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    Predicting clinical outcome with phenotypic clusters in COVID-19 pneumonia HP pneumonia MESHD: 2 an analysis of 12,066 hospitalized patients from the Spanish registry SEMI-3 COVID-19.

    Authors: Manuel Rubio-Rivas; Xavier Corbella; Jose Maria Mora-Lujan; Jose Loureiro Amigo; Almudena Lopez Sampalo; Carmen Yera Bergua; Pedro Jesus Esteve Atienzar; Luis Felipe Diez Garcia; Ruth Gonzalez Ferrer; Susana Plaza Canteli; Antia Perez Pineiro; Begona Cortes Rodriguez; Leyre Jorquer Vidal; Ignacio Perez Catalan; Marta Leon Tellez; Jose Angel Martin Oterino; Maria Candelaria Martin Gonzalez; Jose Luis Serrano Carrillo de Albornoz; Eva Garcia Sardon; Jose Nicolas Alcala Pedrajas; Anabel Martin Urda Diez Canseco; Maria Jose Esteban Giner; Pablo Telleria Gomez; Ricardo Gomez Huelgas; Jose Manuel Ramos Rincon; Nina la Cour Freiesleben; Henriette Svarre Nielsen

    doi:10.1101/2020.09.14.20193995 Date: 2020-09-15 Source: medRxiv

    (1) Background: This study aims to identify different clinical phenotypes in COVID-19 88 pneumonia HP pneumonia MESHD using cluster analysis and to assess the prognostic impact among identified clusters in 89 such patients. (2) Methods: Cluster analysis including 11 phenotypic variables was performed in a 90 large cohort of 12,066 COVID-19 patients, collected and followed-up from March 1, to July 31, 2020, 91 from the nationwide Spanish SEMI-COVID-19 Registry. (3) Results: Of the total of 12,066 patients 92 included in the study, most were males TRANS (7,052, 58.5%) and Caucasian (10,635, 89.5%), with a mean 93 age TRANS at diagnosis of 67 years (SD 16). The main pre-admission comorbidities were arterial 94 hypertension HP hypertension MESHD (6,030, 50%), hyperlipidemia HP hyperlipidemia MESHD (4,741, 39.4%) and diabetes mellitus HP diabetes mellitus MESHD (2,309, 19.2%). The 95 average number of days from COVID-19 symptom onset TRANS to hospital admission was 6.7 days (SD 7). 96 The triad of fever HP fever MESHD, cough HP cough MESHD, and dyspnea HP dyspnea MESHD was present almost uniformly in all 4 clinical phenotypes 97 identified by clustering. Cluster C1 (8,737 patients, 72.4%) was the largest, and comprised patients 98 with the triad alone. Cluster C2 (1,196 patients, 9.9%) also presented with ageusia and anosmia MESHD anosmia HP; 99 cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache HP headache MESHD, and sore throat; and cluster C4 100 (1,253 patients, 10.4%) also manifested with diarrhea HP diarrhea MESHD, vomiting HP vomiting MESHD, and abdominal pain HP abdominal pain MESHD. Compared to 101 each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 102 18.6%; p<0.001). The multivariate study identified phenotypic clusters as an independent factor for 103 in-hospital death. (4) Conclusion: The present study identified 4 phenotypic clusters in patients with 104 COVID-19 pneumonia HP pneumonia MESHD, which predicted the in-hospital prognosis of clinical outcomes.

