Extra-pulmonary Organ Systems Research Articles

Recurring episodes of bundle branch reentry ventricular tachycardia due to aortitis preceded by SARS-CoV-2 infection: a case report

BackgroundSARS-CoV-2 may trigger both vasculitis and arrhythmias as part of a multisystem inflammatory syndrome described in children as well as in adults following COVID-19 infection with only minor respiratory symptoms. The syndrome denotes a severe dysfunction of one or more extra-pulmonary organ systems, with symptom onset approximately 2–5 weeks after the COVID-19 infection. In the present case, a seemingly intractable ventricular tachycardia preceded by SARS-CoV2 infection was only managed following the diagnosis and management of aortitis.Case presentationA 69-year-old woman was hospitalized due to syncope, following a mild COVID-19 infection. She presented with paroxysmal atrial fibrillation and intermittent ventricular tachycardia interpreted as a septum-triggered bundle branch reentry ventricular tachycardia, unaffected by amiodaron, lidocaine and adenosine. A CT-scan revealed inflammation of the aortic arch, extending into the aortic root. In the following days, the tachycardia progressed to ventricular storm with intermittent third-degree AV block. A temporary pacemaker was implanted, and radiofrequency ablation was performed to both sides of the ventricular septum after which the ventricular tachycardia was non-inducible. Following supplemental prednisolone treatment, cardiac symptoms and arrythmia subsided, but recurred after tapering. Long-term prednisolone treatment was therefore initiated with no relapse in the following 14 months.ConclusionWe present a rare case of aortitis complicated with life-threatening ventricular tachycardia presided by Covid-19 infection without major respiratory symptoms. Given a known normal AV conduction prior to the COVID-19 infection, it seems likely that the ensuing aortitis in turn affected the septal myocardium, enabling the reentry tachycardia. Generally, bundle branch reentry tachycardia is best treated with radiofrequency ablation, but if it is due to aortitis with myocardial affection, long-term anti-inflammatory treatment is mandatory to prevent relapse and assure arrhythmia control. Our case highlights importance to recognize the existence of the multisystem inflammatory syndrome in adults (MIS-A) following COVID-19 infection in patients with alarming cardiovascular symptoms. The case shows that the early use of an CT-scan was crucial for both proper diagnosis and treatment option.

Multisystem inflammatory syndrome in adults with COVID-19 requiring mechanical ventilation: A retrospective cohort study.

Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory multisystem condition associated with coronavirus disease (COVID-19). Critically ill COVID-19 patients may develop multiorgan damage and elevated inflammatory responses, thus making it difficult to differentiate between progression to organ damage due to COVID-19 itself or MIS-A. This study aimed to explore the characteristics and complications of MIS-A in critical COVID-19 patients. The Japan Extracorporeal Membrane Oxygenation (ECMO) Network and ICU Collaboration Network developed a web-based database system called the CRoss Intensive Care Unit Searchable Information System (CRISIS) to monitor critical COVID-19 patients throughout Japan. We retrospectively identified patients with MIS-A among critical COVID-19 patients enrolled from March 2020 to December 2021, using CRISIS. Our MIS-A definition required patients to be at least 18 years of age, have laboratory evidence of inflammation, severe dysfunction of at least two extrapulmonary organ systems, and no plausible alternative diagnoses. Of the 1052 patients, 26 (2.5%) were diagnosed with MIS-A. The MIS-A patients had a higher likelihood of using ECMO (13% vs. 46%, p < 0.001) and lower overall survival (77% vs. 42%, p < 0.001) than non-MIS-A patients. More than 80% of the MIS-A cases occurred 3 weeks after the COVID-19 onset. Multisystem inflammatory syndrome in adults can occur in 2.5% of critically ill COVID-19 patients, and the mortality rate is high. Multisystem inflammatory syndrome in adults may be considered when there is a re-elevation of the unexplained inflammatory response and severe dysfunction of at least two extrapulmonary organ systems several weeks after the onset of COVID-19.

