Coronavirus Disease Of 2019 Patients Research Articles

PO-653-03 DELAYED CARDIAC REPOLARIZATION AS A PREDICTOR OF IN-HOSPITAL MORTALITY IN COVID-19 PATIENTS

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic by the World Health Organization (WHO) and has resulted in widespread mortality. The 12- lead ECG is a noninvasive and widely available tool that has been utilized as a risk stratification tool in conjunction with standard vital signs and lab values for many diseases, however its utility in COVID-19 patients has not been explored.

IDF21-0109 Coagulation Disorders in Type 2 Diabetes Mellitus Patients with COVID-19

Background: Type 2 diabetes mellitus (T2DM) correlates with the severity of coronavirus disease of 2019 (COVID-19). Coagulation disorder, together with impaired immune response and increased inflammatory response, is the basis of poor prognostic mechanisms in these patients. COVID-19 patients with T2DM are considered to have coagulation disorders described by the changes in the laboratory results, such as D-Dimer, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), platelets, and fibrinogen.

Characteristics and outcomes of older patients hospitalised for COVID-19 in the first and second wave of the pandemic in The Netherlands: the COVID-OLD study.

Backgroundas the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed.Objectiveto investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands.Methodsthis was a multicentre retrospective cohort study in 16 hospitals in The Netherlands including patients aged ≥ 70 years, hospitalised for COVID-19 in Spring 2020 (first wave) and Autumn 2020 (second wave). Data included Charlson comorbidity index (CCI), disease severity and Clinical Frailty Scale (CFS). Main outcome was in-hospital mortality.Resultsa total of 1,376 patients in the first wave (median age 78 years, 60% male) and 946 patients in the second wave (median age 79 years, 61% male) were included. There was no relevant difference in presence of comorbidity (median CCI 2) or frailty (median CFS 4). Patients in the second wave were admitted earlier in the disease course (median 6 versus 7 symptomatic days; P < 0.001). In-hospital mortality was lower in the second wave (38.1% first wave versus 27.0% second wave; P < 0.001). Mortality risk was 40% lower in the second wave compared with the first wave (95% confidence interval: 28–51%) after adjustment for differences in patient characteristics, comorbidity, symptomatic days until admission, disease severity and frailty.Conclusionscompared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality.The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions.

The Practices of Artificial Intelligence Techniques and Their Worth in the Confrontation of COVID-19 Pandemic: A Literature Review

Today, the medical society is living in the era of artificial intelligence, which is developed and becomes more famous thanks to the coronavirus disease of 2019 (COVID-19) pandemic, which has given the space for artificial intelligence to appear more influential in analyzing medical data and providing very accurate results. This science has deservedly been able to achieve an excellent and vital position among healthcare workers, and it has become a necessary element of their work because of its a great potential for practical decision-making. The prospects of using intelligent systems in the medical field are deemed essential in the health division due to their ability to analyze big data and give exact results, aiming to improve the health of citizens and save their lives. In this article, a set of important information about the vital role of artificial intelligence in the medical field is highlighted. In addition, how this science does manage to confront SARS‐CoV‐2 by highlighting a set of investigations and analyses in predicting the spread of the virus, tracking infections, and diagnosis of cases through chest x-ray images of COVID-19 patients. The database of this article covered more than 40 studies between 2020 and 2021 and investigated the effects of utilizing artificial intelligence techniques in analyzing SARS‐CoV‐2 data. These studies are gathered from PubMed, NCBI, google scholar, Medrxiv, and other sites. This article includes a plethora of information about artificial intelligence and SARS‐CoV‐2. The findings confirm that artificial intelligence has a significant role in the healthcare domain, and it is advised to utilize its applications in the decision-making method.

Epidemiology, Transmission, Clinical Features, Diagnosis, Treatment, and Prevention of COVID19: An Updated Review

Introduction: The novel coronavirus disease of 2019 (COVID-19) appeared almost two years ago in China and quickly created a pandemic and affected all aspects of human life. The virus, termed SARS-CoV-2, is generally asymptomatic but contagious and might have originated from bats. Nowadays, the mechanisms underlying the infection and the incidence of SARS-CoV-2 are distinguishable from previous coronaviruses. Early diagnosis and supportive treatment are necessary to cure the patients with COVID-19. Early evidence recommended that children are just likely as adults to become infected with this novel virus. It is now established that children are more often show gastrointestinal manifestations than adults do, and many children affected by SARS-CoV-2 are asymptomatic. Over 300 vaccine projects are recently developed by the scientific community to treat COVID-19 disease; however, these vaccines might lose efficacy by a number of unpredicted issues, including the emergence of new SARS-CoV-2 mutants. Conclusion: Due to the high prevalence and worldwide widespread of COVID-19, many studies are underway to find treatment modalities and develop new vaccines or antiviral substances to fight the virus. The COVID-19 pandemic is not only a challenge to global health but also has globally affected mental, social, and economic health. Moreover, the post-corona pandemic condition will undoubtedly have many Socioeconomic Challenges. This review study has been focused on epidemiology, virology, transmission methods, clinical features, laboratory findings, and prevalent mutations of the SARS-CoV-2 virus. We hope that information provided within this article will significantly benefit researchers currently investigating COVID-19 patients.

