Case Report: COVID-19 with cytokine storm in a 16-year-old patient: if heart failures&nbsp;comes think about levosimendan

Veronica Rodriguez-Garcia; Jose Luis Guerrero Orriach; Daniel Ariza Villanueva; Jose Manuel Garcia Pinilla; Ainhoa Robles Mezcua; Manuel Rubio Navarro; Jose Cruz Mañas

doi:10.12688/f1000research.50782.2

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Case Report

Revised

Case Report: COVID-19 with cytokine storm in a 16-year-old patient: if heart failures comes think about levosimendan

[version 2; peer review: 1 approved, 3 approved with reservations]

Veronica Rodriguez-Garcia^1,2, Jose Luis Guerrero Orriach^1-3, Daniel Ariza Villanueva², [...] Jose Manuel Garcia Pinilla⁴, Ainhoa Robles Mezcua⁴, Manuel Rubio Navarro^1,2, Jose Cruz Mañas^1,2

Veronica Rodriguez-Garcia^1,2, Jose Luis Guerrero Orriach^1-3, [...] Daniel Ariza Villanueva², Jose Manuel Garcia Pinilla⁴, Ainhoa Robles Mezcua⁴, Manuel Rubio Navarro^1,2, Jose Cruz Mañas^1,2

PUBLISHED 07 Feb 2023

Author details Author details

¹ ANESTHESIA-CARDIOLOGY DEPARTMENT, Malaga, Spain
² Department of Anaesthesia, Virgen de la Victoria University Hospital, Malaga, Spain
³ Department of Pharmacology and Pediatrics, School of Medicine, University of Malaga, Malaga, Spain
⁴ Department of Cardiology, Virgen de la Victoria University Hospital, Malaga, Spain

Veronica Rodriguez-Garcia
Roles: Investigation, Methodology, Supervision, Validation, Writing – Original Draft Preparation

Jose Luis Guerrero Orriach
Roles: Investigation, Methodology

Daniel Ariza Villanueva
Roles: Investigation, Methodology

Jose Manuel Garcia Pinilla
Roles: Investigation

Ainhoa Robles Mezcua
Roles: Conceptualization

Manuel Rubio Navarro
Roles: Methodology

Jose Cruz Mañas
Roles: Writing – Original Draft Preparation

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the Emerging Diseases and Outbreaks gateway.

This article is included in the Coronavirus (COVID-19) collection.

Abstract

Introduction: Our case is unique because the differential diagnosis was a challenge. At first, the patient presented with septic shock and multi-organ failure in the context of a suspected lymphoproliferative syndrome. Once the lymphoproliferative process had been ruled out, hemophagocytic syndrome due to COVID-19 infection was suspected, so he is probably one of the few patients with such an exhaustive study that could contribute to our understanding of COVID-19. We followed therapeutic guidelines that differ from the usual, using adrenalin and levosimendan. Corticosteroids helped to modulate the cytokine storm.
Case report: A 16-year-old adolescent was admitted to the intensive care unit with fever, diarrhea, multiorgan failure and septic shock. He was IgG positive for COVID-19 and IgM negative. Thoraco-abdominal computed tomography demonstrated multiple para-aortic and peri-pancreatic lymphadenopathy and acute respiratory distress syndrome. The first suspected diagnosis was a lymphoproliferative syndrome and bacterial infection. The second possibility was a hemophagocytic syndrome in a patient recovering from COVID-19. He was treated with broad spectrum antibiotics because the differential diagnosis was difficult, and we removed them when the microbiological screening was negative. During the course of the disease he presented with severe biventricular dysfunction, probably due to the cytokine storm, so we used inotropic drugs (adrenaline, levosimendan). Infection with Salmonella species group B was diagnosed later, when the patient was in the Internal Medicine ward, although he was asymptomatic.
Conclusion: The severity of COVID-19 infection ranges from mild to severe, causing serious disease in some people. Although the pathophysiology is not well known, it seems that in some cases an immune storm is triggered, and it is related to more serious and prolonged disease. In our case, heart failure was important, because it could have worsened the prognosis. Fortunately, the response to levosimendan and corticosteroids was adequate and he recovered favorably until discharge.