Diabetes after SARS-CoV-2 infection

The COVID-19 global pandemic represents a unique opportunity to better understand the post-viral and post-infectious condition. More than 2 years into the pandemic, a large body of evidence makes it clear that infection with SARS-CoV-2 can lead to post-acute sequelae in the pulmonary and broad array of extrapulmonary organ systems—collectively referred to by the umbrella term of long COVID.1,2 Evidence also suggests that the myriad clinical abnormalities of long COVID might extend to new onset diabetes.

Mucocutaneous manifestations of COVID-19-related multisystem inflammatory syndrome in adults: an update.

Multisystem inflammatory syndrome in adults (MIS‐A) is an inflammatory condition that affects multiple extrapulmonary organ systems (cardiac, gastrointestinal tract, dermatological and/or neurological), attributed to a postinfectious and atypical complication occurring weeks to months after infection with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). The diagnosis is primarily based on findings encompassing persistent fever, elevated inflammatory markers, multiorgan involvement and a temporal relationship with COVID‐19 infection. The existing literature on MIS‐A, although growing, is limited to case reports and small case series. It is imperative that dermatologists be aware of this entity and aid the critical care team to ensure timely diagnosis and early therapeutic intervention. In this review, we concisely highlight the varied presentations, pathogenesis and treatment options in MIS‐A.

Kidney Outcomes in Long COVID.

COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems-referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available. We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability-weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory. Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of -3.26 (-3.58 to -2.94), -5.20 (-6.24 to -4.16), and -7.69 (-8.27 to -7.12) ml/min per 1.73 m2 per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection. Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease.

MULTISYSTEM INFLAMMATORY SYNDROME OF THE ADULT: AN IMPORTANT CONSEQUENCE OF COVID-19

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Multi-system inflammatory syndrome of the adult (MIS-A) has been recently brought to light by the COVID-19 pandemic. MIS-A is characterized by high fever, elevated inflammatory markers and multi-organ dysfunction. The most commonly affected organs are the cardiac and gastrointestinal systems. Guideline directed treatment has yet to be established. CASE PRESENTATION: A 24 year old male with a history of SARS-COV-2 infection presented to the hospital with a chief complaint of nausea and vomiting. Over the previous few days, the patient reported diarrhea along with high fevers and dyspnea. He was diagnosed with COVID-19 six weeks prior, and his disease course was self-limited. He completed his quarantine with no lasting effects.Vital signs revealed a temperature of 103.6 degrees Fahrenheit, heart rate of 141 beats per minute and a respiratory rate of 29 breaths per minute. He was saturating 89% on room air. He was treated for sepsis with isotonic crystalloids and empiric antibiotics. His oxygen requirement eventually improved with diuresis. The remainder of his laboratory workup was significant for an elevated troponin which peaked at 0.93 ng/mL and an elevated c-Reactive protein of 36.07 mg/dL. His echocardiogram revealed an ejection fraction of 30-35%, left ventricular hypokinesis and an RVSP of 40 mmHg. He was started on intravenous methylprednisolone 60mg q6h with rapid improvement of symptoms, and full dose anticoagulation for an NSTEMI. DISCUSSION: In October of 2020, a report was published by the CDC reviewing 9 cases of MIS-A that were submitted directly, and 7 of which were published from case reports. Five criteria for the diagnosis of MIS-A included severe illness requiring hospitalization in a patient > 21 years of age, currently positive or previous SARS-CoV-2 infection in the last 12 weeks, dysfunction of one or more extra-pulmonary organ systems, elevated inflammatory markers (CRP, ferritin, d-dimer or IL-6) and absence of severe respiratory illness. Of the 16 cases that were reported, 75% were febrile. All patients had evidence of cardiac injury, and 13 out of 16 had gastrointestinal symptoms. All patients also had elevated laboratory markers of inflammation. Treatment varied, as patients were given IVIG, corticosteroids and anti-IL-6 therapies. CONCLUSIONS: Our patient met all criteria for MIS-A. Although he had respiratory symptoms, they improved rapidly with diuresis, which suggests that they may have been related to myocarditis and reduced ejection fraction, rather than a primary pulmonary process such as pneumonia. This case highlights the importance of recognizing MIS-A as a sequela of COVID-19 infection. It can occur weeks after initial COVID-19 infection, or concomitantly with infection and PCR positivity. Treatment has not been clearly established, but our patient improved rapidly with corticosteroid administration and supportive care. REFERENCE #1: Morris, S., Schwartz, N. et. al. (2020). Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection - United Kingdom and UnitedStates - March - August 2020. Morbidity and Mortality Weekly Report, 69(40). REFERENCE #2: Tenforde, M., & Morris, S. (2021). Multisystem Inflammatory Syndrome in Adults. CHEST, 159(2). doi:https://doi.org/10.1016/j.chest.2020.09.097 DISCLOSURES: No relevant relationships by SUNIL KUMAR, source=Web Response No relevant relationships by Julia Ladna, source=Web Response No relevant relationships by Kenneth Wojnowski, source=Web Response