The Study of Clinical Profile of Acute Kidney Injury in COVID-19 Patients

All prior studies have demonstrated that acute renal damage in People who have the coronavirus disease of 2019(COVID-19)areoftendiagnosedandhaveadismalprognosis.AcuterenalinjuryinCOVID-19patientshasnot been well reported in developing countries like India. Examining the clinical traits, biochemistry, and prognosis of acute kidney injury (AKI) in COVID-19 patients is the aim of this article. Methods: The Department of Nephrology at the Sri Aurobindo Medical College and Graduate Institute (M.P.) in Indore, India, conducted this study from April 1, 2020, to January 31, 2021. We examined 130 COVID-19 cases of AKI recorded by SAMC &amp; PGI in Indore. Included 18-year-old and older COVID-19 patients verified by real-time reversepolymerasechainreaction(RT-PCR).Theterm“sepsis”wasemployedinitsconventionalsense.TheKidney Disease Improving Global Outcomes (KDIGO) guidelines of AKI were adhered to. Patients under the age of 18 undergoing renal replacement therapy for CKD in stages I to IV and ESRD were not eligible. Results: A total of 12,438 COVID patients were admitted to our hospital during this period. The incidence of AKI was 1.04% (130). The mean age was 51.2 years. The male-to-female ratio was 1.4:1 (76:54). Commonest symptoms were fever in 71.5% (93) of patients, headache in 62% (81) of patients, and cough in 51.5% (67) of patients, followed bybreathlessnessin37.5%(49)patients.Thetypicalcreatininevaluesatthetimeofadmissionwerewere3.57mg/dl. AKIstage1wasseenin30%(39)cases,stage2in45.5%(59)cases,andstage3in24.5%(32)cases.Themostcommon aetiology was sepsis in 65% (84) and drugs in 14% (18). T2DM was the most common comorbidity in 42% (55) of patients, HTN in 41.5% (54) of patients, Coronary Artery Disease (CAD) in 9.2% (12) of patients, and malignancy in 5% (7) of patients. Oxygen by nasal mask/nasal prongs was required in 59% (77) of patients, BIPAP in 16% (21) of patients, and ventilatory support in 12.5% (16) of patients. The average hospitalization was 12.3 days. Dialysis was required in 16% (21) of patients. Notably, 87% (113) of patients recovered completely, and 13% (17) of patients expired. The majority of patients had elevated inflammatory markers. Erythrocyte sedimentation rate (ESR) and Creactive protein (CRP) were elevated in 81% (105) of patients, and ferritin was raised in 71% (92) of patients. Conclusion: Hospitalized COVID-19 patients commonly get AKI, which is associated with a poor prognosis and high mortality. In COVID-19 patients, increased inflammatory markers, type 2 diabetes, sepsis, older age, and male sex were the main risk factors for developing acute renal injury.

