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1.
Heart Lung ; 58: 1-5, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2086277

ABSTRACT

BACKGROUND: Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19. OBJECTIVE: We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death). METHODS: We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized. RESULTS: Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p<0.001; females: OR=2.31, 95%CI=2.04-2.63, p<0.001; p-interaction=0.005). CONCLUSION: Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.

2.
Crit Care Med ; 50(9): 1348-1359, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-1853257

ABSTRACT

OBJECTIVES: We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation. DESIGN: Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial. SETTING: Five U.S. medical centers. PATIENTS: Adults inpatients with severe COVID-19 disease and hyperinflammation. INTERVENTIONS: Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival, frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR > 1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR > 1] 86.5% and OR = 2.53; p [OR > 1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR] < 1; 99.9%) and ICU admission (OR = 0.26; p [OR < 1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR] < 0.75; p [RR < 1] > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR > 1] 98.1%; OR = 3.36, p [OR > 1] 99.6%; and OR = 3.52, p [OR > 1] 99.8%, respectively). CONCLUSIONS: Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Bayes Theorem , COVID-19/complications , COVID-19/drug therapy , Double-Blind Method , Humans , SARS-CoV-2 , Treatment Outcome
3.
Am J Cardiol ; 170: 112-117, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1787987

ABSTRACT

Gender-specific differences in thrombosis have been reported in hospitalized patients with COVID-19. We sought to investigate the influence of age on the relation between gender and incident thrombosis or death in COVID-19. We identified consecutive adults aged ≥18 years hospitalized with COVID-19 from March 1, 2020, to April 17, 2020, at a large New York health system. In-hospital thrombosis and all-cause mortality were evaluated by gender and stratified by age group. Logistic regression models were generated to estimate the odds of thrombosis or death after multivariable adjustment. In 3,334 patients hospitalized with COVID-19, 61% were men. Death or thrombosis occurred in 34% of hospitalizations and was more common in men (36% vs 29% in women, p <0.001; adjusted odds ratio [aOR] 1.61, 95% confidence interval [CI] 1.36 to 1.91). When stratified by age, men had a higher incidence of death or thrombosis in younger patients (aged 18 to 54 years: 21% vs 9%, aOR 3.17, 95% CI 2.06 to 5.01; aged 55 to 74 years: 39% vs 28%, aOR 1.63, 95% CI 1.28 to 2.10), but not older patients (aged ≥75 years: 55% vs 48%; aOR 1.20, 95% CI 0.90 to 1.59) (interaction p value: 0.01). For the individual end points, men were at higher risk of thrombosis (19% vs 12%; aOR 1.65, 95% CI 1.33 to 2.05) and mortality (26% vs 23%; aOR 1.41, 95% CI 1.17 to 1.69) than women, and gender-specific differences were attenuated with older age. Associations between thrombosis and mortality were most striking in younger patients (aged 18 to 54 years, aOR 8.25; aged 55 to 74 years, aOR 2.38; aged >75 years, aOR 1.88; p for interaction <0.001) but did not differ by gender. In conclusion, the risk of thrombosis or death in COVID-19 is higher in men compared with women and is most apparent in younger age groups.


Subject(s)
COVID-19 , Thrombosis , Adolescent , Adult , COVID-19/epidemiology , Female , Hospital Mortality , Hospitalization , Humans , Male , Middle Aged , Odds Ratio , Sex Characteristics , Thrombosis/epidemiology , Young Adult
4.
Cornea ; 41(5): 562-571, 2022 May 01.
Article in English | MEDLINE | ID: covidwho-1778962

