Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study

Abstract COVID-19 has caused a major global pandemic and necessitated unprecedented public health restrictions in almost every country. Understanding risk factors for severe disease in hospitalised patients is critical as the pandemic progresses. This observational cohort study aimed to characterise the independent associations between the clinical outcomes of hospitalised patients and their demographics, comorbidities, blood tests and bedside observations. All patients admitted to Northwick Park Hospital, London, UK between 12 March and 15 April 2020 with COVID-19 were retrospectively identified. The primary outcome was death. Associations were explored using Cox proportional hazards modelling. The study included 981 patients. The mortality rate was 36.0%. Age (adjusted hazard ratio (aHR) 1.53), respiratory disease (aHR 1.37), immunosuppression (aHR 2.23), respiratory rate (aHR 1.28), hypoxia (aHR 1.36), Glasgow Coma Scale <15 (aHR 1.92), urea (aHR 2.67), alkaline phosphatase (aHR 2.53), C-reactive protein (aHR 1.15), lactate (aHR 2.67), platelet count (aHR 0.77) and infiltrates on chest radiograph (aHR 1.89) were all associated with mortality. These important data will aid clinical risk stratification and provide direction for further research.

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Title: Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study

10.1101/2020.09.24.20200337 ◽

2020 ◽

Author(s):

Jack W Goodall ◽

Thomas A N Reed ◽

Maddalena Ardissino ◽

Paul Bassett ◽

Ashley M Whittington ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Proportional Hazards ◽

Severe Disease ◽

Cox Proportional Hazards ◽

Hospitalized Patients ◽

Reactive Protein ◽

Global Pandemic ◽

Northwick Park Hospital ◽

Observational Cohort

COVID-19 has caused a major global pandemic and necessitated unprecedented public health restrictions in almost every country. Understanding risk factors for severe disease in hospitalized patients is critical as the pandemic progresses. This observational cohort study aimed to characterize the independent associations between the clinical outcomes of hospitalized patients and their demographics, comorbidities, blood tests and bedside observations. All patients admitted to Northwick Park Hospital, London, United Kingdom between 12 March and 15 April 2020 with COVID-19 were retrospectively identified. The primary outcome was death. Associations were explored using Cox proportional hazards modelling. The study included 981 patients. The mortality rate was 36.0%. Age (adjusted hazard ratio (aHR) 1.53), respiratory disease (aHR 1.37), immunosuppression (aHR 2.23), respiratory rate (aHR 1.28), hypoxia (aHR 1.36), Glasgow Coma Score <15 (aHR 1.92), urea (aHR 2.67), alkaline phosphatase (aHR 2.53), C-reactive protein (aHR 1.15), lactate (aHR 2.67), platelet count (aHR 0.77) and infiltrates on chest radiograph (aHR 1.89) were all associated with mortality. These important data will aid clinical risk stratification and provide direction for further research.

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Fibrosis-4 index as a predictor for mortality in hospitalised patients with COVID-19: a retrospective multicentre cohort study

BMJ Open ◽

10.1136/bmjopen-2020-041989 ◽

2020 ◽

Vol 10 (11) ◽

pp. e041989

Author(s):

Jung Gil Park ◽

Min Kyu Kang ◽

Yu Rim Lee ◽

Jeong Eun Song ◽

Na Young Kim ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Hospital Mortality ◽

Proportional Hazards ◽

Severe Infection ◽

Cox Proportional Hazards ◽

Respiratory Support ◽

Hospitalised Patients ◽

Multicentre Cohort Study ◽

Multicentre Cohort

ObjectiveThe reliable risk factors for mortality of COVID-19 has not evaluated in well-characterised cohort. This study aimed to identify risk factors for in-hospital mortality within 56 days in patients with severe infection of COVID-19.DesignRetrospective multicentre cohort study.SettingFive tertiary hospitals of Daegu, South Korea.Participants1005 participants over 19 years old confirmed COVID-19 using real-time PCR from nasopharyngeal and oropharyngeal swabs.MethodsThe clinical and laboratory features of patients with COVID-19 receiving respiratory support were analysed to ascertain the risk factors for mortality using the Cox proportional hazards regression model. The relationship between overall survival and risk factors was analysed using the Kaplan-Meier method.OutcomeIn-hospital mortality for any reason within 56 days.ResultsOf the 1005 patients, 289 (28.8%) received respiratory support, and of these, 70 patients (24.2%) died. In multivariate analysis, high fibrosis-4 index (FIB-4; HR 2.784), low lymphocyte count (HR 0.480), diabetes (HR 1.917) and systemic inflammatory response syndrome (HR 1.714) were found to be independent risk factors for mortality in patients with COVID-19 receiving respiratory support (all p<0.05). Regardless of respiratory support, survival in the high FIB-4 group was significantly lower than in the low FIB-4 group (28.8 days vs 44.0 days, respectively, p<0.001). A number of risk factors were also significantly related to survival in patients with COVID-19 regardless of respiratory support (0–4 risk factors, 50.2 days; 49.7 days; 44.4 days; 32.0 days; 25.0 days, respectively, p<0.001).ConclusionFIB-4 index is a useful predictive marker for mortality in patients with COVID-19 regardless of its severity.

