Natural Evolution of Porcine Epidemic Diarrhea Viruses Isolated from Maternally Immunized Piglets

Simple SummaryDuring the long-term co-evolution of the virus and the host, even closely related vaccines may emerge with incomplete protective immunity due to the mutations or deletions of amino acids at specific antigenic sites. The mutation of PEDV was accelerated by the recombination of different strains and the mutation of the strains adapting to the environment. These mutations either cause immune escape from conventional vaccines or affect the virulence of the virus. Therefore, researching and developing new vaccines with cross-protection through continuous monitoring, isolation and sequencing are important to determine whether their genetic characteristics are changed and to evaluate the protective efficacy of current vaccines. The porcine epidemic diarrhea virus (PEDV) can cause severe piglet diarrhea or death in some herds. Genetic recombination and mutation facilitate the continuous evolution of the virus (PEDV), posing a great challenge for the prevention and control of porcine epidemic diarrhea (PED). Disease materials of piglets with PEDV vaccination failure in some areas of Shanxi, Henan and Hebei provinces of China were collected and examined to understand the prevalence and evolutionary characteristics of PEDV in these areas. Forty-seven suspicious disease materials from different litters on different farms were tested by multiplex PCR and screened by hematoxylin-eosin staining and immunohistochemistry. PEDV showed a positivity rate of 42.6%, infecting the small and large intestine and mesenteric lymph node tissues. The isolated strains infected Vero, PK-15 and Marc-145 multihost cells and exhibited low viral titers in all three cell types, as indicated by their growth kinetic curves. Possible putative recombination events in the isolates were identified by RDP4.0 software. Sequencing and phylogenetic analysis showed that compared with the classical vaccine strain, PEDV SX6 contains new insertion and mutations in the S region and belongs to genotype GIIa. Meanwhile, ORF3 has the complete amino acid sequence with aa80 mutated wild strains, compared to vaccine strains CV777, AJ1102, AJ1102-R and LW/L. These results will contribute to the development of new PEDV vaccines based on prevalent wild strains for the prevention and control of PED in China.

Incidence, characteristics, risk factors and outcomes of diabetic ketoacidosis in COVID-19 patients: Comparison with influenza and pre-pandemic data.

AIMS: This study characterized incidence, patient profiles, risk factors and outcomes of in-hospital diabetic ketoacidosis (DKA) in patients with COVID-19 compared with influenza and pre-pandemic data. METHODS: This study consisted of 13 383 hospitalized patients with COVID-19 (March 2020-July 2022), 19 165 hospitalized patients with influenza (January 2018-July 2022) and 35 000 randomly sampled hospitalized pre-pandemic patients (January 2017-December 2019) in Montefiore Health System, Bronx, NY, USA. Primary outcomes were incidence of in-hospital DKA, in-hospital mortality, and insulin use at 3 and 6 months post-infection. Risk factors for developing DKA were identified. RESULTS: The overall incidence of DKA in patients with COVID-19 and influenza, and pre-pandemic were 2.1%, 1.4% and 0.5%, respectively (p < .05 pairwise). Patients with COVID-19 with DKA had worse acute outcomes (p < .05) and higher incidence of new insulin treatment 3 and 6 months post-infection compared with patients with influenza with DKA (p < .05). The incidence of DKA in patients with COVID-19 was highest among patients with type 1 diabetes (12.8%), followed by patients with insulin-dependent type 2 diabetes (T2D; 5.2%), non-insulin dependent T2D (2.3%) and, lastly, patients without T2D (1.3%). Patients with COVID-19 with DKA had worse disease severity and higher mortality [odds ratio = 6.178 (4.428-8.590), p < .0001] compared with those without DKA. Type 1 diabetes, steroid therapy for COVID-19, COVID-19 status, black race and male gender were associated with increased risk of DKA. CONCLUSIONS: The incidence of DKA was higher in COVID-19 cohort compared to the influenza and pre-pandemic cohort. Patients with COVID-19 with DKA had worse outcomes compared with those without. Many COVID-19 survivors who developed DKA during hospitalization became insulin dependent. Identification of risk factors for DKA and new insulin-dependency could enable careful monitoring and timely intervention.

