Timing and Depth Selection for Sedated Gastroscopy After SARS-CoV-2 Infection—A Retrospective Cohort Study (preprint)

Background Sedated gastroscopy is a crucial procedure for patients with upper respiratory infections. SARS-CoV-2-infected patients are more susceptible to anesthesia-related complications, such as edema, pharyngeal mucosa congestion, laryngospasm, and pulmonary infections.Methods We retrospectively analyzed a total of 386 patients who underwent sedated gastroscopy at the Affiliated Hospital of Qingdao University during the SARS-CoV-2 infection period. The patients were divided into three groups based on SARS-CoV-2 status: Negative (N), Two-week post-SARS-CoV-2 infection (T), and Three-week post-SARS-CoV-2 infection (Th) groups. Based on the anesthesia method, patients were divided into mild/moderate sedation and deep sedation/general anesthesia groups. Additionally, patients were categorized into groups based on COVID-19 severity and vaccination status. We recorded the laryngeal mucosal conditions, the occurrence rates of adverse reactions such as coughing, laryngospasm, and transient oxygen desaturation during the examination, as well as the satisfaction of patients and endoscopists were recorded.Results The T group displayed a significantly higher occurrence rate of adverse reactions when compared to the N and Th group, with decreased satisfaction levels of patients and endoscopists. In the T group, the occurrence rate of adverse reactions was higher in mild to moderate sedation than in deep sedation/general anesthesia methods, while patient and endoscopist satisfaction was lower. In the Th group, there was no statistically significant difference in the examination success rate or patient satisfaction between the mild/moderate sedation and deep sedation/general anesthesia methods; however, endoscopist satisfaction was lower with mild/moderate sedation method than deep sedation/general anesthesia method. There was a significant difference in the gastroscopy success rates of patients with different COVID-19 classifications. A significant difference was observed in the gastroscopy success rates among patients with different vaccination statuses.Conclusions Sedated gastroscopy post-three weeks of SARS-CoV-2 infection is safe. Moreover, using a deep sedation/general anesthesia method for sedated gastroscopy in SARS-CoV-2-infected patients within three weeks is significantly safer.

Analysis of allergy and hypersensitivity reactions to COVID-19 vaccines according to the EudraVigilance database (preprint)

Background: The Coronavirus Disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine. The development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to anti-COVID-19 vaccines’ allergising potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyse the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. Methods: The total number of administrated vaccine doses was extracted on the 5th October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines was extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. Results: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta and 3.1 for Valneva. The most prevalent reported reactions were oedema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. Conclusions: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria.

Predictive validity of the simplified Radiographic Assessment of Lung Edema score for the mortality in critically ill COVID-19 patients with the B.1.617.2 (Delta) variant in Vietnam: a single-centre, cross-sectional study (preprint)

