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      Cardiac Involvement in COVID-19 Patients: A Contemporary Review

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          Abstract

          Background: The widely variable clinical manifestations of SARS-CoV2 disease (COVID-19) range from asymptomatic infections to multiple organ failure and death. Among the organs affected is the heart. This does not only affect people who already have previous cardiovascular problems, but also healthy people. This is a reason not to overlook any symptoms or to perform targeted examinations, even if apparently unrelated to the heart, for quick recognition and timely therapy. Aim of the study: This review recapitulates the current state of knowledge on the potential mechanisms and manifestation of myocarditis in patients with COVID-19 infection. Methods: A web-based search of published data was performed for all relevant studies on patients diagnosed with a COVID-19-induced acute myocarditis, and a total of 50 reports were included. The analysis of the studies evaluated highlights a male predominance, with the average age of patients being 55 years. The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. Finally, we wanted to use a general evaluation without distinguishing between various countries, taking into consideration only the peer or reviewer, regardless of the declared value of the journals that have been published. Results and critical findings: The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. In most patients, elevated levels of cardiac and inflammatory biomarkers were measured. Left ventricular dysfunction and hypokinesis were commonly exhibited symptoms. Cardiac Magnetic Resonance Imaging (CMRI) confirmed the diagnosis of myocarditis with features of cardiac edema and cardiac injury. Nine patients underwent histopathological examination. Treatment with corticosteroids and immunoglobulins was the most applied strategy following the administration of antivirals. Discussion: Despite the exponentially growing knowledge on the management of COVID-19 infection, current available data on SARS-CoV2-correlated myocarditis are still limited, and several difficulties may be encountered in the differential diagnosis of acute myocarditis in the context of COVID-19 disease. Conclusions: While diagnostic criteria and evaluation strategies for myocarditis are well described, no guidelines for the diagnosis and treatment of myocarditis in COVID-19 patients have yet been established. Therefore, further research is needed to advance the understanding of this disease process and define the most appropriate strategic approach in these patients.

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

            Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
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              A novel coronavirus outbreak of global health concern