    Trends in Covid-19 risk-adjusted mortality rates in a single health system

    Authors: Leora Horwitz; Simon A. Jones; Robert J. Cerfolio; Fritz Francois; Joseph Greco; Bret Rudy; Christopher M Petrilli; Ishan Paranjpe; Jessica K De Freitas; Tingyi Wanyan; Kipp W Johnson; Mesude Bicak; Eyal Klang; Young Joon Kwon; Anthony Costa; Shan Zhao; Riccardo Miotto; Alexander W Charney; Erwin Böttinger; Zahi A Fayad; Girish N Nadkarni; Fei Wang; Benjamin S Glicksberg; Laura J. Scott; Karen L. Mohlke; Kerrin S. Small

    doi:10.1101/2020.08.11.20172775 Date: 2020-08-14 Source: medRxiv

    Early reports showed high mortality from Covid-19; by contrast, the current outbreaks in the southern and western United States are associated with fewer deaths, raising hope that treatments have improved. However, in Texas for instance, 63% of diagnosed cases are currently under 50, compared to only 52% nationally in March-April. Current demographics in Arizona and Florida are similar. Therefore, whether decreasing Covid-19 mortality rates are a reflection of changing demographics or represent improvements in clinical care is unknown. We assessed outcomes over time in a single health system, accounting for changes in demographics and clinical factors. Methods We analyzed biweekly mortality rates for admissions between March 1 and June 20, 2020 in a single health system in New York City. Outcomes were obtained as of July 14, 2020. We included all hospitalizations with laboratory-confirmed Covid-19 disease. Patients with multiple hospitalizations (N=157, 3.3%) were included repeatedly if they continued to have laboratory-confirmed disease. Mortality was defined as in-hospital death MESHD or discharge to hospice care. Based on prior literature, we constructed a multivariable logistic regression model to generate expected risk of death MESHD, adjusting for age TRANS; sex; self-reported race and ethnicity; body mass index; smoking history; presence of hypertension HP hypertension MESHD, heart failure MESHD, hyperlipidemia HP hyperlipidemia MESHD, coronary artery disease MESHD, diabetes MESHD, cancer MESHD, chronic kidney disease HP chronic kidney disease MESHD, or pulmonary disease MESHD individually as dummy variables; and admission oxygen saturation, D-dimer, C reactive protein, ferritin, and cycle threshold for RNA detection. All data were obtained from the electronic health record. We then calculated the sum of observed and expected deaths in each two-week period and multiplied each period's observed/expected (O/E) risk by the overall average crude mortality to generate biweekly adjusted rates. We calculated Poisson control limits and indicated points outside the control limits as significantly different, following statistical process control standards. The NYU institutional review board approved the study and granted a waiver of consent. Results We included 4,689 hospitalizations, of which 4,661 (99.4%) had died or been discharged. The median age TRANS, and the proportion male TRANS or with any comorbidity decreased over time; median real-time PCR cycle threshold increased (indicating relatively less concentration of virus) (Table). For instance, median age TRANS decreased from 67 years in the first two weeks to 49 in the last two. Peak hospitalizations were during the fifth and sixth study weeks, which accounted for 40% of the hospitalizations. Median length of stay for patients who died or were discharged to hospice was 8 days (interquartile range, 4-16). Unadjusted mortality dropped each period, from 30.2% in the first two weeks to 3% in the last two weeks, with the last eight weeks being lower than the 95% control limits. Risk adjustment partially attenuated the mortality decline, but adjusted mortality rates in the second-to-last two weeks remained outside the control limits (Figure, Table). The O/E risk of mortality decreased from 1.07 (0.64-1.67) in the first two weeks to 0.39 (0.08-1.12) in the last two weeks. Discussion In this 16-week study of Covid-19 mortality at a single health system, we found that changes in demographics and severity of illness at presentation account for some, but not all, of the decrease in unadjusted mortality. Even after risk adjustment for a variety of clinical and demographic factors, mortality was significantly lower towards the end of the study period. Incremental improvements in outcomes are likely a combination of increasing clinical experience, decreasing hospital volume, growing use of new pharmacologic treatments (such as corticosteroids, remdesivir and anti-cytokine treatments), non-pharmacologic treatments (such as proning), earlier intervention, community awareness, and lower viral load exposure from increasing mask wearing and social distancing. It is also possible that earlier periods had a more virulent circulating strain. In summary, data from one health system suggest that Covid-19 remains a serious disease for high risk patients, but that outcomes may be improving.