MULTISYSTEM INFLAMMATORY SYNDROME IN AN ADULT POST-SARS-COV-2 INFECTION

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: An acute respiratory syndrome associated to the novel coronavirus SARS-CoV-2 has affected the entire world. Pediatric patients can rarely present with a severe complication identified as multisystem inflammatory syndrome in children (MIS-C).(1) After its recognition by the CDC and media reports of young adults with the same syndrome, a series of cases in adults (MIS-A) was published in late 2020.(2) CASE PRESENTATION: A 25-year-old Hispanic male who tested positive for SARS-CoV-2 by RT-PCR six weeks prior presented to the emergency department with one week of sore throat, fever, non-bloody diarrhea, conjunctivitis, and mild confusion. On examination, the patient was febrile, had tender submandibular lymph nodes and redness on the oropharynx. Initial laboratory results showed systemic inflammation. COVID-19 RT-PCR test was negative, coronavirus IgG was positive, and chest radiograph was normal. On the third day, the patient's clinical status deteriorated despite antibiotic use with hypotension and hypoxemia requiring vasopressor support and ICU admission. An echocardiogram showed left ventricular ejection fraction (EF) of 35% with hypokinesia. Due to persistent shock state and elevated inflammatory markers after 36 hours, we started him on methylprednisolone 1.5 mg/kg daily. After 24 hours, clinical status and inflammatory markers improved significantly. A follow-up echocardiogram four weeks after discharge showed normalization of EF. DISCUSSION: Since the beginning of the pandemic, different countries reported cases of a hyperinflammatory process in children that had features similar to atypical Kawasaki disease.(3) A larger study described MIS-C in 99 patients under 21 years of age in New York.(4) The case definition MIS-C was established by the CDC. For a time, it was unknown if this syndrome was specific to children or whether it also occurred in adults. A MIS-A working case definition includes five criteria: severe illness requiring hospitalization in a person aged at least 21 years;a positive test result for current or previous SARS-CoV-2 infection;severe dysfunction of one or more extrapulmonary organ systems;laboratory evidence of severe inflammation;and absence of severe respiratory illness.(2) Case definitions for MIS-C/A with degrees of diagnostic certainty have also been elaborated.(5) We are presenting a patient that meets clinical and laboratory criteria for MIS-A. His respiratory dysfunction occurred after admission when his inflammatory markers were already elevated. This case includes a temporal correlation after the initial peak of COVID-19 cases in Houston by 31 days. CONCLUSIONS: The number of cases of MIS-A is unclear. It is important to keep this condition in our differential in the context of recent SARS-CoV-2 infection for early identification and appropriate treatment to reduce further harm and mortality. REFERENCE #1: 1. Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Published online May 14, 2020. Accessed April 22, 2020. https://emergency.cdc.gov/han/2020/han00432.asp2. Morris SB, Schwartz NG, Patel P, et al. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(40):1450-1456. doi:10.15585/mmwr.mm6940e1 REFERENCE #2: 3. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet. 2020;395(10239):1771-1778. doi:10.1016/S0140-6736(20)31103-X4. Dufort EM, Koumans EH, Chow EJ, et al. Multisystem Inflammatory Syndrome in Children in New York State. N Engl J Med. 2020;383(4):347-358. doi:10.1056/NEJMoa2021756 REFERENCE #3: 5. Vogel TP, Top KA, Karatzios C, et al. Multisystem inflammatory syndrome in children and adults (MIS-C/A): Case definition & guidelines for data collectio , analysis, and presentation of immunization safety data. Vaccine. Published online February 2021:S0264410X21000931. doi:10.1016/j.vaccine.2021.01.054 DISCLOSURES: No relevant relationships by Luis Chug, source=Web Response No relevant relationships by Julin Mathew, source=Web Response No relevant relationships by Nora Moron Cabrera, source=Web Response No relevant relationships by Rohini Rao, source=Web Response No relevant relationships by Juan Salvatierra, source=Web Response

