neuromuscular Diseases ◽

10.3233/jnd-210699 ◽

2021 ◽

pp. 1-3

Author(s):

Setareh Alabaf ◽

Karen O'Connell ◽

Sithara Ramdas ◽

David Beeson ◽

Jacqueline Palace

Keyword(s):

High Risk ◽

Neuromuscular Transmission ◽

Genetic Disorders ◽

Severe Disease ◽

Congenital Myasthenic Syndrome ◽

Referral Centre ◽

History Of ◽

Myasthenic Syndrome ◽

The Uk ◽

Rare Group

Congenital Myasthenic Syndrome (CMS) are a rare group of genetic disorders of neuromuscular transmission. Some subtypes of CMS can be associated with respiratory and bulbar weakness and these patients may therefore be at high risk of developing a severe disease from COVID-19. We screened 73 patients with genetically confirmed CMS who were attending the UK national referral centre for evidence of previous Severe Acute Respiratory Syndrome Corona Virus 2 infection and their clinical outcome. Of 73 patients, seven had history of confirmed COVID-19. None of the infected patients developed a severe disease, and there were no signals that CMS alone carries a high risk of severe disease from COVID-19.

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Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

Scientific Reports ◽

10.1038/s41598-021-87668-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eunyoung Emily Lee ◽

Kyoung-Ho Song ◽

Woochang Hwang ◽

Sin Young Ham ◽

Hyeonju Jeong ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Clustering Analysis ◽

Validation Cohort ◽

Inflammatory Responses ◽

Clinical Course ◽

Severe Disease ◽

Outcome Data ◽

Inflammatory Immune Response ◽

Cluster 2

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

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491. Aerosol-Generating Medical Procedures: Transmission of SARS-CoV-2 and Emerging Viruses

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.684 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S312-S312

Author(s):

Seth D Judson ◽

Vincent J Munster

Keyword(s):

High Risk ◽

Severe Disease ◽

Experimental Studies ◽

Virus Transmission ◽

Nosocomial Transmission ◽

Medical Procedures ◽

Emerging Viruses ◽

Zoonotic Viruses ◽

Increased Risk ◽

Hospital Acquired

Abstract Background During the pandemic of coronavirus disease 2019 (COVID-19), many questions arose regarding risks for hospital-acquired or nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aerosol generating medical procedures (AGMPs), techniques that can generate infectious, virus-laden aerosols, could potentially amplify transmission among healthcare workers (HCWs). Thus, it was widely recommended that HCWs use airborne precautions when performing AGMPs. However, in clinical settings it is often unclear what procedures constitute AGMPs and how the risk varies by procedure or pathogen. We set out to further define AGMPs and assess the risk for nosocomial transmission of SARS-CoV-2 and other high-risk viruses via AGMPs. Methods We identified potential AGMPs and emerging viruses that were high-risk for nosocomial transmission through reviewing experimental and clinical data. Potential AGMPs were those associated with previous virus transmission or mechanically capable of transmission. High-risk viruses were defined as those that cause severe disease in humans for which limited therapies or interventions exist, are infectious via aerosols in humans or non-human primates (NHPs), found in the respiratory tract of infected humans or NHPs, and had previous evidence of nosocomial transmission. Results We identified multiple potential AGMPs, which could be divided into those that generate aerosols or induce a patient to form aerosols, as well as eight families of high-risk viruses. All of the viruses were emerging zoonotic RNA viruses. In the family Coronaviridae, we identified potential evidence for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 transmission via AGMPs. SARS-CoV-1 and SARS-CoV-2 were also found to be similarly stable when aerosolized. Conclusion Multiple emerging zoonotic viruses pose a high risk for nosocomial transmission through a variety of AGMPs. Given the similar stability of SARS-CoV-2 with SARS-CoV-1 when aerosolized and prior nosocomial transmission of SARS-CoV-1 via AGMPs, we suspect that certain AGMPs pose an increased risk for SARS-CoV-2 transmission. Additional experimental studies and on-site clinical sampling during AGMPs are necessary to further risk stratify AGMPs. Disclosures All Authors: No reported disclosures

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Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽

10.3390/v13030514 ◽

2021 ◽

Vol 13 (3) ◽

pp. 514

Author(s):

Denise Utami Putri ◽

Cheng-Hui Wang ◽

Po-Chun Tseng ◽

Wen-Sen Lee ◽

Fu-Lun Chen ◽

...

Keyword(s):

Immune Response ◽

Immune Cells ◽

Mononuclear Cells ◽

Immune Cell ◽

Severe Disease ◽

Viral Rna ◽

Disease Course ◽

Peripheral Blood Mononuclear ◽

Peripheral Immune Cells ◽

Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

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