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We report COVID-19 multisystemic inflammatory syndrome in an adult patient with an atypical presentation (mild abdominal pain) and a negative (repeated) reverse transcriptase-PCR, in the absence of lung involvement on lung ultrasound. In this case, focused cardiac ultrasound revealed signs of myopericarditis and enabled us to focus on the problem that was putting our patient in a perilous situation, with a quick, non-time-consuming and easy-to-access technique. Serology test was performed and SARS-CoV-2 infection was confirmed more than a week after admission to the coronary unit. As the patient had a general good appearance, the potential implications of missing this diagnosis could have been fatal., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4–12 weeks) SARS‐CoV‐2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life‐threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

Weeks and even months after recovering from the SARS-CoV-2 infection, clinically more severe cases are being reported, which are suggestive of COVID-19-related multisystemic inflammatory syndromes (MIS). Firstly on March 2020, this condition was reported to be COVID-19 related to children (MIS-C). Since June 2020, a syndrome similar to multisystem inflammatory syndrome in adults (MIS-A) came to be noticed in adults as well. We reported here a case of 24-year-old young woman who had gone to a hospital with abdominal pain and later developed a severe cough, followed by development of subconjunctival bleeding, pericardial effusion, pleural effusion, and intra-abdominal fluid that we deemed them to be acute multisystemic clinical symptoms, 47 days after she had undergone a COVID-19 infection of mild clinical severity. It should be kept in mind that a multisystemic inflammatory syndrome along with a delayed immune response during COVID-19 disease can be seen not only in children but also in young adults, and seemingly severe clinical and laboratory findings can improve by controlling the inflammatory process. [ABSTRACT FROM AUTHOR]

In this article we describe two cases that presented with persistent fever and a hyperinflammatory state in association with severe acute respiratory syndrome-coronavirus-2 infection with various negative reverse transcription-polymerase chain reaction results. These cases subsequently developed myocarditis with cardiogenic shock that required vasoactive drugs and had a good response to corticosteroid treatment. All cases met criteria for a definitive case of multisystemic inflammatory syndrome in adults, a recently described entity associated with coronavirus disease 2019, which has a good response to immunomodulators and a good prognosis in most cases. < Learning objective: Multisystemic inflammatory syndrome in adults is a severe disease with predominantly cardiac involvement, associated with severe acute respiratory syndrome-coronavirus-2 infection. The presentation of these two cases shows the importance of early recognition, especially in this coronavirus 2019 pandemic scenario in which almost anyone is susceptible to have had contact with the virus. It usually has a good therapeutic response to corticosteroids and invasive diagnostic tests, such as endomyocardial biopsy, could be avoided.> [ABSTRACT FROM AUTHOR]

Recent studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may precede the appearance of dysregulated immune responses, adopting the form of the multisystemic inflammatory syndrome in adults (MIS-A), as previously described in children (MIS-C).1 In this paper is presented the case of a 24-year-old Hispanic woman with a record of persistent positivity for lupus anticoagulant at moderate titers, without previous thrombotic or obstetric events, that was admitted to the hospital after 4 days of fever, headache, odynophagia, bilateral cervical painful lymphadenopathies, abdominal pain, nausea, vomiting, and diffuse exanthema. However, after having reasonably ruled out infectious and autoimmune pathology with normal laboratory, microbiologic, and imaging tests, and considering the recent SARS-CoV-2 infection, MSI-A was suspected and treated with a 2 mg/kg single dose of intravenous immunoglobulins and 1 mg/kg/day prednisone. The patient had experienced a recent SARS-CoV-2 infection, properly confirmed by a polymerase chain reaction (PCR) swab test 20 days before the admission. [Extracted from the article]