High-dimensional characterization of post-acute sequelae of COVID-19

The acute clinical manifestations of COVID-19 have been wellcharacterized1,2, but the post-acute sequelae of this disease have not been comprehensively described. Here we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequelae-including diagnoses, medication use and laboratory abnormalities-in patients with COVID-19 who survived for at least 30days after diagnosis. We show that beyond the first 30days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Our high-dimensional approach identifies incident sequelae in the respiratory system, as well as several other sequelae that include nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain and anaemia. We show increased incident use of several therapeutic agents-including pain medications (opioids and non-opioids) as well as antidepressant, anxiolytic, antihypertensive and oral hypoglycaemic agents-as well as evidence of laboratory abnormalities in several organ systems. Our analysis of an array of prespecified outcomes reveals a risk gradient that increases according to the severity of the acute COVID-19 infection (that is, whether patients were nothospitalized, hospitalized or admitted to intensive care). Our findings show that a substantial burden of health loss that spans pulmonary and several extrapulmonary organ systems is experienced by patients who survive after the acute phase of COVID-19. These results will help to inform health system planning and the development of multidisciplinary care strategies to reduce chronic health loss among individuals with COVID-19.

How Adhesion Molecule Patterns Change While Neutrophils Traffic through the Lung during Inflammation.

In acute pulmonary inflammation, polymorphonuclear cells (PMNs) pass a transendothelial barrier from the circulation into the lung interstitium followed by a transepithelial migration into the alveolar space. These migration steps are regulated differentially by a concept of adhesion molecules and remain—despite decades of research—incompletely understood. Current knowledge of changes in the expression pattern of adhesion molecules mainly derives from in vitro studies or from studies in extrapulmonary organ systems, where regulation of adhesion molecules differs significantly. In a murine model of lung inflammation, we determined the expression pattern of nine relevant neutrophilic adhesion molecules on their way through the different compartments of the lung. We used a flow cytometry-based technique that allowed describing spatial distribution of the adhesion molecules expressed on PMNs during their migration through the lung in detail. For example, the highest expression of CD29 was found in the intravascular compartment, highlighting its impact on the initial adhesion to the endothelium. CD47 showed its peak of expression on the later phase of transendothelial migration, whereas CD11b and CD54 expression peaked interstitial. A pivotal role for transepithelial migration was found for the adhesion molecule CD172a. Thereby, expression may correlate with functional impact for specific migration steps. In vitro studies further confirmed our in vivo findings. In conclusion, we are the first to determine the changes in expression patterns of relevant adhesion molecules on their migration through the different compartments of the lung. These findings may help to further understand the regulation of neutrophil trafficking in the lung.

