key: cord-262415-cj4pjuuc
authors: Eiros, R.; Barreiro-Perez, M.; Martin-Garcia, A.; Almeida, J.; Villacorta, E.; Perez-Pons, A.; Merchan, S.; Torres-Valle, A.; Sanchez-Pablo, C.; Gonzalez-Calle, D.; Perez-Escurza, O.; Toranzo, I.; Diaz-Pelaez, E.; Fuentes-Herrero, B.; Macias-Alvarez, L.; Oliva-Ariza, G.; Lecrevisse, Q.; Fluxa, R.; Bravo-Grandez, J. L.; Orfao, A.; Sanchez, P. L.
title: Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers
date: 2020-07-14
journal: nan
DOI: 10.1101/2020.07.12.20151316
sha: 
doc_id: 262415
cord_uid: cj4pjuuc

Background: Cardiac sequelae of past SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in health-care workers to report evidence of pericarditis and myocarditis after SARS-CoV-2 infection. Methods We studied 139 health-care workers with confirmed past SARS-CoV-2 infection (103 diagnosed by RT-PCR and 36 by serology). Participants underwent clinical assessment, electrocardiography, laboratory tests including immune cell profiling and cardiac magnetic resonance (CMR) imaging. Pericarditis was diagnosed when classical criteria were present, and the diagnosis of myocarditis was based on the updated CMR Lake-Louise-Criteria. Results: Median age was 52 years (IQR 41-57), 100 (72%) were women, and 23 (16%) were previously hospitalized for Covid-19 pneumonia. At examination (10.4 [9.3-11.0] weeks after infection-like symptoms), all participants presented hemodynamic stability. Chest pain, dyspnoea or palpitations were observed in 58 (42%) participants; electrocardiographic abnormalities in 69 (50%); NT-pro-BNP was elevated in 11 (8%); troponin in 1 (1%); and CMR abnormalities in 104 (75%). Isolated pericarditis was diagnosed in 4 (3%) participants, myopericarditis in 15 (11%) and isolated myocarditis in 36 (26%). Participants diagnosed by RT-PCR were more likely to still present symptoms than participants diagnosed by serology (73 [71%] vs 18 [50%]; p=0.027); nonetheless, the prevalence of pericarditis or myocarditis was high in both groups (44 [43%] vs 11 [31%]; p=0.238). Most participants (101 [73%]) showed altered immune cell counts in blood, particularly decreased eosinophil (37 [27%]; p<0.001) and increased CD4-CD8-/loT alpha beta-cell numbers (24 [17%]; p<0.001). Pericarditis was associated with elevated CD4-CD8-/loT alpha beta-cell numbers (p=0.011), while participants diagnosed with myopericarditis or myocarditis had lower (p<0.05) plasmacytoid dendritic cell, NK-cell and plasma cell counts and lower anti-SARS-CoV-2-IgG antibody levels (p=0.027). Conclusions: Pericarditis and myocarditis with clinical stability are frequent long after SARS-CoV-2 infection, even in presently asymptomatic subjects. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late in association with an altered (delayed) innate and adaptative immune response.

T2-weighted hyperinstensity Introduction Pericarditis and myocarditis are the two most frequent cardiac manifestations observed after a viral infection 1, 2 . Symptoms tend to be non-specific and most cases resolve without longterm sequelae. That is why the true incidence of pericarditis and myocarditis after common viral infections -influenza, parvovirus, coxsackievirus, echovirus, adenovirus, echovirus, herpesvirus or cytomegalovirus-is still unknown in the general population.

The novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently causing a sustained covid-19 pandemic, with the risk of causing long-term cardiac sequelae in the infected population 3 . The fear of SARS-CoV-2 causing greater myocardial damage than other conventional viruses is based on its mechanism of infecting human cells by binding to the transmembrane angiotensin-converting-enzyme-2 4 , which is mainly expressed by cells in alveoli and myocardial tissue 5 ; the rise in troponin levels observed in covid-19 patients hospitalized with pneumonia and its association with increased mortality 6, 7 ; and the probably reduced innate antiviral defences against a novel virus 8 .

