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Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), a triple CFTR modulator combination, has proved to be highly effective in Phe508del homozygous and Phe508del/minimal function compound heterozygous people with cystic fibrosis (PwCF).We report preliminary data on the realworld effectiveness and safety of ELX/TEZ/IVA after 6 months of treatment. Method(s):We collected prospective data on PwCF who started ELX/TEZ/IVA and evaluated changes in pulmonary function (spirometry and lung clearance index [LCI]), nutritional status (body mass index [BMI]), sweat chloride, and rate of hospitalization from baseline to 6 months of treatment. Result(s): Between August 2021 and October 2021, ELX/TEZ/IVAwas started in 24 PwCF (12 female,10 Phe508del-homozygous, median age 20.5 (range 13-37), all with pancreatic insufficiency). After 6 months of treatment, all respiratory function indicators improved (median change: +16% percentage predicted forced expiratory volume in 1 second, +12% percentage predicted forced vital capacity, +23% percentage predicted forced expiratory flow at 25/75%, -2 lung clearance index). Improvement was also observed in BMI (+0.41 z-score) and sweat chloride concentrations (-54 mMol/L, 6 PwCF had Cl concentrations within the limit of normality) (Table 1). Over a 6-month period, only one hospitalization due to pulmonary exacerbations was observed, compared with 22 hospitalizations observed in the 6 months before starting ELX/TEZ/IVA (rate per 100 patient-months 15.3 vs 0.7, rate ratio 0.05, 95% CI, 0.01-0.29). Treatment was well tolerated, with only mild and transient adverse events consisting of headache (n = 4), cutaneous rash (n = 2), and mild hemoptysis (n = 2). One PwCF had intestinal subocclusion and required hospitalization. One patient had liver function test elevation after 6 months of therapy during an Changes in clinical variables and sweat test results from baseline through 6 months in patients treated with elexacaftor, tezacaftor and ivacaftor. Data are medians (interquartile ranges). Baseline vs 6 months compared usingWilcoxon signed-rank test. ppFEV1, percentage predicted forced expiratory volume in 1 second;ppFVC, percentage predicted forced vital capacity;ppFEV25/75, percentage predicted forced expiratory flow at 25/75%;LCI, lung clearance index;BMI, body mass index;Cl, chloride. (Table Presented) episode of SARS-COV2 infection, which required adjustment of the dose administered. Conclusion(s): Our data confirm that ELX/TEZ/IVA treatment is safe, well tolerated, and effective in PwCF. ELX/TEZ/IVA improved pulmonary function and nutritional status and remarkably reduced hospitalization rate. Our data indicate that introduction of ELX/TEZ/IVA in CF care will radically change the natural history of and management approach to the disease.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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Introduction: higher value of urea/albumin (U/A) ratio is associated with higher risk of death in patients with pneumonia. It is known that infections by COVID-19 can lead to ICU admission and death, and, in this scenario, the evaluation of this marker can be useful to improve the management of these patients. Objective(s): to evaluate the U/A ratio as a predictor of mortality in patients hospitalized for COVID-19. Method(s): 252 unvacinated patients with COVID-19 hospitalized between April 2020 and February 2021 were included in this cohort and were assessed by complete blood count and laboratory analysis on the first and third day of hospitalization. Result(s): Of the total number of patients, 153 were hospitalized in a ward and, of these, 28 died. Of those who required intensive care (n=99) 72 died. The comparison of the U/A ratio was lower in survivors when compared to the dyed group on the first day of hospitalization (14.0+/-10.3 vs 22.1+/-18.8;p<0.001) and on the third day (19.1+/-16.1 vs 28.3+/-16.8;p=0.005). The absolute variation in urea on the third day from baseline was also lower in the group of survivors (1.59+/-13.8 vs 30.9+/-37.9;p<0.001). The multiple logistic regression model adjusted for age, sex, place of hospitalization and C-reactive protein showed that the U/A ratio on the first day was associated with a higher risk of mortality [OR: 1.04;95%CI: 1.02-1.07;p=0.002]. The U/A ratio on the third day was not associated with risk of death whereas the absolute variation in urea showed an association with mortality [OR: 1.03;(95%CI: 1.01-1.05);p<0.001]. Conclusion(s): the use of the U/A ratio and the urea variation can predict mortality in patients hospitalized for COVID19.
