PCR-confirmed COVID-19 Infections Research Articles

Identification and validation of respiratory subphenotypes in patients with COVID-19 acute respiratory distress syndrome undergoing prone position

BackgroundThe heterogeneity of acute respiratory distress syndrome (ARDS) patients is a challenge for the development of effective treatments. This study aimed to identify and characterize novel respiratory subphenotypes of COVID-19 ARDS, with potential implications for targeted patient management.MethodsConsecutive ventilated patients with PCR-confirmed COVID-19 infection, in which prone positioning was clinically indicated for moderate or severe ARDS, were included in a prospective cohort. The patients were assigned to development or validation cohorts based on a temporal split. The PaO2/FiO2 ratio, respiratory compliance, and ventilatory ratio were assessed longitudinally throughout the first prone session. The subphenotypes were derived and validated using machine learning techniques. A K-means clustering implementation designed for joint trajectory analysis was utilized for the unsupervised classification of the development cohort. A random forest model was trained on the labeled development cohort and used to validate the subphenotypes in the validation cohort.Results718 patients were included in a prospective cohort analysis. Of those, 504 were assigned to the development cohort and 214 to the validation cohort. Two distinct subphenotypes, labeled A and B, were identified. Subphenotype B had a lower PaO2/FiO2 response during the prone session, higher ventilatory ratio, and lower compliance than subphenotype A. Subphenotype B had a higher proportion of females (p < 0.001) and lung disease (p = 0.005), higher baseline SAPS III (p = 0.002) and SOFA (p < 0.001) scores, and lower body mass index (p = 0.05). Subphenotype B had also higher levels of the pro-inflammatory biomarker IL-6 (p = 0.017). Subphenotype B was independently associated with an increased risk of 60-day mortality (OR 1.89, 95% CI 1.51–2.36). Additionally, Subphenotype B was associated with a lower number of ventilator-free days on day 28 (p < 0.001) and a lower hospital length of stay (p < 0.001). The subphenotypes were reproducible in the validation cohort.ConclusionOur study successfully identified and validated two distinct subphenotypes of COVID-19 ARDS based on key respiratory parameters. The findings suggest potential implications for better patient stratification, risk assessment, and treatment personalization. Future research is warranted to explore the utility of these novel subphenotypes for guiding targeted therapeutic strategies in COVID-19 ARDS.

Abstract 4127513: Cardiopulmonary long-term effects 6, 18 and 30 months after severe covid-19 infection

Background: SARS-CoV-2 infection affects the cardiopulmonary system in both the acute and long-term phase. This study aimed to comprehensively assess symptoms and potential long-term impairments 6, 18 and 30 months in patients previously hospitalized for severe Covid-19 infection. Methods: This prospective registry included patients hospitalized for PCR-confirmed Covid-19 infection. Approximately 6 months post-discharge, follow-up examination included patient history, clinical examination, echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a comprehensive laboratory panel. Patients with pathologic findings during the first visit underwent a second (at 18 months) and third (at 30 months) follow-up examination. Those without pathologic findings or who refused further medical examinations were contacted via phone to inquire about symptoms. Results: Between July 2020 and April 2022, 200 patients (91% general ward, 9% intensive care unit) were recruited. Due to dropouts, the second visit was conducted in 170 patients, and the third visit in 139 (74 in person, 65 via telephone). Long Covid criteria were fulfilled by 73% at 6 months, 52% at 18 months and 49% at 30 months post-discharge, with fatigue being the most common symptom (Figure 1). Echocardiography at 6 months showed impaired left ventricular function in 15 patients, with normalization in 80% at 18 months and further 66% at 30 months (Figure 2). cMRI revealed pericardial effusions in 28 patients at 6 months, which resolved in 47% at 18 months and in further 60% at 30 months. Signs of peri- or myocarditis were present in 7 patients at 6 months and were resolved in all 4 patients who attended control studies at 18 months. Chest CT scans at 6 months identified post-infectious residues in 41 patients, with full recovery in 20% at 18 months without further normalization after 30 months. The length of in-hospital stay was identified as a significant predictor for persisting Long Covid 6 months after discharge (95% CI: 1.005 - 1.12, p=0.03). Conclusion: While the prevalence of Long Covid decreased over time, a significant symptom burden persisted at 6, 18 and even 30 months after severe Covid-19 infection. Structural and functional abnormalities were less frequent compared to reported symptoms, posing a challenge in substantiating the causes of these symptoms.