Pericarditis and myocarditis after conventional viral infections both stem from an inadequate or excessive immune response driven by T and B cell-mediated mechanisms 1, 2, 9 . In case of an inadequate response, continued viral replication in the peri-myocardium protracts inflammation by attracting killer T cells and the concomitant production of chemokines and cytokines. In contrast, molecular mimicry can result in the production of autoantibodies against cardiac proteins, leading to a cardio-specific autoimmune response that causes sustained inflammation, effusion or cardiac remodeling. However, the specific immune profiles that occur after SARS-CoV-2 infection, particularly in patients presenting with cardiac sequelae remain unknown 10 .

The present study was designed to search for evidence of pericardial and myocardial involvement after past SARS-CoV-2 infection comprehensively studied by clinical assessment, laboratory tests, electrocardiography and cardiac magnetic resonance (CMR) imaging. Additionally, participants underwent an in-depth characterization of the immune cell compartments in blood and the virus-specific humoral immune response in this clinical scenario. As health-care workers have been the group most affected by SARS-CoV-2 in Spain, but have also been subject to more testing than the rest of the population, we decided to conduct the study in this singular cohort.

This cross-sectional, observational, cohort study consecutively recruited 142 health-care workers with laboratory confirmed SARS-CoV-2 infection in Salamanca, Spain, and who volunteered for the study. Among them, 106 health-care workers tested positive for SARS-CoV-2 by RT-PCR between March 13 and April 25; and 36 health-care workers were diagnosed after testing positive for anti-SARS-CoV-2-IgG antibodies between April 10 and May 22. The purpose of this second group was to also provide data from subjects with past SARS-CoV-2 infection in whom symptoms of viral infection are more likely to be mild and because population-based SARS-CoV-2 seroprevalence studies are becoming more established 11,12 . Study enrolment began on May 25 and finished on June 12, 2020.

Institutional approval (2020/05/490) for the study was provided by the University Hospital of Salamanca Ethics Committee, and all participants provided written informed consent. The study is registered with ClinicalTrials.gov NCT04413071. The responsibility for the study design, data collection and data interpretation lay solely with the study investigators. An internal adjudication monitoring board reviewed all cardiac study findings and adjudicated study outcomes. The authors had full access to all the data and elaborated all materials to submit for publication.

descriptive study in health-care workers Eiros et al. 6 Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers Eiros et al. 7 or positive T1-based tissue characterization markers (abnormal T1-relaxation time or extracellular volume or late gadolinium enhancement), and as supportive LLC criteria either pericardial effusion, or evidence of pericardial inflammation at CMR, or systolic left ventricle wall motion abnormalities. Considering that participants were being examined beyond the acute phase of SARS-CoV-2 infection; myocarditis was defined as having a combination of at least two T2 or T1-based LLC main criteria or having a combination of only one T2 or T1-based LLC main criterion with one additional LLC supportive criterion.

As we were aware that pericarditis and myocarditis occur together in clinical practice, we hence defined as myopericarditis those cases of pericarditis with associated myocarditis on CMR but without left ventricle wall motion abnormalities, and as perimyocarditis those cases where left ventricle wall motion abnormalities were present 19 .