Although COVID-19 is a disease consisting of mostly upper and lower respiratory symptoms, a subset of patients develop cardiac sequelae including myocarditis and pericarditis. For these patients, a standardized set of diagnostic imaging techniques and treatments has not been established. While there have been numerous case reports on this topic, there are few reviews that evaluate the effectiveness of different treatment modalities with a significant number of cases. We reviewed 146 cases of patients (ages ranging from 2 months old to mid 80 s) obtained from searches on PubMed, Google Scholar, and several case report journals. ECG abnormalities, elevated inflammatory markers, and reduced left ventricular ejection fraction were most associated with COVID-19 myocarditis. While classic symptoms of COVID-19 include upper respiratory symptoms, a subset of patients diagnosed with COVID-19 displayed no signs of respiratory disease at all. In 22% of cases, cardiac sequelae was not present until after the patient recovered from COVID-19. Steroids were given in 57.5% of cases. Cardiac MRI was used in 40.4% of cases for diagnosis of myocarditis. Of all the patients who were treated with ECMO, 82.1% of these patients were able to fully recover. The use of cardiac MRI and transthoracic echocardiogram for diagnosis of COVID-19 myocarditis should be heavily considered in any patient with COVID-19 infection. ECMO, IVIG, steroids, and anticoagulants should also be heavily considered. A randomized controlled trial should be conducted to better associate treatments with outcomes. [ABSTRACT FROM AUTHOR]

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Over the last three years, the Coronavirus-19 disease has been a global health emergency, playing a primary role in the international scientific community. Clinical activity and scientific research have concentrated their efforts on facing the pandemic, allowing the description of novel pathologies correlated to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), such as the Multisystemic Inflammatory Syndrome in Children and Adults (MIS-C, MIS-A). Conversely, this shift of attention to COVID-19 disease and its complications could, in some cases, have delayed and underestimated the diagnosis of diseases not associated with SARS-CoV-2, including rare diseases. Here we describe the diagnostic process that led to the definition of a rare vasculitis in a young woman with a recent clinical history of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in adults (MIS-A) is an uncommon but severe and still understudied post-infectious complication of COVID-19. Clinically, the disease manifests itself most often 2–6 weeks after overcoming the infection. Young and middle-aged patients are especially affected. The clinical picture of the disease is very diverse. The dominant symptoms are mainly fever and myalgia, usually accompanied by various, especially extrapulmonary, manifestations. Cardiac damage (often in the form of cardiogenic shock) and significantly increased inflammatory parameters are often associated with MIS-A, while respiratory symptoms, including hypoxia, are less frequent. Due to the seriousness of the disease and the possibility of rapid progression, the basis of a successful treatment of the patient is early diagnosis, based mainly on anamnesis (overcoming the disease of COVID-19 in the recent past) and clinical symptoms, which often imitate other severe conditions such as, e.g., sepsis, septic shock, or toxic shock syndrome. Because of the danger of missing the treatment, it is necessary to initiate it immediately after the suspicion of MIS-A is expressed, without waiting for the results of microbiological and serological examinations. The cornerstone of pharmacological therapy is the administration of corticosteroids and intravenous immunoglobulins, to which the majority of patients clinically react. In this article, the authors describe the case report of a 21-year-old patient admitted to the Clinic of Infectology and Travel Medicine for febrility up to 40.5 °C, myalgia, arthralgia, headache, vomiting, and diarrhea three weeks after overcoming COVID-19. However, as part of the routine differential diagnosis of fevers (imaging and laboratory examinations), their cause was not clarified. Due to the overall worsening of the condition, the patient was transferred to the ICU with suspicion of developing MIS-A (he met all clinical and laboratory criteria). Given the above, reserve antibiotics, intravenous corticosteroids, and immunoglobulins were added to the treatment due to the risk of missing them, with a good clinical and laboratory effect. After stabilizing the condition and adjusting the laboratory parameters, the patient was transferred to a standard bed and sent home. [ABSTRACT FROM AUTHOR]

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

Background and Objectives: Pulmonary fibrosis represents a stage of normal physiologic response to inflammatory aggression, mostly self-limiting and reversible; however, numerous patients treated for SARS-CoV-2 pneumonia present after release from hospital residual lung fibrosis. In this article, we aim to present an optimization method for evaluating pulmonary fibrosis by quantitative analysis, to identify the risk factors/predictors for pulmonary fibrosis in patients with SARS-CoV-2 infection, and to characterize the impact of pulmonary fibrosis on the symptomatology of patients after release from the hospital. Materials and Methods: We performed a prospective observational study on 100 patients with severe forms of pneumonia, with a control group of 61 non-COVID normal patients. Results: We found persistent interstitial changes consistent with fibrotic changes in 69% of patients. The risk of fibrosis was proportional to the values of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and lactate dehydrogenase (LDH), and to the duration of hospitalization. The imaging parameters correlated with increased risk for interstitial fibrosis were the number of affected pulmonary lobes and the percent of interstitial pulmonary fibrosis. Conclusions: The main risk factors for pulmonary fibrosis post-COVID-19 identified in our study are increased ESR, CRP, LDH, duration of hospitalization and the severity of pneumonia. [ABSTRACT FROM AUTHOR]