Cardiopulmonary long-term effects 6, 18 and 30 months after severe COVID-19 infection

Abstract Background SARS-CoV-2 infection affects the cardiopulmonary system in both the acute and long-term phase. This study aimed to comprehensively assess symptoms and potential longterm impairments 6, 18 and 30 months in patients previously hospitalized for severe Covid-19 infection. Methods This prospective registry included patients hospitalized for PCR-confirmed Covid-19 infection. Approximately 6 months post-discharge, follow-up examination included patient history, clinical examination, echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a comprehensive laboratory panel. Patients with pathologic findings during the first visit underwent a second (at 18 months) and third (at 30 months) follow-up examination. Those without pathologic findings or who refused further medical examinations were contacted via phone to inquire about symptoms. Results Between July 2020 and April 2022, 200 patients (91% general ward, 9% intensive care unit) were recruited. Due to dropouts, the second visit was conducted in 170 patients and the third visit in 139 (74 in person, 65 via telephone). Long Covid criteria were fulfilled by 73% at 6 months, 52% at 18 months and 49% at 30 months post-discharge, with fatigue being the most common symptom (Figure 1). Echocardiography at 6 months showed impaired left ventricular function in 15 patients, with normalization in 80% at 18 months and further 66% at 30 months (Figure 2). cMRI revealed pericardial effusions in 28 patients at 6 months, which resolved in 47% at 18 months and in further 60% at 30 months. Signs of peri- or myocarditis were present in 7 patients at 6 months and were resolved in all 4 patients who attended control studies at 18 months. PFT at 6 months detected reduced vital capacity in 17 patients, of whom 10% returned to normal at 18 months and a further 66% showed normalization at 30 months. Chest CT scans at 6 months identified post-infectious residues in 41 patients, with full recovery in 20% at 18 months without further normalization after 30 months. The length of in-hospital stay was identified as a significant predictor for persisting Long Covid 6 months after discharge (95% CI: 1.005 - 1.12, p=0.03). No predictors have been found for Long Covid at 18 and 30 months. Conclusion While the prevalence of Long Covid decreased over time, a significant symptom burden persisted at 6, 18 and even 30 months after severe Covid-19 infection. Structural and functional abnormalities were less frequent compared to reported symptoms, posing a challenge in substantiating the causes of these symptoms.

B-136 From Result to Response: The Development of Laboratory-Based Scoring Models to Predict COVID-19 Patient Outcomes

Abstract Background Patient characteristics relating to increased risk for COVID-19 severity are well-documented, including older age and pre-existing health concerns; however, methods to accurately predict patients’ acute reaction to SARS-CoV-2 infections remain lacking. Identification of specific laboratory tests informative of patient outcomes could effectively screen incoming patients and better inform physicians regarding optimal treatment plans. The aim of this study was to examine associations between frequently ordered laboratory markers and COVID-19 patient mortality to develop an objective laboratory-based scoring system that estimates patients’ risk of mortality. Methods Study participants included inpatients from 3 hospitals recruited into the GENCOV project based in Ontario, Canada. Participants (n=325) were at least 18 years of age, provided consent, and were hospitalized within 1 month of having a PCR confirmed COVID-19 infection between January 2020 and February 2022. Extensive clinical data including patient demographics, laboratory results, and treatment outcomes were extracted from patient’s electronic medical records (EMR). Results for 32 biochemical and hematological tests including complete blood cell counts, coagulation (activated partial thromboplastin time, D-dimer, fibrinogen, prothrombin time), general chemistry (albumin, blood gases, creatine kinase, electrolytes, glucose, triglycerides), inflammatory (lactate dehydrogenase, ferritin, C-reactive protein), liver (alanine aminotransferase, aspartate aminotransferase, total bilirubin), renal (creatinine, urea) and cardiac (troponin, NT-proBNP, BNP) markers were collected from each chart. Univariable logistic regression with nested likelihood ratio tests were used to determine significant associations between laboratory results and patient outcomes. Significant markers were incorporated into multivariable models and variable risk values were assigned. Total calculated risk scores for each participant were compared using univariable and multivariable risk values. Validation of each scoring method was performed on a 20% subset of inpatients. Receiver operating characteristic (ROC) curves evaluated model performance. Results Six laboratory markers were associated with COVID-19 patient mortality when controlling for age and sex. Univariable regression showed that elevated creatinine, elevated lactate, elevated white blood cell, low base excess, low bicarbonate, or low pH results upon admission were significantly associated with increased odds of mortality, in comparison to test results within the reference range for these same markers. Multivariable regression revealed fewer markers (only low bicarbonate and low base excess) showing significant associations with COVID-19 mortality. Area under the ROC curves (AUC) determined that risk scores derived from univariable values performed similarly to multivariable values in validation (0.800 vs 0.802) and development cohorts (0.821 vs 0.829). Total risk scores calculated from the univariable vs multivariable models suggest higher sensitivity (90% vs 85%) than specificity (58% vs 67%) in the validation cohort, whereas the development cohort had higher sensitivity (88%) than specificity (66%) with univariable scores, and higher specificity (81%) than sensitivity (74%) with multivariable scores. Conclusions Laboratory results associated with COVID-19 mortality following both univariable and multivariable analyses suggest hospitalized patients infected with SARS-CoV-2 may present with acidosis. Total risk scores derived from univariable and multivariable values performed similarly in predicting mortality; however, differences in marker significance between models indicate discrepancies with risk interpretation. Further comparison of the created risk score assessments with equivalent models in other populations is warranted.