Descriptive statistics were used to summarized the data; results are presented as the proportion (%) of valid cases for categorical variables and as the median (IQR) for continuous variables. As the participants in our study were not randomly selected, all statistics are deemed descriptive only; nonetheless, differences between groups are also provided and were analysed by Fisher´s exact test for categorical variables and by nonparametric Mann-Whitney or Kruskal-Wallis for continuous data. We compared characteristics of participants and examinations, all Tables, according to the final clinical diagnosis (non-pericardial and myocardial manifestations vs pericarditis vs myopericarditis vs myocarditis). For 2-dimensional visualization of flow cytometry data, multivariate canonical analysis with multidimensional reduction of data via linear discriminant analysis, and the t-distributed stochastic neighbour embedding (t-SNE) machine-learning algorithm visualization tools, were used (Infinicyt software, Cytognos, Salamanca, Spain) 20 . Figure 1 depicts the flowchart for participant selection from the health-care workers. From the 142 recruited health-care workers who signed informed consent, one participant did not complete the CMR for claustrophobia. Two additional participants were excluded because history of severe hypertrophic myocardiopathy in one case, and inherited immune deficiency in the other. Thus, a total of 139 participants completed clinical assessment, electrocardiography, laboratory tests and CMR. Of these, 103 (74%) had been diagnosed by RT-PCR and 36 (26%) by serology.

All participant characteristics are shown in table 1. Median age was 52 years (41-57) and most were female, 100 (72%). By professional categories, 49 (35%) were nurses, 35 (25%) medical doctors, and the remaining 55 (40%) included different profiles such as auxiliary nurses and other hospital staff. A total of 67 (48%) health-care workers were infected while directly attending covid-19 hospitalization wards.

Among the overall study population, 106 (76%) had at least one comorbidity and 8 (6%) health-care workers presented a history of cardiovascular disease; one with chronic ischemia with stent revascularization, three with paroxysmal atrial fibrillation, two with intranodal supraventricular tachycardias treated with ablation, and two with an episode of acute pericarditis several years before.

Most (137 [98%]) health-care workers experienced a viral prodrome at SARS-CoV-2 infection. Fatigue was reported by 117 (84%) participants, fever by 94 (68%), cough by 91 (65%), headache by 90 (65%) and myalgia by 83 (60%). Cardiac symptoms with shortness of breath, chest pain, palpitations or dizziness were reported by 86 (62%) participants.

A total of 27 (19%) health-care workers were previously diagnosed with covid-19 pneumonia and 23 (16%) required hospitalization. Overall, the drug therapy aimed at Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers Eiros et al. 9 Among the participants diagnosed with past infection through anti-SARS-CoV-2-IgG  detection (data for this group, compared to RT-PCR participants, are shown in the appendix  [supplementary table E) , 28 (78%) were previously tested negative by RT-PCR after developing mild SARS-CoV-2 symptoms and 8 (22%) were never RT-PCR tested. A lower percentage of participants diagnosed through positive serology still presented symptoms at examination compared to RT-PCR participants (18 [50%] vs. 73 [71%]; p=0.027); nonetheless, the prevalence of pericarditis, myopericarditis or myocarditis was high in both groups (figure 3).

Most study participants (101 [73%]) displayed altered cell counts in blood for at least one major immune cell population as illustrated in figure 4A- Compared to healthy donors, participants with pericarditis showed the highest median counts in blood of CD4 -CD8 -/lo Tαβ (cytotoxic) T-cells (46 vs 137 cells/μL; p=0.011) and also displayed (similarly to cases with myopericarditis and those with myocarditis) decreased blood counts of FcεRI + CD62L + immunomodulatory monocytes (46 vs 4, 2 and 11, respectively; p=0.020).

Participants diagnosed with myopericarditis tended to share altered immune cell profiles with myocarditis, except for two cases with myopericarditis whose profiles more closely overlapped with those cases with pericarditis (figure 4B). Thus, compared to healthy donors, participants with myopericarditis and those with myocarditis specifically displayed more pronounced decreased counts in blood of plasmacytoid dendritic cells (8 vs 6 and 5 cells/μL, respectively; p<0.001), and NK-cells (260 vs 120 and 177 cells/μL; p<0.001), including the subset of cytotoxic granzyme B (Gz) + CD57of NK-cell, Tγδ and/or TCD8 cells (supplementary 

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descriptive study in health-care workers Eiros et al. 10 This study examined the prevalence of pericarditis and of myocarditis in a cohort of SARS-CoV-2 positive health-care workers in Salamanca, Spain. In the largest cohort of subjects with CMR imaging assessment reported so far, we demonstrate that pericardial and myocardial involvement is highly prevalent after SARS-CoV-2 infection.

