Non-severe Disease Research Articles

Missing clinical trial data: the evidence gap in primary data for potential COVID-19 drugs

BackgroundSeveral drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of overall clinical trial results on public registries or through academic publication. We aimed to analyse the evidence gap in this data by conducting a rapid review of results posting on ClinicalTrials.gov and in academic publications to quantify the number of trials missing results for drugs potentially being repurposed for COVID-19.MethodsClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for results and for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance.ResultsOf 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. Tabular results were available on ClinicalTrials.gov for 1172 (31.2%) completed trials. A further 1066 (28.4%) had published results in the academic literature, but did not report results on ClinicalTrials.gov. Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%).ConclusionsThere is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause unnecessary additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.

Overall reduced lymphocyte especially T and B subsets closely related to the poor prognosis and the disease severity in severe patients with COVID-19 and diabetes mellitus

BackgroundA dysregulated host immune response is common in patients with COVID-19.AimIn this study, we aimed to define the characteristics of lymphocyte subsets and their relationship with disease progression in COVID-19 patients with or without diabetes mellitus (DM).MethodsThe baseline peripheral lymphocyte subsets were compared between 55 healthy controls and 95 patients with confirmed COVID-19, and between severe and non-severe COVID-19 patients with or without DM.ResultsThe prevalence of DM in the COVID-19 group was 20%, and patients with severe COVID-19 had a higher prevalence of DM than those with non-severe disease (P = 0.006). Moreover, a significantly poor prognosis and a higher rate of severity were found in those with DM relative to those without DM (P = 0.001, 0.003). Generally, all lymphocytes and subsets of lymphocytes, especially B and T cells, were significant reduced in COVID-19 patients, particularly in those with DM. Patients with severe COVID-19 and DM had the lowest lymphocyte counts compared with those with severe COVID-19 without DM, and those with non-severe COVID-19 with or without DM. Partially decreased lymphocyte subsets, age and DM were closely related to disease progression and prognosis.ConclusionsThese findings provide a reference for clinicians that immunomodulatory treatment may improve disease progression and prognosis of COVID-19 patients, especially those with severe disease with DM.Trial registration Chinese Clinical Trial Register ChiCTR2000034563

High Prevalence of Hypocalcemia in Non-severe COVID-19 Patients: A Retrospective Case-Control Study.

Purpose: To compare serum total calcium and phosphate levels in patients with non-severe COVID-19 with age, sex, and serum 25-hydroxyvitamin D level matched healthy adult cohort.Methods: In this retrospective case-control study, medical records of patients (≥18 years) diagnosed as non-severe COVID-19 admitted at and discharged from our tertiary care institution during the period from April 10, 2020 and June 20, 2020 were retrieved. Baseline investigations, notably, serum calcium, phosphate, albumin, magnesium, 25-hydroxyvitamin D, and C-reactive protein (CRP), were performed at admission before any form of calcium or vitamin D supplementation were considered. The biochemical parameters were compared with age, sex, and 25-hydroxyvitamin D matched healthy adult controls (1:1 ratio) derived from the Chandigarh Urban Bone Epidemiological Study (CUBES).Results: After exclusion, 72 patients with non-severe COVID-19 (63 mild and 9 moderate disease) and an equal number of healthy controls were included in the final analysis. Age, sex, serum 25-hydroxyvitamin D, and albumin levels were matched between the 2 groups. Hypovitaminosis D and hypocalcemia were seen in 97 and 67% of the patients, respectively. The patients had lower serum calcium (P value <0.001) and phosphate (P = 0.007) compared with the controls. There was no statistically significant correlation between serum calcium and CRP.Conclusions: Hypocalcemia is highly prevalent even in COVID-19 patients with non-severe disease probably implying that hypocalcemia is intrinsic to the disease. Prospective studies with larger number of patients are required to prove this hypothesis and unravel the underlying pathophysiological mechanisms.

Safety and Efficacy of Low-Dose Corticosteroids in Patients With Non-severe Coronavirus Disease 2019: A Retrospective Cohort Study.

