Acute Coronavirus Disease Research Articles

Post-COVID-19 Cardiovascular Sequelae and Myocarditis.

Post coronavirus disease 2019 (COVID-19) cardiovascular (CV) pathological changes, myocarditis, and myocardial infarctions (MIs) are major public health issues. This review discusses acute and chronic COVID-19 cardiac manifestations. The devastating impact of COVID-19 on global healthcare and economies has likely been one of humanity's deadliest calamities in recent decades, as multiple literature and databases were searched from 2020 to 2022. As of April 2022, we identified 73 articles in various electronic databases that discussed the details of COVID-19 and cardiac manifestations. Cardiometabolic risk factors should now, more than ever, be a top priority for clinicians, as their potent role in exacerbating COVID-19 illness severity has been conclusively demonstrated. This review discusses cardiac pathology changes, CV consequences of acute COVID-19, microvascular injury and cardiac complications linked with SARS-CoV2, COVID-19 linked with chronic CV disease, therapeutic drug effects on heart used in COVID-19, and possible investigational approaches and management strategies for post-COVID-19 CV consequences. Highlights Cardiac pathology changes: Effect of COVID-19. Mechanism of development of CV consequences in acute COVID-19: Including autopsy studies. Microvascular injury and cardiac complications: Linked with SARS-CoV2. COVID-19 linked with chronic CV disease. Therapeutic drug effects on heart used in COVID-19. Possible investigational approaches and management strategies for post-COVID-19 CV consequences.

EPH203 Patients Characteristics, Vaccine Uptake, Healthcare Resource Utilization and Costs Associated with Acute COVID-19 during the Omicron Predominant Period in Brazil: A Nationwide Database Study

The coronavirus disease 2019 (COVID-19) pandemic has imposed significant burden on Brazil’s health system. The present study aims to describe patients’ demographic and clinical characteristics, vaccine uptake and assess healthcare resource utilization (HCRU) and costs associated with acute COVID-19 in Brazil during the Omicron predominant period. A population-based retrospective study was conducted using the National Health Data Network (RNDS), National Vaccination Campaign against COVID-19 data and surveillance data in public setting. Individuals with positive COVID-19 test results between January-April 2022 were identified. Patients’ demographics, comorbidities, vaccination status, HCRU for those who were admitted to hospitals and their associated costs were described by age groups. A total of 8,160,715 COVID-19 cases were identified and 2.7% were aged <5 years, 11.6% were 5-19 years, 76.9% were 20-64 years and 8.7% were ≥ 65 years. The presence of comorbidity was 23.1% with a higher prevalence of comorbidities in the elderly (61.8% for 65-74 years and 71.2% for ≥75 years). Regarding COVID -19 vaccination uptake, among those aged ≤19 years, 20-64 years and ≥65 years, 40.6%, 86.5% and 92.2% had primary series, respectively. Among adults, the booster uptake was 47.3% and 75.8% for those aged 20-64 years and ≥ 65 years, respectively. Among those with confirmed COVID-19, regardless of vaccination status, 87% were being symptomatic and 1.7% were hospitalized (3.8% in aged <5 years, 4.2% in 5-19 years, 34.3% in 20-64 years and 57.6% in ≥ 65 years). Among hospitalized patients, 32,6% were admitted to ICU and 80% required mechanical ventilation support. The average cost per day in normal wards and ICU without ventilation was R$291,89 and R$923,90, respectively. Our results quantify the public health and economic burden of COVID-19 in Brazil, suggesting substantial healthcare resources required to manage the COVID-19 pandemic.