Keywords

COVID-19, myocarditis, multiorganic failure, levosimendan, case report.

Corresponding author: Veronica Rodriguez-Garcia

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2023 Rodriguez-Garcia V et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Rodriguez-Garcia V, Guerrero Orriach JL, Ariza Villanueva D et al. Case Report: COVID-19 with cytokine storm in a 16-year-old patient: if heart failures comes think about levosimendan [version 2; peer review: 1 approved, 3 approved with reservations]. F1000Research 2023, 10:244 (https://doi.org/10.12688/f1000research.50782.2) First published: 26 Mar 2021, 10:244 (https://doi.org/10.12688/f1000research.50782.1) Latest published: 07 Feb 2023, 10:244 (https://doi.org/10.12688/f1000research.50782.2)

Revised Amendments from Version 1

We added the complete treatment in the abstract, complete de introduction, case presentation and discussion with the comments the reviewers suggested us.
We describe Kawasaki disease and multisystem inflammatory syndrome, the similarities with hemophagocytic syndrome and the possibilities about diferents treatments.
Also completed important details in the case report and describe the mechanism of heart damage and the role of ACE-2 in COVID-19 and unify all units of measure.

To read any peer review reports and author responses for this article, follow the "read" links in the Open Peer Review table.

Introduction

The first cases of acute respiratory syndrome caused by COVID-19 were diagnosed in Hubei, China, in December 2019. The high rate of infectivity of the microorganism has triggered a pandemic. Symptoms include dry cough, headache, dyspnea, diarrhea, or fever. However, COVID-19 may also cause respiratory failure, kidney failure, cardiac injury, and central nervous system damage. Patients with comorbidities such as hypertension, obesity, pulmonary disease or diabetes are at a higher risk of developing severe symptoms.¹

Although the pathophysiology of the virus remains unknown, several studies have associated COVID-19 with a cytokine storm quite similar to that occurring in hemophagocytic syndrome (macrophage activation syndrome (MAS)). This syndrome is characterized by elevated levels of interleukins (IL-1b, IL-6, IL-10, IL-12), interferon (alpha, gamma), and tumor necrosis factor (TNF-alpha); hypertriglyceridemia; hyperferritinemia; hemophagocytosis in the bone marrow, cerebrospinal fluid, or lymph nodes; and manifests in the form of fever, hepatosplenomegaly, hemorrhagic diathesis, cutaneous rash and alterations of consciousness.² MAS may present as frequent complication of Kawasaki disease.

Kawasaki disease³ is a vasculitis characterized by high fever for more than 5 days, erythema on lips or oral or conjunctival mucosa, erythema and desquamation of the hands and feet, lymphadenopathy, cardiac lesions (coronary artery aneurysms), elevated acute phase reactants and exclusion of any other microbial cause, same as hemophagocytic syndrome and other autoimmune diseases.⁴

On May 2020, the Centers for Disease Control and Preventions (CDC), reported cases of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.⁵ Diagnostic criteria include severe disease requiring hospitalization, fever, laboratory markers of inflammation, multiorgan involvement, positive RT-PCR SARS-CoV-2, antibody test positive during hospitalization or contact with a person infected of COVID-19 within 4 weeks before symptom development. MIS-C also has many similarities with Kawasaki disease.³

Myocardial damage is the leading cause of morbidity and mortality. It is due to cytokines effects and hypoxic conditions rather than SARS-CoV-2 invasion in myocardial cells.⁶

IL-6, cardiac troponins (cTnI/T), and the amino-terminal fraction of the cerebral natriuretic propeptide (NT-proBNP) have been documented to be elevated in patients with cardiac failure secondary to COVID-19.⁷

Viral myocarditis of MIS-C is a widely described condition, with symptoms such as heart failure. It usually develops within one to three weeks of COVID-19 infection. Potential COVID-19 myocarditis therapies are based on inotropic drugs and extracorporeal life support.⁸ Levosimendan should be valued as a useful therapy in this type of patients due to its inotropic effects maintained over time and its associated organ protective effects,⁹ which are essential for cardiocirculatory support in cases such as the one reported in this paper.

