Giving a voice to adults with COVID-19: An analysis of open-ended comments from smell longhaulers and non-longhaulers (preprint)

Smell disorders are commonly reported with COVID-19 infection. Some patients show prolonged smell-related issues, even after the respiratory symptoms are resolved. To explore the concerns of patients, and to provide an overview for each specific smell disorder, we explored the longitudinal survey that was conducted by 1, and contained self-reports on the changes of smell that participants experienced at two time points. People who still suffered from smell disorders at the second time point, hence named longhaulers, were compared to those who were not, hence named non-longhaulers. Specifically, three aims were pursued in this study. First, to classify smell disorders based on the participants self-reports. Second, to classify the sentiment of each self-report using a machine learning approach, and third, to find specific keywords that best describe the smell dysfunction in those self-reports. We found that the prevalence of parosmia and hyposmia was higher in longhaulers than in non-longhaulers. Furthermore, the results suggest that longhaulers stated self-reports with more negative sentiment than non-longhaulers. Finally, we found specific keywords that were more typical for either longhaulers compared to non-longhaulers. Taken together, our work shows consistent findings with previous studies, while at the same time, provides new insights for future studies investigating smell disorders.

Spatiotemporal Accessibility of COVID-19 Healthcare Facilities in Jakarta, Indonesia

During the first year of the COVID-19 pandemic in Jakarta, Indonesia, the government designated some hospitals as specific COVID-19 healthcare centers to meet demand and ensure accessibility. However, the policy demand evaluation was based on a purely spatial approach. Studies on accessibility to healthcare are widely available, but those that consider temporal as well as spatial dynamics are lacking. This study aims to analyze the spatiotemporal dynamics of healthcare accessibility against COVID-19 cases within the first year of the COVID-19 pandemic, and the overall pattern of spatiotemporal accessibility. A two-step floating catchment area (2SFCA) was used to analyze the accessibility of COVID-19 healthcare against the monthly data of the COVID-19 infected population, as the demand. Such a spatiotemporal approach to 2SFCA has never been used in previous studies. Furthermore, rather than the traditional buffer commonly used to define catchments, the 2SFCA in this study was improved with automated delineation based on the road network using ArcGIS Service Areas Analysis tools. The accessibility tends to follow the distance decay principle, which is relatively high in the city's center and low in the outskirts. This contrasts with the city's population distribution, which is higher on the outskirts and lower in the center. This research is a step toward optimizing the spatial distribution of hospital locations to correspond with the severity of the pandemic condition. One method to stop the transmission of disease during a pandemic that requires localizing the infected patient is to designate specific healthcare facilities to manage the sick individuals. 'What-if' scenarios may be used to experiment with the locations of these healthcare facilities, which are then assessed using the methodology described in this work to obtain the distribution that is most optimal.

Lipoprotein(a), venous thromboembolism and COVID-19: A pilot study.

BACKGROUND AND AIMS: Thrombosis is a major driver of adverse outcome and mortality in patients with Coronavirus disease 2019 (COVID-19). Hypercoagulability may be related to the cytokine storm associated with COVID-19, which is mainly driven by interleukin (IL)-6. Plasma lipoprotein(a) [Lp(a)] levels increase following IL-6 upregulation and Lp(a) has anti-fibrinolytic properties. This study investigated whether Lp(a) elevation may contribute to the pro-thrombotic state hallmarking COVID-19 patients. METHODS: Lp(a), IL-6 and C-reactive protein (CRP) levels were measured in 219 hospitalized patients with COVID-19 and analyzed with linear mixed effects model. The baseline biomarkers and increases during admission were related to venous thromboembolism (VTE) incidence and clinical outcomes in a Kaplan-Meier and logistic regression analysis. RESULTS: Lp(a) levels increased significantly by a mean of 16.9 mg/dl in patients with COVID-19 during the first 21 days after admission. Serial Lp(a) measurements were available in 146 patients. In the top tertile of Lp(a) increase, 56.2% of COVID-19 patients experienced a VTE event compared to 18.4% in the lowest tertile (RR 3.06, 95% CI 1.61-5.81; p < 0.001). This association remained significant after adjusting for age, sex, IL-6 and CRP increase and number of measurements. Increases in IL-6 and CRP were not associated with VTE. Increase in Lp(a) was strongly correlated with increase in IL-6 (r = 0.44, 95% CI 0.30-0.56, p < 0.001). CONCLUSIONS: Increases in Lp(a) levels during the acute phase of COVID-19 were strongly associated with VTE incidence. The acute increase in anti-fibrinolytic Lp(a) may tilt the balance to VTE in patients hospitalized for COVID-19.