Follow the heart: A tale of possible infective endocarditis in a patient co-infected with Methicillin-resistant Staphylococcus aureus and Severe Acute Respiratory Syndrome Coronavirus 2

Abstract Introduction Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen responsible for bacteremia and valvular endocarditis. In patients with Coronavirus Disease 2019 (COVID-19), MRSA co-infection represents a challenging scenario, with increased morbidity and mortality. Case presentation We present a case of possible valvular endocarditis in a patient with acute COVID-19 and MRSA bacteremia. A 75-year-old woman presented with severe symptomatic aortic stenosis and moderate mitral stenosis. During hospitalization, she developed COVID-19 pneumonia with acute respiratory failure, and temporal and frontal intraparenchymal cerebral hemorrhage. Blood cultures were positive for MRSA, and the patient was started on a specific antibiotics regimen. The patient subsequently developed multi-organ failure and was transferred to the intensive care unit. Repeated computed tomography of the brain was consistent with a new occipitotemporal cortical hypodensity. Transthoracic echocardiography (TTE) showed a small (4 x 4 mm) mass attached to the aortic valve, but with TTE features inconclusive for infective endocarditis. The patient was scheduled for transesophageal echocardiography, but she suffered cardiac arrest, with no response to resuscitation maneuvers. Conclusions This case reveals the diagnostic and therapeutic challenges raised by MRSA and COVID-19 coinfection in a patient with preexisting valvular heart disease.

Changing Severity and Epidemiology of Adults Hospitalized With Coronavirus Disease 2019 (COVID-19) in the United States After Introduction of COVID-19 Vaccines, March 2021-August 2022.

Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies. Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed. Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period. Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.

Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors.

Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date. Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days]. Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ 2-statistics = 6.45, p = 0.013 and SCD: χ 2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group. Conclusion: Atrial arrhythmic and SCD events are present during the first 12months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.

Presentations, Diagnosis, and Treatment of Post-COVID Viral Myocarditis in the Inpatient Setting: A Narrative Review.

While coronavirus disease 2019 (COVID-19) infection rates have declined, and mortality outcomes have improved with vaccines, targeted antiviral therapies, and improved care practices over the course of the pandemic, post-acute sequelae of SARS CoV-2 infection (PASC, also referred to as "long COVID") has emerged as a significant concern, even among individuals who appear to have fully recovered from their initial infection. Acute COVID-19 infection is associated with myocarditis and cardiomyopathies, but the prevalence and presentation of post-infectious myocarditis are unclear. We provide a narrative review of post-COVID myocarditis, including symptoms and signs, physical exam findings, diagnosis, and treatment strategies. Post-COVID myocarditis has a wide range of presentations, from very mild symptoms to severe ones that can include sudden cardiac death. Several studies have noted what appears to be a bimodal distribution of affected patients, with individuals under age 16 (particularly males) most affected, followed by those over age 50. The gold standard of diagnosis for myocarditis is endomyocardial biopsy and cardiac magnetic resonance imaging with a confirmed diagnosis of COVID-19. However, if these are not available, other studies such as electrocardiogram, echocardiography, and inflammatory markers can guide clinicians to diagnose post-COVID myocarditis when appropriate. Treatment is largely supportive and may include oxygen therapy, intravenous hydration, diuretics, steroids, and antivirals. Post-COVID myocarditis is rare but important to recognize as more patients present with this condition in the inpatient setting.

Psychophysiologic Symptom Relief Therapy for Post-Acute Sequelae of Coronavirus Disease 2019

ObjectiveTo determine if psychophysiologic symptom relief therapy (PSRT) will reduce symptom burden in patients suffering from post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) who had mild/moderate acute COVID-19 disease without objective evidence of organ injury. Patients and MethodsTwenty-three adults under the age of 60 years with PASC for at least 12 weeks after COVID-19 infection were enrolled in an interventional cohort study conducted via a virtual platform between May 18, 2021 and August 7, 2022. Participants received PSRT during a 13-week (approximately 44-hour) course. Participants were administered validated questionnaires at baseline and at 4, 8, and 13 weeks. The primary outcome was a change in somatic symptoms from baseline, measured using the Somatic Symptom Scale-8, at 13 weeks. ResultsThe median duration of symptoms before joining the study was 267 days (interquartile range: 144, 460). The mean Somatic Symptom Scale-8 score of the cohort decreased from baseline by 8.5 (95% CI: 5.7-11.4), 9.4 (95% CI: 6.9-11.9), and 10.9 (95% CI: 8.3-13.5) at 4, 8, and 13 weeks, respectively (all P<.001). Participants also experienced statistically significant improvements across other secondary outcomes including changes in dyspnea, fatigue, and pain (all P<.001). ConclusionPSRT may effectively decrease symptom burden in patients suffering from PASC without evidence of organ injury. The study was registered on clinicaltrials.gov (NCT 04854772).