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Characteristics, outcomes and risk factors for mortality of 522 167 patients hospitalised with COVID-19 in Brazil: a retrospective cohort study

BMJ Open ◽

10.1136/bmjopen-2021-049089 ◽

2021 ◽

Vol 11 (5) ◽

pp. e049089

Author(s):

Marcia C Castro ◽

Susie Gurzenda ◽

Eduardo Marques Macário ◽

Giovanny Vinícius A França

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Cox Proportional Hazards ◽

Secondary Outcome ◽

Hospital Death ◽

Factors Associated ◽

Icu Admission ◽

Hospitalised Patients

ObjectiveTo provide a comprehensive description of demographic, clinical and radiographic characteristics; treatment and case outcomes; and risk factors associated with in-hospital death of patients hospitalised with COVID-19 in Brazil.DesignRetrospective cohort study of hospitalised patients diagnosed with COVID-19.SettingData from all hospitals across Brazil.Participants522 167 hospitalised patients in Brazil by 14 December 2020 with severe acute respiratory illness, and a confirmed diagnosis for COVID-19.Primary and secondary outcome measuresPrevalence of symptoms and comorbidities was compared by clinical outcomes and intensive care unit (ICU) admission status. Survival was assessed using Kaplan Meier survival estimates. Risk factors associated with in-hospital death were evaluated with multivariable Cox proportional hazards regression.ResultsOf the 522 167 patients included in this study, 56.7% were discharged, 0.002% died of other causes, 30.7% died of causes associated with COVID-19 and 10.2% remained hospitalised. The median age of patients was 61 years (IQR, 47–73), and of non-survivors 71 years (IQR, 60–80); 292 570 patients (56.0%) were men. At least one comorbidity was present in 64.5% of patients and in 76.8% of non-survivors. From illness onset, the median times to hospital and ICU admission were 6 days (IQR, 3–9) and 7 days (IQR, 3–10), respectively; 15 days (IQR, 9–24) to death and 15 days (IQR, 11–20) to hospital discharge. Risk factors for in-hospital death included old age, Black/Brown ethnoracial self-classification, ICU admission, being male, living in the North and Northeast regions and various comorbidities. Age had the highest HRs of 5.51 (95% CI: 4.91 to 6.18) for patients≥80, compared with those ≤20.ConclusionsCharacteristics of patients and risk factors for in-hospital mortality highlight inequities of COVID-19 outcomes in Brazil. As the pandemic continues to unfold, targeted policies that address those inequities are needed to mitigate the unequal burden of COVID-19.

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Lymphedema in Endometrial Cancer Survivor: A Nationwide Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10204647 ◽

2021 ◽

Vol 10 (20) ◽

pp. 4647

Author(s):

Su-Jeong Lee ◽

Jun-Pyo Myong ◽

Yun-Hee Lee ◽

Eui-Jin Cho ◽

Sung-Jong Lee ◽

...

Keyword(s):

Risk Factors ◽

Health Care ◽

Endometrial Cancer ◽

Cohort Study ◽

Proportional Hazards ◽

Gynecological Cancer ◽

Risk Groups ◽

Developed Countries ◽

Cox Proportional Hazards ◽

Health Care Resources

Background: Endometrial cancer is the most common gynecological cancer in developed countries. Treatment-related lymphedema negatively affects the quality of life and function of patients. This study investigated the cumulative incidence and risk factors of, and utilization of health care resources for, lymphedema in patients with endometrial cancer. Methods: We conducted a nationwide, retrospective cohort study of women with endometrial cancer who underwent cancer-direct treatment using the Korean National Health Insurance Service (NHIS) database. Patients were categorized by age, region, income, and treatment modality. Cox proportional hazards regression models were used to analyze the incidence and risk factors of lymphedema. We also analyzed utilization of health care resources for lymphedema using diagnostic and treatment claim codes. Results: A total of 19,027 patients with endometrial cancer were evaluated between January 2004 and December 2017. Among them, 2493 (13.1%) developed lymphedema. Age (<40 years, adjusted odds ratio [aOR] = 1 vs. 40–59 years, aOR = 1.413; 95% confidence interval (CI) 1.203–1.66 vs. 60+ years, aOR = 1.472; 95% CI 1.239–1.748) and multimodal treatment (surgery only, aOR = 1 vs. surgery + radiation + chemotherapy, aOR = 2.571; 95% CI 2.27–2.912) are considered to be possible risk factors for lymphedema in patients with endometrial cancer (p < 0.001). The utilization of health care resources for the treatment of lymphedema has increased over the years. Conclusions: Lymphedema is a common complication affecting women with endometrial cancer and leads to an increase in national healthcare costs. Post-treatment surveillance of lymphedema, especially in high-risk groups, is needed.