ABSTRACT

PURPOSE: The purpose of this study was to describe the rationale and design of the Zoster Eye Disease Study (ZEDS). METHODS: ZEDS is a National Eye Institute-supported randomized clinical trial designed to determine whether 1 year of suppressive valacyclovir in patients with herpes zoster ophthalmicus (HZO) reduces complications because there is currently no high-quality evidence to support its use. Eligible patients are 18 years and older, immunocompetent, have a history of a typical rash at disease onset, and have had a record of active epithelial or stromal keratitis or iritis within 1 year before enrollment. Exclusion criteria include estimated glomerular filtration rate less than 45 or pregnancy. The primary endpoint is the time to first occurrence of new or worsening dendriform epithelial keratitis, stromal keratitis without or with ulceration, endothelial keratitis, or iritis due to HZO during 12 months of study treatment requiring prespecified treatment changes. The study has 80% power to detect a 30% difference between treatment groups, with a 30% rate of endpoints by 1 year assumed among controls. Secondary and exploratory questions include whether there is a persistent treatment benefit during the 6 months after treatment, whether development of postherpetic neuralgia varies by treatment group, and whether vaccinations against herpes zoster affect study outcomes and coronavirus disease 19 status. RESULTS: Over approximately 4 years, over 400 study participants have been enrolled. CONCLUSIONS: ZEDS aims to provide scientific evidence on whether suppressive valacyclovir treatment improves outcomes in HZO and should become the standard of care.


Subject(s)
COVID-19 , Herpes Zoster Ophthalmicus , Herpes Zoster , Neuralgia, Postherpetic , Antiviral Agents/therapeutic use , Herpes Zoster Ophthalmicus/complications , Herpes Zoster Ophthalmicus/diagnosis , Herpes Zoster Ophthalmicus/drug therapy , Humans , Neuralgia, Postherpetic/diagnosis , Neuralgia, Postherpetic/drug therapy , Neuralgia, Postherpetic/epidemiology , Valacyclovir/therapeutic use
6.
JAMA ; 327(3): 227-236, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1669289

ABSTRACT

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Heparin/administration & dosage , Inpatients , Purinergic P2Y Receptor Antagonists/administration & dosage , Aged , Aged, 80 and over , Anticoagulants/adverse effects , COVID-19/blood , COVID-19/mortality , Clopidogrel/administration & dosage , Clopidogrel/adverse effects , Comorbidity , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Hemorrhage/chemically induced , Heparin/adverse effects , Hospital Mortality , Humans , Male , Medical Futility , Middle Aged , Outcome Assessment, Health Care , Oxygen Inhalation Therapy/statistics & numerical data , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2Y Receptor Antagonists/adverse effects , Receptors, Purinergic P2Y12 , Respiration, Artificial/statistics & numerical data , Thrombosis/epidemiology , Ticagrelor/administration & dosage , Ticagrelor/adverse effects , Time Factors , Treatment Outcome
7.
JAMA Netw Open ; 5(1): e2147331, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1648384

ABSTRACT

Importance: COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing. Objective: To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP. Data Sources: From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly. Study Selection: Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally. Data Extraction and Synthesis: A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board. Main Outcomes and Measures: Prespecified coprimary end points-the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model-were assessed clinically at 14 days after randomization. Results: Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics. Conclusions and Relevance: This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.


Subject(s)
COVID-19/therapy , Hospitalization , Pandemics , Patient Selection , Plasma , Aged , Bayes Theorem , Female , Humans , Immunization, Passive , Male , Middle Aged , Respiration, Artificial , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome , World Health Organization
8.
Clin Transl Sci ; 15(4): 831-837, 2022 04.
Article in English | MEDLINE | ID: covidwho-1583606

ABSTRACT

Randomized controlled trials (RCTs) remain the gold standard to evaluate clinical interventions, producing the highest level of evidence while minimizing potential bias. Inadequate recruitment is a commonly encountered problem that undermines the completion and generalizability of RCTs-and is even more challenging when enrolling amidst a pandemic. Here, we reflect on our experiences with virtual recruitment of non-hospitalized patients in the United States for ColCorona, an international, multicenter, randomized, placebo-controlled coronavirus disease 2019 (COVID-19) drug trial. Recruitment challenges during a pandemic include constraints created by shelter-in-place policies and targeting enrollment according to national and local fluctuations in infection rate. Presenting a study to potential participants who are sick with COVID-19 and may be frightened, overwhelmed, or mistrusting of clinical research remains a challenge. Strategies previously reported to improve recruitment include transparency, patient and site education, financial incentives, and person-to-person outreach. Active measures taken during ColCorona to optimize United States recruitment involved rapid expansion of sites, adjustment of recruitment scripts, assessing telephone calls versus text messages for initial contact with participants, institutional review board-approved financial compensation, creating an infrastructure to systematically identify potentially eligible patients, partnering with testing sites, appealing to both self-interest and altruism, and large-scale media efforts with varying degrees of success.