              In December, 2019, Wuhan, Hubei province, China, became the centre of an outbreak of pneumonia of unknown cause, which raised intense attention not only within China but internationally. Chinese health authorities did an immediate investigation to characterise and control the disease, including isolation of people suspected to have the disease, close monitoring of contacts, epidemiological and clinical data collection from patients, and development of diagnostic and treatment procedures. By Jan 7, 2020, Chinese scientists had isolated a novel coronavirus (CoV) from patients in Wuhan. The genetic sequence of the 2019 novel coronavirus (2019-nCoV) enabled the rapid development of point-of-care real-time RT-PCR diagnostic tests specific for 2019-nCoV (based on full genome sequence data on the Global Initiative on Sharing All Influenza Data [GISAID] platform). Cases of 2019-nCoV are no longer limited to Wuhan. Nine exported cases of 2019-nCoV infection have been reported in Thailand, Japan, Korea, the USA, Vietnam, and Singapore to date, and further dissemination through air travel is likely.1, 2, 3, 4, 5 As of Jan 23, 2020, confirmed cases were consecutively reported in 32 provinces, municipalities, and special administrative regions in China, including Hong Kong, Macau, and Taiwan. 3 These cases detected outside Wuhan, together with the detection of infection in at least one household cluster—reported by Jasper Fuk-Woo Chan and colleagues 6 in The Lancet—and the recently documented infections in health-care workers caring for patients with 2019-nCoV indicate human-to-human transmission and thus the risk of much wider spread of the disease. As of Jan 23, 2020, a total of 835 cases with laboratory-confirmed 2019-nCoV infection have been detected in China, of whom 25 have died and 93% remain in hospital (figure ). 3 Figure Timeline of early stages of 2019-nCoV outbreak 2019-nCoV=2019 novel coronavirus. In The Lancet, Chaolin Huang and colleagues 7 report clinical features of the first 41 patients admitted to the designated hospital in Wuhan who were confirmed to be infected with 2019-nCoV by Jan 2, 2020. The study findings provide first-hand data about severity of the emerging 2019-nCoV infection. Symptoms resulting from 2019-nCoV infection at the prodromal phase, including fever, dry cough, and malaise, are non-specific. Unlike human coronavirus infections, upper respiratory symptoms are notably infrequent. Intestinal presentations observed with SARS also appear to be uncommon, although two of six cases reported by Chan and colleagues had diarrhoea. 6 Common laboratory findings on admission to hospital include lymphopenia and bilateral ground-glass opacity or consolidation in chest CT scans. These clinical presentations confounded early detection of infected cases, especially against a background of ongoing influenza and circulation of other respiratory viruses. Exposure history to the Huanan Seafood Wholesale market served as an important clue at the early stage, yet its value has decreased as more secondary and tertiary cases have appeared. Of the 41 patients in this cohort, 22 (55%) developed severe dyspnoea and 13 (32%) required admission to an intensive care unit, and six died. 7 Hence, the case-fatality proportion in this cohort is approximately 14·6%, and the overall case fatality proportion appears to be closer to 3% (table ). However, both of these estimates should be treated with great caution because not all patients have concluded their illness (ie, recovered or died) and the true number of infections and full disease spectrum are unknown. Importantly, in emerging viral infection outbreaks the case-fatality ratio is often overestimated in the early stages because case detection is highly biased towards the more severe cases. As further data on the spectrum of mild or asymptomatic infection becomes available, one case of which was documented by Chan and colleagues, 6 the case-fatality ratio is likely to decrease. Nevertheless, the 1918 influenza pandemic is estimated to have had a case-fatality ratio of less than 5% 13 but had an enormous impact due to widespread transmission, so there is no room for complacency. Table Characteristics of patients who have been infected with 2019-nCoV, MERS-CoV, and SARS-CoV7, 8, 10, 11, 12 2019-nCoV * MERS-CoV SARS-CoV Demographic Date December, 2019 June, 2012 November, 2002 Location of first detection Wuhan, China Jeddah, Saudi Arabia Guangdong, China Age, years (range) 49 (21–76) 56 (14–94) 39·9 (1–91) Male:female sex ratio 2·7:1 3·3:1 1:1·25 Confirmed cases 835† 2494 8096 Mortality 25† (2·9%) 858 (37%) 744 (10%) Health-care workers 16‡ 9·8% 23·1% Symptoms Fever 40 (98%) 98% 99–100% Dry cough 31 (76%) 47% 29–75% Dyspnoea 22 (55%) 72% 40–42% Diarrhoea 1 (3%) 26% 20–25% Sore throat 0 21% 13–25% Ventilatory support 9·8% 80% 14–20% Data are n, age (range), or n (%) unless otherwise stated. 2019-nCoV=2019 novel coronavirus. MERS-CoV=Middle East respiratory syndrome coronavirus. SARS-CoV=severe acute respiratory syndrome coronavirus. * Demographics and symptoms for 2019-nCoV infection are based on data from the first 41 patients reported by Chaolin Huang and colleagues (admitted before Jan 2, 2020). 8 Case numbers and mortalities are updated up to Jan 21, 2020) as disclosed by the Chinese Health Commission. † Data as of Jan 23, 2020. ‡ Data as of Jan 21, 2020. 9 As an RNA virus, 2019-nCoV still has the inherent feature of a high mutation rate, although like other coronaviruses the mutation rate might be somewhat lower than other RNA viruses because of its genome-encoded exonuclease. This aspect provides the possibility for this newly introduced zoonotic viral pathogen to adapt to become more efficiently transmitted from person to person and possibly become more virulent. Two previous coronavirus outbreaks had been reported in the 21st century. The clinical features of 2019-nCoV, in comparison with SARS-CoV and Middle East respiratory syndrome (MERS)-CoV, are summarised in the table. The ongoing 2019-nCoV outbreak has undoubtedly caused the memories of the SARS-CoV outbreak starting 17 years ago to resurface in many people. In November, 2002, clusters of pneumonia of unknown cause were reported in Guangdong province, China, now known as the SARS-CoV outbreak. The number of cases of SARS increased substantially in the next year in China and later spread globally, 14 infecting at least 8096 people and causing 774 deaths. 