    The natural history of symptomatic COVID-19 in Catalonia, Spain: a multi-state model including 109,367 outpatient diagnoses, 18,019 hospitalisations, and 5,585 COVID-19 deaths among 5,627,520 people

    Authors: Edward Burn; Cristian Tebe; Sergio Fernandez-Bertolin; Maria Aragon; Martina Recalde; Elena Roel; Albert Prats-Uribe; Daniel Prieto-Alhambra; Talita Duarte-Salles

    doi:10.1101/2020.07.13.20152454 Date: 2020-07-14 Source: medRxiv

    Background The natural history of Coronavirus Disease MESHD 2019 (COVID-19) has yet to be fully described, with most previous reports focusing on hospitalised patients. Using linked patient-level data, we set out to describe the associations between age TRANS, gender TRANS, and comorbidities and the risk of outpatient COVID-19 diagnosis, hospitalisation, and/or related mortality. Methods A population-based cohort study including all individuals registered in Information System for Research in Primary Care (SIDIAP). SIDIAP includes primary care records covering > 80% of the population of Catalonia, Spain, and was linked to region-wide testing, hospital and mortality records. Outpatient diagnoses of COVID-19, hospitalisations with COVID-19, and deaths with COVID-19 were identified between 1st March and 6th May 2020. A multi-state model was used, with cause-specific Cox survival models estimated for each transition. Findings A total of 5,664,652 individuals were included. Of these, 109,367 had an outpatient diagnosis of COVID-19, 18,019 were hospitalised with COVID-19, and 5,585 died after either being diagnosed or hospitalised with COVID-19. Half of those who died were not admitted to hospital prior to their death. Risk of a diagnosis with COVID-19 peaked first in middle- age TRANS and then again for oldest ages TRANS, risk for hospitalisation after diagnosis peaked around 70 years old, with all other risks highest at oldest ages TRANS. Male TRANS gender TRANS was associated with an increased risk for all outcomes other than outpatient diagnosis. The comorbidities studied (autoimmune condition, chronic kidney disease HP chronic kidney disease MESHD, chronic obstructive pulmonary disease HP chronic obstructive pulmonary disease MESHD, dementia HP dementia MESHD, heart disease MESHD, hyperlipidemia HP hyperlipidemia MESHD, hypertension HP hypertension MESHD, malignant neoplasm HP neoplasm MESHD, obesity HP obesity MESHD, and type 2 diabetes MESHD) were all associated with worse outcomes. Interpretation There is a continued need to protect those at high risk of poor outcomes, particularly the elderly TRANS, from COVID-19 and provide appropriate care for those who develop symptomatic disease. While risks of hospitalisation and death MESHD are lower for younger populations, there is a need to limit their role in community transmission TRANS. These findings should inform public health strategies, including future vaccination campaigns.

    COVID-19 among people living with HIV MESHD: A systematic review

    Authors: Hossein Mirzaei; Willi McFarland; Mohammad Karamouzian; Hamid Sharifi

    doi:10.1101/2020.07.11.20151688 Date: 2020-07-14 Source: medRxiv

    This systematic review summarizes the evidence on the earliest patients with COVID-19-HIV co-infection MESHD. We searched PubMed, Scopus, Web of Science, Embase, preprint databases, and Google Scholar from December 01, 2019 to June 1, 2020. From an initial 547 publications and 75 reports, 25 studies provided specific information on COVID-19 patients living with HIV MESHD. Studies described 252 patients, 80.9% were male TRANS, mean age TRANS was 52.7 years, and 98% were on ART. Co-morbidities in addition to HIV and COVID-19 (multimorbidity) included hypertension HP hypertension MESHD (39.3%), obesity HP obesity MESHD or hyperlipidemia HP (19.3%), chronic obstructive pulmonary disease HP chronic obstructive pulmonary disease MESHD (18.0%), and diabetes MESHD (17.2%). Two-thirds (66.5%) had mild to moderate symptoms, the most common being fever HP fever MESHD (74.0%) and cough HP (58.3%). Among patients who died, the majority (90.5%) were over 50 years old, male TRANS (85.7%), and had multimorbidity (64.3%). Our findings highlight the importance of identifying co-infections MESHD, addressing co-morbidities, and ensuring a secure supply of ART for PLHIV during the COVID-19 pandemic.