We decided to carry out a study in health-care workers, as this sector has been disproportionally infected in Spain -approximately 20% of all COVID-19 cases 21 -which provided us with the opportunity to study the prevalence of pericarditis and myocarditis in SARS-CoV-2 infected cases that were confirmed by positive RT-PCR or positive serology. In addition, as the proportion of female health-care workers is high in Spain, our study does not underrepresent women who constituted more than two thirds of recruited participants. Unlike other observational studies suggesting that myocarditis may be slightly more prevalent in men than women 22-24 ; men in our study presented lower prevalence of pericarditis or myocarditis than women (11 [28%] vs. 44 [44%]; p=0.122). This observation could be related, more than to gender, to the higher rate of previous hospitalization for COVID-19 pneumonia in men than women (13 [33%] vs. 10 [10%]; p=0.002) for our cohort. In general, previously hospitalized participants presented lower percentage of pericardial and myocardial injury compared to participants never hospitalized (4 [17%] vs. 51 [44%]; p=0.020). Having been hospitalized, participants received more treatment aimed at inhibiting viral replication (lopinavir-ritonavir or hydroxychloroquine) and reducing inflammation (high-dose glucocorticoids and interleukin inhibitors). The recent Recovery study (NCT04381936) has shown that low-dose dexamethasone reduces mortality in hospitalized COVID-19 patients.

Case reports of myocarditis and pericarditis have been published during the COVID-19 hospitalization phase 25 . A recent retrospective observation in 26 recovered patients with COVID-19 pneumonia presenting cardiac complaints during hospitalization, revealed the presence of myocardial oedema in 14 (54%) patients and late gadolinium enhancement in 8 (31%) patients 26 . Our results are in agreement with these findings as 89 (64%) of our participants presented myocardial injury in T2 or in T1-based CMR. High rates of myocardial damage are also observed in influenza -where elevated cardiac enzymes, electrocardiographic, echocardiographic and histologic findings have been reported in approximately one third of cases 27 .

Importantly, clinical assessment of our participants with pericarditis and myocarditis showed clinical stability without any participant presenting severe pericardial effusion, heart failure or left ventricular dysfunction (only four participants with myocarditis presented wall motion abnormalities). However, follow-up studies are necessary to determine the outcome of cardiac sequelae observed even in asymptomatic and pauci-symptomatic subjects after SARS-CoV-2 infection 28 . Thus, the participants diagnosed of past infection through serology who were more likely to be asymptomatic or mildly symptomatic, and who might better represent the cases detected in population-wide seroprevalence studies 11,12 , presented a similar prevalence of pericardial and myocardial manifestations to RT-PCR positive participants (11 [31%] vs 44 [43%]; p=0.238).

At present, there is much interest in the long-term sequelae of COVID-19. It is intriguing that pericarditis, myopericarditis or myocarditis were observed that long after SARS-CoV-2 infection (over 10 weeks after initial viral prodrome at infection) and also in some presently asymptomatic subjects (15 [11%] of the study population; one every three-final pericarditis, myopericarditis or myocarditis diagnosis). These long-term manifestations may be due to an inadequate innate and adaptative immune response. In recent months, important advances have been achieved in the understanding of the immunology of COVID-19 10 . However, there is still very limited data on the longer-term immunological consequences of past SARS-CoV-2 infection, and no study has specifically focused in the settings of pericarditis and myocarditis. Herein, in-depth investigation of the distribution of major and minor populations of immune cells in blood showed a high frequency of overall altered immune profiles. Several of the immune cell alterations identified mimic abnormalities reported during active infection, including decreased eosinophil, NK-cell, and (plasmacytoid) dendritic cell counts 29,30 . In . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