Self-Reported Depression and Anxiety among Graduate Students during the COVID-19 Pandemic: Examining Risk and Protective Factors

Depression and anxiety among students in higher education are well-established public health concerns with rates that have steadily increased over the past several decades. The global COVID-19 pandemic caused a need for rapid transition on campuses to online learning, a disruption of research, and uncertainty about meeting program requirements and employment. Graduate students often feel overlooked at the best of times and the potential for the pandemic to worsen this perception cannot be understated. This study examined the rates of self-reported depressive and anxiety symptoms among graduate students who were located at the national epicenter of the COVID-19 pandemic in the United States in the spring of 2020. Demographic characteristics, loneliness, and coping to determine potential risk and protective factors were also examined. A comprehensive online survey was created including the University of California Los Angeles (UCLA) 3-Item Loneliness Scale, the Patient Health Questionnaire Depression Scale (PHQ-9), and the Generalized Anxiety Disorder scale (GAD-7). Descriptive statistics, Pearson's chi-squared test, Spearman's correlation, and unadjusted and adjusted multivariable logistic ordinal regression models were used to describe the sample and to assess factors associated with depression and anxiety. 341 surveys were analyzed;respondents had a mean age of 31.88, 68% were female, 63% were White, and 23% identified as lesbian/gay/bisexual. Approximately 89% of students reported moderate-severe depression, and 76% moderate-severe anxiety. Risk factors associated with depression (p < 0.05) were being "sometimes' lonely”, "often/always lonely”, and time spent searching COVID-19 information. Emotional support, having children, and perceived emotional/mental health were protective against depression (p < 0.05). Risk factors associated with anxiety were "‘often/always lonely”, identifying as lesbian/gay/bisexual, and time searching COVID-19 information. Coping, having children, being born outside of the U.S., and perceived emotional/mental health were protective against anxiety (p < 0.05). Based on study findings, it is recommended that universities include more focused interventions for graduate students in consideration of their unique personal and professional needs. Graduate students are part of the emerging professional workforce and as such employers are also advised to integrate wellness and mental health programs and interventions into their employee assistance programs.

Reduced Cholesterol Levels during Acute Human Babesiosis.

BACKGROUND: Babesiosis, an intra-erythrocytic protozoan disease, is an emerging zoonotic parasitic disease worldwide. Cholesterol levels are correlated with severe infections, such as sepsis and COVID-19, and anecdotal reports suggest that high-density lipoprotein (HDL) cholesterol declines during acute babesiosis. Our aim was to describe the cholesterol levels in patients with acute babesiosis diagnosed in an endemic area in New York, hypothesizing that HDL levels correlate with the severity of infection. METHODS: We reviewed the medical records of adult patients with babesiosis diagnosed by identification of Babesia parasites on a thin blood smear and confirmed by polymerase chain reaction from 2013 to 2018, who also had available a lipid profile drawn at the time of clinical presentation. Additional lipid profile levels were considered as "baseline" if they were drawn within 2 months before or after the infection as part of routine care. RESULTS: A total of 39 patients with babesiosis had a lipid profile drawn on presentation. The patients were divided into two groups for comparison based on the treating physician's clinical decision: 33 patients who were admitted to the hospital and 8 patients who were evaluated as outpatients. A history of hypertension was more common in admitted patients (37% vs. 17%, p = 0.02). The median levels of low-density lipoprotein (LDL) and HDL were significantly reduced in admitted patients compared to non-admitted patients (46 vs. 76 mg/dL, p = 0.04; and 9 vs. 28.5 mg/dL, p = 0.03, respectively). In addition, LDL and HDL levels returned to baseline values following resolution of acute babesiosis. CONCLUSION: LDL and HDL levels are significantly reduced during acute babesiosis, suggesting that cholesterol depletion may predict disease severity. Pathogen and host factors may contribute to a reduction in serum cholesterol levels during acute babesiosis.

Initial mean arterial blood pressure (MABP) measurement is a risk factor for mortality in hypertensive COVID-19 positive hospitalized patients.