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Background: The severity of Covid-19 and its long-term effects in people with cystic fibrosis (pwCF) are poorly defined. Aim and objectives: To evaluate respiratory outcomes 6 months after SARS-Cov-2 infection in pwCF. Method(s): The study was based on pwCF enrolled from October 15, 2020 to June 30, 2021 in the DECO COVID-19 project, a multicentre prospective study supported by the Italian Ministry of Health (COVID-2020-12371781), that involved 3 Regional Reference Centres for CF (Milan, Rome and Verona). We enrolled pwCF tested with real time polymerase chain reaction (RT-PCR) for SARS-Cov-2 on nasopharyngeal swab for suggestive symptoms of Covid19 and/or for hospital admission. After 6 months follow up, we compared changes in percent predicted forced expiratory volume in one second (ppFEV1) and the rate of pulmonary exacerbations between patients positive or negative for SARS-Cov-2. Result(s): We enrolled 28 pwCF with RT-PCR confirmed infection (median age: 30 years, range: 6-66) and 130 negative to RT-PCR test (median age: 24 years, range: 5-63). The median baseline ppFEV values (range) were 91 (34-114) and 79 (25-117) in those positive and negative to RT-PCR, respectively (P= 0.256). After 6 months ppFEV1 changes were not significantly different between groups (median, interquartile range: 0.8% -5.0;4.0 among positive and +2%, -5.0;6.0 among those who tested negative, P = 0.618). The rates of pulmonary exacerbations were 0.17 per person-month among patients who tested positive and 0.14 in negative pwCF (Incidence rate ratio: 1.19, 95% CI: 0.80-1.76). Conclusion(s): In our CF population, SARS-Cov-2 infection did not impact negatively on respiratory outcomes at 6 months follow up.
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Introduction: Mechanical ventilation (MV) is a known risk to impact in respiratory and functional capacity postCOVID-19 infection. Objective(s): Assess pulmonary function, muscular strength and quality of life in post-COVID-19 patients submitted or not to MV. Method(s): During March of 2020 and July 2021 we had 983 hospitalized COVID-19 patients and 527 patients were discharged and invited to be followed at the multidisciplinary assistance. From the total, 116 patients [57% male, 59(52-67) years] were evaluated 60 days after first symptoms appearance through pulmonary function testing, manovacuometry, handgrip test and Saint George's Respiratory Questionnaire (SGRQ). There were no vaccinated subjects. Result(s): 34% of the patients needed intensive care (n=39), of which, 51% needed MV (n=20). MV group showed statistically significant weaker handgrip strength [27(18-35) kgf vs 35(26-45) kgf;p=0,025] and maximum inspiratory pressure predicted percentile reduction (86+/-23,5% vs 101+/-27,6%;p=0,043) when compared to non-MV group. We did not observe SGRQ differences between the groups. However, females showed statistically significant higher impact in quality of life in all SGRQ domains compared to males. There were no differences in pulmonary function. Conclusion(s): MV submitted patients presented worsened respiratory and peripheral muscular strengths without difference in pulmonary function and quality of life. Women showed higher impact in quality of life regardless of MV use.
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Introduction: Some patients affected by COVID-19 remain hospitalized due exclusively to persistent hypoxemia. The indication of long-term home oxygen therapy (LTOT) has become a strategy adopted to reduce the length of hospital stay. The influence of the degree of severity of disease involvement on the effectiveness of the strategy is unknown. Objective(s): To evaluate the clinical characteristics of patients with LTOT indication according to the type of hospitalization in COVID-19 patients. Method(s): An exploratory cross-sectional study of associated factors in stable discharged COVID-19 patients using LTOT were consecutively included. Result(s): Between April and December 2021, a total of 62 patients with LTOT indication were evaluated 15 days after hospital discharge. Of these, 32 of them required intensive care unit (ICU) at some point during their hospitalization. When we compared the ICU and ward care groups, we observed differences in age (55.84 +/-13.5 vs 68.42 +/- 14.8, p=0.001) and time of hospitalization (31.63 +/- 21.8 v 17.65 +/-9, p=0.002). However, we did not identify statistical differences between groups on gender and degree of pulmonary involvement on tomography during hospitalization. After 15 days of discharge, there was no statistically significant difference between the two groups in terms of the number of patients who needed to maintain LTOT for more period (8 vs 11). Conclusion(s): Regardless of the severity of hospitalization, most patients did not need to maintain LTOT for more than 15 days. LTOT proved to be a temporary and effective strategy to shorten the length of stay in both groups in stable COVID-19 patients.