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Routine Use of Immunosuppressants is Associated with Mortality in Hospitalised Patients with COVID-19

10.21203/rs.3.rs-40131/v1 ◽

2020 ◽

Author(s):

Phyo K Myint ◽

Ben Carter ◽

Fenella Barlow-Pay ◽

Roxanna Short ◽

Alice G Einarsson ◽

...

Keyword(s):

Proportional Hazards ◽

Reference Group ◽

Cox Proportional Hazards ◽

Close Monitoring ◽

Specific Patient ◽

Covariate Data ◽

Logistic Regression Models ◽

Hospitalised Patients ◽

Observational Cohort ◽

Study Population

Abstract Background: Whilst there is literature on impact of the SARS viruses in the severely immunosuppressed, and those who develop exaggerated immune response, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations.Methods: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, carried out in UK and Italy. Data were collected between 27th February and 28th April 2020 by trained data collectors and included all unselected consecutive admissions with Covid-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. The primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge (length of stay). Data were analysed with mixed-effects, Cox proportional hazards and Logistic regression models using non-users of immunosuppressants as the reference group.Results: 1184 patients were eligible for inclusion. The median (IQR) age was 74(62-83), 676(57%) were male, and 299(25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113(~10%) were on immunosuppressants. We found that any immunosuppressant use was associated with increased mortality: aHR 1.87,95%CI:1.30,2.69 (time to mortality) and aOR1.71,95%CI:1.01-2.88 (14-day mortality). There also appeared to be a dose-response relationship.Conclusion: Despite the possibility of indication bias, until further evidence emerges we recommend adhering to public health measures stringently, a low threshold to seek medical advice and close monitoring of worsening symptoms in those who take immunosuppressants routinely regardless of their indication.

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Association Between Severity of Leptospirosis and Subsequent Major Autoimmune Diseases: A Nationwide Observational Cohort Study

Frontiers in Immunology ◽

10.3389/fimmu.2021.721752 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chih-Chung Chen ◽

Yao-Min Hung ◽

Lu-Ting Chiu ◽

Mei-Chia Chou ◽

Renin Chang ◽

...

Keyword(s):

Sensitivity Analysis ◽

Cohort Study ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Proportional Hazards ◽

Age Groups ◽

Cox Proportional Hazards ◽

Observational Cohort Study ◽

Research Database ◽

Observational Cohort

IntroductionInfections play a role in autoimmune diseases (AD). Leptospirosis has been linked to the trigger of systemic lupus erythematosus.ObjectiveTo investigate subsequent risk of major AD in hospitalized Taiwanese for Leptospirosis.MethodsRetrospective observational cohort study was employed. The enrolled period was from 2000 to 2012. In the main model, we extracted 4026 inpatients with leptospirosis from the Taiwan National Health Insurance Research Database (NHIRD) and 16,104 participants without leptospirosis at a 1:4 ratio propensity-score matched (PSM) by age, gender, index year, and comorbidities. The follow-up period was defined as the time from the initial diagnosis of leptospirosis to major AD occurrence or 2013. This study was re-analyzed by frequency-matching as a sensitivity analysis for cross-validation. Univariable and multivariable Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsThe adjusted HR (95% CI) of major ADs for the leptospirosis group was 4.45 (3.25–6.79) (p < 0.001) compared to the controls after full adjustment. The risk of major ADs was 5.52-fold (95% CI, 3.82–7.99) higher in leptospirosis patients hospitalized for seven days and above than the controls, while 2.80-fold (95% CI, 1.68–5.61) in those hospitalized less than seven days. The sensitivity analysis yields consistent findings. Stratified analysis revealed that the association between leptospirosis and major ADs was generalized in both genders, and all age groups.ConclusionsSymptomatic leptospirosis is associated with increased rate of subsequent major ADs, and the risk seems to be higher in severe cases.