BACKGROUND: Hypertension (HTN) is associated with severe COVID-19 infection; however, it remains unknown if the level of blood pressure (BP) predicts mortality. We tested whether the initial BP in the emergency department of hospitalized patients portends mortality in COVID-19 positive(+) patients. METHODS: Data from COVID-19(+) and negative (-) hospitalized patients at Stony Brook University Hospital from March to July 2020 were included. The initial mean arterial BPs (MABPs) were categorized into tertiles (T) of MABP (65-85 [T1], 86-97 [T2] and ≥98 [T3] mmHg). Differences were evaluated using univariable (t-tests, chi-squared) tests. Multivariable (MV) logistic regression analyses were computed to assess links between MABP and mortality in hypertensive COVID-19 patients. RESULTS: 1549 adults were diagnosed with COVID-19 (+) and 2577 tested negative (-). Mortality of COVID-19(+) was 4.4-fold greater than COVID-19(-) patients. Though HTN prevalance did not differ between COVID-19 groups, the presenting systolic BP, diastolic BP, and MABP were lower in the COVID-19(+) vs (-) cohort. When subjects were categorized into tertiles of MABP, T2 tertile of MABP had the lowest mortality and the T1 tertile of MABP had greatest mortality compared to T2; however, no difference in mortality was noted across tertiles of MABP in COVID-19 (-). MV analysis of COVID-19 (+) subjects exposed death as a risk factor for T1 MABP. Next, the mortality of those with a historic diagnosis of hypertension or normotension were studied. On MV analysis, T1 MABP, gender, age, and first respiratory rate correlated with mortality while lymphocyte count inversely correlated with death in hypertensive COVID-19 (+) patients while neither T1 nor T3 categories of MABP predicted death in non-hypertensives. CONCLUSIONS: Low-normal admitting MABP in COVID-19 (+) subjects with a historical diagnosis of HTN is associated with mortality and may assist in identifying those at greatest mortality risk.

Longitudinal Chest X-ray Scores and their Relations with Clinical Variables and Outcomes in COVID-19 Patients.

Background: This study evaluated the temporal characteristics of lung chest X-ray (CXR) scores in COVID-19 patients during hospitalization and how they relate to other clinical variables and outcomes (alive or dead). Methods: This is a retrospective study of COVID-19 patients. CXR scores of disease severity were analyzed for: (i) survivors (N = 224) versus non-survivors (N = 28) in the general floor group, and (ii) survivors (N = 92) versus non-survivors (N = 56) in the invasive mechanical ventilation (IMV) group. Unpaired t-tests were used to compare survivors and non-survivors and between time points. Comparison across multiple time points used repeated measures ANOVA and corrected for multiple comparisons. Results: For general-floor patients, non-survivor CXR scores were significantly worse at admission compared to those of survivors (p < 0.05), and non-survivor CXR scores deteriorated at outcome (p < 0.05) whereas survivor CXR scores did not (p > 0.05). For IMV patients, survivor and non-survivor CXR scores were similar at intubation (p > 0.05), and both improved at outcome (p < 0.05), with survivor scores showing greater improvement (p < 0.05). Hospitalization and IMV duration were not different between groups (p > 0.05). CXR scores were significantly correlated with lactate dehydrogenase, respiratory rate, D-dimer, C-reactive protein, procalcitonin, ferritin, SpO2, and lymphocyte count (p < 0.05). Conclusions: Longitudinal CXR scores have the potential to provide prognosis, guide treatment, and monitor disease progression.

Patient Self-Report Superior to Electronic Medical Record Abstraction for Identifying Positive COVID-19 Symptoms at Illness Onset.