BackgroundTo date, several pharmacological agents have been employed in the treatment and management of the coronavirus disease 2019 (COVID-19). While the utility of corticosteroids in severe COVID-19 infection is now widely touted, their efficacy in thwarting the progression of non-severe disease remains elusive.MethodsA retrospective cohort study involving 25 patients with a confirmed diagnosis of non-severe COVID-19 infection was conducted. Subjects were assigned to either the steroid or the non-steroid group. A low-dose, short-course corticosteroid regimen was administered for seven days and the disease outcomes were recorded and compared among the two groups. The Kolmogorov-Smirnov test was employed to discern the data normality.ResultsIn patients treated with low-dose, short-course steroids, the overall all-cause mortality was significantly lower compared with the non-steroid group (8.3% and 61.5%, respectively; p = 0.005). The prevalence of acute respiratory distress syndrome in the steroid group was significantly lower than that in the non-steroid group at the seven-day mark (16.7% and 84.6%, respectively; p = 0.002). Within the steroid group, the incidence of developing secondary complications was also markedly lower than that in the non-steroid group.ConclusionsIn patients afflicted with non-severe COVID-19, the employment of low-dose, short-course corticosteroids may confer a therapeutic advantage, significantly curtailing the mortality rate, the length of hospital stay, and the risk of developing secondary complications.

Factors Associated with Worsening Oxygenation in Patients with Non-severe COVID-19 Pneumonia.

BackgroundThis study aimed to determine the parameters for worsening oxygenation in non-severe coronavirus disease 2019 (COVID-19) pneumonia.MethodsThis retrospective cohort study included cases of confirmed COVID-19 pneumonia in a public hospital in South Korea. The worsening oxygenation group was defined as that with SpO2 ≤94% or received oxygen or mechanical ventilation (MV) throughout the clinical course versus the non-worsening oxygenation group that did not experience any respiratory event. Parameters were compared, and the extent of viral pneumonia from an initial chest computed tomography (CT) was calculated using artificial intelligence (AI) and measured visually by a radiologist.ResultsWe included 136 patients, with 32 (23.5%) patients in the worsening oxygenation group; of whom, two needed MV and one died. Initial vital signs and duration of symptoms showed no difference between the two groups; however, univariate logistic regression analysis revealed that a variety of parameters on admission were associated with an increased risk of a desaturation event. A subset of patients was studied to eliminate potential bias, that ferritin ≥280 μg/L (p=0.029), lactate dehydrogenase ≥240 U/L (p=0.029), pneumonia volume (p=0.021), and extent (p=0.030) by AI, and visual severity scores (p=0.042) were the predictive parameters for worsening oxygenation in a sex-, age-, and comorbid illness-matched case-control study using propensity score (n=52).ConclusionOur study suggests that initial CT evaluated by AI or visual severity scoring as well as serum markers of inflammation on admission are significantly associated with worsening oxygenation in this COVID-19 pneumonia cohort.

Role of electrolytes in determining severity in COVID-19

Introduction: Coronavirus disease 2019 (COVID-19) is a viral disease which originated in the city of Wuhan (China) and progressively spread to all the continents and brought the world to a standstill. Various severity markers have been seen to play a role in the COVID-19. International studies have demonstrated role of serum electrolyte in COVID-19 as a potential severity marker. Hence, this study was undertaken in Indian patients. Material and methods: 100 COVID-19 reverse transcription polymerase chain reaction (RT-PCR) positive patient of non-severe and severe disease of either gender getting admitted to hospital and above 18 years were enrolled in the month of August to September 2020. The mean values of electrolytes and high-sensitivity C-reactive protein (HsCRP) in non- severe and severe disease were compared and correlated. Results: 100 patients including 70 of non-severe and 30 of severe disease were evaluated. The mean sodiumwas 134.03±6.77mEq/L and 135.5± 6.77mEq/l in the non-severe and the severe groups respectively (p value=0.91); potassium was 4.24±0.61mEq/l and 4.52±0.80 mEq/l respectively (p value=0.75); corrected serum calcium was 8.38±0.74 mg/dl and 8.48±0.74mg/dl respectively (p value = 0.95); phosphorus levels was 3.66±1.99mg/dl and 3.45±1.63 respectively (p value = 0.52); and serum magnesium level was 2.15±0.3 mEq/l and 2.03±0.56 mEq/l (p value = 0.18). The mean level of HsCRP was 30.95±49.41 mg/L in non- severe while 94.78±79.62 mg/L in severe infection (p value=0.03). In the severe group, the electrolyte values were found to be poorly correlated with the hsCRP levels. Conclusion: Electrolytes does not serve as severity markers in COVID-19 in an Indian population.