Increasing incidence of parosmia and phantosmia in patients recovering from COVID-19 smell loss (preprint)

ImportanceSudden smell loss is a specific early symptom of COVID-19, with an estimated prevalence of ~40% to 75%. Smell impairment affects physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. ObjectiveTo characterize smell function and recovery up to 11 months post COVID-19 infection. Settings, ParticipantsThis longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial respiratory symptoms, chemosensory function and COVID-19 diagnosis survey (S1) between April and September 2020 and completed a follow-up survey (S2) between September 2020 and February 2021; 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. Main Outcomes & MeasuresPrimary outcomes are ratings of smell and taste function on a visual analog scale, and self-report of parosmia (smell distortions) and phantosmia (unexplained smells). Secondary outcomes include a checklist of other COVID-19 symptoms. ResultsOn follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID. During COVID-19 illness, the ability to smell was slightly lower among those who did not recover their pre-illness ability to smell at S2. Conclusions and RelevanceWhile smell loss improves for many individuals who lost it due to COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is also associated with wider COVID-19 symptoms and may persist for many months after COVID-19 onset. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long term sequelae; more research into treatment options is strongly warranted given that conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health. Trial registrationThis project was pre-registered at OSF: https://osf.io/3e6zc. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/21262763v2_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@b2aceforg.highwire.dtl.DTLVardef@77a539org.highwire.dtl.DTLVardef@1004dbborg.highwire.dtl.DTLVardef@ef5c9c_HPS_FORMAT_FIGEXP M_FIG C_FIG Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the characteristics of smell and taste recovery of COVID-19 patients? FindingsIn this preregistered observational study of 1,468 participants, smell loss is associated with a higher number of COVID-19 symptoms, and may persist for at least 11 months following disease onset. While a majority of participants report quantitative improvement in their ability to smell, the prevalence of parosmia and phantosmia increases substantially at follow-up. Taste recovers faster than smell, suggesting taste and smell recover separately and can be distinguished by the respondents. MeaningOlfactory dysfunction appears to be a component of long-COVID, with parosmia as a prominent symptom in almost half of those with smell loss. More research into treatment is needed, especially given that olfactory dysfunction is associated with depression and loss of appetite. Health professionals should be aware of these common and long lasting effects.

Cardiovascular risk factors and COVID-19 outcomes in hospitalised patients: a prospective cohort study.

OBJECTIVES: Recent reports suggest a high prevalence of hypertension and diabetes in COVID-19 patients, but the role of cardiovascular disease (CVD) risk factors in the clinical course of COVID-19 is unknown. We evaluated the time-to-event relationship between hypertension, dyslipidaemia, diabetes and COVID-19 outcomes. DESIGN: We analysed data from the prospective Dutch CovidPredict cohort, an ongoing prospective study of patients admitted for COVID-19 infection. SETTING: Patients from eight participating hospitals, including two university hospitals from the CovidPredict cohort were included. PARTICIPANTS: Admitted, adult patients with a positive COVID-19 PCR or high suspicion based on CT-imaging of the thorax. Patients were followed for major outcomes during the hospitalisation. CVD risk factors were established via home medication lists and divided in antihypertensives, lipid-lowering therapy and antidiabetics. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary outcome was mortality during the first 21 days following admission, secondary outcomes consisted of intensive care unit (ICU) admission and ICU mortality. Kaplan-Meier and Cox regression analyses were used to determine the association with CVD risk factors. RESULTS: We included 1604 patients with a mean age of 66±15 of whom 60.5% were men. Antihypertensives, lipid-lowering therapy and antidiabetics were used by 45%, 34.7% and 22.1% of patients. After 21-days of follow-up; 19.2% of the patients had died or were discharged for palliative care. Cox regression analysis after adjustment for age and sex showed that the presence of ≥2 risk factors was associated with increased mortality risk (HR 1.52, 95% CI 1.15 to 2.02), but not with ICU admission. Moreover, the use of ≥2 antidiabetics and ≥2 antihypertensives was associated with mortality independent of age and sex with HRs of, respectively, 2.09 (95% CI 1.55 to 2.80) and 1.46 (95% CI 1.11 to 1.91). CONCLUSIONS: The accumulation of hypertension, dyslipidaemia and diabetes leads to a stepwise increased risk for short-term mortality in hospitalised COVID-19 patients independent of age and sex. Further studies investigating how these risk factors disproportionately affect COVID-19 patients are warranted.

Adverse outcomes in COVID-19 and diabetes: a retrospective cohort study from three London teaching hospitals.