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Effects of Olive Mill Wastewater and Two Natural Extracts as Nitrification Inhibitors on Activity of Nitrifying Bacteria, Soil Nitrate Leaching Loss, and Nitrogen Metabolism of Celery (Apium graveolens L.). Minimizing nitrification of fertilizer ammonium (NH4 +) can reduce nitrate (NO3 -) contamination of groundwater and increase nitrogen (N) use efficiency (NUE). Olive mill wastewater (OMW), hydroalcoholic extracts of Mentha piperita L.(Mp) and Artemisia annua L.(Aa), and the synthetic nitrification inhibitor (NI) dicyandiamide (DCD) were investigated. The three natural products and DCD reduced activity of nitrifying bacteria and decreased NO3 - leached, compared to the untreated control. OMW proved to be an almost equally effective natural alternative to DCD as a NI.
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Background. Infection with SARS-CoV-2 and the resulting host immune response has been primarily characterized in middle and older aged populations due to a higher incidence of symptoms in these age groups. Due to reduced severity of disease, children were poorly studied and assumed to be less frequently infected compared to older age groups. We measured the viral load and adaptive immune response across the age-spectrum to define the age-dependent viral and host responses. Methods. From March 2020-March 2022, we enrolled individuals across the age spectrum who presented to U.S. military medical treatment facilities with COVID-19-like symptoms. In this longitudinal cohort study, demographic and clinical data were collected in addition to nasopharyngeal swabs and peripheral blood. Magnitude of viral RNA was measured by quantitative PCR (qPCR) from nasopharyngeal samples and SARS-CoV-2-specific IgG antibodies were measured from blood with multiplex microsphere immunoassays. Results. 4,768 SARS-CoV-2 positive participants were enrolled, among whom 42, 64, 89, 380, 948 and 245 individuals were in age brackets 0-4y, 5-11y, 12-17y, 18-44, 45-64y, and >65y, respectively. Viral load as measured by qPCR was determined to be similar across age groups within the first week post symptom onset. The magnitude of the IgG antibody response against the spike protein was also compared across age groups at early and convalescent time points and was higher in those over the age of 65 years. Conclusion. Early viral load during acute infection did not correlate with age in individuals who experienced COVID-19. These findings diverge from other respiratory viruses, such as respiratory syncytial virus and influenza where children tend to have higher viral loads. In contrast, the magnitude of the antibody response against the spike protein correlated with older age at acute and convalescent time points. Together our data suggest that the host response against SAR-CoV-2 differs with age and is not associated with the acute viral load. Defining age-dependent immunity against SARS-CoV-2 has the potential to identify key immunologic responses that can be used to optimize treatment and vaccine strategies.
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Background. Characterizing, diagnosing, and caring for 'long COVID' patients has proven to be challenging due to heterogenous symptoms and broad definitions of these post-acute sequelae. Here, we take a machine learning approach to identify discrete clusters of long COVID symptoms which may define specific long COVID phenotypes. Figure 1: (A) Principal component analysis followed by K-means clustering identified three groups of participants. (B) Heatmap depicting three distinct clusters (high values are in red and low value are in blue);Cluster 1 exhibits sensory symptoms (e.g., loss of smell and/or taste), Cluster 2 exhibits fatigue and difficulty thinking (e.g., changes in ability to think) symptoms, and Cluster 3 exhibits difficulty breathing and exercise intolerance symptoms. (C) Clinical and demographic characteristics of 97 military health system beneficiaries by identified clusters Methods. The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal COVID-19 cohort study with data and biospecimens collected from 10 military treatment facilities and online recruitment. Demographic and clinical characteristics were collected using case report forms and surveys completed at enrollment and at 1, 3, 6, 9, and 12 months. For this analysis, we identified those who reported any moderate to severe persistent symptoms on surveys collected 6-months post-COVID-19 symptom onset. Using the survey responses, we applied principal component analysis (PCA) followed by unsupervised machine learning clustering algorithm K-means to identify groups with distinct clusters of symptoms. Results. Of 1299 subjects with 6-month survey responses, 97 (7.47%) reported moderate to severe persistent symptoms. Among these subjects, three clusters were identified using PCA (Figure 1A). Cluster 1 is characterized by sensory symptoms (loss of taste and/or smell), Cluster 2 by fatigue and difficulty thinking, and Cluster 3 by difficulty breathing and exercise intolerance (Figure 1B). More than half of these subjects (57%) were female, 64% were 18-44 years old, and 64% had no comorbidities at enrollment (Figure 1C). Those in the sensory symptom cluster were all outpatients at the time of initial COVID-19 presentation (p < 0.01). The difficulty breathing and exercise intolerance symptom-clusters had a higher proportion of older participants (Age group >= 45-64) with more comorbidities (CCI >= 1-2). Conclusion. We identified three distinct 'long COVID' phenotypes among those with moderate to severe COVID-19 symptoms at 6-months post-symptom onset. With further validation and characterization, this framework may allow more precise classification of long COVID cases, and potentially improve the diagnosis, prognosis, and treatment of post- infectious sequelae.