Introduction: Most initial COVID-19 research focused on hospitalized patients. Presenting symptomatology in the outpatient setting was poorly characterized, making it difficult for primary care physicians to predict which patients would require hospitalization. The purpose of this study was to characterize the presenting symptoms of COVID-19 infection and baseline patient characteristics and evaluate for correlation with disease severity, duration, and chronicity in the outpatient setting. Methods: A total of 107 adult, English-speaking patients with suspected and confirmed COVID-19 cases at the 3 primary care practices of Stony Brook University Hospital were studied between March and December 2020. Survey data were collected from patient telephone interviews and electronic medical record abstraction. The potential risk factors assessed included participant demographics, medical comorbidities, and the number and type of symptoms at illness onset. Outcome measures included symptom duration, hospitalizations, and persistence of symptoms at 12 weeks from study enrollment. Results: Patient self-report survey elicited nearly twice as many symptoms described at illness onset as those recorded in the electronic medical record (p<0.0001). A higher number of symptoms at illness onset was positively associated with symptom duration and chronicity. The presence of fever and hypoxia at the onset of illness were each positively associated with eventual hospitalization for COVID-19 disease. Conclusions: Early in the setting of newly emerging infectious diseases, particularly those such as COVID-19 that involve multiple organ systems, patient self-report of symptoms using a complete review of systems rather than electronic medical record abstraction alone may be key for accurate disease identification and characterization as well as prediction of eventual disease severity, duration, and chronicity.

Incidence of new-onset in-hospital and persistent diabetes in COVID-19 patients: comparison with influenza.

BACKGROUND: This study investigated the incidences and risk factors associated with new-onset persistent type-2 diabetes during COVID-19 hospitalization and at 3-months follow-up compared to influenza. METHODS: This retrospective study consisted of 8216 hospitalized, 2998 non-hospitalized COVID-19 patients, and 2988 hospitalized influenza patients without history of pre-diabetes or diabetes in the Montefiore Health System in Bronx, New York. The primary outcomes were incidences of new-onset in-hospital type-2 diabetes mellitus (I-DM) and persistent diabetes mellitus (P-DM) at 3 months (average) follow-up. Predictive models used 80%/20% of data for training/testing with five-fold cross-validation. FINDINGS: I-DM was diagnosed in 22.6% of patients with COVID-19 compared to only 3.3% of patients with influenza (95% CI of difference [0.18, 0.20]). COVID-19 patients with I-DM compared to those without I-DM were older, more likely male, more likely to be treated with steroids and had more comorbidities. P-DM was diagnosed in 16.7% of hospitalized COVID-19 patients versus 12% of hospitalized influenza patients (95% CI of difference [0.03,0.065]) but only 7.3% of non-hospitalized COVID-19 patients (95% CI of difference [0.078,0.11]). The rates of P-DM significantly decreased from 23.9% to 4.0% over the studied period. Logistic regression identified similar risk factors predictive of P-DM for COVID-19 and influenza. The adjusted odds ratio (0.90 [95% CI 0.64,1.28]) for developing P-DM was not significantly different between the two viruses. INTERPRETATION: The incidence of new-onset type-2 diabetes was higher in patients with COVID-19 than influenza. Increased risk of diabetes associated with COVID-19 is mediated through disease severity, which plays a dominant role in the development of this post-acute infection sequela. FUNDING: None.

COVID-19 Patients in the COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx.

Background: Early in the pandemic, we established COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx and implemented a detailed evaluation protocol to assess physical, emotional, and cognitive function, pulmonary function tests, and imaging for COVID-19 survivors. Here, we report our findings up to five months post-acute COVID-19. Methods: Main outcomes and measures included pulmonary function tests, imaging tests, and a battery of symptom, physical, emotional, and cognitive assessments 5 months post-acute COVID-19. Findings: Dyspnea, fatigue, decreased exercise tolerance, brain fog, and shortness of breath were the most common symptoms but there were generally no significant differences between hospitalized and non-hospitalized cohorts (p > 0.05). Many patients had abnormal physical, emotional, and cognitive scores, but most functioned independently; there were no significant differences between hospitalized and non-hospitalized cohorts (p > 0.05). Six-minute walk tests, lung ultrasound, and diaphragm excursion were abnormal but only in the hospitalized cohort. Pulmonary function tests showed moderately restrictive pulmonary function only in the hospitalized cohort but no obstructive pulmonary function. Newly detected major neurological events, microvascular disease, atrophy, and white-matter changes were rare, but lung opacity and fibrosis-like findings were common after acute COVID-19. Interpretation: Many COVID-19 survivors experienced moderately restrictive pulmonary function, and significant symptoms across the physical, emotional, and cognitive health domains. Newly detected brain imaging abnormalities were rare, but lung imaging abnormalities were common. This study provides insights into post-acute sequelae following SARS-CoV-2 infection in neurological and pulmonary systems which may be used to support at-risk patients and develop effective screening methods and interventions.