INTRODUCTION: Patients with diabetes mellitus admitted to hospital with COVID-19 have poorer outcomes. However, the drivers of poorer outcomes are not fully elucidated. We performed detailed characterization of patients with COVID-19 to determine the clinical and biochemical factors that may be drivers of poorer outcomes. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study of 889 consecutive inpatients diagnosed with COVID-19 between March 9 and April 22, 2020 in a large London National Health Service Trust. Unbiased multivariate logistic regression analysis was performed to determine variables that were independently and significantly associated with increased risk of death and/or intensive care unit (ICU) admission within 30 days of COVID-19 diagnosis. RESULTS: 62% of patients in our cohort were of non-white ethnic background and the prevalence of diabetes was 38%. 323 (36%) patients met the primary outcome of death/admission to the ICU within 30 days of COVID-19 diagnosis. Male gender, lower platelet count, advancing age and higher Clinical Frailty Scale (CFS) score (but not diabetes) independently predicted poor outcomes on multivariate analysis. Antiplatelet medication was associated with a lower risk of death/ICU admission. Factors that were significantly and independently associated with poorer outcomes in patients with diabetes were coexisting ischemic heart disease, increasing age and lower platelet count. CONCLUSIONS: In this large study of a diverse patient population, comorbidity (ie, diabetes with ischemic heart disease; increasing CFS score in older patients) was a major determinant of poor outcomes with COVID-19. Antiplatelet medication should be evaluated in randomized clinical trials among high-risk patient groups.

Cardiovascular risk factors are independently associated with COVID-19 mortality: a prospective cohort study (preprint)

Objectives: Recent reports suggest a high prevalence of hypertension and diabetes in COVID-19 patients, but the role of cardiovascular disease (CVD) risk factors in the clinical course of COVID-19 is unknown. We evaluated the time-to-event relationship between hypertension, dyslipidemia, diabetes, and COVID-19 outcomes. Design: We analyzed data from the prospective Dutch COVID-PREDICT cohort, an ongoing prospective study of patients admitted for COVID-19 infection. Setting: Patients from 8 participating hospitals, including two university hospitals from the COVID-PREDICT cohort were included. Participants: Admitted, adult patients with a positive COVID-19 polymerase chain reaction (PCR) or high suspicion based on CT-imaging of the thorax. Patients were followed for major outcomes during hospitalization. CVD risk factors were established via home medication lists and divided in antihypertensives, lipid lowering therapy, and antidiabetics. Primary and secondary outcomes measures: The primary outcome was mortality during the first 21 days following admission, secondary outcomes consisted of ICU-admission and ICU-mortality. Kaplan-Meier and Cox-regression analyses were used to determine the association with CVD risk factors. Results: We included 1604 patients with a mean age of 66+-15 of whom 60.5% were men. Antihypertensives, lipid lowering therapy, and antidiabetics were used by 45%, 34.7%, and 22.1% of patients. After adjustment for age and sex, the presence of [≥]2 risk factors was associated with increased mortality risk (HR 1.52, 95%CI 1.15-2.02), but not with ICU-admission. Moreover, the use of [≥]2 antidiabetics and [≥]2 antihypertensives was associated with mortality independent of age and sex with HRs of respectively 2.09 (95%CI 1.55-2.80) and 1.46 (95%CI 1.11-1.91). Conclusions: The accumulation of hypertension, dyslipidemia and diabetes leads to a stepwise increased risk for short-term mortality in hospitalized COVID-19 patients independent of age and sex. Further studies investigating how these risk factors disproportionately affect COVID-19 patients are warranted.

Severe COVID-19 and Diabetes: A Retrospective Cohort Study from Three London Teaching Hospitals (preprint)

Patients with diabetes mellitus admitted to hospital with COVID-19 caused by infection with the novel coronavirus (SARS-CoV-2) have poorer outcomes. However, the drivers for this are not fully elucidated. We performed a retrospective cohort study, including detailed pre-hospital and presenting clinical and biochemical factors of 889 patients diagnosed with COVID-19 in three constituent hospitals of a large London NHS Trust. 62% of patients with severe COVID-19 were of non-White ethnic backgrounds and the prevalence of diabetes was 38%. 323 (36%) patients met the primary outcome of death or admission to the intensive care unit (ICU) within 30 days of diagnosis. Male gender, advancing age and the Clinical Frailty Scale, an established measure of multimorbidity, independently predicted poor outcomes on multivariate analysis. Diabetes did not confer an independent risk for adverse outcomes in COVID-19, although patients with diabetes and ischaemic heart disease were at particular risk. Additional risk factors which significantly and independently associated with poorer outcomes in patients with diabetes were age, male gender and lower platelet count. Antiplatelet medication was associated with a lower risk of death/ICU admission and should be evaluated in randomised clinical trials amongst high risk patient groups.