The study of clinical profile of acute kidney injury in COVID-19 patients

Aim:All prior studies have demonstrated that acute renal damage in People who have the coronavirus disease of2019 (COVID-19) are often diagnosed and have a dismal prognosis. Acute renal injury in COVID-19 patients hasnot been well reported in developing countries like India. Examining the clinical traits, biochemistry, and prognosisof acute kidney injury (AKI) in COVID-19 patients is the aim of this article. Methods:The Department of Nephrology at the Sri Aurobindo Medical College and Graduate Institute (M.P.) inIndore, India, conducted this study from April 1, 2020, to January 31, 2021. We examined 130 COVID-19 casesof AKI recorded by SAMC and PGI in Indore. Included 18 year-old and older COVID-19 patients verified by real-time reverse polymerase chain reaction (RT-PCR). The term “sepsis” was employed in its conventional sense. TheKidney Disease Improving Global Outcomes (KDIGO) guidelines of AKI were adhered to. Patients under the age of18 undergoing renal replacement therapy for CKD in stages I to IV and ESRD were not eligible. Results:A total of 12,438 COVID patients were admitted to our hospital during this period. The incidence ofAKI was 1.04% (130). The mean age was 51.2 years. The male-to-female ratio was 1.4:1 (76:54). Commonestsymptoms were fever in 71.5% (93) of patients, headache in 62% (81) of patients, and cough in 51.5% (67) ofpatients, followed by breathlessness in 37.5% (49) patients. The typical creatinine values at the time of admissionwere 3.57 mg/dl. AKI stage 1 was seen in 30% (39) cases, stage 2 in 45.5% (59) cases, and stage 3 in 24.5%(32) cases. The most common etiology was sepsis in 65% (84) and drugs in 14% (18). T2DM was the mostcommon comorbidity in 42% (55) of patients, HTN in 41.5% (54) of patients, Coronary Artery Disease (CAD) in9.2% (12) of patients, and malignancy in 5% (7) of patients. Oxygen by nasal mask/nasal prongs was requiredin 59% (77) of patients, BIPAP in 16% (21) of patients, and ventilatory support in 12.5% (16) of patients. Theaverage hospitalization was 12.3 days. Dialysis was required in 16% (21) of patients. Notably, 87% (113) of patientsrecovered completely, and 13% (17) of patients expired. The majority of patients had elevated inflammatorymarkers. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated in 81% (105) of patients,and ferritin was raised in 71% (92) of patients. Conclusion:Hospitalized COVID-19 patients commonly get AKI, which is associated with a poor prognosis andhigh mortality. In COVID-19 patients, increased inflammatory markers, type 2 diabetes, sepsis, older age, and malesex were the main risk factors for developing acute renal injury.

Faecal calprotectin in COVID-19 patients with intestinal symptoms

Extra-pulmonary manifestations of the Coronavirus disease of 2019 (COVID-19) have been increasingly reported, especially gastrointestinal and hepatic system dysfunction. The concern of faecal-oral transmission for COVID-19 was raised. To study the trend of faecal calprotectin in COVID-19 patients with intestinal symptoms. Forty confirmed cases of COVID-19 infection presenting with diarrhoea were subjected to a thorough history taking, clinical examination, and routine laboratory investigations. They were treated according to the Egyptian MOH guidelines. Faecal calprotectin (FC) concentration was measured at initial presentation and after 3 months. Those who had persistently elevated levels ≥ 200 µg/g were subjected to colonoscopic examination and histopathological examination. Forty confirmed cases of COVID-19 without diarrhoea were recruited as a control group in the initial FC evaluation. Faecal calprotectin was found to be significantly elevated in the studied COVID-19 patients who presented with diarrhoea, with a mean value 260 ±80 µg/g compared to the those without diarrhoea, with a mean value of 31.6 ±12.9 µg/g (p < 0.001). Moreover, 20% (8 patients) had an elevated level exceeding 200 µg/g 3 months after recovery; among them, 5 patients showed mild colonoscopic changes whereas 3 patients showed severe ileocolitis. Out of the 3 patients with marked ileocolitis, 2 showed histopathological changes raising the diagnosis of Crohn's disease. Faecal calprotectin was found to be elevated in COVID-19 patients with intestinal symptoms, especially diarrhoea, with or without colonoscopic and histopathological changes.

Cytokine Storm and Immunomodulation in COVID-19: A Review

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has taken over the world, and more than 38 lakh deaths had been reported till now due to this infectious disease. It has been declared a global pandemic by the world health organization. SARS-CoV-2 causes coronavirus disease of 2019 (COVID-19), and the major problem called “Cytokine storm” is reported, which may lead to death among the COVID-19 patients. This study aimed to review the Cytokine storm and its mechanism along with few immunomodulatory therapies for SARSCoV- 2 infection suppression effectively. Methods: The recently published works of literature were selected and reviewed based on the subject of this study. The databases, including Pubmed, ScienceDirect, Scopus, and Google Scholar, were searched extensively. Results: The review of the literature showed that an uncontrolled immune response causes excess inflammation. Evidence from recent trials has demonstrated that cytokine storms can be an important factor in the COVID-19 severity, leading to multiple organ failure and death. Conclusion: This study reviewed immunomodulatory therapies and strategies for SARS-CoV-2 infected patients to suppress the immune response. Ultimately, the cytokine storm can prove to be a boon and reduce the significant death tolls to SARS-CoV-2 infection.

Association of systemic complications with mortality in coronavirus disease of 2019: A cohort study on intensive care unit patients.