12 The international spread of SARS-CoV in 2003 was attributed to its strong transmission ability under specific circumstances and the insufficient preparedness and implementation of infection control practices. Chinese public health and scientific capabilities have been greatly transformed since 2003. An efficient system is ready for monitoring and responding to infectious disease outbreaks and the 2019-nCoV pneumonia has been quickly added to the Notifiable Communicable Disease List and given the highest priority by Chinese health authorities. The increasing number of cases and widening geographical spread of the disease raise grave concerns about the future trajectory of the outbreak, especially with the Chinese Lunar New Year quickly approaching. Under normal circumstances, an estimated 3 billion trips would be made in the Spring Festival travel rush this year, with 15 million trips happening in Wuhan. The virus might further spread to other places during this festival period and cause epidemics, especially if it has acquired the ability to efficiently transmit from person to person. Consequently, the 2019-nCoV outbreak has led to implementation of extraordinary public health measures to reduce further spread of the virus within China and elsewhere. Although WHO has not recommended any international travelling restrictions so far, 15 the local government in Wuhan announced on Jan 23, 2020, the suspension of public transportation, with closure of airports, railway stations, and highways in the city, to prevent further disease transmission. 16 Further efforts in travel restriction might follow. Active surveillance for new cases and close monitoring of their contacts are being implemented. To improve detection efficiency, front-line clinics, apart from local centres for disease control and prevention, should be armed with validated point-of-care diagnostic kits. Rapid information disclosure is a top priority for disease control and prevention. A daily press release system has been established in China to ensure effective and efficient disclosure of epidemic information. Education campaigns should be launched to promote precautions for travellers, including frequent hand-washing, cough etiquette, and use of personal protection equipment (eg, masks) when visiting public places. Also, the general public should be motivated to report fever and other risk factors for coronavirus infection, including travel history to affected area and close contacts with confirmed or suspected cases. Considering that substantial numbers of patients with SARS and MERS were infected in health-care settings, precautions need to be taken to prevent nosocomial spread of the virus. Unfortunately, 16 health-care workers, some of whom were working in the same ward, have been confirmed to be infected with 2019-nCoV to date, although the routes of transmission and the possible role of so-called super-spreaders remain to be clarified. 9 Epidemiological studies need to be done to assess risk factors for infection in health-care personnel and quantify potential subclinical or asymptomatic infections. Notably, the transmission of SARS-CoV was eventually halted by public health measures including elimination of nosocomial infections. We need to be wary of the current outbreak turning into a sustained epidemic or even a pandemic. The availability of the virus' genetic sequence and initial data on the epidemiology and clinical consequences of the 2019-nCoV infections are only the first steps to understanding the threat posed by this pathogen. Many important questions remain unanswered, including its origin, extent, and duration of transmission in humans, ability to infect other animal hosts, and the spectrum and pathogenesis of human infections. Characterising viral isolates from successive generations of human infections will be key to updating diagnostics and assessing viral evolution. Beyond supportive care, 17 no specific coronavirus antivirals or vaccines of proven efficacy in humans exist, although clinical trials of both are ongoing for MERS-CoV and one controlled trial of ritonavir-boosted lopinavir monotherapy has been launched for 2019-nCoV (ChiCTR2000029308). Future animal model and clinical studies should focus on assessing the effectiveness and safety of promising antiviral drugs, monoclonal and polyclonal neutralising antibody products, and therapeutics directed against immunopathologic host responses. We have to be aware of the challenge and concerns brought by 2019-nCoV to our community. Every effort should be given to understand and control the disease, and the time to act is now. This online publication has been corrected. The corrected version first appeared at thelancet.com on January 29, 2020
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Infect Dis Rep
                Infect Dis Rep
                idr
                Infectious Disease Reports
                MDPI
                2036-7430
                2036-7449
                01 June 2021
                June 2021
                : 13
                : 2
                : 494-517
                Affiliations
                [1 ]AOU Policlinico Consorziale di Bari-Ospedale Giovanni XXIII, Coronary Unit and Electrophysiology/Pacing Unit, Cardio-Thoracic Department, Policlinico University Hospital of Bari, 70124 Bari, Italy; carrettacardiologia@ 123456gmail.com
                [2 ]AOU Policlinico Consorziale di Bari-Ospedale Giovanni XXIII, Cardiac Surgery, Policlinico University Hospital of Bari, 70124 Bari, Italy; dr.alinemariasilva@ 123456gmail.com (A.M.S.); prof_d.dagostino@ 123456libero.it (D.D.)
                [3 ]Department of Clinical Disciplines, School of Technical Medical Sciences, University of Elbasan “A. Xhuvani”, 3001 Elbasan, Albania; skender.topi@ 123456uniel.edu.al
                [4 ]AOU Policlinico Consorziale di Bari-Ospedale Giovanni XXIII, Clinical Pathology Unit, Policlinico University Hospital of Bari, 70124 Bari, Italy; robertolovero69@ 123456gmail.com
                [5 ]Emergency/Urgent Department, National Poisoning Center, Riuniti University Hospital of Foggia, 71122 Foggia, Italy
                [6 ]Department of Interdisciplinary Medicine, Microbiology and Virology Unit, University of Bari “Aldo Moro”, Piazza G. Cesare, 11, 70124 Bari, Italy; angelika.wegierska@ 123456yahoo.it
                [7 ]Department of Biomedical Sciences and Human Oncology—Section of Pharmacology, School of Medicine, University of Bari “Aldo Moro”, Policlinico University Hospital of Bari, p.zza G. Cesare 11, 70124 Bari, Italy; monica.montagnani@ 123456uniba.it
                Author notes
                [†]

                These authors equally contributed as co-last authors.

                Author information
                https://orcid.org/0000-0002-5697-8185
                https://orcid.org/0000-0001-5671-8124
                Article
                idr-13-00048
                10.3390/idr13020048
                8293198
                34206074
                26530ada-d405-4f5a-8b52-a5093f3c59b1
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 02 May 2021
                : 26 May 2021
                Categories
                Review

                sars-cov-2,viral myocarditis,cardiomyopathy,endomyocardial biopsy,cardiac magnetic resonance,cardiovascular therapy

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