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descriptive study in health-care workers Eiros et al. 11 contrast, other alterations are described here for the first time and have not been reported during the acute phase of the infection. These new alterations include abnormally high numbers of monocytes (i.e. recently produced classical monocytes) and lymphocytes, such as T-cells, particularly CD4 -CD8 -/lo , TCD4 cells and TCD8 cells, and B-lymphocytes together with decreased counts of myeloid-derived suppressor cells, immature (CD16-CD62L-) neutrophils, both immunomodulatory FcεRI + CD62L + and intermediate (i.e. CD14+CD16+) monocytes and circulating plasma cells. Altogether, these findings may partially reflect (the normal and an altered) immune recovery after SARS-CoV-2 infection. Thus, while persistence of eosinopenia and expansion of CD4 -CD8 -/lo T-cells in blood were detected across all groups of participants suggesting it is part of the immune recovery after COVID-19; NK-cells were specifically decreased among participants with myopericarditis and myocarditis in association with (persistent) tissue damage. Nonetheless, the altered immune profiles in participants without pericardial and myocardial manifestations, could also be due to persistence of tissue damage and recovery in other organs affected by SARS-CoV-2, such as the lung, more than just reflecting normal immune recovery. Anyhow, more detailed analysis of the altered immune profiles among the different groups of participants showed that those with myopericarditis or myocarditis had closer to normal lymphocyte counts, but reduced numbers in blood of circulating eosinophils, plasmacytoid dendritic cells and particularly, NK-cells. Such unique profile mimics what has been described recently during the acute phase of SARS-CoV-2 infection, suggesting an ongoing cytotoxic response with increased tissue migration or death by apoptosis of specific subsets of cytotoxic cells. In line with this hypothesis, we found here lower numbers of granzymeB+CD57-memory and effector TCD8-, Tγδ-and/or NK-cells among participants with myopericarditis or myocarditis. Of note, these participants with myocardial injury also showed particularly lower counts in blood of (recently produced) plasma cells, together with lower anti-SARS-CoV-2-IgG plasma levels. These findings suggest that a less pronounced (potentially insufficient) or a delayed humoral response may occur in these subjects, which may lead to decreased neutralization, opsonization and/or clearance of the virus locally at the peri-myocardium; local viral persistence would favour an increased tissue-homing (or early death) of eosinophils, immunomodulatory and intermediate monocytes, in addition to cytotoxic (effector) cells. Altogether, the above findings suggest that an inadequate (potentially delayed) immune response might happen in a substantial fraction of patients with past SARS-CoV-2 infection, with differently altered profiles in subjects who present myopericarditis or myocarditis.

The study analysis was limited to health-care workers in Salamanca and therefore may have limited external generalizability to other non-health-care settings. However, the strength of this study is the addition of non-hospitalized participants and also the inclusion of participants diagnosed of past SARS-CoV-2 infection through serology, who also had a high prevalence of pericarditis and myocarditis. Seropositive participants, although less symptomatic than RT-PCR participants, presented mild symptoms in almost all cases; unfortunately, we cannot draw conclusions regarding the prevalence of pericarditis and myocarditis in the completely asymptomatic general population. Finally, the study relied solely on descriptive observations and cannot provide any conclusion on the benefit of antiviral and anti-inflammatory treatments during the acute phase of infection or whether the prevalence of pericarditis and myocarditis after SARS-CoV-2 infection is higher in women than men.

This study shows that pericarditis and myocarditis are frequent long after SARS-CoV-2 infection and also in some presently asymptomatic subjects; in addition, we provide herein evidence for an altered immune cell distribution in blood which affects cells involved in both the innate (e.g. eosinophils and monocytes) and the adaptative cellular (e.g. CD4 -CD8 -/lo Tαβ + , TCD4 and TCD8 T-cells) and humoral (e.g. plasma cells and anti-Sars-CoV-2 IgG levels)

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immune responses; nonetheless, a direct link between such altered immune profiles and the presence of pericardial and myocardial injury still needs to be established. These observations will probably apply to the general population infected, and may indicate that cardiac sequelae might occur late. Although all study participants presented clinical stability and non-severe cardiac complications, prospective monitoring will be necessary to address the future clinical consequences of these findings.