Prevalence of persistent symptoms after having COVID-19 in a cohort in Suriname.

To determine the prevalence of persistent symptoms after having coronavirus disease 2019 (COVID-19) in a cohort in Suriname, and assess the factors associated with long COVID. A sample of adults 18 years and older who were registered 3-4 months previously in a national database because of a positive COVID-19 test were selected. They were interviewed about socioeconomic characteristics, pre-COVID-19 health status and lifestyle, and symptoms during and after COVID-19. A subset of participants underwent a physical examination to determine body mass index, waist circumference, cardiovascular parameters, lung function, and functionality. A total of 106 participants (mean age 49 (standard deviation 15) years; 62.3% female) were interviewed, of whom 32 were physically examined. The greatest proportion of participants was of Hindustani descent (22.6%). Overall, 37.7% of participants were physically inactive, 26.4% had hypertension or diabetes mellitus, and 13.2% had been previously diagnosed with heart disease. Most participants (56.6%) had experienced mild COVID-19 and 14.2% had experienced severe COVID-19. A large proportion (39.6%) had experienced at least one persistent symptom after recovery from acute COVID-19 and more women were affected (47.0% of women versus 27.5% of men). Fatigue and alopecia were the most common symptoms, followed by dyspnea and sleep disturbance. Differences were observed between ethnic groups. Based on physical examination, 45.0% of the subset was obese and 67.7% had very high waist-circumference. About 40% of the cohort had at least one persistent symptom 3-4 months after having had COVID-19, with differences observed by sex and ethnic group.

Interaction of COVID-19 With Common Cardiovascular Disorders.

The onset and widespread dissemination of the severe acute respiratory syndrome coronavirus-2 in late 2019 impacted the world in a way not seen since the 1918 H1N1 pandemic, colloquially known as the Spanish Flu. Much like the Spanish Flu, which was observed to disproportionately impact young adults, it became clear in the early days of the coronavirus disease 2019 (COVID-19) pandemic that certain groups appeared to be at higher risk for severe illness once infected. One such group that immediately came to the forefront and garnered international attention was patients with preexisting cardiovascular disease. Here, we examine the available literature describing the interaction of COVID-19 with a myriad of cardiovascular conditions and diseases, paying particular attention to patients diagnosed with arrythmias, heart failure, and coronary artery disease. We further discuss the association of acute COVID-19 with de novo cardiovascular disease, including myocardial infarction due to coronary thrombosis, myocarditis, and new onset arrhythmias. We will evaluate various biochemical theories to explain these findings, including possible mechanisms of direct myocardial injury caused by the severe acute respiratory syndrome coronavirus-2 virus at the cellular level. Finally, we will discuss the strategies employed by numerous groups and governing bodies within the cardiovascular disease community to address the unprecedented challenges posed to the care of our most vulnerable patients, including heart transplant recipients, end-stage heart failure patients, and patients suffering from acute coronary syndromes, during the early days and height of the COVID-19 pandemic.

Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients.

Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course. This study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). 1H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes. Here, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients. The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.

Effective prognostic and clinical risk stratification in COVID-19 using multimodality biomarkers.