Peripheral T cell lymphopenia in COVID-19: potential mechanisms and impact.

SummaryImmunopathogenesis involving T lymphocytes, which play a key role in defence against viral infection, could contribute to the spectrum of COVID-19 disease and provide an avenue for treatment. To address this question, a review of clinical observational studies and autopsy data in English and Chinese languages was conducted with a search of registered clinical trials. Peripheral lymphopenia affecting CD4 and CD8 T cells was a striking feature of severe COVID-19 compared with non-severe disease. Autopsy data demonstrated infiltration of T cells into organs, particularly the lung. Seventy-four clinical trials are on-going that could target T cell-related pathogenesis, particularly IL-6 pathways. SARS-CoV-2 infection interrupts T cell circulation in patients with severe COVID-19. This could be due to redistribution of T cells into infected organs, activation induced exhaustion, apoptosis, or pyroptosis. Measuring T cell dynamics during COVID-19 will inform clinical risk-stratification of hospitalised patients and could identify those who would benefit most from treatments that target T cells.

Liver function test abnormalities in COVID-19 patients and factors affecting them - a retrospective study.

Aim of the studyWe aimed to study liver function test abnormalities in our COVID-19 patients and factors affecting them and to evaluate whether liver function test abnormalities are related to the severity of COVID-19.Material and methodsOur retrospective study included 118 patients who were SARS-CoV-2 positive. Their median age was 40 years. Fifty percent were male. Clinical and biochemical data were collected from patient records during the period from the start of June 2020 to the end of July 2020. Liver function test abnormalities included: alanine aminotransferase (ALT) > 40 U/l, aspartate aminotransferase (AST) > 40 U/l, serum albumin < 3.5 mg/dl, total bilirubin > 1.2 mg/dl, and international normalized ratio (INR) > 1.2.ResultsForty-four percent of COVID-19 patients had liver function test (LFT) abnormalities. In patients with severe SARS-CoV-2, AST, total bilirubin and INR levels were significantly higher than in patients with the non-severe disease. Levels of hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum ferritin, D-dimer, and serum glucose were significantly higher in SARS-CoV-2 patients with LFT abnormalities than those with normal liver function.ConclusionsLFT abnormalities are very common in SARS-CoV2 positive patients, especially those with the severe form. Levels of ESR, CRP, serum ferritin, and D-dimer were higher in COVID-19 patients with LFT abnormalities than those with normal LFT. High serum ferritin levels might be potential risk factors for LFT abnormalities.

Can Monocytopenia Be a New Indicator in Determining Survival in Covid-19 Disease?

Monocytes play a central role in Covid-19 infection. Monocytopenia is especially observed in patients with severe infection. In our study, we aimed to investigate the effects of monocytopenia on survival in patients presenting with the suspicion of Covid-19. Patients diagnosed with Covid-19 who received inpatient or outpatient treatment in the pandemic clinic of Umraniye Training and Research Hospital between April 2020 and July 2020 were included in our retrospective cohort study. Patients were divided into two groups, severe and non-severe. Demographic data, laboratory parameters, those who were monocytopenic at presentation, those who developed monocytopenia during follow-up, and those with persistent monocytopenia were noted. The study included 471 patients with a mean age of 50.4 ± 18.2 years. Sixty-seven (14.2%) patients had severe and 404 (85.8%) had non-severe disease. The minimum value of monocytes detected during the follow-up in severe patients was significantly lower (p < 0.001). As patients were grouped into those with monocytopenia at the time of admission, those with monocytopenia developing during their follow-up, and those whose monocytopenia at admission persisted, they were compared with regards to the presence or absence of severe disease. Newly developing monocytopenia and persistent monocytopenia were significant in patients with severe disease (p < 0.001, p = 0,001 respectively). Also, among non-surviving patients, there was a significant difference in survival times in the monocytopenia group (p = 0.029). In our study, we found more developing and persistent monocytopenia in the severe group, and the survival time was low, especially in those with newly developing monocytopenia. The development of monocytopenia in the daily hemogram follow-up of the patients may increase the possibility of mortality, which suggests that monocytopenia may be a new marker in determining survival.