Applying vibroacoustic therapy in the treatment of patients with COVID-associated pneumonia

Introduction. Pneumonia is a group of acute infectious (mainly bacterial) diseases of various etiology, pathogenesis, and morphological characteristics characterized by focal lesions of the respiratory tract of the lungs with the obligatory presence of intraalveolar exudation. Currently, a wide range of not only pharmacological, but also physiotherapeutic methods of treatment is available. Vibroacoustic therapy is also used to facilitate the discharge of bronchopulmonary secretions.Aim. To evaluate the effectiveness of vibroacoustic pulmonary therapy using the BARK VibroLUNG device (manufactured by BARK Technology, Kazakhstan) in patients with COVID-19.Materials and methods. 70 patients with PCR-confirmed positive COVID-19 infection were included in the study. The patients were divided into 2 groups, which statistically did not differ from each other. Group 1 (n = 35) underwent vibroacoustic pulmonary therapy (VALT) in combination with basic treatment. Group 2 (n = 35) received only basic treatment. VALT was performed for 7 days, 2 sessions per day for 20 minutes.Results. Against the background of complex therapy in combination with the course of VALT, patients in the study group showed a statistically significant decrease in the duration of hospitalization to 19 (12–29) days, as opposed to 27 (24–34) days (p = 0.003) in the control group. When comparing the changes in the indicators of the surviving patients of the study group, a positive dynamics of the main indicators against the background of VALT was obtained: ∆VAS -2 (-3; -1), р = 0.000; ∆SpO2– 6 (2; 7), р = 0.002; ∆PaO2–13 (2; 19), р= 0.001 in comparison with the dynamics of similar indicators of the control group.Conclusions. The results have shown the effectiveness of vibroacoustic therapy in the treatment of patients with coronavirus pneumonia. This method can optimize healthcare costs for the treatment of COVID-19, as there is a significant decrease of duration of hospitalization.

Use of artificial intelligence to develop predictive algorithms of cough and PCR-confirmed COVID-19 infections based on inputs from clinical-grade wearable sensors

There have been over 769 million cases of COVID-19, and up to 50% of infected individuals are asymptomatic. The purpose of this study aimed to assess the use of a clinical-grade physiological wearable monitoring system, ANNE One, to develop an artificial intelligence algorithm for (1) cough detection and (2) early detection of COVID-19, through the retrospective analysis of prospectively collected physiological data from longitudinal wear of ANNE sensors in a multicenter single arm study of subjects at high risk for COVID-19 due to occupational or home exposures. The study employed a two-fold approach: cough detection algorithm development and COVID-19 detection algorithm development. For cough detection, healthy individuals wore an ANNE One chest sensor during scripted activity. The final performance of the algorithm achieved an F-1 score of 83.3% in twenty-seven healthy subjects during biomarker validation. In the COVID-19 detection algorithm, individuals at high-risk for developing COVID-19 because of recent exposures received ANNE One sensors and completed daily symptom surveys. An algorithm analyzing vital parameters (heart rate, respiratory rate, cough count, etc.) for early COVID-19 detection was developed. The COVID-19 detection algorithm exhibited a sensitivity of 0.47 and specificity of 0.72 for detecting COVID-19 in 325 individuals with recent exposures. Participants demonstrated high adherence (≥ 4 days of wear per week). ANNE One shows promise for detection of COVID-19. Inclusion of respiratory biomarkers (e.g., cough count) enhanced the algorithm's predictive ability. These findings highlight the potential value of wearable devices in early disease detection and monitoring.

Persistent Smell Disorders After COVID-19 Infection and Their Impact on Quality of Life.