BackgroundEvaluating the prognosis of COVID-19 patients who may be at risk of mortality using the simple chest X-ray (CXR) severity scoring systems provides valuable insights for treatment decisions. This study aimed to assess how well the simplified Radiographic Assessment of Lung Edema (RALE) score could predict the death of critically ill COVID-19 patients in Vietnam. MethodsFrom July 30 to October 15, 2021, we conducted a cross-sectional study on critically ill COVID-19 adult patients at an intensive care centre in Vietnam. We calculated the areas under the receiver operator characteristic (ROC) curve (AUROC) to determine how well the simplified RALE score could predict hospital mortality. In a frontal CXR, the simplified RALE score assigns a score to each lung, ranging from 0 to 4. The overall severity score is the sum of points from both lungs, with a maximum possible score of 8. We also utilized ROC curve analysis to find the best cut-off value for this score. Finally, we utilized logistic regression to identify the association of simplified RALE score with hospital mortality. ResultsOf 105 patients, 40.0% were men, the median age was 61.0 years (Q1-Q3: 52.0-71.0), and 79.0% of patients died in the hospital. Most patients exhibited bilateral lung opacities on their admission CXRs (99.0%; 100/102), with the highest occurrence of opacity distribution spanning three (18.3%; 19/104) to four quadrants of the lungs (74.0%; 77/104) and a high median simplified RALE score of 8.0 (Q1-Q3: 6.0-8.0). The simplified RALE score (AUROC: 0.747 [95% CI: 0.617-0.877]; cut-off value [≥]5.5; sensitivity: 93.9%; specificity: 45.5%; PAUROC <0.001) demonstrated a good discriminatory ability in predicting hospital mortality. After adjusting for confounding factors such as age, gender, Charlson Comorbidity Index, serum interleukin-6 level upon admission, and admission severity scoring systems, the simplified RALE score of [≥]5.5 (adjusted OR: 18.437; 95% CI: 3.215-105.741; p =0.001) was independently associated with an increased risk of hospital mortality. ConclusionsThis study focused on a highly selected cohort of critically ill COVID-19 patients with a high simplified RALE score and a high mortality rate. Beyond its good discriminatory ability in predicting hospital mortality, the simplified RALE score also emerged as an independent predictor of hospital mortality.

COVID-related Constrictive Pericarditis Requiring Pericardiectomy: A Case Report (preprint)

Background The COVID-19 pandemic was primarily considered a respiratory malady in the early phases of the outbreak. However, as more patients suffer from this illness, a myriad of symptoms emerge in organ systems separate from the lungs. Among those patients with cardiac involvement, myocarditis, pericarditis, myocardial infarction, and arrhythmia were among the most common manifestations. Pericarditis with pericardial effusion requiring medical or interventional treatments has been previously reported in the acute setting. Notably, chronic pericarditis with pericardial thickening resulting in constriction requiring sternotomy and pericardiectomy has not been published to date.Case Presentation A patient with COVID-19-associated constrictive pericarditis three years after viral infection requiring pericardiectomy was reported. The COVID-19 infection originally manifested as anosmia and ageusia. Subsequently, the patient developed dyspnea, fatigue, right-sided chest pressure, bilateral leg edema, and abdominal fullness. Following recurrent right pleural effusions and a negative autoimmune work-up, the patient was referred for cardiothoracic surgery for pericardiectomy when radiographic imaging and hemodynamic assessment were consistent with constrictive pericarditis. Upon median sternotomy, the patient’s pericardium was measured to be 8 mm thick. Descriptions of the clinical, diagnostic, and therapeutic features are provided. Within the first week after the operation, the patient’s dyspnea resolved; one month later, leg edema and abdominal bloating were relieved.Conclusions Although an association between COVID-19 and cardiac complications has been established, this case adds another element of virus severity and chronic manifestations. The need for sternotomy and pericardiectomy to treat COVID-19-related constrictive pericarditis is believed to be the first reported diagnosis.

Improving Fairness of Automated Chest X-ray Diagnosis by Contrastive Learning (preprint)

Purpose: Limited studies exploring concrete methods or approaches to tackle and enhance model fairness in the radiology domain. Our proposed AI model utilizes supervised contrastive learning to minimize bias in CXR diagnosis. Materials and Methods: In this retrospective study, we evaluated our proposed method on two datasets: the Medical Imaging and Data Resource Center (MIDRC) dataset with 77,887 CXR images from 27,796 patients collected as of April 20, 2023 for COVID-19 diagnosis, and the NIH Chest X-ray (NIH-CXR) dataset with 112,120 CXR images from 30,805 patients collected between 1992 and 2015. In the NIH-CXR dataset, thoracic abnormalities include atelectasis, cardiomegaly, effusion, infiltration, mass, nodule, pneumonia, pneumothorax, consolidation, edema, emphysema, fibrosis, pleural thickening, or hernia. Our proposed method utilizes supervised contrastive learning with carefully selected positive and negative samples to generate fair image embeddings, which are fine-tuned for subsequent tasks to reduce bias in chest X-ray (CXR) diagnosis. We evaluated the methods using the marginal AUC difference ($\delta$ mAUC). Results: The proposed model showed a significant decrease in bias across all subgroups when compared to the baseline models, as evidenced by a paired T-test (p<0.0001). The $\delta$ mAUC obtained by our method were 0.0116 (95\% CI, 0.0110-0.0123), 0.2102 (95% CI, 0.2087-0.2118), and 0.1000 (95\% CI, 0.0988-0.1011) for sex, race, and age on MIDRC, and 0.0090 (95\% CI, 0.0082-0.0097) for sex and 0.0512 (95% CI, 0.0512-0.0532) for age on NIH-CXR, respectively. Conclusion: Employing supervised contrastive learning can mitigate bias in CXR diagnosis, addressing concerns of fairness and reliability in deep learning-based diagnostic methods.