Background:Since the beginning of the coronavirus disease of 2019 (COVID-19) pandemic, concerns raised by the growing number of deaths worldwide. Acute respiratory distress syndrome (ARDS) and extrapulmonary complications can correlate with prognosis in COVID-19 patients. This study evaluated the association of systemic complications with mortality in severely affected COVID-19 patients.Materials and Methods:This retrospective study was done on 51 intensive care unit (ICU)-admitted COVID-19 adult patients who were admitted to the ICU ward of Khorshid hospital, affiliated with Isfahan University of Medical Sciences. Only the patients who had a definite hospitalization outcome (dead vs. survivors) were included in the study. Daily clinical and paraclinical records were used to diagnose in-hospital complications in these patients.Results:The sample was comprised of 37 males (72.5%) and 14 females (27.4%). The median age of patients was 63 years (Min: 20, Max: 84), with the mortality rate of 47.1%. In total, 70.6% of patients had at least one coexisting disorder. Chronic kidney disease was associated with the worse outcome (29.16% of dead patients against 3.70 of survived ones). Mechanical ventilation was used in 58.8% of patients. Patients who had received invasive ventilation were more likely to die (87.50% of dead patients against 7.40 of survivors), Complications including sepsis and secondary infections (odds ratio: 8.05, confidence interval: 2.11–30.63) was the strongest predictors of mortality.Conclusion:Complications including sepsis and secondary infections can increase the risk of death in ICU-admitted COVID-19 patients. Therefore, it is substantial that the physicians consider preventing or controlling these complications.

Potentials of Varied Inflammatory Indices in the Prediction of COVID-19 Severity Among Nigerians

<i>Background: </i>The coronavirus disease of 2019 (COVID-19) is theorized to be associated with significant inflammatory episodes. This tends to define the severity and culminates in adverse consequences of the disease. Therefore, the current study evaluated the potentials of varied inflammatory markers/indices that define the COVID-19 severity. <i>Methods: </i>This was a retrospective analysis of pre-treatment data obtained from patients with positive real-time polymerase chain reaction (RT-PCR)-confirmed COVID-19 disease in one of the treatment centers in Port Harcourt, South-south Nigeria. Data were obtained from case notes, medical review charts, nurses’ charts, and laboratory records by trained research assistants in the treatment center using pretested data acquisition templates. Abstracted data were compared between the severe positive and severe negative subgroups and the potentials of varied inflammatory indices were evaluated among the severe positive subgroup using standard protocols. <i>Results: </i>A total of 600 eligible cases were studied. Among the eligible cases, 543 (90.5%) had severe negative disease, while 57 (9.5%) had severe positive disease. The severe positive COVID-19 patients had higher mean blood levels of urea, creatinine, pro-calcitonin, C-reactive protein (CRP), ferritin, higher Glasgow prognostic scores (GPS), fibrinogen, D-dimer, fibrinogen-albumin ratio, total white cell count, neutrophil counts, composite neutrophil/lymphocyte ratio (NLR), composite platelet to lymphocyte ratio but lower potassium, albumin, hemoglobin levels, and isolated lymphocyte and platelet counts compared to the severe positive COVID-19 subjects (p<0.05). The C-reactive protein, GPS, D-dimer, and the composite NLR ratio indices significantly predicted COVID-19 severity on the crude regression model which was maintained in the adjusted model. However, serum CRP concentrations (AUC: 0.95; 95% CI: 0.82-1.00; p<0.001) maintained a more robust predictive potential compared to the GPS (AUC: 0.94; 95% CI: 0.84-1.00; p<0.001), D-dimer levels (AUC: 0.89; 95% CI: 0.79-0.94; p=0.004), and the composite NLR (AUC: 0.87; 95% CI: 0.77-0.92). <i>Conclusion: </i>The current study corroborates the role of inflammation in the COVID-19 disease severity. The clinical utility of these inflammation-induced markers/indices especially the CRP, GPS, D-dimer, and the NLR should be prioritized among Nigerians during the management of the disease.

Clinical and Epidemiology Characteristics of COVID-19 Cases Detected During Mass Screening Campaign from July to October 2020 in Bujumbura, Burundi.

