Myocarditis after SARS-CoV-2 vaccine: is that so simple?

SARS-CoV-2 vaccination is associated with potential side effects, particularly following second vaccine dose. Recent case series have reported a potential association between SARS-CoV-2 vaccination and acute myocarditis, predominantly in young males. We hereby describe a previously healthy 17-year-old man, with no past cardiac history, who presented to the emergency department with persistent chest pain and fever (up to 38 °C). The patient had received the first dose of Cominarty (BioNTech/Pfizer) vaccine 10 days before symptom onset and reported flu-like symptoms and conjunctivitis involving both eyes one week before administration of the first vaccine dose. On that occasion, no COVID test was performed and the patient was treated with anti-inflammatory drugs and antibiotic eye drops. On admission, laboratory tests were performed (Troponin-I Δ 19 500–23 270 ng/l. CRP 23 mg/dl, ESR 43 s, WBC 17 570 cell/mm3) as well as COVID-19 PCR, Serological tests and Autoimmune disorders panel all resulting negative. CT coronary angiogram did not reveal any spontaneous coronary artery dissection or anomalous origin of coronary arteries and Calcium Score was 0. Transthoracic echocardiography showed a depressed LVEF (36%) with concomitant posterior and inferior wall as well as posterior and anterior basal interventricular septum hypokinesia. Endomyocardial biopsy revealed multifocal lymphocytic myocarditis with sub-endomyocardial and interstitial fibrosis. CMR was also performed (1-week after presentation) demonstrating mildly depressed systolic function (LVEF 47%), with hypokinesia of the posterior and inferior wall, increased signal intensity on T2 maps (58 ms, n.v. <55 ms), prolonged native T1 values (1083 ms, n.v. <1030 ms) as well as subepicardial and intramyocardial LGE enhancement of infero-lateral segments reflecting intercellular fibrosis. Thereafter, the patient was discharged with medical therapy including ACE-inhibitor, colchicine, and ibuprofen. Given the close proximity between SARS-CoV-2 vaccine administration and the absence of other predisposing conditions, the aetiology of myocarditis was attributed to the vaccine. In addition, as the patient suffered from flu-like symptoms and conjunctivitis 1 week before the vaccine, a previous paucisymptomatic SARS-CoV-2 infection was suspected and anti-SARS-Coronavirus Nucleocapsid Protein antibody test revealed high antibody levels with low IgG avidity. Given that myocarditic symptoms evolved after complete Sars-Cov2 symptom resolution, our first hypothesis is that the infection is unlikely to be the cause of acute myocarditis in this patient. Indeed, current literature on COVID-related myocarditis reports close temporal association between respiratory symptoms and myocarditis onset. In support to our hypothesis, recent trials have reported that myocarditis more frequently occurs following administration of mRNA vaccines especially in male adolescents and young adults like our patient. However, cardiac side effects typically occur after full vaccination and symptoms appear within three days following the second dose, which does not fully apply to this case. Notwithstanding this, more recent studies have reported myocarditis even after first vaccination dose in patients with previous COVID-19 infection, analogously to the case described. This case suggests a complex interaction between immunological factors and covid infection/vaccination with potential significant implications on the cardiovascular system. From current literature, much uncertainty remains regarding time interval criteria for reliable post-vaccination myocarditis diagnosis, hence large-scale clinical trials are needed to address this issue.

COVID-19 ARDS Is Characterized by Increased Dead Space Ventilation Compared With Non-COVID ARDS.

BACKGROUND: ARDS in patients with coronavirus disease 2019 (COVID-19) is characterized by microcirculatory alterations in the pulmonary vascular bed, which could increase dead-space ventilation more than in non-COVID-19 ARDS. We aimed to establish if dead-space ventilation is different in patients with COVID-19 ARDS when compared with patients with non-COVID-19 ARDS. METHODS: A total of 187 subjects with COVID-19 ARDS and 178 subjects with non-COVID-19 ARDS who were undergoing invasive mechanical ventilation were included in the study. The association between the ARDS types and dead-space ventilation, compliance of the respiratory system, subjects' characteristics, organ failures, and mechanical ventilation was evaluated by using data collected in the first 24 h of mechanical ventilation. RESULTS: Corrected minute ventilation (V˙E), a dead-space ventilation surrogate, was higher in the subjects with COVID-19 ARDS versus in those with non-COVID-19 ARDS (median [interquartile range] 12.6 [10.2-15.8] L/min vs 9.4 [7.5-11.6] L/min; P < .001). Increased corrected V˙E was independently associated with COVID-19 ARDS (odds ratio 1.24, 95% CI 1.07-1.47; P = .007). The best compliance of the respiratory system, obtained after testing different PEEPs, was similar between the subjects with COVID-19 ARDS and the subjects with non-COVID-19 ARDS (mean ± SD 38 ± 11 mL/cm H2O vs 37 ± 11 mL/cm H2O, respectively; P = .61). The subjects with COVID-19 ARDS received higher median (interquartile range) PEEP (12 [10-14] cm H2O vs 8 [5-9] cm H2O; P < .001) and lower median (interquartile range) tidal volume (5.8 [5.5-6.3] mL/kg vs 6.6 [6.1-7.3] mL/kg; P < .001) than the subjects with non-COVID-19 ARDS, being these differences maintained at multivariable analysis. In the multivariable analysis, the subjects with COVID-19 ARDS showed a lower risk of anamnestic arterial hypertension (odds ratio 0.18, 95% CI 0.07-0.45; P < .001) and lower neurologic sequential organ failure assessment score (odds ratio 0.16, 95% CI 0.09-0.27; P < .001) than the subjects with non-COVID-19 ARDS. CONCLUSIONS: Indirect measurements of dead space were higher in subjects with COVID-19 ARDS compared with subjects with non-COVID-19 ARDS. The best compliance of the respiratory system was similar in both ARDS forms provided that different PEEPs were applied. A wide range of compliance is present in every ARDS type; therefore, the setting of mechanical ventilation should be individualized patient by patient and not based on the etiology of ARDS.

Corrected Minute Ventilation Is Associated With Mortality in ARDS Caused by COVID-19.

BACKGROUND: The ratio of dead space to tidal volume (VD/VT) is associated with mortality in patients with ARDS. Corrected minute ventilation ([Formula: see text]) is a simple surrogate of dead space, but, despite its increasing use, its association with mortality has not been proven. The aim of our study was to assess the association between [Formula: see text] and hospital mortality. We also compared the strength of this association with that of estimated VD/VT and ventilatory ratio. METHODS: We performed a retrospective study with prospectively collected data. We evaluated 187 consecutive mechanically ventilated subjects with ARDS caused by novel coronavirus disease (COVID-19). The association between [Formula: see text] and hospital mortality was assessed in multivariable logistic models. The same was done for estimated VD/VT and ventilatory ratio. RESULTS: Mean ± SD [Formula: see text] was 11.8 ± 3.3 L/min in survivors and 14.5 ± 3.9 L/min in nonsurvivors (P < .001) and was independently associated with mortality (adjusted odds ratio 1.15, P = .01). The strength of association of [Formula: see text] with mortality was similar to that of VD/VT and ventilatory ratio. CONCLUSIONS: [Formula: see text] was independently associated with hospital mortality in subjects with ARDS caused by COVID-19. [Formula: see text] could be used at the patient's bedside for outcome prediction and severity stratification, due to the simplicity of its calculation. These findings need to be confirmed in subjects with ARDS without viral pneumonia and when lung-protective mechanical ventilation is not rigorously applied.