Nervous system diseases are associated with the severity and mortality of patients with COVID-19: a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) has become a global pandemic. Previous studies showed that comorbidities in patients with COVID-19 are risk factors for adverse outcomes. This study aimed to clarify the association between nervous system diseases and severity or mortality in patients with COVID-19. We performed a systematic literature search of four electronic databases and included studies reporting the prevalence of nervous system diseases in COVID-19 patients with severe and non-severe disease or among survivors and non-survivors. The included studies were pooled into a meta-analysis to calculate the odds ratio (OR) with 95% confidence intervals (95%CI). We included 69 studies involving 17 879 patients. The nervous system diseases were associated with COVID-19 severity (OR = 3.19, 95%CI: 2.37 to 4.30, P < 0.001) and mortality (OR = 3.75, 95%CI: 2.68 to 5.25, P < 0.001). Specifically, compared with the patients without cerebrovascular disease, patients with cerebrovascular disease infected with COVID-19 had a higher risk of severity (OR = 3.10, 95%CI: 2.21 to 4.36, P < 0.001) and mortality (OR = 3.45, 95% CI: 2.46 to 4.84, P < 0.001). Stroke was associated with severe COVID-19 disease (OR = 1.95, 95%CI: 1.11 to 3.42, P = 0.020). No significant differences were found for the prevalence of epilepsy (OR = 1.00, 95%CI: 0.42 to 2.35, P = 0.994) and dementia (OR = 2.39, 95%CI: 0.55 to 10.48, P = 0.247) between non-severe and severe COVID-19 patients. There was no significant association between stroke (OR = 1.79, 95%CI: 0.76 to 4.23, P = 0.185), epilepsy (OR = 2.08, 95%CI: 0.08 to 50.91, P = 0.654) and COVID-19 mortality. In conclusion, nervous system diseases and cerebrovascular disease were associated with severity and mortality of patients with COVID-19. There might be confounding factors that influence the relationship between nervous system diseases and COVID-19 severity as well as mortality.

Severity of COVID-19 in bacillus Calmette-Guérin vaccinated population.

PurposeConsidering the cross-protection reported for bacillus Calmette-Guérin (BCG) vaccination on viral respiratory infections, it has been proposed that it could reduce the severity of coronavirus disease 2019 (COVID-19). The objective of the current study is to investigate the association between the severity of COVID-19 with prior BCG vaccination in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Materials and MethodsAdult patients (18 years or above) with positive SARS-CoV-2 polymerase chain reaction admitted in July 2020 were included in this cross-sectional study. Patients were classified into non-severe, severe, and critical diseases. History of prior BCG vaccination and the presence of a BCG vaccination scar were recorded.ResultsOut of 103 patients, 64 patients with prior history of BCG vaccinations were compared with 39 patients without BCG vaccination in childhood. The median age was 55 years and 64 years in BCG vaccinated & non-BCG vaccinated patients (p-value=0.002). There was male predominance in both groups and frequent comorbid illnesses were hypertension and diabetes mellitus. Severe COVID-19 was found in 91 patients (88.3%) followed by non-severe disease and critical diseases i.e., 7 (6.8%) and 5 (4.9%) patients, respectively. No association of prior BCG vaccination with disease severity of COVID-19 was found in this study and mortality was 8.7%. Out of nine patients who expired only 2 (22.2%) had a prior history of BCG vaccination (p-value=0.01). Secondary infections were present in 26 patients and the majority had pneumonia.ConclusionThe BCG vaccine has no impact on the severity of COVID-19 but could have a protective role with a low mortality rate in already infected patients.