Background: The current coronavirus disease pandemic has brought recognition of multisystem inflammatory syndrome in adults as a de novo entity, temporally associated with severe acute respiratory syndrome coronavirus 2 viral infection in adults. Hypothesis about its true pathophysiology remains controversial. Case report: The patient was a 22-year-old African American female presenting to the emergency department with fever, sore throat, and neck swelling for the past 3 days. During her initial emergency department visit, her blood pressure was stable at 110/57 mmHg, temperature of 39.4 °C, and heart rate of 150 beats per minute. While in the emergency department, she received broad-spectrum antibiotics (vancomycin and ceftriaxone) and 30 cc/kg bolus of normal saline. Originally, she was admitted to a telemetry floor. The following night, a rapid response code was called due to hypotension. At that time, her blood pressure was 80/57 mmHg. She appeared comfortable without signs of respiratory distress. She received intravenous fluids and vasopressors, and was transferred to the intensive care unit. The patient had reported a previous coronavirus disease infection a few weeks prior. She was diagnosed and treated for multisystem inflammatory syndrome in adults. Intravenous immunoglobulin infusion was initiated and completed on hospital day 5. She was weaned off vasopressors by day 6, and discharged home on day 11. Conclusion: Our case report is an example of the presentation, diagnosis, and management of multisystem inflammatory syndrome. Our research into previous case reports illustrates the wide range of presentations, degree of end organ damage, and treatment modalities. This diagnosis needs to be considered in the presence of recent coronavirus disease infection with new-onset end organ failure, as prompt diagnosis and treatment is crucial for better outcomes. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome (MIS), which develops after a past covid-19 infection. MIS can be described in different tissue inflammation, including the heart, lung, kidney, brain, skin, eye, and or gastrointestinal organs at the presence of COVID-19. Initially, MIS was described in Europe in children infected with SARS-CoV-2, then it was recently seen in the USA in 2020. MIS is a rare but serious disease condition associated with COVID-19 that can affect children (MIS-C) and adults (MIS-A). Case presentation: A 44-year-old male who showed MIS-A in 59-day after his first covid-19 contact history. The patient presented to our emergency department with complaints of high fever, nausea, weakness, redness of the eyes, headache, and joint pain. On the second day of his hospitalization, a maculopapular skin lesion was seen in most of the skin. His fever could not be controlled even given paracetamol and broad effective antibiotics. His clinical, radiological, and laboratory findings showed that he had MIS-A. The patient was given intravenous pulse methylprednisolone and intravenous immunoglobulin (IVIG). These treatments, then, resulted in improvement of his clinical conditions, including fever and skin lesions, on the second day of the treatment. The patient was discharged in 14 days after the treatment. Conclusion: This report indicated that diagnosis and treatment of MIS-A could result in reducing patient morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background During the Coronavirus disease 2019 (COVID-19) pandemic, reports have emerged of a multisystem inflammatory syndrome in adults (MIS-A). Multisystem inflammatory syndrome in adults can affect various organ systems, including cardiovascular, gastrointestinal, and neurologic systems without significant respiratory involvement. Case summary A previously healthy 43-year-old man presented with fevers and abdominal pain then rapidly deteriorated into cardiogenic shock. His constellation of symptoms along with elevated inflammatory markers in the setting of a recent SARS-CoV-2 infection was consistent with the diagnosis of MIS-A. He also had a comprehensive infectious workup that was unremarkable, ruling out other potential infectious aetiologies for his presentation. He subsequently improved through supportive measures and after administration of intravenous immunoglobulin (IVIG). He later demonstrated recovery of cardiac function and cardiac magnetic resonance imaging (MRI) showed signs consistent with myocarditis. Discussion As the COVID-19 pandemic continues to be an ongoing issue, it is important to recognize MIS-A, a rare and potentially deadly clinical syndrome that can lead to profound cardiovascular complications. Non-invasive imaging modalities such as cardiac MRI can play a role in the identification of myocarditis. In addition to supportive management, adjunctive therapies such as IVIG may be efficacious in MIS-A and should be further investigated. [ABSTRACT FROM AUTHOR]