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Background. Omicron SARS-CoV-2 infections are associated with less frequent olfactory sensory loss and a predominance of pharyngitis symptoms compared to prior variants, with proposed diagnostic implications. We examined whether such symptomology predicts a higher RNA abundance in the oropharynx. We further investigated how age, symptom-day, vaccination history and clinical severity correlate with viral load to inform clinical prognostication and transmission modeling. Methods. The EPICC study is a longitudinal cohort of COVID-19 cases enrolled through U.S military medical treatment facilities. Demographic and clinical characteristics were measured with interviews and surveys. Nasopharyngeal (NP), oropharyngeal (OP) and nasal swabs (NS) were collected for SARS-CoV-2 qPCR and sequence genotyping. Multivariable linear regression models were fit to estimate the effect of anatomical site on SARS-CoV-2 RNA abundance (a proxy for viral load), adjusting for sampling time, vaccine history and host age. Results. We analyzed 77 sequence-confirmed Omicron cases;no BA.2 cases were detected. The median age was 38.8 years. 81.8% were vaccinated and 15.6% cases were hospitalized. 80.0%, 21.8%, and 65.5% reported nasal congestion, loss of smell or taste, and sore throat, respectively. The median RNA abundance was lowest in OP swabs (p < 0.001) (Fig 1). Linear regression confirmed that OP sampling was associated with lower viral load (p < 0.001). We further noted that greater age and symptom-day were independent correlates of viral load (Table 1). By bivariate analysis there was a trend toward lower RNA abundance in vaccinated subjects (p = 0.35). RNA abundance (at any site) was substantially higher in hospitalized (10634 N2 genome equivalents [GE]/reaction) versus outpatient cases (1419 N1 GE/reaction) but this was not statistically significant (p = 0.26). Conclusion. We noted prevalent sore throat symptoms and infrequent sensory loss in Omicron cases. Despite this, viral load was highest in NP/NS collected swabs as has been noted in prior variants. We note an age correlation with RNA abundance, and provide a viral load decay rate which may be useful for transmission modeling. Vaccination and clinical severity may also correlate with Omicron viral load, as noted with prior SARS-CoV-2 variants.
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Background. COVID-19 may have deleterious effects on the fitness of active duty US military service members. We seek to understand the long-term functional consequences of SARS-CoV-2 infection in this critical population, and in other military healthcare beneficiaries. Methods. The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal cohort study to describe the outcomes of SARS-CoV-2 infection in US Military Health System beneficiaries. Subjects provided information about difficulties experienced with daily activities, exercise, and physical fitness performance via electronic surveys. Subjects completed surveys at enrollment and at 1, 3, 6, 9, and 12 months. Results. 5,910 subjects completed survey fitness questions, 3,244 (55%) of whom tested SARS-CoV-2 positive at least once during the period of observation. Over 75% of subjects were young adults and over half were male (Table 1). 1,093 (34.3%) of SARS-CoV-2-positive subjects reported new or increased difficulty exercising compared to 393 (14.8%) SARS-CoV-2 negative subjects (p < 0.01) (Table 2). The most commonly reported symptoms related to problems with exercise and activities were dyspnea and fatigue.Among the active-duty members who answered the question about their service-mandated physical fitness test scores, 43.2% of SARS-CoV-2-positive participants reported that their scores had worsened in the study period, compared with 24.3%of SARS-CoV-2 negative participants.Among SARS-CoV-2-positive subjects, reports of difficulty exercising and performing daily activities were highest within one month of the first positive test, decreasing in prevalence among the cohort only slightly to 24% and 18%, respectively, at 12 months (Figure 1). Conclusion. A substantial proportion of military service-members in this cohort have reported impairment of their service-mandated physical fitness scores after COVID-19;this proportion is significantly higher than those who are SARS-CoV-2 negative and persists to 12 months in many;similar complaints were reported among non-active duty. Further objective evaluation of post-COVID fitness impairment in this population is warranted. (Figure Presented).