The differential diagnosis was quite difficult and interesting. First, a septic shock and a lymphoproliferative syndrome. Then we thought about MAS as well, so he has an exhaustive study at the immune and hematological level, which could help to understand COVID-19.

Besides that, we follow therapeutic guidelines that differ from the usual, using levosimendan¹⁰ as an inotropic agen with very good results and corticosteroids¹¹^,¹² which helped to modulate the autoimmune response due to the cytokine storm. Tocilizumab,¹³ anakinra or immunoglobulins were not used.¹⁴^,¹⁵

Case presentation

Patient information

The patient was a 16-year-old Spanish adolescent, Caucasian, with no allergies, with mild intermittent extrinsic asthma treated with corticosteroids and aerosols (salmeterol 25 mcg/fluticasone 250 mcg two inhalations twice a day). He has no relevant past interventions and no medical, family or psychosocial history (including genetic) of interest. He presented with general discomfort, asthenia and fever (38°C) for three days and was treated with paracetamol 1g/8 hours and azithromycin 500 mg/24 hours for three days at home. After seven days, he came to the emergency department with persistence of symptoms, shortness of breath, arthromyalgia and diarrhea (two diarrheal stools without pathological products).

Clinical findings

Physical examination revealed a bad general condition. He was dehydrated (dry mucous membranes), but aware, oriented and collaborative. Blood pressure was 70/30 mmHg, heart rate was 110 bpm, respiratory rate was 18 bpm, SpO₂ 98% and axillary temperature was 38.5°C. Lung auscultation found bibasilar crackles and heart auscultation found no murmurs. He had hepatosplenomegaly, oliguria, no edemas, no cutaneous rash and no arthritis. He had diuresis of 170 ml in 12 hours. The results of laboratory testing were: white blood cell count 10200 μL⁻¹ (4000-11500 μL⁻¹), with 8420 (1800-8000 μL⁻¹) neutrophils, hemoglobin 12.5 g.dl⁻¹ (13-17.5 g.dl⁻¹), platelet count 104000 μL⁻¹ (140000-450000 μL⁻¹), serum C-reactive protein level 269.4 mg.l⁻¹ (<5 mg.l⁻¹), alanine aminotransferase level 81 U/L (7-49 U/L), aspartate aminotransferase level 71 U/L (13-40 U/L), total bilirubin level 3.30 mg.dl⁻¹ (0.2-1 mg.dl⁻¹), direct bilirubin level 2.73 mg.dl⁻¹ (<0.3 mg.dl⁻¹), high sensitiviry cardiac troponin I 1135 ng.l⁻¹, blood urea nitrogen 48 mg.dl⁻¹ (20-50 mg.dl⁻¹), creatinine 2.72 mg.dl⁻¹ (0.7-1.3 mg.dl⁻¹), erythrocyte sedimentation rate of 12 mm/h (<15 mm/h), procalcitonin 1.96 ng.ml⁻¹ (<0.1 ng.ml⁻¹), arterial pH 7.32 (7.35-7.45), pCO₂ 50.2 mmHg (35-45), pO₂ 92 (75-100) mmHg, HCO₃ 23 mmol/L (22-26 mmol/L), SpO₂ 98% (96-100%), lactic acid 2.2 mmol.l⁻¹ (0.5-2 mmol.l⁻¹), ferritin 655.4 ng.ml⁻¹ (22-322 ng.ml⁻¹), triglycerides 161 mg/dL (22-150 mg/dL), uric acid 11.3 mg/dL (4.4-7.6 mg/dL), prothrombin activity 64.7% (70-130%), international normalized ratio 1.28 (0.8-1.2), activated partial thromboplastin time (aPTT) 28.9 seconds (20.6-31 seconds), aPTT ratio 1.16 (0.8-1.2) and D-dimer 7.500 ng/mL (220-500 ng/mL). The evolution of laboratory parameters during admission to the Intensive Care Unit (ICU) is shown in Table 1.