Background The COVID-19 pandemic has led to various health challenges, including the disruption of people's sense of smell. Olfactory disorders have been reported as a lingering consequence of COVID-19, with diverse patterns of smell dysfunction experienced by patients. Objectives This study aimed to investigate the impact of persistent smell disorders on the quality of life of individuals who recovered from COVID-19 in Taif, Saudi Arabia. Methodology A descriptive cross-sectional study was conducted in Taif, Saudi Arabia, between October 2023 and January 2024. The study included adults with a history of PCR-confirmed COVID-19 infection in Taif city. Data were collected using a validated online survey employing a convenience sampling technique. Statistical analysis was carried out using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), and chi-squared tests were used to assess the relationships. Results The study included 429 participants. A total of 52.7% of the respondents reported a loss of smell after recovering from COVID-19, and 14.9% reported a persistent loss of their sense of smell. The most common types of smell disorders experienced were hyposmia, anosmia, and parosmia. The study revealed emotional distress, changes in eating habits, and social impact among participants with smell disorders. Conclusion This study highlights the high prevalence of persistent smell disorders among individuals who recovered from COVID-19 in Taif, Saudi Arabia. The findings emphasize the complex nature of these disorders and their impact on patients' quality of life. This study contributes valuable information that can inform healthcare practices and support services for individuals experiencing post-COVID-19 smell disorders.

Severe COVID-19 and its cardiopulmonary effects 6 and 18 months after hospital discharge.

SARS-CoV-2 infection affects the cardiopulmonary system in the acute as well as long-term phase. The aim of the present study was to comprehensively assess symptoms and possible long-term impairments 6 and 18 months after hospitalization for severe COVID-19 infection. This prospective registry included patients with PCR-confirmed COVID-19 infection requiring hospitalization. Follow-up approximately 6 months post discharge comprised a detailed patient history, clinical examination, transthoracic echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a laboratory panel. At the time of the second follow-up visit at 18 months, patients without pathologic findings during the first study visit were contacted by phone to inquire about the course of their symptoms. In all other patients all initial examinations were repeated. Two hundred Patients, who were hospitalized for COVID-19, were contacted by phone and were recruited for the study. Due to dropouts the second study visit was performed in 170 patients. A comparison between the two study visits at 6 and 18 months post discharge showed the following results: Six months after discharge, 73% and 18 months after discharge 52% fulfilled the criteria for Long COVID with fatigue being the most common symptom (49%). Echocardiography at 6 months post discharge showed an impaired left ventricular function in 8% of which 80% returned to normal. Six months post discharge, cMRI revealed pericardial effusion in 17% which resolved in 47% of the 15 patients who underwent a control cMRI. Signs of peri- or myocarditis were present in 5% of the patients and were resolved in all 4 patients who attended control studies. At 6 months, chest CT scans identified post-infectious residues in 24%. In the 25 repeated chest CT scans 20% showed full recovery. Length of in-hospital stay was identified as a significant predictor for persisting Long COVID (95% CI: 1.005-1.12, p = 0.03). Comparing 6 to 18 months, the prevalence of Long COVID decreased over time, but a high symptom burden remained. Structural and functional abnormalities were less frequent than the portrayed symptoms, and it thus remains a challenge to substantiate the symptoms.

A Pragmatic Study of Cardiovascular Disease During Long-Term COVID-19

BackgroundMany patients diagnosed with COVID-19 have persistent cardiovascular symptoms, but whether this represents a true cardiac process is unclear. This study assessed whether symptoms associated with long COVID among patients referred for cardiovascular evaluation are associated with objective abnormalities on cardiac testing to explain their clinical presentation. MethodsA retrospective cohort study of 40,462 unique patients diagnosed with COVID-19 at our tertiary referral was conducted and identified 363 patients with persistent cardiovascular symptoms a minimum of 4 weeks after polymerase chain reaction confirmed COVID-19 infection. Patients had no cardiovascular symptoms prior to COVID-19 infection. Each patient was referred for cardiovascular evaluation at a tertiary referral center. The incidence and etiology of abnormalities on cardiovascular testing among patients with long COVID symptoms are reported here. The cohort was subsequently divided into 3 categories based on the dominant circulating severe acute respiratory syndrome coronavirus 2 variant at the time of initial infection for further analysis. ResultsAmong 40,462 unique patients diagnosed with COVID-19 at our tertiary referral center from April 2020 to March 2022, 363 (0.9%) patients with long COVID were evaluated by Cardiology for possible cardiac sequelae from COVID and formed the main study cohort. Of these, 229 (63%) were vaccinated and 47 (12.9%) had severe initial infection, receiving inpatient treatment for COVID prior to developing long COVID symptoms. Symptoms were associated with a cardiac cause in 85 (23.4%), of which 52 (14.3%) were attributed to COVID; 39 (10.7%) with new cardiac disease from COVID, and 13 (3.6%) to worsening of pre-existing cardiac disease after COVID infection. The median troponin change in 45 patients with troponin measurements within 4 weeks of acute infection was +4 ng/dL (9 to 13 ng/dL). Among the total cohort with long COVID, 83.7% were diagnosed during the pre-Delta phase, 13.2% during the Delta phase, and 3.1% during the Omicron phase of the pandemic. There were 6 cases of myocarditis, 11 rhythm disorders, 8 cases of pericarditis, 5 suspected cases of endothelial dysfunction, and 33 cases of autonomic dysfunction. ConclusionThis pragmatic retrospective cohort study suggests that patients with long COVID referred for cardiovascular evaluation infrequently have new, objective cardiovascular disease to explain their clinical presentation. A multidisciplinary, patient-centered approach is warranted for symptom management along with conservative use of diagnostic testing.