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Background: The BNT162b2 mRNAvaccine (Pfizer-BioNTech) was the first anti-SARS-CoV-2 vaccine approved and has shown 95% efficacy against severe COVID-19. The vaccine elicits a combined humoral and cellular adaptive immune response, albeit with high between-subject variability. The humoral response wanes 4 to 6 months after vaccination and, considered alone, does not appear to be indicative of protective immune memory. The role of cell-mediated immune response, which may be more relevant in the long-term protection against SARS-CoV-2, has not been clarified. Our aim was to evaluate the humoral and cell-mediated immune responses induced by administration of the BNT162b2 vaccine 6 to 8 months after the second dose in people with cystic fibrosis (PwCF) and the possible relationship between the anti-SARS-CoV-2 immunoglobulin (Ig)G-S antibodies (Spike protein) titer and the CD4+/CD8+ cell-mediated response. Method(s): One hundred thirteen PwCF (43 male, median age 21, range 11- 64) were enrolled, including 12 patients with virologically confirmed prior SARS-CoV-2 infection. Patients receiving chronic steroid therapy and transplant recipients were excluded. Serum IgG-S was determined by Elecsys anti-SARS-CoV-2 S (Roche) enzyme immunoassay with cut-off for positive response at 0.8 U/mL;cell-mediated immune response was measured using the STANDARDTM F CoviFERON FIA (interferon-gamma) system, a newrapid interferon gamma release assay (IGRA),with cut-off for positive response at 0.30 U/mL on standard F2400 (SD Biosensor, Inc. Korea). Result(s): All patients showed a humoral response 6 to 8 months after the second vaccine dose, with a median antibody titer of 1,288 U/mL (interquartile range [IQR] 610-2397). PwCF who were previously infected by SARS-CoV-2 had higher antibody titers than those naive to the virus (median 6,302, IQR 4272-8349 vs 1,180, IQR 535-1742;p < 0.001). Sixtyone patients (54%) developed a cell-mediated immune response against SARS-CoV-2. Antibody titer was higher in patients with a positive cellmediated response (median 1453, IQR 778-4473) than in those without (median 1054, IQR 510-1498) ( p = 0.01). Conclusion(s): All patients developed an adequate humoral response after two doses of BNT162b2 vaccine;the antibody titer was higher in patients with previous SARS-CoV-2 infection than in naive patients. We documented a cell-mediated response in 54% of patients, and this was associated with a higher antibody titer. Further studies are needed to understand whether development of cell-mediated immune response is elicited with greater protection against severe COVID-19 in PwCF. If this were the case, this rapid and relatively inexpensive test might be a useful tool to determine the best timing for additional vaccine doses in this clinically vulnerable population. Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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Multivalent ligands of the C-type lectin receptor DC-SIGN have emerged as effective antiadhesive agents against various pathogens. Some years ago, we described a hexavalent DC-SIGN ligand, Polyman-26, designed to bridge two of the four binding sites displayed by the receptor. In this work, we present our efforts to accomplish simultaneous coordination of all four carbohydrate binding sites of DC-SIGN through the synthesis of cross-shaped glycodendrimers. The tailored rigid scaffold allowed multivalent presentation of glycomimetics in a spatially defined fashion, while providing good water solubility to the constructs. Evaluation of the biological activity by SPR assays revealed strong binding avidity towards DC-SIGN and increased selectivity over langerin. Inhibition of DC-SIGN binding to SARS-CoV-2 spike protein and of DC-SIGN mediated Ebola virus trans-infection testifies for the glycodendrimers potential application in infection diseases. The tetravalent platform described here is easily accessible and can be used in modular fashion with different ligands, thus lending itself to multiple applications.