Table 1. Sepsis parameters.

	ICU admission	Three days after admission	Six days after admission	ICU discharge
Leukocytes	10600 μL⁻¹	31280 μL⁻¹	25320 μL⁻¹	12600 μL⁻¹
Neutrophils	8720 μL⁻¹	27730 μL⁻¹	21190 μL⁻¹	9348 μL⁻¹
CRP	252.3 mg.l⁻¹	92.9 mg.l⁻¹	46 mg.l⁻¹	12.2 mg.l⁻¹
Procalcitonine	1.96 ng.l⁻¹	23.22 ng.l⁻¹	0.27 ng.l⁻¹	0.1 ng.l⁻¹
Lactic acid	2.2 mmol.l⁻¹	2.7 mmol.l⁻¹	1.1 mmol.l⁻¹	1.2 mmol.l⁻¹
Hemoglobin	13.2 g.dl⁻¹	9.4 g.dl⁻¹	10.5 g.dl⁻¹	10.2 g.dl⁻¹
Platelets	105000 μL⁻¹	248000 μL⁻¹	584000 μL⁻¹	874000 μL⁻¹
Ferritin	655.4 ng.ml⁻¹	402 ng.ml⁻¹	497 ng.ml⁻¹	521.6 ng.ml⁻¹
D-dimer	7172 ng.ml⁻¹	4103 ng.ml⁻¹	2724 ng.ml⁻¹	833 ng.ml⁻¹
Fibrinogen	546.8 mg.dl⁻¹	316.8 mg.dl⁻¹	323.7 mg.dl⁻¹	286.7 mg.dl⁻¹
LDH	188 U.l⁻¹	359 U.l⁻¹	248 U.l⁻¹	136 U.l⁻¹
CK	22 U.l⁻¹	49 U.l⁻¹	34 U.l⁻¹	15 U.l⁻¹
Troponin I	1135 ng.l⁻¹	308.4 ng.l⁻¹	130.3 ng.l⁻¹	12.3 ng.l⁻¹
Creatinine	2.72 mg.dl⁻¹	1.41 mg.dl⁻¹	0.65 mg.dl⁻¹	0.61 mg.dl⁻¹
Bilirubin	2.9 mg.dl⁻¹	0.8 mg.dl⁻¹	0.7 mg.dl⁻¹	0.5 mg.dl⁻¹

Diagnostic assessment

A nasopharyngeal swab and reverse transcriptase-polymerase chain reaction (RT-PCR) for COVID-19 (Cepheid-Xpert^® Xpress CoV-2 plus) was negative, but COVID-19 serology was IgM negative and IgG positive. Microbiological screening (urine, blood, sputum and stool culture), serological tests (virus, parasites, fungi and bacteria), and a Mantoux test were carried out. His thoracoabdominal CT scan showed multiple para-aortic and peri-pancreatic lymphadenopathy (compatible with lymphoproliferative syndrome as the most likely diagnosis) and acute respiratory distress syndrome (ARDS). There was no sign of pulmonary thromboembolism, but there were signs of pulmonary hypertension. He was admitted to the ICU and treated with broad spectrum antibiotics (imipenem 1 g/8 h, linezolid 600 mg/12 h) and a low dose of norepinephrine (0.05 mcg/kg/min).

An investigation of lymphoproliferative syndrome considering the possibility of MAS secondary to COVID-19 was carried out, including autoimmune tests. Protein electrophoresis showed an inflammatory pattern and a direct Coombs test was negative. A bone marrow biopsy showed reactive cells, without atypical cellularity, discarding lymphoproliferative or MAS. Tests for autoimmune diseases revealed a low level of C3 and positivity for lupus anticoagulant. The rest of the antibody tests were negative.