    Clinical, Behavioral and Social Factors Associated with Racial Disparities in Hospitalized and Ambulatory COVID-19 Patients from an Integrated Health Care System in Georgia

    Authors: Felipe Lobelo; Alan X Bienvenida; Serena Leung; Armand N Mbanya; Elizabeth J. Leslie; Kate E Koplan; S. Ryan Shin

    doi:10.1101/2020.07.08.20148973 Date: 2020-07-10 Source: medRxiv

    Introduction: Racial and ethnic minorities have shouldered a disproportioned burden of coronavirus disease MESHD 2019 (COVID-19) infection MESHD to date in the US, but data on the various drivers of these disparities is limited. Objectives: To describe the characteristics and outcomes of COVID-19 patients and explore factors associated with hospitalization risk by race. Methods: Case series of 448 consecutive patients with confirmed COVID-19 seen at Kaiser Permanente Georgia (KPGA), an integrated health care system serving the Atlanta metropolitan area, from March 3 to May 12, 2020. KPGA members with laboratory-confirmed COVID-19. Multivariable analyses for hospitalization risk also included an additional 3489 persons under investigation (PUI) with suspected infection MESHD. COVID-19 treatment and outcomes, underlying comorbidities and quality of care management metrics, socio-demographic and other individual and community-level social determinants of health (SDOH) indicators. Results: Of 448 COVID-19 positive members, 68,3% was non-Hispanic Black (n=306), 18% non-Hispanic White (n=81) and 13,7% Other race (n=61). Median age TRANS was 54 [IQR 43-63) years. Overall, 224 patients were hospitalized, median age TRANS 60 (50-69) years. Black race was a significant factor in the Confirmed + PUI, female TRANS and male TRANS models (ORs from 1.98 to 2.19). Obesity HP was associated with higher hospitalization odds in the confirmed, confirmed + PUI, Black and male TRANS models (ORs from 1.78 to 2.77). Chronic disease MESHD control metrics ( diabetes MESHD, hypertension HP hypertension MESHD, hyperlipidemia HP hyperlipidemia MESHD) were associated with lower odds of hospitalization ranging from 48% to 35% in the confirmed + PUI and Black models. Self-reported physical inactivity was associated with 50% higher hospitalization odds in the Black and Female TRANS models. Residence in the Northeast region of Atlanta was associated with lower hospitalization odds in the Confirmed + PUI, White and female TRANS models (ORs from 0.22 to 0.64) Conclusions: We found that non-Hispanic Black KPGA members had a disproportionately higher risk of infection TRANS risk of infection TRANS infection MESHD and, after adjusting for covariates, twice the risk of hospitalization compared to other race groups. We found no significant differences in clinical outcomes or mortality across race/ethnicity groups. In addition to age TRANS, sex and comorbidity burden, pre-pandemic self-reported exercise, metrics on quality of care and control of underlying cardio-metabolic diseases MESHD, and location of residence in Atlanta were significantly associated with hospitalization risk by race groups. Beyond well-known physiologic and clinical factors, individual and community-level social indicators and health behaviors must be considered as interventions designed to reduce COVID-19 disparities and the systemic effects of racism are implemented.