Coronavirus disease of 2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2 Virus). It was reported for the first time in Wuhan city, Hubei province of China. The first cases of COVID-19 in Burundi were identified on 31st March 2020. Several signs and symptoms, including mainly; fever, dry cough, fatigue, myalgia, and dyspnea are the most prominent characteristics of the disease. The aim of this study was to provide description of the clinical and epidemiological characteristics of COVID-19 cases identified during the mass screening campaign conducted between July and October, 2020 in Burundi. We conducted a retrospective secondary analysis of data of clients to the mass screening campaign in Bujumbura city that was run between July and October 2020. Clients with complete data and tested for COVID-19 with Reverse Transcription Polymerase Chain Reaction (RT-PCR) were included in the study. Epi-Info 7.2.2.6 was used to perform descriptive and analytical statistics and Quantum Geographic Information System (QGIS) was used for cases mapping. Association between positive cases and independent variables such as sex, history of contact with confirmed COVID-19 case was measured using chi-square statistical test at a p-value of .05. The study included 20,114 participants. 243 (1.2%) were tested positive for COVID-19. The mean age for confirmed cases was 33 (±15) years. The majority of cases (72.8%) were between 20 and 59 years of age and they were predominantly males (67.9%). 164 (67.5%) were symptomatic and cough was the most frequent symptom observed 109 (66.5%), followed by rhinorrhea 69 (42.1%). Fever was present in only 18 (11.0%) of symptomatic patients. Participants with a history of contact with a COVID-19 confirmed case (aOR=2.2; 95%CI [1.6-3.0]; p-value <.001), were more likely to be positive for COVID-19. Also, those who were coughing (aOR=1.47; 95%CI [1.06-2.05]; p-value=.023) and having sore throat (aOR=2.4; 95%CI [1.1-4.9]; p-value=.02) were more likely to test positive for COVID-19. This study revealed that a significant proportion (32.5%) of COVID-19 patients were silent carriers of the virus. Data highlighted that high proportion of cases were among the active age group and contacts with confirmed cases, and noted high proportion of asymptomatic cases at diagnosis. Measures including routine testing of asymptomatic contacts could contribute to tackling corona virus in Burundi.

454. Impact of Covid-19 on Infectious Disease Fellows in the United States: A National Survey to Identify Targets for Intervention

BackgroundThe Coronavirus disease of 2019 (COVID-19) global health crisis has resulted in an unprecedented strain on healthcare systems, reorganization of medical training programs and disruption in professional and personal lives of medical trainees. The impact of COVID-19 on infectious disease (ID) fellows, who are frontline healthcare professionals, has not been assessed.MethodsWe conducted a national survey of adult and pediatric ID fellows to assess impact on educational activities, availability of personal protective equipment (PPE), well-being, and career prospects. Anxiety and burnout were assessed by 7-item generalized anxiety disorder scale and abbreviated Maslach burnout inventory respectively. Invitations to participate in the survey were sent via email to all ID fellows through Accreditation Council for Graduate Medical Education (ACGME) fellowship directors. Survey responses collected from August 1 to September 30, 2020 have been reported.Results136 fellows completed the survey (Table 1). 84% reported their institution had provided evidence-based didactics for management of COVID-19 and 53% indicated their general ID didactics were affected by the pandemic. 86% of fellows were involved in care of patients with COVID-19, and 31% reported a shortage of PPE affecting their clinical duties. Those living in highly impacted states (CA, FL, NY, TX) at the time of the survey were 1.70 times as likely to experience moderate to severe anxiety (vs. minimal to moderate) than those in other states; similarly, those who saw ≥11 COVID-19 patients weekly and reported PPE shortages were 2.5 and 2.0 times as likely, respectively, to experience moderate to severe anxiety compared to their peers who took care of 10 or fewer COVID-19 patients and did not experience PPE shortages. Burnout scores were not significant (Table 2).Table 1. Demographics, Responses to Personal Exposure, Educational Activities and Career Prospects Table 2. Stress, Burnout, Anxiety , Sleep and Quality of Life Among Survey Participants. ConclusionIt is imperative that ID fellows feel adequately protected and supported during this pandemic. Pandemic preparedness should be included in the ID fellowship curriculum. Interventions for anxiety and burnout reduction should be implemented. ID fellowship programs should continue to accept feedback from fellows to ensure their ongoing safety, well-being, and education as we navigate this pandemic.Disclosures All Authors: No reported disclosures

First evidence of human-to-dog transmission of SARS-CoV-2 B.1.160 variant in France.