COVID-19-associated coagulopathy and anticoagulants

The patients infected with SARS-CoV-2 have a prothrombotic state. The incidence of thromboembolic complications in patients with severe disease is much higher than in those with non-severe disease. Coagulation parameters, D-dimers, fibrinogen and platelet count are important for the identification and intervention of thromboinflammation, as early as possible. Low-molecular-weight heparin and unfractionated heparin are the anticoagulants of choice in the prevention of thrombotic complications.

Effect of liver injury on prognosis and treatment of hospitalized patients with COVID-19 pneumonia.

BackgroundLiver injury is common in patients with coronavirus disease 2019 (COVID-19), although its effect on patient outcomes has not been well studied. This study aimed to evaluate the effect of liver injury on the prognosis and treatment of patients with COVID-19 pneumonia.MethodsIn this retrospective, single-center study, data on 109 hospitalized patients with COVID-19 pneumonia were extracted and analyzed. The primary composite end-point event was the use of mechanical ventilation or death.ResultsAt admission, of the 109 patients enrolled, 56 patients (51.4%) were diagnosed with severe disease, and 39 (35.8%) presented with liver injury, which mainly manifested as elevated levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) accompanied simultaneously by an increase in the level of γ-glutamyl transferase. A primary composite end-point event occurred in 21 patients (19.3%). Liver injury was more prevalent in patients with severe disease than in those with non-severe disease (46.4% vs. 24.5%, P=0.017). However, there was no significant difference found between severe and non-severe patients in the use of mechanical ventilation, mortality, hospital stay, or use and dosage of glucocorticoids between individuals with and without liver injury (all P>0.05). The degree of disease severity (OR =7.833, 95% CI, 1.834–31.212, P=0.005) and presence of any coexisting illness (OR =4.736, 95% CI, 1.305–17.186, P=0.018) were predictable risk factors for primary composite end-point events, whereas liver injury had no significance in this aspect (OR =0.549, 95% CI, 0.477–5.156, P=0.459).ConclusionsLiver injury was more common in severe cases of COVID-19 pneumonia than in non-severe cases. However, liver injury had no negative effect on the prognosis and treatment of COVID-19 pneumonia.

Clinical Characteristics and Risk Factors for COVID-19 Infection and Disease Severity: A Nationwide Observational Study in Estonia

Background: COVID-19 pandemic has required overloading of health systems all over the world. For reliable risk stratification, knowledge on factors predisposing to SARS-CoV-2 infection and to severe COVID-19 disease course is needed for decision-making at the individual, provider, and government levels. Data to identify these factors should be easily obtainable.Methods: Retrospective cohort study of nationwide e-health databases in Estonia. We used longitudinal health records from 66,295 people tested positive for SARS-CoV-2 RNA from 26 February 2020 to 28 February 2021 and 254,958 randomly selected controls from the reference population with no known history of SARS-CoV-2 infection or clinical COVID-19 diagnosis (case to control ratio 1:4) to predict risk factors of infection and severe course of COVID-19. We analysed sociodemographic and health characteristics of study participants.Findings: The SARS-CoV-2 infection risk was slightly higher among women, and was higher among those with comorbid conditions or obesity. Dementia (RRR 3.77, 95%CI 3.30⎼4.31), renal disease (RRR 1.88, 95%CI 1.56⎼2.26), and cerebrovascular disease (RRR 1.81, 95%CI 1.64⎼2.00) increased the risk of infection. Of all SARS-CoV-2 infected people, 92% had a non-severe disease course, 4.8% severe disease (requiring hospitalisation), 1.7% critical disease (needing intensive care), and 1.5% died. Male sex, increasing age and comorbid burden contributed significantly to more severe COVID-19, and the strength of association for male sex increased with the increasing severity of COVID-19 outcome. The strongest contributors to critical illness (expressed as RRR with 95% CI) were renal disease (7.71, 4.71⎼12.62), the history of previous myocardial infarction (3.54, 2.49⎼5.02) and obesity (3.56, 2.82⎼4.49). The strongest contributors to a lethal outcome were renal disease (6.48, 3.74⎼11.23), cancer (3.81, 3.06⎼4.75), liver disease (3.51, 1.36⎼9.02) and cerebrovascular disease (3.00, 2.31⎼3.89).Interpretation: We found divergent effect of age and gender on infection risk and severity of COVID-19 ⎼ age and gender did not contribute substantially to infection risk, but did so for the risk of severe disease. Co-morbid health conditions, especially those affecting renin-angiotensin system, had impact on both, the risk of infection and severe disease course. Age and male sex had the most significant impact on the risk of severe COVID-19.Funding Information: Research was carried out with the support of Estonian Research Council, European Regional Development Fund and European Social Fund via IT Academy programme.Declaration of Interests: The authors declared no potential conflicts of interest.Ethics Approval Statement: The study was approved by the Research Ethics Committee of the University of Tartu.

