ABSTRACT
A 24-year-old healthy man, smoker (2 pack-years), was admitted to the Cardiology Unit for chest pain and fever occurred 2 days after anti-SARS-CoV-2 vaccination. There were no pathological findings at physical examination. The electrocardiogram showed diffuse ST elevation. Laboratory tests showed a significant increment of Troponin I levels (4697 ng/l→ 6236 ng/l after 3 h), White Blood Cells (17 610/mmc) and C-Reactive Protein (8.36mg/dl). Echocardiography showed normal left ventricular systolic function with no evidence of pericarditis. These findings were consistent with a probable case of acute myocarditis. Cardiac magnetic imaging demonstrated myocardial oedema of the posterior wall of the left ventricle at T2-weighted images, with patchy areas of subepicardial late gadolinium enhancement. Based on Centers for Disease Control and Prevention myocarditis diagnostic criteria, a diagnosis of acute myocarditis was made and treatment with Non-Steroidal Anti-Inflammatory Drugs was started. Regarding etiology agent determination, in the COVID19 era, the first suspect was anti-SARS-CoV-2 mRNA-vaccine-induced myocarditis. Several case series and analyses of a large national health care organization database helped to identify features linked to these types of myocarditis. The highest incidence was observed among male juvenile subjects, usually 48-72 h after the second dose of vaccination, with elevated levels of spike antibody for SARS-CoV-2. Nevertheless, in the presented clinical case, the patient had received the first dose of BNT162b2 vaccination two days before hospital admission and showed negative serology tests for SARS-CoV-2. In recent medical history, two days before the onset of fever and chest pain, the patient had episodes of diarrhea which persisted during the first week of hospitalization. All immunological and microbiological tests result negative, except for a stool culture positive for Campylobacter coli. Interestingly a revision of literature showed several cases of myocarditis linked to Campylobacter species. In particular, of 13 reported cases, 12 (92%) were male with a mean age of 26±8.8 years, and cardiac symptoms present generally 2-4 days after diarrhea. In this particular setting, the first and more obvious hypothesis was strongly questioned because of an unexpected finding in the stool culture. In fact, Campylobacter spp. related myocarditis is an extremely rare condition, even if this pathogen is associated with important immunological interferences, as shown by its relationship with the Guillain-Barre syndrome. Further, myocarditis related to mRNA anti-SARS-CoV-2 vaccine is considered a rare complication. We hypothesized that the association of the two components could have acted synergistically to produce an immune system activation against cardiac muscle. Additional investigations are required to clarify the link between vaccination and possible improper immune response. In conclusion, this case represents a typical example in which the cause of the disease should be well investigated because the initial etiological theory is not definitive, especially in the SARS-CoV-2 era.
ABSTRACT
Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.