Subject(s)
COVID-19 , Text Messaging , COVID-19/epidemiology , Humans , Multicenter Studies as Topic , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2 , United States/epidemiology
9.
JAMA Intern Med ; 182(2): 115-126, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1567885

ABSTRACT

Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures: The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results: Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance: In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration: ClinicalTrials.gov Identifier: NCT04364737.


Subject(s)
Blood Component Transfusion , COVID-19/therapy , Critical Illness/therapy , Adult , Aged , Double-Blind Method , Female , Hospitalization/statistics & numerical data , Humans , Immunization, Passive , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Treatment Outcome , United States
10.
Contemp Clin Trials Commun ; 24: 100875, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1527631

ABSTRACT

PURPOSE: To describe steps taken that enabled a high rate of retention and early resumption of enrollment in the Zoster Eye Disease Study (ZEDS), a randomized controlled trial funded by the National Eye Institute, during the first 13 months (3/1/2020-3/31/2021) of the COVID-19 pandemic. METHODS: A number of responses were implemented in ZEDS when the focus shifted to retention of study participants at the beginning of the pandemic including frequent communication with the participating clinical centers (PCCs) about remote visits, local lab work, shipping study medication, and completion of revised case report forms. Additional payments were provided to the PCCs. Remote activation of PCCs continued. Screening and enrollment visits gradually resumed when allowed. RESULTS: Communication with PCCs increased, and average attendance at monthly coordinator teleconferences went up from 17 to 47. Remote visits peaked in April 2020, accounting for 75% (33/44) of study visits, then declined to less than 10% of study visits beginning August 2020. Overall, 97% (590/609) of study visits were completed. Only 5.5% (9/165) of study participants withdrew consent, and 2.4% (4/165) were lost to follow-up. Enrollment returned to pre-pandemic levels by September 2020. DISCUSSION: Strong communication and unwavering commitment, combined with the technological capability for remote work, visits, and shipment of study medication, were key to the successful retention of study participants and resumption of enrollment. CONCLUSIONS: Rapid responses to challenges to trials caused by the COVID-19 pandemic can enable them to continue successfully and provide insights into the planning of future trials.

11.
J Thromb Haemost ; 19(12): 3139-3153, 2021 12.
Article in English | MEDLINE | ID: covidwho-1526388

ABSTRACT

OBJECTIVE: Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID-19-associated pathogenesis. The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization. APPROACH AND RESULTS: In a cohort of 3915 hospitalized COVID-19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication, and biomarkers of inflammation and thrombosis, we find platelet count, size, and immaturity are associated with increased critical illness and all-cause mortality. Bone marrow, lung tissue, and blood from COVID-19 patients revealed the presence of SARS-CoV-2 virions in megakaryocytes and platelets. Characterization of COVID-19 platelets found them to be hyperreactive (increased aggregation, and expression of P-selectin and CD40) and to have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. In vitro mechanistic studies highlight that the interaction of SARS-CoV-2 with megakaryocytes alters the platelet transcriptome, and its effects are distinct from the coronavirus responsible for the common cold (CoV-OC43). CONCLUSIONS: Platelet count, size, and maturity associate with increased critical illness and all-cause mortality among hospitalized COVID-19 patients. Profiling tissues and blood from COVID-19 patients revealed that SARS-CoV-2 virions enter megakaryocytes and platelets and associate with alterations to the platelet transcriptome and activation profile.