Thrombotic microangiopathy with kidney involvement in a patient with coronavirus disease 2019: A case report and literature review (preprint)

Background and aim: Millions of people worldwide have suffered from coronavirus disease 2019 (COVID-19). COVID-19 can lead to coagulopathy and thrombosis, presenting as pulmonary artery thromboembolism, deep vein thrombosis, and thrombotic microangiopathy (TMA), the latter being a rare finding in affected patients’ kidneys. Prior reports have rarely addressed the pathophysiology, clinical presentations, and therapeutic options in patients with COVID-19-associated TMA. Case presentation: We herein described a case of renal biopsy-proven TMA after COVID-19 in a 36-year-old woman. Initial examination revealed inflammation, acute kidney injury (AKI), anemia, and thrombocytopenia. She was diagnosed with hemolytic uremic syndrome, pulmonary infection, and COVID-19. After treatment, her condition stabilized but remained hemodialysis-dependent after discharge. One week later, she was re-hospitalized, and physical examination showed anemia and bilateral lower extremity edema. Abdominal ultrasound showed increased bilateral kidney echogenicity. Whole-exome sequencing detected an unknown variant of the C3 gene associated with hemolytic uremic syndrome susceptibility type 5/complement C3 deficiency. Kidney biopsy showed renal artery lesions, including small arteriole endothelial swelling, intimal thickening, mucinous degeneration, luminal occlusion, and small arterial wall necrosis. She received plasma exchange and steroids with significant renal function recovery. Conclusion: TMA likely contributed to AKI after COVID-19,thus supporting the notion that TMA plays an important role in the pathogenesis of COVID-19-related kidney injury. When diagnosing and treating COVID-19 patients with abnormal renal function, clinicians should incorporate kidney biopsy and genetic testing for the complement system, identify renal-limited and systemic TMA, and treat accordingly, which can improve patient outcomes.

Association of Obstructive Sleep Apnea with Post-Acute Sequelae of SARS-CoV-2 infection (PASC) (preprint)

BackgroundObstructive sleep apnea (OSA) is associated with COVID-19 infection. Fewer investigations have assessed OSA as a possible risk for the development of Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Research QuestionIn a general population, is OSA associated with increased odds of PASC-related symptoms and with an overall definition of PASC? Study DesignCross-sectional survey of a general population of 24,803 U.S. adults. ResultsCOVID-19 infection occurred in 10,324 (41.6%) participants. Prevalence rates for a wide variety of persistent (> 3 months post infection) putative PASC-related physical and mental health symptoms ranged from 6.5% (peripheral edema) to 19.6% (nervous/anxious). In logistic regression models adjusted for demographic, anthropometric, comorbid medical and socioeconomic factors, OSA was associated with all putative PASC-related symptoms with the highest adjusted odds ratios (aOR) being fever (2.053) and nervous/anxious (1.939) respectively. Elastic net regression identified the 13 of 37 symptoms most strongly associated with COVID-19 infection. Four definitions of PASC were developed using these symptoms either weighted equally or proportionally by their regression coefficients. In all 4 logistic regression models using these definitions, OSA was associated with PASC (range of aORs: 1.934-2.071); this association was mitigated in those with treated OSA. In the best fitting overall model requiring [≥]3 symptoms, PASC prevalence was 21.9%. ConclusionIn a general population sample, OSA is associated with the development of PASC-related symptoms and a global definition of PASC. A PASC definition requiring the presence of 3 or more symptoms may be useful in identifying cases and for future research.