Coronavirus Disease 2019 (COVID-19) Perinatal Outcomes Across the Pandemic at an Academic Medical Center in New York City.

OBJECTIVE: To investigate perinatal complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy in the four major waves of the coronavirus disease 2019 (COVID-19) pandemic in the Bronx, New York. METHODS: This retrospective cohort study included all patients who delivered at a single academic medical center between March 1, 2020, and February 13, 2022. SARS-CoV-2 positivity was defined as a positive SARS-CoV-2 test result during pregnancy. Primary outcomes were preterm birth, low birth weight, stillbirth, cesarean delivery, and preeclampsia associated with SARS-CoV-2 infection. Secondary analyses examined outcomes by predominant variant at the time of infection. Group differences in categorical variables were tested using χ2 tests. RESULTS: Of the 8,983 patients who delivered, 638 (7.1%) tested positive for SARS-CoV-2 infection during pregnancy. Age, race, ethnicity, and major comorbidities did not differ significantly between the SARS-CoV-2-positive and SARS-CoV-2-negative cohorts (P>.05). Primary outcomes did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative cohorts (P>.05). There was a marked increase in positive SARS-CoV-2 test results in individuals who gave birth during the Omicron wave (140/449, 31.2%). However, among patients who tested positive for SARS-CoV-2 infection, the preterm birth rate during the Omicron wave (9.9%) was significantly lower than during the original wave (20.3%) and the Alpha (18.4%) wave (P<.05). Vaccination rates were low before the Omicron wave and rose to 47.2% during the Omicron wave among individuals hospitalized with SARS-CoV-2 infection. Finally, second-trimester infection was significantly associated with worse perinatal outcomes compared with third-trimester infection (P<.05). CONCLUSION: There was a general trend toward improvement in preterm birth rates across the pandemic among pregnant patients with SARS-CoV-2 infection. The Omicron variant was more infectious, but the preterm birth rate during the Omicron wave was low compared with that during the original wave and the Alpha wave.

Longitudinal medical subspecialty follow-up of critically and non-critically ill hospitalized COVID-19 survivors up to 24 months after discharge.

Medical specialty usage of COVID-19 survivors after hospital discharge is poorly understood. This study investigated medical specialty usage at 1-12 and 13-24 months post-hospital discharge in critically ill and non-critically ill COVID-19 survivors. This retrospective study followed ICU (N = 89) and non-ICU (N = 205) COVID-19 survivors who returned for follow-up within the Stony Brook Health System post-hospital discharge. Follow-up data including survival, hospital readmission, ongoing symptoms, medical specialty care use, and ICU status were examined 1-12 and 13-24 months after COVID-19 discharge. "New" (not previously seen) medical specialty usage was also identified. Essentially all (98%) patients survived. Hospital readmission was 34%, but functional status scores at discharge were not associated with hospital readmission. Many patients reported ongoing [neuromuscular (50%) respiratory (39%), chronic fatigue (35%), cardiovascular (30%), gastrointestinal (28%), neurocognitive (22%), genitourinary (22%), and mood-related (13%)] symptoms at least once 1-24 months after discharge. Common specialty follow-ups included cardiology (25%), vascular medicine (17%), urology (17%), neurology (16%), and pulmonology (14%), with some associated with pre-existing comorbidities and with COVID-19. Common new specialty visits were vascular medicine (11%), pulmonology (11%), and neurology (9%). ICU patients had more symptoms and follow-ups compared to the non-ICU patients. This study reported high incidence of persistent symptoms and medical specialty care needs in hospitalized COVID-19 survivors 1-24 months post-discharge. Some specialty care needs were COVID-19 related or exacerbated by COVID-19 disease while others were associated with pre-existing medical conditions. Longer follow-up studies of COVID-19 survivor medical care needs are necessary.