Subject(s)
COVID-19 , Thrombosis , Blood Platelets , Humans , SARS-CoV-2 , Severity of Illness Index
12.
Sci Adv ; 7(37): eabh2434, 2021 Sep 10.
Article in English | MEDLINE | ID: covidwho-1405214

ABSTRACT

Given the evidence for a hyperactive platelet phenotype in COVID-19, we investigated effector cell properties of COVID-19 platelets on endothelial cells (ECs). Integration of EC and platelet RNA sequencing revealed that platelet-released factors in COVID-19 promote an inflammatory hypercoagulable endotheliopathy. We identified S100A8 and S100A9 as transcripts enriched in COVID-19 platelets and were induced by megakaryocyte infection with SARS-CoV-2. Consistent with increased gene expression, the heterodimer protein product of S100A8/A9, myeloid-related protein (MRP) 8/14, was released to a greater extent by platelets from COVID-19 patients relative to controls. We demonstrate that platelet-derived MRP8/14 activates ECs, promotes an inflammatory hypercoagulable phenotype, and is a significant contributor to poor clinical outcomes in COVID-19 patients. Last, we present evidence that targeting platelet P2Y12 represents a promising candidate to reduce proinflammatory platelet-endothelial interactions. Together, these findings demonstrate a previously unappreciated role for platelets and their activation-induced endotheliopathy in COVID-19.

14.
Eur Heart J ; 42(23): 2270-2279, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1032166

ABSTRACT

BACKGROUND: A systemic inflammatory response is observed in coronavirus disease 2019 (COVID-19). Elevated serum levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with severe disease in bacterial or viral infections. We aimed to explore associations between CRP concentration at initial hospital presentation and clinical outcomes in patients with COVID-19. METHODS AND RESULTS: Consecutive adults aged ≥18 years with COVID-19 admitted to a large New York healthcare system between 1 March and 8 April 2020 were identified. Patients with measurement of CRP were included. Venous thrombo-embolism (VTE), acute kidney injury (AKI), critical illness, and in-hospital mortality were determined for all patients. Among 2782 patients hospitalized with COVID-19, 2601 (93.5%) had a CRP measurement [median 108 mg/L, interquartile range (IQR) 53-169]. CRP concentrations above the median value were associated with VTE [8.3% vs. 3.4%; adjusted odds ratio (aOR) 2.33, 95% confidence interval (CI) 1.61-3.36], AKI (43.0% vs. 28.4%; aOR 2.11, 95% CI 1.76-2.52), critical illness (47.6% vs. 25.9%; aOR 2.83, 95% CI 2.37-3.37), and mortality (32.2% vs. 17.8%; aOR 2.59, 95% CI 2.11-3.18), compared with CRP below the median. A dose response was observed between CRP concentration and adverse outcomes. While the associations between CRP and adverse outcomes were consistent among patients with low and high D-dimer levels, patients with high D-dimer and high CRP have the greatest risk of adverse outcomes. CONCLUSIONS: Systemic inflammation, as measured by CRP, is strongly associated with VTE, AKI, critical illness, and mortality in COVID-19. CRP-based approaches to risk stratification and treatment should be tested.


Subject(s)
C-Reactive Protein , COVID-19 , Adolescent , Adult , C-Reactive Protein/analysis , Humans , Retrospective Studies , Risk Factors , SARS-CoV-2
17.
Am Heart J ; 231: 93-95, 2021 01.
Article in English | MEDLINE | ID: covidwho-917186

ABSTRACT

We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses nationwide from 2012 to 2014 and compared this to the incidence among patients hospitalized with COVID-19 at a large health system in New York. Non-COVID-19 viral respiratory illness was complicated by acute MI in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%. The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (5% vs 16%; P< .001). BACKGROUND: Thrombosis is a prominent feature of the novel Coronavirus disease 2019 (COVID-19). The incidence of thrombosis during hospitalization for non-COVID-19 viral respiratory infections is uncertain. We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses compared to COVID-19. METHODS: Adults age >18 years hospitalized with a non-COVID-19 viral respiratory illness between 2002 and 2014 were identified. The primary study outcome was a composite of venous and arterial thrombotic events, including myocardial infarction (MI), acute ischemic stroke, and venous thromboembolism (VTE), as defined by ICD-9 codes. The incidence of thrombosis in non-COVID-19 viral respiratory illnesses was compared to the recently published incidence of thrombosis in COVID-19 from 3,334 patients hospitalized in New York in 2020. RESULTS: Among 954,521 hospitalizations with viral pneumonia from 2002 to 2014 (mean age 62.3 years, 57.1% female), the combined incidence of arterial and venous thrombosis was 5.0%. Acute MI occurred in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%. Patients with thrombosis had higher in-hospital mortality (14.9% vs 3.3%, P< .001) than those without thrombosis. The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (median age 64; 39.6% female) in 2020 (5% vs 16%; P< .001) CONCLUSION: In a nationwide analysis of hospitalizations for viral pneumonias, thrombosis risk was lower than that observed in patients with COVID-19. Investigations into mechanisms of thrombosis and risk reduction strategies in COVID-19 and other viral respiratory infections are necessary.