Initial Experience of Long-Term Prophylaxis with Lanadelumab for Hereditary Angioedema in China: a Clinical Observation of Four patients. (preprint)

Background Hereditary angioedema (HAE) is a rare genetic disorder caused by a deficiency or dysfunction of C1 esterase inhibitor (C1-INH), which leads to recurrent episodes of bradykininmediated edema. Lanadelumab is a plasma kallikrein inhibitor that is the only first line therapy for long term prophylaxis (LTP) of HAE attacks in China since 2021.Objectives To observe the clincial efficacy and safety of lanadelumab in Chinese patients with HAE in a small population of four patients.Method Four HAE patients from three academic centers in China was included. Demographic characteristics, clinical manifestions and life quality of HAE patients were recorded before and after LTP treatment of lanadelumab .The primary outcome is the attack frequence of symptoms, and disease-related work loss days. The secondary outcome is the improved life quality of patients. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Angioedema Quality of Life Questionnaire (AE-QoL).Results Lanadelumab led to the reductions of 98.04% and 100% in attack rate and treated attack rate respectively. Three patients of four (75%) reported complete remission from attacks after starting the administration of lanadelumab. Two patients had significant improvements on AE-QoL and DLQI (both scores reduction rate were 100%) in early period of treatment (4 weeks and 2 weeks, respectively) and all the patients had significant improvement on missed work days/year (reduction rate was 100%). The efficacy of lanadelumab was stable during vaccination and infection with COVID-19. No treatment-related serious/severe treatment emergent adverse events (TEAEs) occured during the treatment of lanadelumab.Conclusions Our study first demonstrated the clinical efficacy of lanadelumab with highly safety in Chinese HAE patients. A reasonable dosage plan can ensure the stability of therapeutic effects of lanadelumab. Moreover, lanadelumab also play a protective role to prevent attack in the case of COVID-19 infection.

Microvascular injuries, secondary edema, and inconsistencies in lung vascularization between affected and nonaffected pulmonary segments of non-critically ill hospitalized COVID-19 patients presenting with clinical deterioration.

PURPOSE: We aimed to better understand the pathophysiology of SARS-CoV-2 pneumonia in non-critically ill hospitalized patients secondarily presenting with clinical deterioration and increase in oxygen requirement without any identified worsening factors. METHODS: We consecutively enrolled patients without clinical or biological evidence for superinfection, without left ventricular dysfunction and for whom a pulmonary embolism was discarded by computed tomography (CT) pulmonary angiography. We investigated lung ventilation and perfusion (LVP) by LVP scintigraphy, and, 24 h later, left and right ventricular function by Tc-99m-labeled albumin-gated blood-pool scintigraphy with late (60 mn) tomographic albumin images on the lungs to evaluate lung albumin retention that could indicate microvascular injuries with secondary edema. RESULTS: We included 20 patients with confirmed SARS-CoV-2 pneumonia. All had CT evidence of organizing pneumonia and normal left ventricular ejection fraction. No patient demonstrated preserved ventilation with perfusion defect (mismatch), which may discard a distal lung thrombosis. Patterns of ventilation and perfusion were heterogeneous in seven patients (35%) with healthy lung segments presenting a relative paradoxical hypoperfusion and hypoventilation compared with segments with organizing pneumonia presenting a relative enhancement in perfusion and preserved ventilation. Lung albumin retention in area of organizing pneumonia was observed in 12 patients (60%), indicating microvascular injuries, increase in vessel permeability, and secondary edema. CONCLUSION: In hospitalized non-critically ill patients without evidence of superinfection, pulmonary embolism, or cardiac dysfunction, various types of damage may contribute to clinical deterioration including microvascular injuries and secondary edema, inconsistencies in lung segments vascularization suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others. SUMMARY STATEMENT: Microvascular injuries and dysregulation of the balance in perfusion between segments affected by COVID-19 and others are present in non-critically ill patients without other known aggravating factors. KEY RESULTS: In non-critically ill patients without evidence of superinfection, pulmonary embolism, macroscopic distal thrombosis or cardiac dysfunction, various types of damage may contribute to clinical deterioration including 1/ microvascular injuries and secondary edema, 2/ inconsistencies in lung segments vascularization with hypervascularization of consolidated segments contrasting with hypoperfusion of not affected segments, suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.