Microbiological screening, serological test and Mantoux were all negative, supporting the theory of an exaggerated systemic inflammatory response due to COVID-19. Septic shock was ruled out, so we decided to withdraw antibiotics. Only a rectal swab was positive for COVID-19.

During his time in hospital, the patient presented with acute confusion and agitation. He had no meningeal signs on examination. Cranial CT scan was normal and symptoms remitted within 24 hours.

An electrocardiograph showed atrial fibrillation and diffuse T wave inversion. Transthoracic echocardiography (TTE) was performed regularly, due to elevated cardiac enzymes. The first TTE was normal, but on the third day of admission demonstrated moderate biventricular dysfunction that progressed to severe in the following 24 hours, and atrial fibrillation. The evolution of echocardiographic parameters during admission to the ICU is shown in Table 2.

Table 2. Echocardiographic parameters.

	Day 3	Day 4	4 hours after levosimendan	12 hours after levosimendan	24 hours after levosimendan	ICU discharge
LVEF	46%	32%	40%	45%	50%	65%
LVIDD	59 mm	56 mm	Normal	Normal	53 mm	53 mm
SPAP	55-60 mmHg	45 mmHg	40 mmHg	40 mmHg	35 mmHg	35 mmHg
S Wave	15 cm/seg	8 cm/seg	12 cm/seg	15 cm/seg	15 cm/seg	15 cm/seg
TAPSE	25 mm	11 mm	17 mm	23 mm	23 mm	17 mm

Therapeutic intervention

From the beginning our patient was treated with a nasal cannula at 3 liters/minute for five days and a venturi mask at 40% FiO₂ for four days. Also, broad spectrum antibiotics (at the beginning, 1 g/8 h imipenem and 600 mg/12 h linezolid for six days, and on the third day of admission, 500 mg/24 h daptomycin and 200 mg/24 h fluconazole were added to the regimen) and a low dose of norepinephrine (0.05 mcg/kg/min) were administered.

When the possibility of a septic shock was ruled out, antibiotics were withdrawn and 8 mg/24 hours dexamethasone was started to try to contain the cytokine storm. The dose was increased to 12 mg when he suffered with confusion, agitation and heart failure. The patient was treated with adrenalin up to 0.1 mcg/kg/min, 12.5 mg/24 hours levosimendan and 20 mg/8-12 hours furosemide for eight days. A bolus of 150 mg amiodaron followed by an infusion of 600 mg in 24 hours was administered when atrial fibrillation was targeted. He was given enoxaparin 60 mg/24 hours during the first days and then it was increased to 60 mg/12 hours.

A new TTE that was performed four hours after levosimendan was initiated showed a moderate improvement in left ventricular function and a slight improvement in right ventricular function. In 12 hours, the cardiac function returned to normal and sinus rhythm was recovered (Table 2).

Outcomes

Hemodynamic support therapy was withdrawn, and oxygen therapy, furosemide and dexamethasone were progressively reduced. He didn’t have any adverse events with the medication; it was well tolerated.

In a few days, the clinical picture resolved and the patient was discharged to the Internal Medicine ward. The evolution of his condition was very favorable. He was afebrile, hemodynamically stable, with good food tolerance and without other clinical symptoms. Microbiological screening was repeated by Internal Medicine and a stool culture was positive for group B Salmonella species. The patient had no symptoms, but ciprofloxacin was administered for seven days and then he was discharged hemodynamically stable, eupneic and with oxygen saturation of 99% with oxygen supply of 0.28%. Two weeks later he left the hospital.

A timeline with information from the current episode of care is shown in Table 3.

Table 3. Timeline with information from the current episode of care.