Subject(s)
COVID-19 , Ischemic Stroke , Myocardial Infarction , Pneumonia, Viral , Respiratory Tract Infections , Thrombosis , Venous Thromboembolism , COVID-19/diagnosis , COVID-19/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Ischemic Stroke/diagnosis , Ischemic Stroke/epidemiology , Ischemic Stroke/etiology , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Myocardial Infarction/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Respiratory Tract Infections/complications , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/virology , Risk Assessment , SARS-CoV-2/isolation & purification , Thrombosis/epidemiology , Thrombosis/virology , United States/epidemiology , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
18.
Arterioscler Thromb Vasc Biol ; 40(9): 2045-2053, 2020 09.
Article in English | MEDLINE | ID: covidwho-889978

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge and opportunity for translational investigators to rapidly develop safe and effective therapeutic interventions. Greater risk of severe disease in COVID-19 patients with comorbid diabetes mellitus, obesity, and heart disease may be attributable to synergistic activation of vascular inflammation pathways associated with both COVID-19 and cardiometabolic disease. This mechanistic link provides a scientific framework for translational studies of drugs developed for treatment of cardiometabolic disease as novel therapeutic interventions to mitigate inflammation and improve outcomes in patients with COVID-19.


Subject(s)
Betacoronavirus , Cardiovascular Diseases/epidemiology , Coronavirus Infections/epidemiology , Inflammation/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Cardiovascular System , Comorbidity , Humans , Risk Factors , SARS-CoV-2
20.
Arterioscler Thromb Vasc Biol ; 40(10): 2539-2547, 2020 10.
Article in English | MEDLINE | ID: covidwho-729442

ABSTRACT

OBJECTIVE: To determine the prevalence of D-dimer elevation in coronavirus disease 2019 (COVID-19) hospitalization, trajectory of D-dimer levels during hospitalization, and its association with clinical outcomes. Approach and Results: Consecutive adults admitted to a large New York City hospital system with a positive polymerase chain reaction test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) between March 1, 2020 and April 8, 2020 were identified. Elevated D-dimer was defined by the laboratory-specific upper limit of normal (>230 ng/mL). Outcomes included critical illness (intensive care, mechanical ventilation, discharge to hospice, or death), thrombotic events, acute kidney injury, and death during admission. Among 2377 adults hospitalized with COVID-19 and ≥1 D-dimer measurement, 1823 (76%) had elevated D-dimer at presentation. Patients with elevated presenting baseline D-dimer were more likely than those with normal D-dimer to have critical illness (43.9% versus 18.5%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), any thrombotic event (19.4% versus 10.2%; adjusted odds ratio, 1.9 [95% CI, 1.4-2.6]; P<0.001), acute kidney injury (42.4% versus 19.0%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), and death (29.9% versus 10.8%; adjusted odds ratio, 2.1 [95% CI, 1.6-2.9]; P<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS: Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.


Subject(s)
Coronavirus Infections/blood , Coronavirus Infections/mortality , Critical Illness/epidemiology , Disease Progression , Fibrin Fibrinogen Degradation Products/metabolism , Hospital Mortality/trends , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , Adult , Aged , Biomarkers/blood , COVID-19 , Cause of Death , Cohort Studies , Coronavirus Infections/physiopathology , Databases, Factual , Female , Hospitals, Urban , Humans , Male , Middle Aged , New York City/epidemiology , Pandemics , Pneumonia, Viral/physiopathology , Prevalence , Retrospective Studies , Risk Assessment , Severe Acute Respiratory Syndrome/blood , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/physiopathology , Severity of Illness Index
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