Assessment of the state of children after COVID-19 and other acute respiratory infections using the ISARIC COVID-19 survey

Introduction. The state of children had suffered from COVID-19 causes various persistent symptoms affecting on patient well-being and quality of life which is a significant healthcare issue. &#x0D; The aim of the work. To assess health and well-being of children following COVID-19 and other acute respiratory infections. &#x0D; Materials and methods. This is a case-control study including children with history of PCR-confirmed COVID-19 (n = 261) and other acute respiratory infections (n = 198). Patients were assessed 6 months and 1 year after the infection using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 questionnaire for children. The prevalence of symptoms including fatigue, weakness, lack of energy, as well as the emotional well-being, social relationships, and social activity of children was evaluated. &#x0D; Results. Children with history of COVID-19 in six months had significantly higher rates of weakness and decreased school attendance compared to children with other acute respiratory infections. 12 months after infection, children in the case group were significantly more likely to experience poor concentration, weakness, a decreased sense of belonging and school attendance. However, 12 months after infection, control group had significantly higher rates of fatigue. &#x0D; Conclusion. Children with a history of mild COVID-19 and other acute respiratory infections may experience ongoing health problems for 1 year after the infection, requiring greater attention from healthcare professionals and family members.

Cardiopulmonary long-term impairment in patients 6 and 18 months post severe Covid-19 infection

Abstract Background Covid-19 infection affects the cardiopulmonary system in the acute as well as long-term phase. The aim of the present study was to deliver a comprehensive report of symptoms and possible long-term impairments 6 and 18 months after hospitalization for severe Covid-19 infection. Methods This prospective registry included patients after PCR-confirmed Covid-19 infection, who were treated as in-patients at our Covid-19 department. Follow-up approximately 6 months post discharge comprised a detailed patient history, clinical examination, transthoracic echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a comprehensive laboratory panel including brain natriuretic peptide and troponin T. At the time of the second follow-up visit at 18 months, patients who did not show any abnormalities during the first study visit or refused to return for a follow-up visit, were contacted by phone to inquire about the course of symptoms (n=42). In all other patients with abnormalities during the first study visit, blood testing, echocardiography and 6MWT were repeated. CT, cMRI and lung function test were only performed in case of pathological findings during the first study visit. Results Between July 2020 and April 2022 200 patients were recruited (91% general ward, 9% intensive care unit). Due to dropouts the second study visit was only performed in 149 patients. A comparison between the two study visits at 6 and 18 months post discharge showed the following results: Six months after discharge, 73% and 18 months after discharge 52% fulfilled the criteria for Long-Covid with fatigue being the most common symptom (figure 1). Echocardiography at 6 months post discharge showed a reduced left ventricular function in 8% (n=15), of which 80% returned to normal at 18 months (n=5, figure 2). Six months post discharge, cMRI revealed pericardial effusion in 17% (n=25) and resolved in 43% of the 7 patients who underwent a control cMRI. Signs of peri- or myocarditis were present in 5% of the patients (n=7) at 6 months and were resolved in all 4 patients in control studies. PFT detected reduced vital capacity in 11% of patients (n=17). Values improved in 50% and normalized in 10% of the 10 patients, who attended the second study visit. At 6 months, pulmonary CT scans identified post-infectious residues in 22% (n= 39), of which 24% showed full recovery. A predictor for persisting Long-Covid was the length of in-hospital stay (95% CI: 1.005 - 1.12, p=0.03) as an indicator for the severity of the initial disease course. Conclusion Comparing 6 to 18 months after severe Covid-19 infection, the prevalence of Long-Covid decreased over time, but a high symptom burden remains. Structural and functional abnormalities were less frequent compared to the portrayed symptoms, and it remains a challenge to substantiate the symptoms.SymptomsFunctional and Structural changes

Ongoing symptoms and functional impairment 12 weeks after testing positive for SARS-CoV-2 or influenza in Australia: an observational cohort study

ObjectiveIn a highly vaccinated Australian population, we aimed to compare ongoing symptoms and functional impairment 12 weeks after PCR-confirmed COVID-19 infection with PCR-confirmed influenza infection.Methods and analysisThe study commenced on...