Role of Mincle in Alveolar Macrophage-Dependent Innate Immunity against Mycobacterial Infections in Mice

The role of macrophage-inducible C-type lectin Mincle in lung innate immunity against mycobacterial infection is incompletely defined. In this study, we show that wild-type (WT) mice responded with a delayed Mincle induction on resident alveolar macrophages and newly immigrating exudate macrophages to infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG), peaking by days 14-21 posttreatment. As compared with WT mice, Mincle knockout (KO) mice exhibited decreased proinflammatory mediator responses and leukocyte recruitment upon M. bovis BCG challenge, and they demonstrated increased mycobacterial loads in pulmonary and extrapulmonary organ systems. Secondary mycobacterial infection on day 14 after primary BCG challenge led to increased cytokine gene expression in sorted alveolar macrophages of WT mice, but not Mincle KO mice, resulting in substantially reduced alveolar neutrophil recruitment and increased mycobacterial loads in the lungs of Mincle KO mice. Collectively, these data show that WT mice respond with a relatively late Mincle expression on lung sentinel cells to M. bovis BCG infection. Moreover, M. bovis BCG-induced upregulation of C-type lectin Mincle on professional phagocytes critically shapes antimycobacterial responses in both pulmonary and extrapulmonary organ systems of mice, which may be important for elucidating the role of Mincle in the control of mycobacterial dissemination in mice.

Interrelationships Between Pulmonary and Extrapulmonary Involvement in Systemic Sclerosis: A Longitudinal Analysis

(1) To evaluate the relationship between the degree of pulmonary involvement by systemic sclerosis (SSc) and the degree of involvement of other organ systems by SSc at baseline. (2) To assess the degree of impairment in lung function at presentation and the annual rate of change in lung function to predict the rate of progression of involvement of extrapulmonary organ systems by SSc over time. (3) To determine whether survival in patients with SSc can be predicted from the degree of lung function impairment at baseline or from the annual rate of change in lung function. Semiquantitative indices of pulmonary and extrapulmonary involvement and pulmonary function tests (PFTs) were analyzed and compared in 62 nonsmoking scleroderma patients enrolled in a 3-year prospective drug trial, vs 47 in a "study group" who underwent serial evaluation. The other 16 "early withdrawals" withdrew prior to the second evaluation. The indices of organ system involvement were based on clinical, physiologic, and biochemical findings as previously published. The PFTs included total lung capacity (TLC), forced vital capacity (FVC), FEV1, and single-breath diffusing capacity for carbon monoxide (Dsb). Annualized rates of change in PFTs and indices of extrapulmonary involvement were calculated for each subject from data collected on at least 2 separate occasions at least 6 months apart. Spearman rank correlations were performed between individual baseline PFTs (expressed as percent predicted) and (a) indices of extrapulmonary involvement at baseline, (b) annualized rates of change in PFTs, and (c) annualized rates of change in indices of extrapulmonary involvement. Correlations also were performed between the rate of change in each lung function measure and rates of change in indices of extrapulmonary involvement. The ability of PFTs at baseline and their rates of change to predict cumulative survival was assessed by Cox stepwise regression. The degree of impairment in baseline PFTs was related to involvement of the right side of the heart but not to other extrapulmonary system involvement. Baseline PFTs were not related to the rate of subsequent decline of lung function or worsening of extrapulmonary organ system involvement. Subsequent annual rates of decline in lung function were related to worsening skin and upper gastrointestinal involvement. Cumulative survival may be related to the rate of decline in DCO, TLC, and FVC, but was not predicted by impairment in any measure of lung function. With the exception of involvement of the right side of the heart consistent with cor pulmonale, the degree of pulmonary involvement by SSc was not correlated with the extent of extrapulmonary involvement. The degree of pulmonary involvement by SSc did not predict subsequent worsening of either pulmonary or extrapulmonary involvement. Worsening pulmonary involvement by SSc, in general, does not correlate with worsening involvement of extrapulmonary organ systems, except for the skin and upper gastrointestinal tract. A rapid decline in DCO or lung volumes may predict poor survival.