Prevalence of phalangeal bone marrow edema on MRI before and during the COVID-19 pandemic and correlation with chilblain skin lesions.

OBJECTIVE: The purpose of this study is to establish the prevalence bone marrow edema of the phalanges of the feet and hands before and during the COVID-19 pandemic on MRI studies and correlate with clinically chilblain skin lesions and epidemiological data. METHODS: This observational retrospective study. In patients with confirmed bone marrow edema of the phalanges, epidemiological data and clinical findings were collected, including the history of current or remote COVID-19 infection and vaccination status. The two-proportion test was used to compare the frequency of bone marrow edema in the phalanges before and during the pandemic, and the comparison between the categories variables was performed using the one-proportion test. RESULTS: Of the total of 7215 patients, only 20 presented isolated bone marrow edema of the digits in MRI studies; 2 (0.05%) were found two years before the pandemic's beginning, and 18 (0.64%) after the pandemic's onset, demonstrating an increase of 13-fold in this period. 16 were women with a mean age of 40.3 years and 4 were men with a mean age of 53.5 years. The most frequently reported clinical symptoms by the patients were pain (85.0%), and erythema of the skin (45.0%). Of the 18 patients found after the pandemic's onset, only 27.8% had COVID-19 infections confirmed by RT-PCR before the imaging study, and all cases were mild. CONCLUSION: This study demonstrated a significant increase in the prevalence of bone marrow edema of the phalanges after the onset of the COVID-19 pandemic, particularly in middle-aged and younger women.

Thrombocytopenia, anasarca, and renal insufficiency as severe and rare complications of Hodgkin lymphoma: a case report.

BACKGROUND: Patients with Hodgkin lymphoma exhibit various clinical presentations. Needle biopsy of the lymph nodes is a minimally invasive procedure and a useful diagnostic method for malignant lymphomas. However, at times it is difficult to differentiate malignant lymphomas from reactive lymph node changes using a small amount of biopsy material. CASE PRESENTATION: A 77-year-old Japanese man was referred to the emergency department of our hospital owing to high fever and disturbance of consciousness. We diagnosed sepsis due to an acute biliary tract infection because he presented with Charcot's triad-fever, jaundice, and right-sided abdominal pain. However, he did not respond well to antimicrobial therapy and his high fever persisted. Considering the swelling of the right cervical, mediastinal, and intraperitoneal lymph nodes and splenomegaly detected on computed tomography, a differential diagnosis of malignant lymphoma was needed. Hence, we performed a needle biopsy of the right cervical lymph node; however, the amount of sample obtained was insufficient in establishing a definitive diagnosis of malignant lymphoma. Furthermore, during hospitalization, the patient developed thrombocytopenia, anasarca, and renal insufficiency. These symptoms seemed to be the typical signs of the thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, and organomegaly syndrome. Next, an external incisional mass biopsy of the right cervical lymph node was performed, which helped identify Hodgkin and Reed-Sternberg cells. Collectively, we established a definitive diagnosis of Hodgkin lymphoma with lymphoma-associated hemophagocytic syndrome. CONCLUSIONS: This case highlights the importance of performing an external incisional mass biopsy of the lymph nodes for the early diagnosis and treatment, if malignant lymphoma is strongly suspected.