Burden of respiratory morbidity amongst survivors of COVID-19 infection in Lagos, Southwest Nigeria

&lt;b&gt;Background&lt;/b&gt;: COVID-19 disease is associated with long-term effects in some survivors. There exists dearth of information about the burden of respiratory morbidity among COVID-19 survivors in Nigeria. This study was designed to identify the common respiratory symptoms of long COVID-19 to educate and increase index of suspicion of healthcare practitioners caring for such patient for optimal care.&lt;br /&gt; &lt;b&gt;Material and methods&lt;/b&gt;: This is a cross-sectional survey that took place at the adult pulmonology clinic of Lagos State University Teaching Hospital Ikeja. The individuals who were treated for PCR confirmed COVID-19 infection referred for unresolved symptoms 4 weeks following discharge that consented were recruited. A proforma was used to obtain information on socio-demographic characteristics, medical history, and comorbidities. The degree of dyspnea was assessed using MRC(Medical Research Council) dyspnea scale while the functional capacity of patients was assessed using Six-minute walk test (6mwt). The analysis of the data collected was done using descriptive statistics, and chi-square was used to test for association.&lt;br /&gt; &lt;b&gt;Results&lt;/b&gt;: Ninety-four subjects participated. The mean age of participants was 49.48±17.8 years, with male: female ratio of 1:1.1. The median duration of admission due to COVID-19 infection was 10.0 (7.0-15.8) days. The common symptoms were fatigue (85.1%), loss of smell (71.3%), dyspnea 53(56.4%), and Cough (62.8%). Dyspnea was present in 62.8% using the MRC dyspnea scale, while the 6-meter walk test showed inadequate functional capacity in 61.7%, and both showed significant association. (X&lt;sup&gt;2&lt;/sup&gt;=18.606, P=0.001*)&lt;br /&gt; &lt;b&gt;Conclusion&lt;/b&gt;: Respiratory morbidity remains a significant post covid condition. There is a need to raise awareness amongst healthcare workers, particularly within the primary healthcare setting for early identification and referral of COVID-19 survivors with prolonged respiratory symptoms to pulmonology clinics for optimal care. There is also a need for further research on predictors of post COVID syndrome and treatment modalities.

Persistent Symptoms and IFN-γ-Mediated Pathways after COVID-19.

After COVID-19, patients have reported various complaints such as fatigue, neurological symptoms, and insomnia. Immune-mediated changes in amino acid metabolism might contribute to the development of these symptoms. Patients who had had acute, PCR-confirmed COVID-19 infection about 60 days earlier were recruited within the scope of the prospective CovILD study. We determined the inflammatory parameters and alterations in tryptophan and phenylalanine metabolism in 142 patients cross-sectionally. Symptom persistence (pain, gastrointestinal symptoms, anosmia, sleep disturbance, and neurological symptoms) and patients' physical levels of functioning were recorded. Symptoms improved in many patients after acute COVID-19 (n = 73, 51.4%). Still, a high percentage of patients had complaints, and women were affected more often. In many patients, ongoing immune activation (as indicated by high neopterin and CRP concentrations) and enhanced tryptophan catabolism were found. A higher phenylalanine to tyrosine ratio (Phe/Tyr) was found in women with a lower level of functioning. Patients who reported improvements in pain had lower Phe/Tyr ratios, while patients with improved gastrointestinal symptoms presented with higher tryptophan and kynurenine values. Our results suggest that women have persistent symptoms after COVID-19 more often than men. In addition, the physical level of functioning and the improvements in certain symptoms appear to be associated with immune-mediated changes in amino acid metabolism.

#4363 MULTINATIONAL COMPARATIVE EFFICACY OF 6 DIFFERENT COVID-19 VACCINES FOR THE PREVENTION OF BREAKTHROUGH INFECTION AND MORTALITY IN HD PATIENTS