Clinical predictors of recovery of COVID-19 associated-abnormal liver function test 2 months after hospital discharge.

This study investigated whether acute liver injury (ALI) persisted and identified predictors of ALI recovery [as indicated by alanine aminotransferase (ALT) level] at hospital discharge and 2 months post-discharge for 7595 hospitalized COVID-19 patients from the Montefiore Health System (03/11/2020-06/03/2021). Mild liver injury (mLI) was defined as ALT = 1.5-5 ULN, and severe livery injury (sLI) was ALT ≥ 5 ULN. Logistic regression was used to identify predictors of ALI onset and recovery. There were 4571 (60.2%), 2306 (30.4%), 718 (9.5%) patients with no liver injury (nLI), mLI and sLI, respectively. Males showed higher incidence of sLI and mLI (p < 0.05). Mortality odds ratio was 4.15 [95% CI 3.41, 5.05, p < 0.001] for sLI and 1.69 [95% CI 1.47, 1.96, p < 0.001] for mLI compared to nLI. The top predictors (ALT, lactate dehydrogenase, ferritin, lymphocytes) accurately predicted sLI onset up to three days prior. Only 33.5% of mLI and 17.1% of sLI patients (survivors) recovered completely at hospital discharge. Most ALI patients (76.7-82.4%) recovered completely ~ 2 months post-discharge. The top predictors accurately predicted recovery post discharge with 83.2 ± 2.2% accuracy. In conclusion, most COVID-19 patients with ALI recovered completely ~ 2 months post discharge. Early identification of patients at-risk of persistent ALI could help to prevent long-term liver complications.

Small GTPase-A Key Role in Host Cell for Coronavirus Infection and a Potential Target for Coronavirus Vaccine Adjuvant Discovery.

Small GTPases are signaling molecules in regulating key cellular processes (e.g., cell differentiation, proliferation, and motility) as well as subcellular events (e.g., vesicle trafficking), making them key participants, especially in a great array of coronavirus infection processes. In this review, we discuss the role of small GTPases in the coronavirus life cycle, especially pre-entry, endocytosis, intracellular traffic, replication, and egress from the host cell. Furthermore, we also suggest the molecules that have potent adjuvant activity by targeting small GTPases. These studies provide deep insights and references to understand the pathogenesis of coronavirus as well as to propose the potential of small GTPases as targets for adjuvant development.

Risk Factors Associated With Increased Anxiety Sensitivity in Children and Adolescents in Northwest China During COVID-19 Pandemic Lockdown

Purpose A large body of evidence has revealed that the sudden outbreak of public health emergencies induces dramatic effects on the mental health of the general public. We aimed to investigate the level of anxiety sensitivity and its risk factors in children and adolescents from northwest China during the COVID-19 pandemic lockdown in early 2020. Methods A cross-sectional survey was conducted through the Wenjuanxing platform using a convenience sampling method between 18 and 26 February 2020. The self-designed questionnaire contained sociodemographic characteristics, factors associated with the COVID-19 pandemic, and the Childhood Anxiety Sensitivity Index (CASI) scale. The data from 1,091 valid questionnaires from students aged 9–17 years were analyzed using ANOVA, multiple linear regression, and binary logistic regression. Results The average CASI scores were 11.47 ± 6.631, and 642 students (58.9%) had prominent anxiety sensitivity. Gender, education level, family members participating in anti-COVID-19 work, getting ill and needing medical help during the lockdown, feeling afraid or having heart palpitations on hearing things associated with COVID-19, believing that COVID-19 would have adverse impacts on themselves or their family in the future, and fear of infection were identified as significant factors for elevated levels of anxiety sensitivity (p < 0.05). We established a multiple linear regression model for the anxiety sensitivity score. Risk factors found for anxiety sensitivity in children and adolescents during the COVID-19 lockdown included studying in secondary or high school, becoming ill during the pandemic, feeling afraid or experiencing rapid heartbeat or palpitations on hearing about the COVID-19 pandemic, thinking that COVID-19 would have an adverse impact on themselves or their family in the future, and fear of infection. Conclusions During the COVID-19 pandemic and home quarantine, scores measuring the prevalence of anxiety sensitivity in children and adolescents from northwest China were elevated. We should develop measures that especially target possible risk factors to intervene against and prevent anxiety sensitivity in children and adolescents in both the current and future pandemics.