Immunological and Hematological Response in COVID-19.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. Through the renin-angiotensin system, the virus may impact the lung circulation, but the expression on endothelium may conduct to its activation and further systemic damage. While precise mechanisms underlying these phenomena remain to be further clarified, the understanding of the disease, its clinical course, as well as its immunological and hematological implications is of paramount importance in this phase of the pandemic. This review summarizes the evidence gathered until 12 June; electronic databases were screened for pertinent reports on coronavirus and inflammatory and hematological changes. Search was conducted by two independent investigators; keywords used were "SARS-CoV-2," "COVID-19," "inflammation," "immunological," and "therapy." The viral infection is able to trigger an excessive immune response in predisposed individuals, which can result in a "cytokine storm" that presents an hyperinflammation state able to determine tissue damage and vascular damage. An explosive production of proinflammatory cytokines such as TNF-α IL-1β and others occurs, greatly exaggerating the generation of molecule-damaging reactive oxygen species. These changes are often followed by alterations in hematological parameters. Elucidating those changes in SARS-CoV-2-infected patients could help to understand the pathophysiology of disease and may provide early clues to diagnosis. Several studies have shown that hematological parameters are markers of disease severity and suggest that they mediate disease progression. According to the available literature, the primary hematological symptoms-associated COVID-19, and which distinguish patients with severe disease from patients with nonsevere disease, are lymphocytopenia, thrombocytopenia, and a significant increase in D-dimer levels. SARS-CoV-2 infection triggers a complex response altering inflammatory, hematological, and coagulation parameters. Measuring these alterations at certain time points may help identify patients at high risk of disease progression and monitor the disease severity.

Evaluation of clinical and laboratory findings in severe group COVID-19 pregnants without comorbidity.

COVID - 19 disease may be seen with different clinical presentations in pregnant women. Comorbid diseases are important factors affecting the progression of this disease. In this study, we aimed to evaluate the clinical and laboratory findings in pregnant women with COVID - 19 who had no comorbid disease. This retrospective designed study included 217 patients with Covid PCR positive in typically COVID - 19 clinic. The patients were classified into asymptomatic, nonsevere, and severe disease groups. The symptoms, laboratory results, hospital followups and intensive care records of the patients and the findings of new borns are presented. Most of the patients (78%) were in the third trimester of pregnancy, and 103 patients in the study group had severe disease. Fever in the non-severe group and respiratory distress in the severe group were the most common symptoms in the patients. The severe clinical manifestations were specifically observed in the third trimester patients. In the severe group, neutrophil, lactat dehydrogenase, ferritin, CK - MB, IL - 6, and hospital stay were statistically higher than those in other groups (p < 0.05). Increase in BUN and creatine were the most predictive parameters in intensive care admission. While the intensive care unit (ICU) requirement was higher in patients in the severe group, premature birth was observed more frequently in the severe group (p < 0.05) .

An Effective Machine Learning Approach for Identifying Non-Severe and Severe Coronavirus Disease 2019 Patients in a Rural Chinese Population: The Wenzhou Retrospective Study.