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Background: Myocardial strain assessed with speckle tracking echocardiography is a sensitive marker of cardiac dysfunction, with longterm prognostic value in many cardiac conditions. Both left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were affected by severe SARS-CoV 2 infection but little is known about cardiac involvement in patients with asymptomatic/ mild disease that did not require hospitalization. Aim: To assess if subclinical myocardial dysfunction could be identified using LV-GLS and RV-LS in patients with previous asymptomatic/ mild SARS-CoV 2 infection. Methods: 40 young adults patients (70% males, mean age 24.4 ± 8.4 years), who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or only mildly symptomatic, without previous known comorbidities/cardiovascular risk factors, were retrospectively included. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study at least 3 months after diagnosis. A total of 44 age, sex, and body surface area comparable healthy subjects were used as control group. Results: LV-GLS was within normal limits but significantly lower in the cases group compared to controls (-22.7 ± 1.6% vs. -25.7 ± 2.3%;p < 0.001). Left ventricular ejection fraction (63.3 ± 4.1% vs 63.9 ± 4.6%;p = 0.5), tricuspid annular plane systolic excursion (24.3 ± 3.7 vs. 23.7 ± 3.3;p = 0.5) and RV-LS (-23.2 ± 3 vs. -23.6 ± 2.7;p = 0.6) were comparable between the two groups. Moreover, in the infection group, there were 25 subjects (30.1% vs 9.6% in the control group, p < 0.001) with a regional peak systolic strain of the left ventricle below -16% in at least two segments. At multivariable logistic regression corrected for age, gender and body surface area, previous SARS-CoV-2 infection was an independent predictor of reduced LV-GLS values (p < 0.001). Conclusion: SARS-CoV-2 infection may affect left ventricular deformation in 30% of young adults patients despite an asymptomatic or only mildly symptomatic acute illness. Speckle tracking echocardiography could help in early identification of patients with subclinical cardiac involvement. Since long-term complications of COVID-19 are not yet known, myocardial deformation imaging could be important for risk stratification, treatment and planning of long-term follow-up.
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Background. The long-term health effects after SARS-CoV-2 infection remain poorly understood. We evaluated health and healthcare usage after SARS-CoV-2 infection via surveys and longitudinal electronic medical record (EMR) review within the Military Health System (MHS). Methods. We studied MHS beneficiaries enrolled in the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) cohort from March to December 2020. COVID-19 illness symptom severity and duration were derived from surveys initiated in late 2020. In addition, multi-year healthcare encounter history before and after onset of COVID-19 symptoms was collected from the MHS EMR. Odds of organ-system clinical diagnoses within the 3 months pre- and post-symptom onset were calculated using generalized linear models, controlling for age, sex, and race, and including participant as a random effect. Results. 1,015 participants were included who were SARS-CoV-2 positive, symptomatic, and had 3-month follow-up data available in the EMR (Table 1). 625 of these participants had survey data collected more than 28 days post-symptom onset, among whom 17% and 6% reported persistent symptoms at 28-84 days, and 85+ days, respectively. 9.6% had not resumed normal activities by one month. The most frequently reported symptoms persisting beyond 28 days were dyspnea, loss of smell and/or taste, fatigue, and exercise intolerance (Figure 1A). When compared with the period 61 to 90 days prior to symptom onset, the first month post-symptom onset period was associated with increases of pulmonary (aOR = 57, 95% CI 28-112), renal (aOR = 29, 95% CI 10-84), cardiovascular (aOR = 7, 95% CI 5-11), and neurological diagnoses (aOR = 3, 95% CI 2-4) (Figures 1B and 1C). Cardiovascular disease diagnoses remained elevated through 3 months (aOR = 2, 95% CI 1-3). Fig1A. Symptoms reported by EPICC participants with illnesses longer than 28 days;1B. Percent of participants with organ system specific diagnoses on each day, 90 days pre- and post-symptom onset;1C. Odds of organ system specific diagnoses within each month, +/- 3 months of symptom onset, were calculated using generalized linear models, controlling for age, sex, and race and included participants as a random effect. Odds shown are relative to the earliest period included in the model, 61-90 days before onset. Conclusion. In this MHS cohort, a significant proportion of participants had persistent symptoms and cardiovascular disease diagnoses 3 months after COVID-19 illness onset. These findings emphasize the long-term morbidity of COVID-19 and the importance of mitigating SARS-CoV-2 infections. Further analyses will evaluate demographic, clinical, and biomarker predictors of medium-to-long term organ-specific post-acute sequelae.