Outcomes of Hospitalized Patients With COVID-19 With Acute Kidney Injury and Acute Cardiac Injury.

PURPOSE: This study investigated the incidence, disease course, risk factors, and mortality in COVID-19 patients who developed both acute kidney injury (AKI) and acute cardiac injury (ACI), and compared to those with AKI only, ACI only, and no injury (NI). METHODS: This retrospective study consisted of hospitalized COVID-19 patients at Montefiore Health System in Bronx, New York between March 11, 2020 and January 29, 2021. Demographics, comorbidities, vitals, and laboratory tests were collected during hospitalization. Predictive models were used to predict AKI, ACI, and AKI-ACI onset. Longitudinal laboratory tests were analyzed with time-lock to discharge alive or death. RESULTS: Of the 5,896 hospitalized COVID-19 patients, 44, 19, 9, and 28% had NI, AKI, ACI, and AKI-ACI, respectively. Most ACI presented very early (within a day or two) during hospitalization in contrast to AKI (p < 0.05). Patients with combined AKI-ACI were significantly older, more often men and had more comorbidities, and higher levels of cardiac, kidney, liver, inflammatory, and immunological markers compared to those of the AKI, ACI, and NI groups. The adjusted hospital-mortality odds ratios were 17.1 [95% CI = 13.6-21.7, p < 0.001], 7.2 [95% CI = 5.4-9.6, p < 0.001], and 4.7 [95% CI = 3.7-6.1, p < 0.001] for AKI-ACI, ACI, and AKI, respectively, relative to NI. A predictive model of AKI-ACI onset using top predictors yielded 97% accuracy. Longitudinal laboratory data predicted mortality of AKI-ACI patients up to 5 days prior to outcome, with an area-under-the-curve, ranging from 0.68 to 0.89. CONCLUSIONS: COVID-19 patients with AKI-ACI had markedly worse outcomes compared to those only AKI, ACI and NI. Common laboratory variables accurately predicted AKI-ACI. The ability to identify patients at risk for AKI-ACI could lead to earlier intervention and improvement in clinical outcomes.

Comparing body mass index and obesity-related comorbidities as predictors in hospitalized COVID-19 patients.

The association between body mass index (BMI) and poor COVID-19 outcomes in patients has been demonstrated across numerous studies. However, obesity-related comorbidities have also been shown to be associated with poor outcomes. The purpose of this study was to determine whether BMI or obesity-associated comorbidities contribute to elevated COVID-19 severity in non-elderly, hospitalized patients with elevated BMI (≥25 kg/m2 ). This was a single-center, retrospective cohort study of 526 hospitalized, non-elderly adult (aged 18-64) COVID-19 patients with BMI ≥25 kg/m2 in suburban New York from March 6 to May 11, 2020. The Edmonton Obesity Staging System (EOSS) was used to quantify the severity of obesity-related comorbidities. EOSS was compared with BMI in multivariable regression analyses to predict COVID-19 outcomes. We found that higher EOSS scores were associated with poor outcomes after demographic adjustment, unlike BMI. Specifically, patients with increased EOSS scores had increased odds of acute kidney injury (adjusted odds ratio [aOR] = 6.40; 95% CI 3.71-11.05), intensive care unit admission (aOR = 10.71; 95% CI 3.23-35.51), mechanical ventilation (aOR = 3.10; 95% CI 2.01-4.78) and mortality (aOR = 5.05; 95% CI 1.83-13.90). Obesity-related comorbidity burden as determined by EOSS was a better predictor of poor COVID-19 outcomes relative to BMI, suggesting that comorbidity burden may be driving risk in those hospitalized with elevated BMI.