Since the start of the coronavirus disease of 2019 (COVID‐19) pandemic, several episodes of human‐to‐animal severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission have been described in different countries. The role of pets, especially domestic dogs, in the COVID‐19 epidemiology is highly questionable and needs further investigation. In this study, we report a case of COVID‐19 in a French dog living in close contact with its owners who were COVID‐19 patients. The dog presented rhinitis and was sampled 1 week after its owners (a man and a woman) were tested positive for COVID‐19. The nasal swabs for the dog tested remained positive for SARS‐CoV‐2 by reverse transcription quantitative real‐time PCR (RT‐qPCR) 1 month following the first diagnosis. Specific anti‐SARS‐CoV‐2 antibodies were detectable 12 days after the first diagnosis and persisted for at least 5 months as tested using enzyme‐linked immunoassay (ELISA) and automated western blotting. The whole‐genome sequences from the dog and its owners were 99%–100% identical (with the man and the woman's sequences, respectively) and matched the B.1.160 variant of concern (Marseille‐4 variant), the most widespread in France at the time the dog was infected. This study documents the first detection of B.1.160 in pets (a dog) in France, and the first canine genome recovery of the B.1.160 variant of global concern. Moreover, given the enhanced infectivity and transmissibility of the Marseille‐4 variant for humans, this case also highlights the risk that pets may potentially play a significant role in SARS‐CoV‐2 outbreaks and may transmit the infection to humans. We have evidence of human‐to‐dog transmission of the Marseille‐4 variant since the owners were first to be infected. Finally, owners and veterinarians must be vigilent for canine COVID‐19 when dogs are presented with respiratory clinical signs.

Insomnia Disorder Among Coronavirus Disease Survivors: A South Korean Nationwide Cohort Study.

ObjectiveWe investigated the prevalence and associated factors of insomnia disorder among survivors of coronavirus disease of 2019 (COVID-19). MethodsThis population-based cohort study used data from the National Health Insurance Service COVID-19 cohort database from January 1 to June 4, 2020. COVID-19 patients were defined as individuals whose test confirmed that they were infected, regardless of the severity, and survivors were defined as individuals who recovered from the infection. ResultsA total of 299,968 individuals were included in the final analysis, and 6,934 were considered as COVID-19 survivors, while the control group comprised 292,764 individuals. In the multivariable model after covariate adjustment, COVID-19 survivors had a 3.33-fold higher prevalence of insomnia disorder than the control group (odds ratio [OR]: 3.33, 95% confidence interval [CI]: 2.98–3.73; p<0.001). In the sensitivity analysis, the COVID-19 survivors with no specific treatment and the survivors with specific treatment were associated with a 3.16-fold (OR: 3.16, 95% CI: 2.77–3.59; p<0.001) and 3.89-fold (OR: 3.89, 95% CI: 3.17–4.78; p<0.001) higher prevalence of insomnia disorder than the control group. ConclusionIn South Korea, 5.4% of COVID-19 survivors were diagnosed with insomnia disorder at 6 months follow-up. Thus, insomnia disorder is a public health issue for COVID-19 survivors.

Quo Vadis, COVID-19?

Quo Vadis, COVID-19?

Cardiopulmonary exercise testing in COVID-19 patients at 3 months follow-up

BackgroundLong-term effects of Coronavirus Disease of 2019 (COVID-19) and their sustainability are of the utmost relevance. For the chronic phase, the main concerns are the development of pulmonary interstitial disease and/or lingering cardiovascular involvement. How to intercept, assess, and treat these patients with long-term consequences of COVID-19 remains uncertain.PurposeWe aimed to determine: 1) functional capacity of COVID-19 survivors by cardiopulmonary exercise testing (CPET); 2) those characteristics associated with CPET performance; 3) safety and tolerability of CPET.MethodsWe prospectively enrolled consecutive patients with laboratory-confirmed COVID-19 discharged alive at a single hospital in northern Italy. At 3-month from hospital discharge, complete clinical evaluation, trans-thoracic echocardiography, cardiopulmonary exercise testing (CPET), pulmonary function test (PFT), and dominant leg extension (DLE) maximal strength evaluation were performed.ResultsFrom 225 patients discharged from March to November 2020 we excluded 12 incomplete/missing cases, and 13 unable to perform CPET leading to a final population of 200 patients. At PFT all median parameters were within normality range.Median percent-predicted peak oxygen uptake (%pVO2) was 88% (78.3–103.1). Ninety-nine (49.5%) patients had %pVO2 below, whereas 101 (50.5%) above the 85% predicted value (indicating normality).Sixteen (16.2%) patients had respiratory, 28 (28.9%) cardiac, 21 (21.2%) mixed-cardiopulmonary, and 34 (34.3%) non-cardiopulmonary limitation of exercise. One-hundred sixty (80.0%) patients complain at least one symptom, without relationship with peakVO2.Multivariate linear regression analysis showed percent-predicted forced expiratory volume in one-second (β=5.29, p=0.023), percent-predicted diffusing capacity of lungs for carbon monoxide (β=6.31, p=0.001), and DLE maximal strength (β=14.09, p=0.008) independently associated with peakVO2.At sensitivity analysis, the results of previous multivariate linear regression analysis were also similar among sub-groups of patients with no previous significant disease in anamnesis (cardiovascular disease except for arterial hypertension, respiratory disease, kidney disease, or cancer) and of those with a length of hospital stay ≤7 days.None major event was reported during/after CPET, whereas only two cases (1.0%) had a mild symptomatic hypotension post exercise. None of the involved health professionals developed COVID-19.ConclusionsCPET after COVID-19 is safe and about 1/3rd of COVID-19 survivors show functional capacity limitation mainly explained by muscular impairment, calling for future research to identify patients at higher risk of long-term effects that may benefit from careful surveillance and targeted rehabilitation.Funding AcknowledgementType of funding sources: None. Types of mainly CPET limitationPeak VO2 per leg extension strength