A case report of laryngeal edema caused by COVID-19 (preprint)

Background Laryngeal edema is caused by the exudation of submucosal tissue fluid from the laxity of the pharynx and can lead to obstruction of the upper airway. It is commonly caused by post-extubation, drug allergy, and bacterial infection. During the current COVID-19 pandemic situation, laryngeal edema is a relatively rare but fatal complication of COVID-19. Taking measures to prevent laryngeal edema can reduce the incidence of sudden life-threatening events in the course of treatment.Case presentation: Here, we report a case in a Chinese male with COVID-19 complicated with laryngeal edema. The initial diagnosis of COVID-19 was followed by a sudden onset of inspiratory dyspnea during hospitalization. At the time of tracheal intubation, laryngeal edema was seen, and a positive bacterial culture suggested a secondary bacterial infection.Conclusion We report a rare case of laryngeal edema complicated by COVID-19. The patient recovered after prompt intubation and treatment. Close monitoring of patients' inflammation indicators and auxiliary bacterial monitoring can effectively prevent the occurrence of laryngeal edema caused by COVID-19.

Acute Necrotizing Encephalopathy Post SARS-CoV-2 Infection in an Adult Patient: Case Report (preprint)

Purpose Show the MRI findings in a rare case of Acute Necrotizing Encephalopathy Post SARS-CoV-2 Infection in an Adult PatientIntroduction Acute necrotizing encephalopathy is a rare condition characterized by the presence of symmetrical multifocal lesions with predominantly thalamic involvement, as well as involvement of the brainstem, white matter of the brain, and cerebellum.Case Presentation We describe a case of a 26-year-old male, with a medical history of medulloblastoma that was disease-free after treatment, and who tested positive in a PCR for SARS-CoV-2 in cerebrospinal fluid. Upon evaluation at the emergency department one week later, the patient was found to be awake, oriented, and focused, and could maintain attention for periods. Mixed dysarthria persisted, characterized by being flaccid and hypokinetic. On magnetic resonance imaging, there were multiple hemorrhagic lesions with surrounding edema in the right thalamus with an extension to the posterior arm of the internal capsule, a smaller one, in the left thalamus, and another expanded to the ipsilateral peduncle.Conclusion Acute necrotizing encephalopathy presents a great clinical and diagnostic challenge, Close clinical and radiological follow-up is essential, and magnetic susceptibility sequences (T2 or SWI) should be included in the diagnosis protocol.

Prevalence and risk factors of adverse effects after the first COVID-19 booster dose: evidence from Greece (preprint)

Background: In general, COVID-19 vaccines are safe and effective, but minor adverse effects are common. Objective: To estimate the prevalence of adverse effects after the first COVID-19 booster dose, and to identify possible risk factors. Material and methods: We conducted a cross-sectional study with a convenience sample in Greece during November 2022. We measured several adverse effects after the booster dose, such as pain at the injection site, swelling at the injection site, fatigue, muscle pain, headaches, fever, chills, nausea, etc. We considered gender, age, chronic disease, self-assessment of health status, COVID-19 diagnosis, and self-assessment of COVID-19 course as possible predictors of adverse effects. Results: In our sample, 96% developed at least one adverse effect. Half of the participants (50.2%) developed one to five adverse effects, 35.9% developed six to ten adverse effects, and 9.5% developed 11 to 16 adverse effects. Mean number of adverse effects was 5.5. The most frequent adverse effects were pain at the injection site (84.3%), fatigue (70.8%), muscle pain (61%), swelling at the injection site (55.2%), headache (49.8%), fever (42.9%), and chills (41%). Females developed more adverse effects than males (p<0.001). Also, we found a positive relationship between severity of COVID-19 symptoms and adverse effects of COVID-19 vaccines (p=0.005). Moreover, younger age was associated with increased adverse effects (p<0.001). Conclusions: Almost all participants in our study developed minor adverse effects after the booster dose. Female gender, worse clinical course of COVID-19, and decreased age were associated with increased adverse effects.