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Background. The risk factors of venous thromboembolism (VTE) in COVID-19 warrant further study. We leveraged a cohort in the Military Health System (MHS) to identify clinical and virological predictors of incident deep venous thrombosis (DVT), pulmonary embolism (PE), and other VTE within 90-days after COVID-19 onset. Methods. PCR or serologically-confirmed SARS-CoV-2 infected MHS beneficiaries were enrolled via nine military treatment facilities (MTF) through April 2021. Case characteristics were derived from interview and review of the electronic medical record (EMR) through one-year follow-up in outpatients and inpatients. qPCR was performed on upper respiratory swab specimens collected post-enrollment to estimate SARS-CoV-2 viral load. The frequency of incident DVT, PE, or other VTE by 90-days post-COVID-19 onset were ascertained by ICD-10 code. Correlates of 90-day VTE were determined through multivariate logistic regression, including age and sampling-time-adjusted log10-SARS-CoV-2 GE/reaction as a priori predictors in addition to other demographic and clinical covariates which were selected through stepwise regression. Results. 1473 participants with SARS-CoV-2 infection were enrolled through April 2021. 21% of study participants were inpatients;the mean age was 41 years (SD = 17.0 years). The median Charlson Comorbidity Index score was 0 (IQR = 0 -1, range = 0 - 13). 27 (1.8%) had a prior history of VTE. Mean maximum viral load observed was 1.65 x 107 genome equivalents/reaction. 36 (2.4%) of all SARS-CoV-2 cases (including inpatients and outpatients), 29 (9.5%) of COVID-19 inpatients, and 7 (0.6%) of outpatients received an ICD-10 diagnosis of any VTE within 90 days after COVID-19 onset. Logistic regression identified hospitalization (aOR = 11.1, p = 0.003) and prior VTE (aOR = 6.2 , p = 0.009) as independent predictors of VTE within 90 days of symptom onset. Neither age (aOR = 1.0, p = 0.50), other demographic covariates, other comorbidities, nor SARS-CoV-2 viral load (aOR = 1.1, p = 0.60) were associated with 90-day VTE. Conclusion. VTE was relatively frequent in this MHS cohort. SARS-CoV-2 viral load did not increase the odds of 90-day VTE. Rather, being hospitalized for SARS-CoV-2 and prior VTE history remained the strongest predictors of this complication.
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INTRODUCTION: The National Emergency Tele-Critical Care Network (NETCCN) was developed to address limited and geographically unevenly distributed critical care (CC) providers during COVID-19 pandemic surges. Although designed for on-demand access to CC experts, for pandemic response, NETCCN continues to evolve and must be flexible and adaptable to future mass casualty/disasters. We report a pilot using tele-critical care (TCC) through NETCCN in emergency medical services (EMS). METHODS: We deployed a mobile device enabled cloud based, easy to use and learn, secure, HIPAA compliant TCC app developed for NETCCN in an emergency medical services (EMS) pilot designed to facilitate rapid communication via text, voice, video and file sharing between paramedics in the field, and emergency medicine specialists. A 30-minute session trained participants on the app, including account creation, login, and functions. EMS providers were encouraged to replace existing telephone communication triage protocols with the NETCCN mobile app. We collected the number/nature of consults, and narrative feedback. RESULTS: The pilot ran for 30 days and was used on average 3 times/week. No patient data was entered into the system, and the app was solely used for its communication features. The most common use case was terminating resuscitation. Debrief and feedback confirmed that the app was easy to use, not significantly affected by connectivity issues, and elicited several barriers to adoption by EMS providers: 1) manual input of patient data 2) perception of being micromanaged. Overall impression of the app and its utility was positive by both remote and EMS providers, and discussion elicited strategies to improve adoption: 1) incorporate TCC into protocols for interfacility critical care transport 2) automate patient data entry (e.g. scan driver's license)). CONCLUSIONS: We demonstrated that the NETCCN TCC app is quickly and easily usable in the EMS setting, but that further optimization is required to promote adoption. Novel non-disaster use cases like this can provide means to stabilize and sustain a system designed primarily for infrequent “as needed” response. Additionally, feedback and problem solving for these novel use cases can be an effective way to enhance system flexibility with dividends for future disaster use.