Abstract Background and Aims COVID-19 vaccines induce specific immune responses to reduce COVID-19 infections and severe complications. Dialysis patients exhibit increased COVID-19-related incidence rates and mortality due to poor immune responses. We studied retrospectively the efficacy of 6 different COVID-19 vaccines as well as the combination of vaccines for the prevention of new COVID-19 infections and related mortality in a large multi-national hemodialysis cohort. Method All patients from 22 countries in Europe, Asia, Africa, and South America, 18 years or older, registered within in the network of a multi-national dialysis provider on January 31st 2021, were included into the study. We analyzed the incidence of symptomatic COVID-19 in HD patients with vaccination status after 2 doses of 6 different SARS-CoV-2 vaccines in comparison to HD patients who did not receive any vaccine. Patients were screened for COVID-19 symptoms at each dialysis visit and SARS-CoV-2 PCR tests were performed in all symptomatic patients. All PCR-confirmed COVID-19 infections, and deaths occurring between January 31st, and July 15th, 2021 were analyzed. Results were stratified by vaccine type and compared to unvaccinated patients. Data are presented as incidence rate ratios per 1000 patient days and odds ratios vs. no vaccine (95% CI). Results Of 38342 eligible patients registered on the index date, 2413 were excluded due to a positive SARS-CoV-2 PCR within 3 months before baseline and 26 were excluded due to unclear vaccination data. The remaining 35903 patients were analyzed. 7816 patients (21.7%) had received a single vaccine dose and 18853 patients (52.5%) had received two doses of any COVID-19 vaccine (Vaxzevria 3180 and 1321, Comirnaty 2823 and 13116, Spikevax 185 and 1521, Sputnik V 1194 and 432, Sinovac 266 and 1722, Sinopharm 168 and 416, or any combination of two different vaccines 325). The 9119 patients (25.4%) who remained unvaccinated during the observational period showed an incidence rate of 0.74/1000 patient days. In the cohort of patients vaccinated two times, 232 developed Covid-19. The lowest incidence rate ratio was observed in patients that had received Spikevax 0.06 (0.02-0.14). By contrast, patients after Sinopharm, Sinovac, and Sputnik V exhibited highest incidence rate ratios 0.53 (0.21-1.09), 0.46 (0.34-0.61), 0.68 (0.34-1.23), respectively. The largest sub-cohort of 13116 patients, who had received Comirnaty, however, had an incidence rate ratio of 0.15 (0.12-0.17). Albeit incidence rates and ratios were heterogenous, all vaccines including Sputnik V showed a significant efficacy to reduce mortality compared to no vaccine. Conclusion Combinations of different vaccines and two doses of mRNA-based vaccines very effectively prevented breakthrough infections. Despite considerable differences in preventing COVID-19 infections, all vaccines effectively reduced mortality, compared to no vaccines, in this high-risk dialysis patient cohort.

A study protocol of external validation of eight COVID-19 prognostic models for predicting mortality risk in older populations in a hospital, primary care, and nursing home setting

BackgroundThe COVID-19 pandemic has a large impact worldwide and is known to particularly affect the older population. This paper outlines the protocol for external validation of prognostic models predicting mortality risk after presentation with COVID-19 in the older population. These prognostic models were originally developed in an adult population and will be validated in an older population (≥ 70 years of age) in three healthcare settings: the hospital setting, the primary care setting, and the nursing home setting.MethodsBased on a living systematic review of COVID-19 prediction models, we identified eight prognostic models predicting the risk of mortality in adults with a COVID-19 infection (five COVID-19 specific models: GAL-COVID-19 mortality, 4C Mortality Score, NEWS2 + model, Xie model, and Wang clinical model and three pre-existing prognostic scores: APACHE-II, CURB65, SOFA). These eight models will be validated in six different cohorts of the Dutch older population (three hospital cohorts, two primary care cohorts, and a nursing home cohort). All prognostic models will be validated in a hospital setting while the GAL-COVID-19 mortality model will be validated in hospital, primary care, and nursing home settings. The study will include individuals ≥ 70 years of age with a highly suspected or PCR-confirmed COVID-19 infection from March 2020 to December 2020 (and up to December 2021 in a sensitivity analysis). The predictive performance will be evaluated in terms of discrimination, calibration, and decision curves for each of the prognostic models in each cohort individually. For prognostic models with indications of miscalibration, an intercept update will be performed after which predictive performance will be re-evaluated.DiscussionInsight into the performance of existing prognostic models in one of the most vulnerable populations clarifies the extent to which tailoring of COVID-19 prognostic models is needed when models are applied to the older population. Such insight will be important for possible future waves of the COVID-19 pandemic or future pandemics.

Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial

ObjectiveTo evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms.DesignProspective, open-label, multicentre, stratified, randomised clinical trial.SettingFive...

The effect of post-COVID-19 on gustatory and olfactory function: A preliminary case-controlled study.