Molecular pathology of acute respiratory distress syndrome, mechanical ventilation and abnormal coagulation in severe COVID-19 (preprint)

Systemic inflammation in critically ill patients can lead to serious consequences such as acute respiratory distress syndrome (ARDS), a condition characterized by the presence of lung inflammation, edema, and impaired gas exchange, associated with poor survival. Understanding molecular pathobiology is essential to improve critical care of these patients. To this end, we use multimodal profiles of SARS-CoV-2 infected hospitalized participants to the Biobanque Quebecoise de la COVID-19 (BQC-19) to characterize endophenotypes associated with different degrees of disease severity. Proteomic, metabolomic, and genomic characterization supported a role for neutrophil-associated procoagulant activity in severe COVID-19 ARDS that is inversely correlated with sphinghosine-1 phosphate plasma levels. Fibroblast Growth Factor Receptor (FGFR) and SH2-containing transforming protein 4 (SHC4) signaling were identified as molecular features associated with endophenotype 6 (EP6). Mechanical ventilation in EP6 was associated with alterations in lipoprotein metabolism. These findings help define the molecular mechanisms related to specific severe outcomes, that can be used to identify early unfavorable clinical trajectories and treatable traits to improve the survival of critically ill patients.

Excess burden of respiratory and abdominal conditions following COVID-19 infections during the ancestral and Delta variant periods in the United States: An EHR-based cohort study from the RECOVER Program (preprint)

Importance The frequency and characteristics of post-acute sequelae of SARS-CoV-2 infection (PASC) may vary by SARS-CoV-2 variant. Objective To characterize PASC-related conditions among individuals likely infected by the ancestral strain in 2020 and individuals likely infected by the Delta variant in 2021. Design Retrospective cohort study of electronic medical record data for approximately 27 million patients from March 1, 2020-November 30, 2021. Setting Healthcare facilities in New York and Florida. Participants Patients who were at least 20 years old and had diagnosis codes that included at least one SARS-CoV-2 viral test during the study period. Exposure Laboratory-confirmed COVID-19 infection, classified by the most common variant prevalent in those regions at the time. Main Outcome(s) and Measure(s) Relative risk (estimated by adjusted hazard ratio [aHR]) and absolute risk difference (estimated by adjusted excess burden) of new conditions, defined as new documentation of symptoms or diagnoses, in persons between 31-180 days after a positive COVID-19 test compared to persons with only negative tests during the 31-180 days after the last negative test. Results We analyzed data from 560,752 patients. The median age was 57 years; 60.3% were female, 20.0% non-Hispanic Black, and 19.6% Hispanic. During the study period, 57,616 patients had a positive SARS-CoV-2 test; 503,136 did not. For infections during the ancestral strain period, pulmonary fibrosis, edema (excess fluid), and inflammation had the largest aHR, comparing those with a positive test to those with a negative test, (aHR 2.32 [95% CI 2.09 2.57]), and dyspnea (shortness of breath) carried the largest excess burden (47.6 more cases per 1,000 persons). For infections during the Delta period, pulmonary embolism had the largest aHR comparing those with a positive test to a negative test (aHR 2.18 [95% CI 1.57, 3.01]), and abdominal pain carried the largest excess burden (85.3 more cases per 1,000 persons). Conclusions and Relevance We documented a substantial relative risk of pulmonary embolism and large absolute risk difference of abdomen-related symptoms after SARS-CoV-2 infection during the Delta variant period. As new SARS-CoV-2 variants emerge, researchers and clinicians should monitor patients for changing symptoms and conditions that develop after infection.