In acute COVID-19 patients, effective clinical risk stratification has important implications on treatment and therapeutic resource distribution. This article reviews the evidence behind a wide range of biomarkers with prognostic value in COVID-19. Patient characteristics and co-morbidities, such as cardiovascular and respiratory diseases, are associated with increased mortality risk. Peripheral oxygen saturation and arterial oxygenation are predictive of severe respiratory compromise, whilst risk scores such as the 4C-Score enable multi-factorial prognostic risk estimation. Blood tests such as markers of inflammation, cardiac injury and D-dimer, and abnormalities on electrocardiogram are linked to inpatient prognosis. Of the imaging modalities, lung ultrasound and echocardiography enable bedside assessment of prognostic abnormalities in COVID-19. Chest radiograph (CXR) and computed tomography (CT) can inform about prognostic pulmonary pathologies, whilst cardiovascular CT detects high-risk features such as coronary artery and aortic calcification. Dynamic changes in biomarkers, such as blood tests, CXR, CT and ECG findings, can further inform about disease severity and prognosis. Despite the vast volumes of existing evidence, several gaps exist in our understanding of COVID-19 biomarkers. Firstly, the pathophysiological basis on which these markers can foretell prognosis in COVID-19 remains poorly understood. Secondly, certain under-explored tests such as thoracic impedance assessment and cardiovascular magnetic resonance imaging deserve further investigation. Lastly, the prognostic value of most biomarkers in COVID-19 are derived from retrospective analyses. Prospectively studies are required to validate these markers for guiding clinical decision-making and to facilitate their translation into clinical management pathways. This article is protected by copyright. All rights reserved.

A Narrative Review on the Potential Role of Vitamin D3 in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has challenged global health systems and economies from January 2020. COVID-19 caused by the infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) has acute respiratory and cardiometabolic symptoms that can be severe and lethal. Long-term physiological and psychological symptoms, known as long COVID-19, persist affecting multiple organ systems. While vaccinations support the fight against SARS-CoV-2, other effective mechanisms of population protection should exist given the presence of yet unvaccinated and at-risk vulnerable groups, global disease comorbidities, and short-lived vaccine responses. The review proposes vitamin D3 as a plausible molecule for prevention, protection, and disease mitigation of acute and long COVID-19. Epidemiological studies have shown that individuals who were deficient in vitamin D3 had worse COVID-19 health outcomes and mortality rates. Higher doses of vitamin D3 supplementation may improve health and survivorship in individuals of various age groups, comorbidities, and severity of disease symptoms. Vitamin D3's biological effects can provide protection and repair in multiple organ systems affected by SARS-CoV-2. Vitamin D3 supplementation can potentially support disease-mitigation in acute and long COVID-19.

Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4+ T-cell response with pre-primed responses directed against common cold coronaviruses.

The nonstructural protein 12 (NSP12) of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has a high sequence identity with common cold coronaviruses (CCC). Here, we comprehensively assessed the breadth and specificity of the NSP12-specific T-cell response after in vitro T-cell expansion with 185 overlapping 15-mer peptides covering the entire SARS-CoV-2 NSP12 at single-peptide resolution in a cohort of 27 coronavirus disease 2019 (COVID-19) patients. Samples of nine uninfected seronegative individuals, as well as five pre-pandemic controls, were also examined to assess potential cross-reactivity with CCCs. Surprisingly, there was a comparable breadth of individual NSP12 peptide-specific CD4+ T-cell responses between COVID-19 patients (mean: 12.82 responses; range: 0-25) and seronegative controls including pre-pandemic samples (mean: 12.71 responses; range: 0-21). However, the NSP12-specific T-cell responses detected in acute COVID-19 patients were on average of a higher magnitude. The most frequently detected CD4+ T-cell peptide specificities in COVID-19 patients were aa236-250 (37%) and aa246-260 (44%), whereas the peptide specificities aa686-700 (50%) and aa741-755 (36%), were the most frequently detected in seronegative controls. In CCC-specific peptide-expanded T-cell cultures of seronegative individuals, the corresponding SARS-CoV-2 NSP12 peptide specificities also elicited responses in vitro. However, the NSP12 peptide-specific CD4+ T-cell response repertoire only partially overlapped in patients analyzed longitudinally before and after a SARS-CoV-2 infection. The results of the current study indicate the presence of pre-primed, cross-reactive CCC-specific T-cell responses targeting conserved regions of SARS-CoV-2, but they also underline the complexity of the analysis and the limited understanding of the role of the SARS-CoV-2 specific T-cell response and cross-reactivity with the CCCs.