The aim of the study was to analyze objective and subjective olfactory/gustatory function in post-COVID-19 infection (PCI). Patients with past PCR-confirmed COVID-19 infection and persistent olfactory/gustatory complaints were investigated. Olfactory threshold and identification, gustatory detection, identification, and magnitude scaling were tested. A total of 42 PCI subjects were compared to 41 age- and gender-matched controls with no COVID-19 history. All PCI tested had mild COVID-19 disease. Mean interval between COVID-19 confirmations to testing was 7.4 ± 3.1 months. PCI subjects complained of combined dysfunction in 85.7%, isolated olfactory or gustatory dysfunction in 7.1% each. Combined complaints were significantly higher in PCI (p < 0.001). Objective testing showed significantly higher prevalence of dysfunction in PCI versus controls for hyposmia (73.8%, 12.2%), anosmia (11.9%, 0%), odor identification (68.5%, 83.0%), hypogeusia (23% and 2.4%, respectively), and impaired magnitude scaling, (p < 0.05). All PCI subjects with hypogeusia had abnormal gustatory magnitude scaling. While most PCI subjects complained of combined gustatory and olfactory dysfunction, objective testing showed in the majority an isolated single sense dysfunction, with a low level of agreement between subjective and objective findings. Abnormal objective results for all olfactory and gustatory functions tested may suggest a central rather than peripheral mechanism, although concomitant mechanisms cannot be excluded.

Simple prediction of COVID-19 convalescent plasma units with high levels of neutralization antibodies

BackgroundHyperimmune convalescent COVID-19 plasma (CCP) containing anti-SARS-CoV-2 neutralizing antibodies (NAbs) was proposed as a therapeutic option for patients early in the new coronavirus disease pandemic. The efficacy of this therapy depends on the quantity of neutralizing antibodies (NAbs) in the CCP units, with titers ≥ 1:160 being recommended. The standard neutralizing tests (NTs) used for determining appropriate CCP donors are technically demanding and expensive and take several days. We explored whether they could be replaced by high-throughput serology tests and a set of available clinical data.MethodsOur study included 1302 CCP donors after PCR-confirmed COVID-19 infection. To predict donors with high NAb titers, we built four (4) multiple logistic regression models evaluating the relationships of demographic data, COVID-19 symptoms, results of various serological testing, the period between disease and donation, and COVID-19 vaccination status.ResultsThe analysis of the four models showed that the chemiluminescent microparticle assay (CMIA) for the quantitative determination of IgG Abs to the RBD of the S1 subunit of the SARS-CoV-2 spike protein was enough to predict the CCP units with a high NAb titer. CCP donors with respective results > 850 BAU/ml SARS-CoV-2 IgG had a high probability of attaining sufficient NAb titers. Including additional variables such as donor demographics, clinical symptoms, or time of donation into a particular predictive model did not significantly increase its sensitivity and specificity.ConclusionA simple quantitative serological determination of anti-SARS-CoV-2 antibodies alone is satisfactory for recruiting CCP donors with high titer NAbs.

Detection of SARS-CoV-2 IgG antibodies and inflammatory cytokines in saliva-a pilot study.

The pandemic caused by SARS-CoV-2 virus continues to have a profound effect worldwide. However, COVID-19 induced oral facial manifestations have not been fully described. We conducted a prospective study to demonstrate feasibility of anti-SARS-CoV-2 IgG and inflammatory cytokine detection in saliva. Our primary objective was to determine whether COVID-19 PCR positive patients with xerostomia or loss of taste had altered serum or saliva cytokine levels compared to COVID-19 PCR positive patients without those oral symptoms. Our secondary objective was to determine the correlation between serum and saliva COVID-19 antibody levels. For cytokine analysis, saliva and serum were obtained from 17 participants with PCR-confirmed COVID-19 infection at three sequential time points, yielding 48 saliva samples and 19 paired saliva-serum samples from 14 of the 17 patients. For COVID-19 antibody analyses, an additional 27 paired saliva-serum samples from 22 patients were purchased. The saliva antibody assay had 88.64% sensitivity [95% Confidence Interval (CI) 75.44%, 96.21%] to detect SARS-CoV-2 IgG antibodies compared to serum antibody. Among the inflammatory cytokines assessed - IL-6, TNF-α, IFN-γ, IL-10, IL-12p70, IL-1β, IL-8, IL-13, IL-2, IL-5, IL-7 and IL-17A, xerostomia correlated with lower levels of saliva IL-2 and TNF-α, and elevated levels of serum IL-12p70 and IL-10 (p<0.05). Loss of taste was observed in patients with elevated serum IL-8 (p<0.05). Further studies are needed to construct a robust saliva-based COVID-19 assay to assess antibody and inflammatory cytokine response, which has potential utility as a non-invasive monitoring modality during COVID-19 convalescence.