This paper has proposed an effective intelligent prediction model that can well discriminate and specify the severity of Coronavirus Disease 2019 (COVID-19) infection in clinical diagnosis and provide a criterion for clinicians to weigh scientific and rational medical decision-making. With indicators as the age and gender of the patients and 26 blood routine indexes, a severity prediction framework for COVID-19 is proposed based on machine learning techniques. The framework consists mainly of a random forest and a support vector machine (SVM) model optimized by a slime mould algorithm (SMA). When the random forest was used to identify the key factors, SMA was employed to train an optimal SVM model. Based on the COVID-19 data, comparative experiments were conducted between RF-SMA-SVM and several well-known machine learning algorithms performed. The results indicate that the proposed RF-SMA-SVM not only achieves better classification performance and higher stability on four metrics, but also screens out the main factors that distinguish severe COVID-19 patients from non-severe ones. Therefore, there is a conclusion that the RF-SMA-SVM model can provide an effective auxiliary diagnosis scheme for the clinical diagnosis of COVID-19 infection.

518. Factors Associated with Severe COVID-19 among Patients Hospitalized in Rhode Island

BackgroundTo better understand patient factors that impact clinical outcomes in COVID-19, we performed a retrospective cohort study of patients hospitalized with COVID-19 in Rhode Island to identify patient and clinical characteristics associated with severe disease.MethodsWe analyzed 259 patients admitted to our academic medical center during a three month period with confirmed COVID-19. Clinical data was extracted via chart review and lab results within the first 24 hours of admission were extracted directly from electronic medical records. Patients were divided in two groups based upon the highest level of supplemental oxygen (O2) required during hospitalization: severe COVID-19 (high flow O2, non-invasive, or invasive mechanical ventilation) and non-severe COVID-19 (low flow O2 or no supplemental O2). SAS 9.4 (Cary, NC) was used for statistical analyses. Chi-square or Fisher’s exact tests for categorical variables and the Student’s t-test for continuous variables were used to compare demographics, baseline comorbidities, and clinical data between the severe and non-severe groups.Table 1: Demographics ResultsOf 259 patients, 166 (64%) had non-severe disease, and 93 (36%) severe disease; median age [IQR] was 62 [51,73]. There were 138(53%) males and 75 (29%) Hispanics. Among non-Hispanics,124(48%) were White, 48(19%) African Americans, and 12(5%) other races. Sixty (23%) were admitted from a nursing facility and the in-hospital mortality rate was 15% (38/259). Severe COVID-19 was associated with older age (p=0.02), admission from nursing facility (p=0.009), increased BMI (p=0.03), diabetes mellitus (p=0.0002), and COPD (p=0.03). At the time of presentation, severe COVID-19 was associated with tachypnea, hypoxia, hypotension (all p< 0.0001), elevated BUN (p=0.002) and AST (p=0.001), and acute or chronic kidney injury (p=0.01). Median hospital stay [IQR] was 11 days [7,18] in the severe vs. 6 days [3,11] in the non-severe group. In the severe group, 72% required ICU admission and 39% died.Table 2: Medical comorbidities Table 3: Presenting symptoms and signs in the first 48 hours of admission Table 4: Basic labs in the first 24 hours ConclusionIn this cohort of patients with COVID-19, specific comorbidities, and vital signs at presentation were associated with severe COVID-19. These findings help clinicians with early identification and triage of high risk patients.Disclosures All Authors: No reported disclosures

Inflammatory and hematologic markers as predictors of severe outcomes in COVID-19 infection: A systematic review and meta-analysis.