Association of blood viscosity and device-free days among hospitalized patients with COVID-19

BackgroundIncreased estimated whole blood viscosity (eWBV) predicts higher mortality in patients hospitalized for coronavirus disease 2019 (COVID-19). This study assesses whether eWBV is an early predictor of non-fatal outcomes among patients hospitalized for acute COVID-19 infection.MethodsThis retrospective cohort study included 9278 hospitalized COVID-19 patients diagnosed within 48 h of admission between February 27, 2020 to November 20, 2021 within the Mount Sinai Health System in New York City. Patients with missing values for major covariates, discharge information, and those who failed to meet the criteria for the non-Newtonian blood model were excluded. 5621 participants were included in the main analysis. Additional analyses were performed separately for 4352 participants who had measurements of white blood cell count, C-reactive protein and D-dimer. Participants were divided into quartiles based on estimated high-shear blood viscosity (eHSBV) and estimated low-shear blood viscosity (eLSBV). Blood viscosity was calculated using the Walburn–Schneck model. The primary outcome was evaluated as an ordinal scale indicating the number of days free of respiratory organ support through day 21, and those who died in-hospital were assigned a value of -1. Multivariate cumulative logistic regression was conducted to evaluate the association between quartiles of eWBV and events.ResultsAmong 5621 participants, 3459 (61.5%) were male with mean age of 63.2 (SD 17.1) years. The linear modeling yielded an adjusted odds ratio (aOR) of 0.68 (95% CI 0.59–0.79, p value < 0.001) per 1 centipoise increase in eHSBV.ConclusionsAmong hospitalized patients with COVID-19, elevated eHSBV and eLSBV at presentation were associated with an increased need for respiratory organ support at 21 days. These findings are highly relevant, as they demonstrate the utility of eWBV in identifying hospitalized patients with acute COVID-19 infection at increased risk for non-fatal outcomes in early stages of the disease.

Investigation of Blood Plasma Viral Nucleocapsid Antigen as a Marker of Active Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Infection.

Nasopharyngeal qualitative reverse-transcription polymerase chain reaction (RT-PCR) is the gold standard for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is not practical or sufficient in every clinical scenario due to its inability to distinguish active from resolved infection. Alternative or adjunct testing may be needed to guide isolation precautions and treatment in patients admitted to the hospital. We performed a single-center, retrospective analysis of residual clinical specimens and medical record data to examine blood plasma nucleocapsid antigen as a candidate biomarker of active SARS-CoV-2. Adult patients admitted to the hospital or presenting to the emergency department with SARS-CoV-2 ribonucleic acid (RNA) detected by RT-PCR from a nasopharyngeal swab specimen were included. Both nasopharyngeal swab and a paired whole blood sample were required to be available for analysis. Fifty-four patients were included. Eight patients had positive nasopharyngeal swab virus cultures, 7 of whom (87.5%) had concurrent antigenemia. Nineteen (79.2%) of 24 patients with detectable subgenomic RNA and 20 (80.0%) of 25 patients with N2 RT-PCR cycle threshold ≤ 33 had antigenemia. Most individuals with active SARS-CoV-2 infection are likely to have concurrent antigenemia, but there may be some individuals with active infection in whom antigenemia is not detectable. The potential for high sensitivity and convenience of a blood test prompts interest in further investigation as a screening tool to reduce reliance on nasopharyngeal swab sampling and as an adjunct diagnostic test to aid in clinical decision making during the period after acute coronavirus disease 2019.

Multidisciplinary Center Care for Long COVID Syndrome–A Retrospective Cohort Study