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Clinical course and risk factors of fatal adverse outcomes in COVID-19 patients in Korea: a nationwide retrospective cohort study

Scientific Reports ◽

10.1038/s41598-021-89548-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Juhyun Song ◽

Dae Won Park ◽

Jae-hyung Cha ◽

Hyeri Seok ◽

Joo Yeong Kim ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Retrospective Cohort ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Cox Proportional Hazards Model ◽

Icu Admission ◽

Hazards Model

AbstractWe investigated association between epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients and clinical outcomes in Korea. This nationwide retrospective cohort study included 5621 discharged patients with COVID-19, extracted from the Korea Disease Control and Prevention Agency (KDCA) database. We compared clinical data between survivors (n = 5387) and non-survivors (n = 234). We used logistic regression analysis and Cox proportional hazards model to explore risk factors of death and fatal adverse outcomes. Increased odds ratio (OR) of mortality occurred with age (≥ 60 years) [OR 11.685, 95% confidence interval (CI) 4.655–34.150, p < 0.001], isolation period, dyspnoea, altered mentality, diabetes, malignancy, dementia, and intensive care unit (ICU) admission. The multivariable regression equation including all potential variables predicted mortality (AUC = 0.979, 95% CI 0.964–0.993). Cox proportional hazards model showed increasing hazard ratio (HR) of mortality with dementia (HR 6.376, 95% CI 3.736–10.802, p < 0.001), ICU admission (HR 4.233, 95% CI 2.661–6.734, p < 0.001), age ≥ 60 years (HR 3.530, 95% CI 1.664–7.485, p = 0.001), malignancy (HR 3.054, 95% CI 1.494–6.245, p = 0.002), and dyspnoea (HR 1.823, 95% CI 1.125–2.954, p = 0.015). Presence of dementia, ICU admission, age ≥ 60 years, malignancy, and dyspnoea could help clinicians identify COVID-19 patients with poor prognosis.

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Risk Factors and Blood Pressure Control Targets Associated With the Clinical Outcome of Elderly COVID-19 Patients With Hypertension: a Retrospective Cohort Study

10.21203/rs.3.rs-711780/v1 ◽

2021 ◽

Author(s):

Ting Li ◽

Maomao Wang ◽

Yifei Wang ◽

Pei Zhang ◽

Yang Wang ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Cohort Study ◽

Clinical Outcome ◽

Retrospective Cohort ◽

Proportional Hazards ◽

Pressure Control ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Blood Pressures

Abstract Background: COVID-19 is a global pandemic, especially among the elderly. Our study aimed to explore the risk factors and identify the blood pressure control targets associated with the clinical outcome of elderly COVID-19 patients with hypertension. Methods: In this retrospective cohort study, elderly COVID-19 patients who were admitted to Wuhan Huoshenshan Hospital from February 8 to 17, 2020 was included. Demographic, medical history, clinical data, and laboratory test data were collected from medical records. The adverse clinical outcomes were intensive care unit (ICU) admission and death. Difference between hypertension and non-hypertension groups were compared. Hypertension group were further divided into 3 subgroups according to their maximum blood pressures. Kaplan–Meier (K–M) method was used to find the differences both between hyperntesion and non-hypertension groups, and among the 3 hypertension subgroups. Univariable and multivariable Cox proportional hazards regression model were used to find risk factors.Results: All 133 elderly COVID-19 patients (79 patients with hypertension) were included. (1) Univariate analysis between hypertension and non-hypertension patients showed most laboratory tests were significantly (P < 0.05, or P < 0.01), particularly in adverse clinical outcomes (32.91% vs 7.41% at 30 days, P < 0.05). (2) Multivariate Cox proportional hazards models confirmed hypertension (HR 3.202, 95% CI:1.164 - 8.807) were the most important independent risk factors of outcomes in elderly patients, as well as low lymphocyte count, while the statistical difference of other values diminished. (3) Hypertension group were further divided into 3 subgroups according to their maximum blood pressures. K-M analysis showed maximum systolic blood pressure (SBP) ≥160mmHg subgroup (P < 0.01) and maximum blood pressure (DBP) ≥90mmHg subgroup (P < 0.05) experienced more adverse outcomes than others. (4) Multivariate Cox-proportional hazard model confirmed that maximum SBP≥160mmHg and maximum DBP ≥90mmHg were risk factors (HR 8.279, 95% CI: 1.346, 50.914; HR 5.080, 95% CI: 1.606,16.071; respectively). Conclusions: Hypertension is the most important independent risk factor of adverse outcomes in elderly COVID-19 patients, controlling the maximum blood pressure levels under 160/90 mmHg will decrease large part risks of adverse outcomes, the first week are key treatment period for patient prognosis.

