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1.
EBioMedicine ; 74: 103722, 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1536517

ABSTRACT

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411 .

2.
PLoS One ; 16(9): e0256767, 2021.
Article in English | MEDLINE | ID: covidwho-1381284

ABSTRACT

A report published last year by the Centers for Medicare & Medicaid Services (CMS) highlighted that COVID-19 case counts are more likely to be high in lower quality nursing homes than in higher quality ones. Since then, multiple studies have examined this association with a handful also exploring the role of facility quality in explaining resident deaths from the virus. Despite this wide interest, no previous study has investigated how the relation between quality and COVID-19 mortality among nursing home residents may have changed, if at all, over the progression of the pandemic. This understanding is indeed lacking given that prior studies are either cross-sectional or are analyses limited to one specific state or region of the country. To address this gap, we analyzed changes in nursing home resident deaths across the US between June 1, 2020 and January 31, 2021 (n = 12,415 nursing homes X 8 months) using both descriptive and multivariable statistics. We merged publicly available data from multiple federal agencies with mortality rate (per 100,000 residents) as the outcome and CMS 5-star quality rating as the primary explanatory variable of interest. Covariates, based on the prior literature, consisted of both facility- and community-level characteristics. Findings from our secondary analysis provide robust evidence of the association between nursing home quality and resident deaths due to the virus diminishing over time. In connection, we discuss plausible reasons, especially duration of staff shortages, that over time might have played a critical role in driving the quality-mortality convergence across nursing homes in the US.


Subject(s)
COVID-19/mortality , Nursing Homes , Pandemics , Quality of Health Care , SARS-CoV-2 , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , United States/epidemiology
4.
Blood ; 136(Supplement 1):34-34, 2020.
Article in English | PMC | ID: covidwho-1339029

ABSTRACT

IntroductionCoronavirus disease (COVID-19) may induce a hypercoagulable state, leading to microvascular and macrovascular thromboses, as shown in observational and autopsy studies (Giannis, Ziogas, and Gianni 2020;Carsana et al. 2020;Lax et al. 2020). Empiric therapeutic anticoagulation has been recommended by some authors (Barnes etal. 2020;Kollias et al. 2020). The risks and benefits of empiric therapeutic anticoagulation in COVID-19 is unclear and subject to further investigation. The objective of our observational study was to determine if there was a survival benefit with the empiric use of therapeutic anticoagulation in hospitalized patients with COVID-19 compared to prophylactic doses of anticoagulation.Materials and methodsWe performed a retrospective, multi-institutional cohort study of patients over the age of 18, admitted to hospital with COVID-19, between March 10, 2020, and May 3, 2020. We excluded patients who were discharged or died on the same or following day of hospital admission. Our 'exposed' group was defined as any patient who received therapeutic anticoagulation during the hospitalization, with low molecular weight heparin (LMWH), unfractionated heparin (UFH), direct-acting oral anticoagulants (DOAC) or warfarin. Our 'control' group consisted of patients who received a prophylactic dose of anticoagulation during their hospital stay.The primary endpoint was the time from admission to discharge or death. Patients without a primary endpoint event had their data censored on May 20, 2020. Cox proportional-hazards regression models were used to estimate the association between treatment and in-hospital mortality by adjusting for demographic and clinical factors. Before conducting the outcome analyses, multiple imputations (10 imputations) were performed for missing data. Due to the non-randomized nature of the study and the reduction of the effects of confounding, inverse probability weighting was utilized. Secondary objectives included requirement for intubation, duration of intubation, length of hospital stay, and readmission rates.ResultsA total of 1033 patients were included in the study. Among them, 381 patients (36.8%) received therapeutic doses of anticoagulation with UFH, LMWH, warfarin, or DOAC. The remaining 652 patients (63.1%) received prophylactic doses of anticoagulation. Baseline characteristics showed that the group with therapeutic anticoagulation had higher body mass index, higher rates of congestive heart failure, chronic obstructive pulmonary disease, coronary artery disease, and admission d-dimer levels (Table 1) and significantly higher mortality rate (28.6% vs. 20.2%;p=0.002) (Figure 1, survival curve). However, there was no difference in the risk of in-hospital mortality between the groups using unadjusted and adjusted Cox regressions (Table 2). No benefit was seen in the subgroup analysis of intubated patients as well. In addition, the exposed group had higher rates of intubation (13.3 % versus 7.7%;p = 0.01) and were more likely to be re-admitted (10.3% versus 5.2 %;p = 0.007;survivors only). Median length of stay was significantly longer in the exposed group (7 vs. 6 days;p=0.028;survivors only).ConclusionOur result showed that therapeutic anticoagulation in hospitalized COVID19 patients was not associated with a reduction in in-hospital mortality compared to prophylactic anticoagulation. In addition, patients in the fully anticoagulated group were intubated more often, had a longer length of stay, and higher readmission rate. Well-designed prospective randomized studies are needed to define the dose of anticoagulation in COVID 19 patients.LimitationRetrospective cohort design, as well as multi-institutional nature.

5.
Diagnostics (Basel) ; 11(6)2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1270018

ABSTRACT

Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including "RT-PCR or viral load", "SARS-CoV-2 and RT-PCR", "Ct value and viral load", "Ct value or COVID-19". Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.

6.
Pathogens ; 10(5)2021 May 07.
Article in English | MEDLINE | ID: covidwho-1224096

ABSTRACT

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection's outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

7.
Vaccines (Basel) ; 9(5)2021 Apr 29.
Article in English | MEDLINE | ID: covidwho-1217123

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines' molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.

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