After two previous episodes, in 2002 and 2012, when two highly pathogenic coronaviruses (SARS, MERS) with a zoonotic origin emerged in humans and caused fatal respiratory illness, we are today experiencing the COVID-19 pandemic produced by SARS-CoV-2. The main question of the year 2021 is if naturally- or artificially-acquired active immunity will be effective against the evolving SARS-CoV-2 variants. This review starts with the presentation of the two compartments of antiviral immunity—humoral and cellular, innate and adaptive—underlining how the involved cellular and molecular actors are intrinsically connected in the development of the immune response in SARS-CoV-2 infection. Then, the SARS-CoV-2 immunopathology, as well as the derived diagnosis and therapeutic approaches, will be discussed. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome (MIS) is a new systemic inflammatory acute onset disease that mainly affects children (MIS-C) and, at a lesser frequency, adults (MIS-A); it typically occurs 3–6 weeks after acute SARS-CoV infection. It has been postulated and shown in adults that MIS may occur after SARS-CoV-2 vaccination (MIS-V). Our current case is one of the first published cases with a multisystem inflammatory syndrome in an 18-year-old adolescent after the SARS-CoV-2 vaccine from Pfizer/BionTech (BNT162b2), who fulfills the published level 1 criteria for a definitive disease: age < 21 years, fever > 3 consecutive days, pericardial effusion, elevated CRP/NT-BNP/Troponin T/D-dimeres, cardiac involvement, and positive SARS-CoV-2 antibodies. The disease starts 10 weeks after the second vaccination, with a fever (up to 40 °C) and was treated with amoxicillin for suspected pneumonia. The SARS CoV-2-PCR and several antigen tests were negative. With an ongoing fever, he was hospitalized 14 days later. A pericardial effusion (10 mm) was diagnosed by echocardiography. The C-reactive protein (174 mg/L), NT-BNP (280 pg/mL), and Troponin T (28 pg/mL) values were elevated. Due to highly elevated D-dimeres (>35,000 μg/L), a pulmonary embolism was excluded by thoracal computer tomography. If the boy did not improve with intravenous antibiotics, he was treated with intravenous immunoglobulins; however, the therapy was discontinued after 230 mg/kg if he developed high fever and hypotension. A further specialized clinic treated him with colchicine and ibuprofen. The MIS-V was discovered late, 4 months after the onset of the disease. As recently shown in four children with MIS-C after SARS-CoV-2 infection and a girl with Hashimoto thyroiditis after BNT162b2 vaccination, we found elevated functional autoantibodies against G-protein-coupled receptors that may be important for pathophysiology but are not conclusive for the diagnosis of MIS-C. Conclusion: We are aware that a misattribution of MIS-V as a severe complication of coronavirus vaccination can lead to increased vaccine hesitancy and blunt the global COVID-19 vaccination drive. However, the pediatric population is at a higher risk for MIS-C and a very low risk for COVID-19 mortality. The publication of such cases is very important to make doctors aware of this complication of the vaccination, so that therapy with intravenous immunoglobulins can be initiated at an early stage. [ABSTRACT FROM AUTHOR]

Retinopathy, small fiber neuropathy (SFN), and encephalopathy associated with recoverin antibodies have not been previously reported as side effects of BNT162b2 vaccination in a patient with HLA-B27-associated spondylarthritis. The patient is a 47-year-old male with a 10-year history of HLA-B27-associated spondylarthritis without recurrence, who developed acute and post-acute COVID vaccination syndrome (ACVS/PACVS) after the first dose of the BNT162b2 vaccine. The PACVS manifested as cerebral disease, eye disease, and SFN. Two years after the onset of the adverse effects, recurrent elevated recoverin antibodies were detected. Despite the administration of various treatments, most symptoms persisted for more than three years, and only a few interventions such as glucocorticoids, hyperbaric oxygen therapy, botulinum toxin, inuspheresis, and HELP (heparin-induced extracorporeal LDL precipitation) apheresis showed a transient beneficial effect. In conclusion, this case offers an example of a collection of symptoms following SARS-CoV-2 vaccination (SC2V) in a patient with a specific autoimmune disorder and positivity for anti-recoverin antibodies. These clinical manifestations may be triggered by an exaggerated immune response known as multisystemic inflammatory syndrome in adults to SC2V. Clinicians should report other similar cases to determine if a pattern exists., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Finsterer et al.)