BackgroundPersistent multi-organ symptoms after coronavirus disease 2019 (COVID-19) have been termed “long COVID” or “post-acute sequelae of SARS-CoV-2 infection.” The complexity of these clinical manifestations posed challenges early in the pandemic as different ambulatory models formed out of necessity to manage the influx of patients. Little is known about the characteristics and outcomes of patients seeking care at multidisciplinary post-COVID centers. MethodsWe performed a retrospective cohort study of patients evaluated at our multidisciplinary comprehensive COVID-19 center in Chicago, Ill, between May 2020 and February 2022. We analyzed specialty clinic utilization and clinical test results according to severity of acute COVID-19. ResultsWe evaluated 1802 patients a median of 8 months from acute COVID-19 onset, including 350 post-hospitalization and 1452 non-hospitalized patients. Patients were seen in 2361 initial visits in 12 specialty clinics, with 1151 (48.8%) in neurology, 591 (25%) in pulmonology, and 284 (12%) in cardiology. Among the patients tested, 742/916 (81%) reported decreased quality of life, 284/553 (51%) had cognitive impairment, 195/434 (44.9%) had alteration of lung function, 249/299 (83.3%) had abnormal computed tomography chest scans, and 14/116 (12.1%) had elevated heart rate on rhythm monitoring. Frequency of cognitive impairment and pulmonary dysfunction was associated with severity of acute COVID-19. Non-hospitalized patients with positive SARS-CoV-2 testing had findings similar to those with negative or no test results. ConclusionsThe experience at our multidisciplinary comprehensive COVID-19 center shows common utilization of multiple specialists by long COVID patients, who harbor frequent neurologic, pulmonary, and cardiologic abnormalities. Differences in post-hospitalization and non-hospitalized groups suggest distinct pathogenic mechanisms of long COVID in these populations.

Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progen-itors--

Abstract Through epigenetic mechanisms, systemic inflammation may trigger innate immune memory and persistent changes in hematopoietic cells; however, it has been difficult to investigate these phenotypes in the context of human disease, such as severe coronavirus disease 2019 (COVID-19). We developed a new workflow to isolate circulating hematopoietic stem and progenitor cells (HSPC) from peripheral blood, combining single-cell RNA/ATAC-seq. With this method, we were able to capture the diversity of circulating HSPC as seen in bone marrow, allowing for the non-invasive investigation of hematopoiesis as well as epigenomic changes after COVID-19. Following severe COVID-19, we observed both transcriptomic and epigenetic changes in HSPC and its progeny innate immune cells, and they persisted for months to a year. Different transcription factor activities (including IRF, AP-1, and CTCF) were associated with these alterations, which altered the regulation of inflammatory programs. Severe COVID-19 patients’ HSPC displayed long-lasting increases in myelopoiesis and granulopoiesis, and circulating monocytes responded more strongly to subsequent stimulation. We found that epigenomic changes in HSPC were retained and passed onto differentiated progeny innate immune cells. In addition, we demonstrate that administration of an anti-IL-6 blockade during acute severe COVID-19 can normalize the persistent phenotypes, suggesting that IL-6 plays a role in the development of epigenetic memory. In conclusion, epigenetic reprogramming of HSPC may underlie altered immune function subsequent to infection and has broad applicability, particularly for millions of COVID-19 survivors with incomplete recovery.

Association between SARS-CoV-2 anti-spike antibody titers and the development of post-COVID conditions: A retrospective observational study.

The symptoms that persist after an acute coronavirus disease 2019 (COVID-19) are referred to as post- COVID conditions. Although the cause of post-COVID conditions remains unclear, the host immune response to SARS-CoV-2 may be involved. Hence, we aimed to investigate the effect of serum antibody titers against SARS-CoV-2 on the development of post-COVID conditions. We conducted a retrospective observational study of COVID-19-recovered individuals who attended the clinic at the National Center for Global Health and Medicine between January 2020 and April 2021. Serum SARS-CoV-2 anti-spike antibody titers were measured and a questionnaire survey was used to collect information on the presence of post-COVID conditions and demographic characteristics of the participants. Participants were then divided into two groups: high peak antibody titer group [≥ 0.759 OD450 value], and low peak antibody titer group [< 0.759 OD450 value] and compared their frequency of post-COVID conditions. Of 526 individuals attending the clinic, 457 (86.9%) responded to the questionnaire. We analyzed the data of 227 (49.7%) participants with measurements of serum antibody titers during the peak period. The incidence of depressed mood was significantly higher in the group with higher antibody titers (odds ratio: 2.34, 95% CI: 1.17-4.67, p = 0.016). There was no significant difference in the frequency of the remaining symptoms between the two groups. Among post-COVID conditions, the depressed mood was more frequent in the group with high serum antibody titers which suggests a difference in pathogenesis between depressive mood and other post-COVID conditions that requires further investigation.