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The challenge of managing severe delirium: an observational study of the effects of pharmacological and supportive care on delirium duration and resolution in 602 patients

10.21203/rs.2.18810/v1 ◽

2019 ◽

Author(s):

Carl Moritz Zipser ◽

Peter Hayoz ◽

Silvana Knöpfel ◽

Peter Peyk ◽

Maria Schubert ◽

...

Keyword(s):

Clinical Practice ◽

Supportive Care ◽

Proportional Hazards ◽

Dual Therapy ◽

Estimating Equation ◽

Cox Proportional Hazards ◽

Routine Clinical Practice ◽

Hospitalised Patients ◽

Observational Cohort ◽

Management Approaches

Abstract Background: Delirium is the most common neuropsychiatric disorder seen in hospitalised patients. Current guidelines recommend only using antipsychotics with distressed patients. Nonetheless, in routine clinical practice, multiple psychotropics are commonly administered. More evidence on the short-term benefits of various management approaches in patients with delirium is required. Methods: In this observational cohort study, 602 delirious patients were followed for twenty days. Supportive care was provided to all patients in addition to either no psychotropic therapy, monotherapy, dual therapy, or polytherapy defined as three or more psychotropic drugs. The effectiveness of interventions regarding delirium resolution and symptom severity was determined by Cox proportional hazards regression and generalized estimating equation models. Results: Psychotropics were commonly used to manage delirium. In total, 12.1% of patients received polytherapy, 37.2% dual therapy, 37.7% monotherapy, and 12.1% supportive care alone (i.e., almost half of the patients received ≥ two psychotropics). Patients who received polytherapy had higher initial baseline delirium severity and exposed the mixed subtype more often; with the latter delirium lasted longer and recovery was less frequent than in mild delirium. Providing supportive care alone in mild delirium was superior to all psychotropic approaches. Conclusions: In routine clinical practice, the use of multiple psychotropics is common. In our study, however, despite combined supportive management and polypharmacy, patients with severe delirium suffer longer from delirium and have lower resolution rates. For the management of patients with mild delirium supportive care alone can be considered. When psychotropics are considered, single psychotropics and dose optimisation are recommended. These findings underline the challenge of managing severe delirium.

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Risk factors for the recurrence of relapsing polychondritis

10.21203/rs.3.rs-808558/v1 ◽

2021 ◽

Author(s):

Tsuneyasu Yoshida ◽

Hajime Yoshifuji ◽

Mirei Shirakashi ◽

Akiyoshi Nakakura ◽

Kosaku Murakami ◽

...

Keyword(s):

Risk Factors ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Relapsing Polychondritis ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

C Reactive Protein ◽

Reactive Protein ◽

Initial Recurrence ◽

Pre Treatment

Abstract Background Although the survival rates of relapsing polychondritis (RP) have increased remarkably, the high recurrence rate remains a significant concern for physicians and patients. This retrospective study aimed to investigate the risk factors for RP recurrence. Methods Patients with RP who presented to Kyoto University Hospital from January 2000 to March 2020 and fulfilled Damiani's classification criteria were included. Patients were classified into recurrence and non-recurrence groups. Risk factors for RP recurrence were analysed using a Cox proportional hazards model, and Kaplan–Meier survival curves were drawn. Results Thirty-four patients were included. Twenty-five patients (74%) experienced 64 recurrences (mean: 2.56 recurrences per patients). The median duration before the first recurrence was 202 [55 − 382] days. The median prednisolone dose at the initial recurrence was 10 [5 − 12.75] mg/day. Tracheal involvement was significantly more frequent in the recurrence group at the initial presentation (44.0% vs. 0.0%, p = 0.0172) than in the non-recurrence group, and pre-treatment C-reactive protein levels were significantly high (4.7 vs 1.15 mg/dL, p = 0.0024). The Cox proportional hazards model analysis revealed that tracheal involvement (HR 4.266 [1.535 − 13.838], p = 0.0048), pre-treatment C-reactive protein level (HR 1.166 [1.040 − 1.308], p = 0.0085), and initial prednisolone monotherapy (HR 4.443 [1.515 − 16.267], p = 0.0056) may be associated with recurrence. The median time before the initial recurrence was significantly longer in patients who received combination therapy with prednisolone and immunosuppressants or biologics (400 vs 70 days, p = 0.0015). Conclusions Tracheal involvement, pre-treatment C-reactive protein level, and initial prednisolone monotherapy were risk factors for recurrence in patients with RP. Initial combination therapy with prednisolone and immunosuppressants may delay recurrence.

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