Clinical predictors of acute cardiac injury and normalization of troponin after hospital discharge from COVID-19.

BACKGROUND: Although acute cardiac injury (ACI) is a known COVID-19 complication, whether ACI acquired during COVID-19 recovers is unknown. This study investigated the incidence of persistent ACI and identified clinical predictors of ACI recovery in hospitalized patients with COVID-19 2.5 months post-discharge. METHODS: This retrospective study consisted of 10,696 hospitalized COVID-19 patients from March 11, 2020 to June 3, 2021. Demographics, comorbidities, and laboratory tests were collected at ACI onset, hospital discharge, and 2.5 months post-discharge. ACI was defined as serum troponin-T (TNT) level >99th-percentile upper reference limit (0.014ng/mL) during hospitalization, and recovery was defined as TNT below this threshold 2.5 months post-discharge. Four models were used to predict ACI recovery status. RESULTS: There were 4,248 (39.7%) COVID-19 patients with ACI, with most (93%) developed ACI on or within a day after admission. In-hospital mortality odds ratio of ACI patients was 4.45 [95%CI: 3.92, 5.05, p<0.001] compared to non-ACI patients. Of the 2,880 ACI survivors, 1,114 (38.7%) returned to our hospitals 2.5 months on average post-discharge, of which only 302 (44.9%) out of 673 patients recovered from ACI. There were no significant differences in demographics, race, ethnicity, major commodities, and length of hospital stay between groups. Prediction of ACI recovery post-discharge using the top predictors (troponin, creatinine, lymphocyte, sodium, lactate dehydrogenase, lymphocytes and hematocrit) at discharge yielded 63.73%-75.73% accuracy. INTERPRETATION: Persistent cardiac injury is common among COVID-19 survivors. Readily available patient data accurately predict ACI recovery post-discharge. Early identification of at-risk patients could help prevent long-term cardiovascular complications. FUNDING: None.

Six-month follow-up of functional status in discharged patients with coronavirus disease 2019.

BACKGROUND: The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors. METHODS: We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge. RESULTS: We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33-12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06-10.81, p = 0.039). CONCLUSIONS: A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required.

Prophylactic versus therapeutic dose anticoagulation effects on survival among critically ill patients with COVID-19.

INTRODUCTION: Although patients with severe COVID-19 are known to be at high risk of developing thrombotic events, the effects of anticoagulation (AC) dose and duration on in-hospital mortality in critically ill patients remain poorly understood and controversial. The goal of this study was to investigate survival of critically ill COVID-19 patients who received prophylactic or therapeutic dose AC and analyze the mortality rate with respect to detailed demographic and clinical characteristics. MATERIALS AND METHODS: We conducted a retrospective, observational study of critically ill COVID-19 patients admitted to the ICU at Stony Brook University Hospital in New York who received either prophylactic (n = 158) or therapeutic dose AC (n = 153). Primary outcome was in-hospital death assessed by survival analysis and covariate-adjusted Cox proportional hazard model. RESULTS: For the first 3 weeks of ICU stay, we observed similar survival curves for prophylactic and therapeutic AC groups. However, after 3 or more weeks of ICU stay, the therapeutic AC group, characterized by high incidence of acute kidney injury (AKI), had markedly higher death incidence rates with 8.6 deaths (95% CI = 6.2-11.9 deaths) per 1,000 person-days and about 5 times higher risk of death (adj. HR = 4.89, 95% CI = 1.71-14.0, p = 0.003) than the prophylactic group (2.4 deaths [95% CI = 0.9-6.3 deaths] per 1,000 person-days). Among therapeutic AC users with prolonged ICU admission, non-survivors were characterized by older males with depressed lymphocyte counts and cardiovascular disease. CONCLUSIONS: Our findings raise the possibility that prolonged use of high dose AC, independent of thrombotic events or clinical background, might be associated with higher risk of in-hospital mortality. Moreover, AKI, age, lymphocyte count, and cardiovascular disease may represent important risk factors that could help identify at-risk patients who require long-term hospitalization with therapeutic dose AC treatment.