    Association of hyperlipidemia HP hyperlipidemia MESHD and statin use with severity of COVID-19

    Authors: Wilnard YT Tan; Barnaby E Young; David Chien Lye; Daniel EK Chew; Rinkoo Dalan

    doi:10.21203/rs.3.rs-40008/v1 Date: 2020-07-03 Source: ResearchSquare

    Background and Aims: We aim to study the association of  hyperlipidemia MESHD and statin use with COVID-19 severity.Methods: We analysed a retrospective cohort of 717 patients admitted to a tertiary centre in Singapore for COVID-19 infection MESHD. Clinical outcomes of interest were oxygen saturation ≤94% requiring supplemental oxygen, intensive-care unit (ICU) admission , invasive mechanical-ventilation and death. Logistic regression models were used to study the  association between hyperlipidemia HP hyperlipidemia MESHD and clinical outcomes adjusted for age TRANS, gender TRANS and ethnicity.  Statin treatment effect was determined , in a nested case-control design, through logistic treatment models with 1:3 propensity matching for age TRANS, gender TRANS and ethnicity. All statistical tests were two-sided, and statistical significance was taken as p < 0.05.Results: One hundred fifty-six (21.8%) patients had hyperlipidemia HP hyperlipidemia MESHD and 97% were on statins. There were no significant associations between hyperlipidemia HP hyperlipidemia MESHD and clinical outcomes. Logistic treatment models showed a lower chance of ICU admission for statin users when compared to non-statin users (ATET: b-0.12(-0.23,-0.01); p=0.028). There were no other significant differences in other outcomes.Conclusion: Treated hyperlipidemia HP hyperlipidemia MESHD was not an independent risk factor for severe COVID-19. Statin use independently associated with lower ICU admission. This supports current practice to continue prescription of statins in COVID-19 patients.

    A tertiary center experience of multiple myeloma HP multiple myeloma MESHD patients with COVID-19: lessons learned and the path forward

    Authors: Bo Wang; Oliver Van Oekelen; Tarek Mouhieddine; Diane Marie Del Valle; Joshua Richter; Hearn Jay Cho; Shambavi Richard; Ajai Chari; Sacha Gnjatic; Miriam Merad; Sundar Jagannath; Samir Parekh; Deepu Madduri

    doi:10.1101/2020.06.04.20122846 Date: 2020-06-05 Source: medRxiv

    Background: The COVID-19 pandemic, caused by SARS-CoV-2 virus, has resulted in over 100,000 deaths in the United States. Our institution has treated over 2,000 COVID-19 patients during the pandemic in New York City. The pandemic directly impacted cancer MESHD patients and the organization of cancer MESHD care. Mount Sinai Hospital has a large and diverse multiple myeloma HP myeloma MESHD ( MM MESHD) population. Herein, we report the characteristics of COVID-19 infection MESHD and serological response in MM MESHD patients in a large tertiary care institution in New York. Methods: We performed a retrospective study on a cohort of 58 patients with a plasma SERO-cell disorder (54 MM MESHD, 4 smoldering MM MESHD) who developed COVID-19 between March 1, 2020 and April 30, 2020. We report epidemiological, clinical and laboratory characteristics including persistence of viral detection by polymerase chain reaction (PCR) and anti- SARS-CoV-2 antibody SERO testing, treatments initiated, and outcomes. Results: Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age TRANS was 67 years; 52% of patients were male TRANS and 63% were non-white. Hypertension HP Hypertension MESHD (64%), hyperlipidemia HP hyperlipidemia MESHD (62%), obesity HP obesity MESHD (37%), diabetes mellitus HP diabetes mellitus MESHD (28%), chronic kidney disease HP chronic kidney disease MESHD (24%) and lung disease MESHD (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age TRANS (>70 years), male TRANS sex, cardiovascular risk, and patients not in complete remission (CR) or stringent CR were significantly (p<0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p<0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia MESHD, non-white race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 SERO at a median of 32 days after initial diagnosis. Median time to PCR negativity was 43 (range 19-68) days from initial positive PCR. Conclusions: Drug exposure and MM MESHD disease status at the time of contracting COVID-19 had no bearing on mortality. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia MESHD were associated with higher mortality. The majority of patients mounted an antibody SERO response to SARS-CoV-2. These findings pave a path to identification of vulnerable MM MESHD patients who need early intervention to improve outcome in future outbreaks of COVID-19.

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