Factors influencing medium- and long-term occupational impact following COVID-19.

Significant numbers of individuals struggle to return to work following acute coronavirus disease 2019 (COVID-19). The UK Military developed an integrated medical and occupational pathway (Defence COVID-19 Recovery Service, DCRS) to ensure safe return to work for those with initially severe disease or persistent COVID-19 sequalae. Medical deployment status (MDS) is used to determine ability to perform job role without restriction ('fully deployable', FD) or with limitations ('medically downgraded', MDG). To identify which variables differ between those who are FD and MDG 6 months after acute COVID-19. Within the downgraded cohort, a secondary aim is to understand which early factors are associated with persistent downgrading at 12 and 18 months. Individuals undergoing DCRS had comprehensive clinical assessment. Following this, their electronic medical records were reviewed and MDS extracted at 6, 12 and 18 months. Fifty-seven predictors taken from DCRS were analysed. Associations were sought between initial and prolonged MDG. Three hundred and twenty-five participants were screened, with 222 included in the initial analysis. Those who were initially downgraded were more likely to have post-acute shortness of breath (SoB), fatigue and exercise intolerance (objective and subjective), cognitive impairment and report mental health symptoms. The presence of fatigue and SoB, cognitive impairment and mental health symptoms was associated with MDG at 12 months, and the latter two, at 18 months. There were also modest associations between cardiopulmonary function and sustained downgrading. Understanding the factors that are associated with initial and sustained inability to return to work allows individualized, targeted interventions to be utilized.

Does Elevated Inflammatory Markers Predict Functional Outcomes in Hospitalized Patients with COVID-19 and Acute stroke? (P14-5.007)

<h3>Objective:</h3> To determine if elevated inflammatory markers are associated with worse functional outcomes in SARS-CoV-2 positive patients presenting with acute cerebrovascular events. <h3>Background:</h3> The association of acute Coronavirus disease 2019 (COVID-19) with both arterial and venous thromboembolic events is well-established. One of the several proposed mechanisms is excessive inflammatory response. We aim to assess if higher inflammatory markers are associated with worse functional outcomes <h3>Design/Methods:</h3> Medical records of adult patients admitted to our institution between 3/2020 and 8/2021 with positive SARS-COV-2 and acute cerebrovascular events were reviewed (n=29). Demographics, neuroradiological and pertinent lab findings were collected. Functional outcomes were assessed using binarized mRS scores (worse 4–6 vs better 0–3) ascertained on discharge day. A series of logistic regression models were utilized to assess the association of inflammatory markers with stroke outcomes. Variables assessed were; [admission day heart rate, temperature and white blood cell count], binarized maximum procalcitonin ( &gt; 0.1 ng/mL vs &lt;/= 0.1 ng/mL) and maximum ferritin level. All analyses were conducted using SAS software. <h3>Results:</h3> Among 29 patients (mean age 63.6 +/− 13.4 years, 65.5% males), tested parameters of inflammation were not shown to be significantly associated with stroke outcomes in an adjusted logistic regression model. When assessing stroke outcome via binarized modified Rankin stroke scale, binarized maximum procalcitonin level showed 1.95 times the odds of a poor outcome (OR: 1.95, 95% CI: 0.05, 84.3, p-value: 0.73). Additionally, temperature on admission showed 1.59 times the odds of a poor outcome (OR: 1.59, 95% CI: 0.42, 6.07, p-value: 0.17). <h3>Conclusions:</h3> Among patients with acute cerebrovascular events associated with positive SARS-COV-2 result, no significant associations of worse functional outcomes in those with elevated inflammatory markers were observed. A trend of higher mRS scores on discharge in those with elevated procalcitonin and those with fever on admission was noted. Further research is needed to confirm these findings <b>Disclosure:</b> Dr. Elsekaily has nothing to disclose. Dr. Ansari has nothing to disclose. Dr. Sheikh has nothing to disclose. Dr. Ayub has nothing to disclose. Dr. Triay has nothing to disclose. Miss Angelette has nothing to disclose. Ms. Gaudet has nothing to disclose. Dr. Kelley has nothing to disclose.