BackgroundLaboratory testing is commonly performed in patients with COVID-19. Each of the laboratory parameters has potential value for risk stratification and prediction of COVID-19 outcomes. This systematic review and meta-analysis aimed to evaluate the difference between these parameters in severe and nonsevere disease and to provide the optimal cutoff value for predicting severe disease.MethodWe performed a systematic literature search through electronic databases. The variables of interest were serum procalcitonin, albumin, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) levels in each group of severity outcomes from COVID-19.ResultsThere were a total of 4848 patients from 23 studies. Our meta-analysis suggest that patients with severe COVID-19 infections have higher procalcitonin, (mean difference 0.07; 95% CI 0.05–0.10; p < 0.00001), CRP (mean difference 36.88; 95% CI 29.10–44.65; p < 0.00001), D-Dimer (mean difference 0.43; 95% CI 0.31–0.56; p < 0.00001), and LDH (mean difference 102.79; 95% CI 79.10–126.49; p < 0.00001) but lower levels of albumin (mean difference −4.58; 95% CI −5.76 to −3.39; p < 0.00001) than those with nonsevere COVID-19 infections. The cutoff values for the parameters were 0.065 ng/mL for procalcitonin, 38.85 g/L for albumin, 33.55 mg/L for CRP, 0.635 μ/L for D-dimer, and 263.5 U/L for LDH, each with high sensitivity and specificity.ConclusionThis meta-analysis suggests elevated procalcitonin, CRP, D-dimer, and LDH and decreased albumin can be used for predicting severe outcomes in COVID-19.

Autonomic dysfunction, cardio-pulmonary parameters and masked heart failure in non-severe chronic obstructive pulmonary disease

Въведение: Автономната дисфункция (АД) и параметрите при кардиопулмоналното тестване (КПТ) се асоциират със сърдечна недостатъчност със запазена систолна функция (heart failure with preserved ejection fraction – HFpEF) в общата популация. При пациенти с нетежка хронична обструктивна белодробна болест (ХОББ) тяхното клинично значение и връзка с маскираната HFpEF е неизяснено. Цел: Целта на проучването е да се определят връзката и клиничното значение на АД и кардиопулмоналните параметри с HFpEF при пациенти с нетежък ХОББ, които се оплакват от задух при усилие, без клинично изявено сърдечно-съдово заболяване (ССЗ) (исхемична болест, сърдечна недостатъчност, неконтролирана артериална хипертония). Методи и резултати: При 68 пациенти с нетежък ХОББ без изявено ССЗ е приложено КПТ. Проведена е ехокардиография в покой и 1-2 минути след натоварването. Пациентите са разделени на две групи въз основа на стрес-индуцираното съотношение E/e’: пациенти с левокамерна диастолна дисфункция (ЛКДД) – E/e’ > 15 (пациенти с маскирана HFpEF) и пациенти без стрес-ЛКДД (пациенти без маскирана HFpEF). Хронотропната недостатъчност включва намаления индекс на хронотропен отговор (ИХО Заключение: Неправилното възстановяване на сърдечната честота след натоварването е единственият независим предиктор за маскирана HFpEF при пациенти с нетежък ХОББ. По-ниските нива на ’VO2, кислороден пулс, физическо натоварване, както и по-високото ’VE/’VCO2 съотношение се асоциират с маскирана HFpEF, като вероятно са нейно последствие, а не тригер. Background: Autonomic dysfunction (AD) and cardio-pulmonary exercise testing (CPET) parameters have been associated with masked heart failure with preserved ejection fraction (HFpEF) in the general population. Their clinical significance for masked HFpEF in chronic obstructive pulmonary disease (COPD) is however elusive. Aim: The aim of the study was to determine the prevalence, correlation and clinical significance of AD and CPET with masked HFpEF, in non-severe COPD patients, complaining of exertional dyspnea, without clinically overt cardio-vascular (CV) comorbidities (ischaemic heart disease, heart failure, uncontrolled arterial hypertension). Methods and results: We applied CPET and echocardiography in 68 COPD subjects. Echocardiography was performed before CPET and 1-2 minutes after peak exercise. Patients were divided into two groups: patients with and without masked HFpEF. Peak E/e’ – 15 was applied as a cut-off. Chronotropic incompetence (CI) was assumed if both failure to reach the target heart rate (HR) on exercise and diminished heart rate reserve Conclusion: Abnormal HRR is the only independent predictor of masked HFpEF in non-severe COPD patients. Despite of being associated with masked HFpEF, the lower ’VO2, lower oxygen pulse, higher ’VE/’VCO2 slope and lower exercise load seem to be the consequences, rather than the triggers for it.