Highly Efficient SARS-CoV-2 Infection of Human Cardiomyocytes: Spike Protein-Mediated Cell Fusion and Its Inhibition.

ABSTRACTSevere cardiovascular complications can occur in coronavirus disease of 2019 (COVID-19) patients. Cardiac damage is attributed mostly to the aberrant host response to acute respiratory infection. However, direct infection of cardiac tissue by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also occurs. We examined here the cardiac tropism of SARS-CoV-2 in spontaneously beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). These cardiomyocytes express the angiotensin-converting enzyme 2 (ACE2) receptor but not the transmembrane protease serine 2 (TMPRSS2) that mediates spike protein cleavage in the lungs. Nevertheless, SARS-CoV-2 infection of hiPSC-CMs was prolific; viral transcripts accounted for about 88% of total mRNA. In the cytoplasm of infected hiPSC-CMs, smooth-walled exocytic vesicles contained numerous 65- to 90-nm particles with canonical ribonucleocapsid structures, and virus-like particles with knob-like spikes covered the cell surface. To better understand how SARS-CoV-2 spreads in hiPSC-CMs, we engineered an expression vector coding for the spike protein with a monomeric emerald-green fluorescent protein fused to its cytoplasmic tail (S-mEm). Proteolytic processing of S-mEm and the parental spike were equivalent. Live cell imaging tracked spread of S-mEm cell-to-cell and documented formation of syncytia. A cell-permeable, peptide-based molecule that blocks the catalytic site of furin and furin-like proteases abolished cell fusion. A spike mutant with the single amino acid change R682S that disrupts the multibasic furin cleavage motif was fusion inactive. Thus, SARS-CoV-2 replicates efficiently in hiPSC-CMs and furin, and/or furin-like-protease activation of its spike protein is required for fusion-based cytopathology. This hiPSC-CM platform enables target-based drug discovery in cardiac COVID-19.IMPORTANCE Cardiac complications frequently observed in COVID-19 patients are tentatively attributed to systemic inflammation and thrombosis, but viral replication has occasionally been confirmed in cardiac tissue autopsy materials. We developed an in vitro model of SARS-CoV-2 spread in myocardium using induced pluripotent stem cell-derived cardiomyocytes. In these highly differentiated cells, viral transcription levels exceeded those previously documented in permissive transformed cell lines. To better understand the mechanisms of SARS-CoV-2 spread, we expressed a fluorescent version of its spike protein that allowed us to characterize a fusion-based cytopathic effect. A mutant of the spike protein with a single amino acid mutation in the furin/furin-like protease cleavage site lost cytopathic function. Of note, the fusion activities of the spike protein of other coronaviruses correlated with the level of cardiovascular complications observed in infections with the respective viruses. These data indicate that SARS-CoV-2 may cause cardiac damage by fusing cardiomyocytes.

Remdesivir induces persistent mitochondrial and structural damage in human induced pluripotent stem cell-derived cardiomyocytes.