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Petrilli 

Melero-Alegria JI, Cascon M, Romero A, et al. SALMANTICOR study. Rationale and design of a population-based study to identify structural heart disease abnormalities: a spatial and machine learning analysis. BMJ Open 2019; 9(2): e024605.

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The copyright holder for this preprint this version posted July 14, 2020. . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted July 14, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 14, 2020. Data are n (%) and median (range). * Obesity was considered if body-mass index of 30 or more. † Alcohol use was considered an average of at least one drink a day. ‡ All participants with previous pulmonary disease referred asthma. § High-dose intravenous glucocorticoids was considered when at least a bolus of methylprednisolone of 250 mg was administered. P value for comparison among the four participants groups. Additional p value comparisons: p value <0·05 no (non-pericardial and myocardial manifestations) vs presence of pericardial and myocardial manifestations; ¶ p value <0·05 no (nonpericardial and myocardial manifestations) vs myopericarditis; ** p value <0·05 no (non-pericardial and myocardial manifestations) vs myocarditis.

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It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted July 14, 2020. Data are n (%) and median (IQR). * Data regarding time from symptoms onset to examination was not possible to calculate for 2 patients who were totally asymptomatic. † Only one case with pericarditis and another case with myopericarditis in participants diagnosed of past SARS-CoV-2 infection through serology. ‡ Long-QT interval was defined as a rate-corrected (Bazett) QT interval exceeding 450 milliseconds in males and 460 milliseconds in females. § The 99 th percentile of troponin values for our laboratory is

Pericardial effusion greater than 3 mm. ¶ Pericardial thickness of 3 mm on T1-weighted spin-echo CMR. P value for comparison among the four participants groups. Additional p value comparisons: ** p value <0·05 no (non-pericardial and myocardial manifestations) vs presence of pericardial and myocardial manifestations; † † p value <0·05 no (non-pericardial and myocardial manifestations) vs pericarditis; ‡ ‡ p value <0·05 no (non-pericardial and myocardial manifestations) vs myopericarditis; § § p value <0·05 no (non-pericardial and myocardial manifestations) vs myocarditis.

.

It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 14, 2020. 

CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 14, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 14, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

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The copyright holder for this preprint this version posted July 14, 2020. T1map  T1map  T1map  T1map  T1map  T1map  T1map  T1map T1map 

ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS)

Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options

Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019

We thank all health-care workers participating in this study, to all the personnel of the University Hospital of Salamanca for their extraordinary work in their fight against this pandemic, and all other participating institutions. We also would like to thank Prof Dr Jacques JM van Dongen and both his group (Leiden University Medical Center) and the EuroFlow Consortia for their contribution in the design, construction and validation of the EuroFlow LST and IMM tubes used herein.

Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers Eiros et al. 13 Data are median (IQR) of cells/μL of blood or n (%) of cases lower than 5th percentile (↓5 th p) and higher than 95th percentile (↑95 th p) for each cell subset in agematched healthy donors. Left p value for comparisons between healthy donors vs all participants. Right p value for comparison among the four participants groups. Additional p value comparisons: * p value <0·05 healthy donors vs no (non-pericardial and myocardial manifestations); † p value <0·05 healthy donors vs pericarditis; ‡ p value <0·05 healthy donors vs myopericarditis; § p value <0·05 healthy donors vs myocarditis; p value <0·05 no (non-pericardial and myocardial manifestations) vs myocarditis. ¶ p value <0·05 no (non-pericardial and myocardial manifestations) vs myopericarditis plus myocarditis. MDSC= myeloid-derived suppressor cells; m= myeloid..

It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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