AimsRemdesivir is a prodrug of an adenosine triphosphate analogue and is currently the only drug formally approved for the treatment of hospitalised COVID-19 patients. Nucleoside/nucleotide analogues have been shown to induce mitochondrial damage and cardiotoxicity, and this may be exacerbated by hypoxia, which frequently occurs in severe COVID-19 patients. Although there have been few reports of adverse cardiovascular events associated with remdesivir, clinical data are limited. Here, we investigated whether remdesivir induced cardiotoxicity using an in vitro human cardiac model.Methods and ResultsHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to remdesivir under normoxic and hypoxic conditions to simulate mild and severe COVID-19 respectively. Remdesivir induced mitochondrial fragmentation, reduced redox potential and suppressed mitochondrial respiration at levels below the estimated plasma concentration under both normoxic and hypoxic conditions. Non-mitochondrial damage such as electrophysiological alterations and sarcomere disarray were also observed. Importantly, some of these changes persisted after the cessation of treatment, culminating in increased cell death. Mechanistically, we found that inhibition of DRP1, a regulator of mitochondrial fission, ameliorated the cardiotoxic effects of remdesivir, showing that remdesivir-induced cardiotoxicity was preventable and excessive mitochondrial fission might contribute to this phenotype.ConclusionsUsing an in vitro model, we demonstrated that remdesivir can induce cardiotoxicity in hiPSC-CMs at clinically relevant concentrations. These results reveal previously unknown potential side-effects of remdesivir and highlight the importance of further investigations with in vivo animal models and active clinical monitoring to prevent lasting cardiac damage to patients.Translational perspectiveAdult cardiomyocytes have limited ability to regenerate, thus treatment-induced cardiotoxicity can potentially cause irreparable harm. Remdesivir is currently the only FDA approved treatment for COVID-19 but clinical safety data are limited. Using human pluripotent stem cell-derived cardiomyocytes, we revealed that remdesivir induced persistent mitochondrial and structural abnormalities at clinically relevant concentrations. We advise confirmatory experiments in in vivo animal models, investigations of cardioprotective strategies, and closer patient monitoring such that treatment-induced cardiotoxicity does not contribute to the long term sequelae of COVID-19 patients.

LEFT ATRIAL THROMBUS AND COVID-19-ASSOCIATED COAGULOPATHY

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: COVID-19 (Coronavirus Disease of 2019) is a global pandemic caused by the rapidly spreading SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). Although COVID-19 primarily affects the respiratory system, evidence suggests a strong predisposition for pro-thrombotic states with COVID-19 infection, manifesting as both venous and arterial thromboembolism. COVID-19 associated coagulopathy and its varying complications contribute to a significant portion or morbidity and mortality in addition to respiratory failure. CASE PRESENTATION: A 75-year-old woman with stage IV colorectal carcinoma, rheumatic mitral valve stenosis status-post recent balloon valvulotomy, and atrial fibrillation on warfarin presented with fever, cough, anosmia, ageusia, dyspnea, generalized weakness, and anorexia. She was admitted for neutropenic fever, acute hypoxic respiratory failure, and sepsis in the context of COVID-19 pneumonia. Computed tomography angiogram (CTA) of the chest showed bilateral infiltrates consistent with COVID-19 pneumonia, as well as a more unusual finding of a large 7 x 4 x 7 cm left atrial mass (Figure 1), consistent in appearance with a thrombus. Comparison with CTA chest one month prior confirmed that the thrombus was acute. On admission, the patient also had a supratherapeutic INR of 4. Echocardiography confirmed the suspicion for thrombus and redemonstrated restricted mitral valve leaflets consistent with rheumatic valvular stenosis. The patient was treated with supplemental oxygen, remdesivir, vancomycin, cefepime and filgrastim. She responded well and had resolution of her neutropenia, sepsis, and hypoxia. Because she formed the thrombus while on warfarin, decision was made to discontinue warfarin and transition to enoxaparin for anticoagulation. She was subsequently discharged home on hospice. DISCUSSION: Although venous thromboembolism is commonly encountered with COVID-19 patients, to our knowledge this case represents the first report of COVID-19 associated left atrial thrombus. Rheumatic mitral valve disease is a known risk factor for left atrial thrombus formation and colorectal carcinoma may have also contributed to hypercoagulability. However, the patient in our vignette had a supratherapeutic INR at the time of thrombus formation. Furthermore, the absence of thrombus on imaging one month prior confirms a temporal association with COVID-19 infection. As such, evidence suggests that hypercoagulability secondary to COVID-19 contributed to the formation of her left atrial thrombus. CONCLUSIONS: This case adds to the growing body of literature surrounding the profound hypercoagulability provoked by SARS-CoV-2 infection and reiterates the role of anticoagulation in the management of COVID-19 patients during the ongoing pandemic. REFERENCE #1: Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109:102433. REFERENCE #2: Incidence of thrombotic complications in critically ill ICU patients with COVID-19. lok FA, Kruip MJHA, van der Meer NJM, et al. Thromb Res. 2020;191:145–147. REFERENCE #3: Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–847. DISCLOSURES: No relevant relationships by Nikhila Janakiram, source=Web Response No relevant relationships by Eva Ma, source=Web Response No relevant relationships by Andreas Mauer, source=Web Response