Initial patient assessment	- A 16-year-old Spanish adolescent, Caucasian, no allergies, extrinsic asthma treated with corticosteroids and aerosols occasionally. - No relevant past interventions and no medical, family or psychosocial history (including genetic) of interest.
	- Blood pressure 70/30 mmHg, heart rate 110 bpm, respiratory rate 18 bpm, axillary temperature 38.5°C. - Lung auscultation: bibasilar crackles. - Heart auscultation without murmurs. - Hepatosplenomegaly, oliguria, no edemas, no cutaneous rash and no arthritis. - Diuresis 170 ml in 12 hours.
	- General discomfort, asthenia and fever (38°C) for three days. - He was treated with paracetamol and azithromycin at home. - Six days after, he came to the emergency department with persistence of symptoms, shortness of breath, arthromyalgia and diarrhea.
Diagnostic evaluation and therapeutic interventions	- Nasopharyngeal swab RT-PCR and serology of COVID-19. - Blood test, protein electrophoresis. - Thoracoabdominal CT scan. - Microbiological screening and serological test. - Bone marrow biopsy. - Autoimmune test. - Cranial CT scan. - Electrocardiograph, transthoracic echocardiography.
	- Paracetamol 1 g/8 h and azithromycin 500 mg/24 h for three days. - Broad spectrum antibiotics (imipenem 1 g/8 h, linezolid 600 mg/12 h for six days). Daptomycin 500 mg/24 h and fluconazole 200 mg/24 h were added on the third day of admission. - Nasal cannula 3 liters/minute for five days and then venturi mask at 40% for four days. - Norepinephrine 0.05 μcg/kg/min for four days. - Dexamethasone 8 mg/24 h for three days and later 12 mg/24 h for four days. - Enoxaparin 60 mg/24 h for three days and then 60mg/12h until discharge. - Adrenalin 0.1 μcg/kg/min for two days. - Levosimendan 12.5 mg in 24 hours. - Furosemide 20 mg/8-12 h for eight days. - Bolus of amiodaron 150 mg, followed of an infusion of 600 mg in 24 h.
Outcomes and follow-up	- After a good recovery in ICU, the patient was discharged to the Internal Medicine ward. - He was afebrile, hemodynamically stable, without antibiotics and decreasing dosage of corticosteroids. - A new stool culture was positive for group B Salmonella species. - He had no symptoms, but ciprofloxacin was administered for seven days and then he was discharged.
	- In a follow-up visit to the Internal Medicine clinic he remained asymptomatic and without sequelae. - Cardiac magnetic resonance imaging was performed, which was normal.

Discussion

Systemic inflammatory response syndrome (SIRS)¹⁶ may be caused by sepsis of bacterial origin, but sometimes it is difficult to substantiate and the differential diagnosis from non-infectious/autoimmune conditions is a challenge. Definitive diagnosis requires isolation of a microorganism, but occasionally this is not possible.¹⁷

Although the etiology of many autoimmune diseases is uncertain, it is suspected that they are preceded by an active infection, as Kawasaki disease, MAS or MIS-C after COVID-19.¹⁸^,¹⁹

We ruled out any type of active bacterial infection and he met criteria for MIS-C diagnosis (severe illness that required hospitalization, age less than 21 years, fever, multiorgan failure, elevated acute phase reactants (lack of IL-6 determination), antibody SARS-CoV-2 IgG positive and a rectal swab positive, while a nasopharyngeal swab and reverse transcriptase-polymerase chain reaction (RT-PCR) were negative. Angiotensin-converting enzyme 2 (ACE2) is expressed in the respiratory system less than in the intestinal epithelia, but respiratory symptoms are usually more severe. In fact, it is described that some patients remained stool positive after respiratory samples were negative, which could explain the results.²⁰

Feldstein et al.²¹ showed that one third of the patients tested negative for SARS-CoV-2 by RT-PCR, but had detectable antibodies and in a small subgroup, an interval of 25 days was reported between the infection for COVID-19 and hospitalization for MIS-C. A considerable proportion of patients were infected at least 1-2 weeks before the beginning of MIS-C.

Despite MIS-C seems to be a rare complication of COVID-19, the reason why it develops in some patients and not in others could be related to differences in the nasal expression/gene polymorphisms of ACE-2 and, the gateway for SARS-CoV-2.²²

An alteration in the innate immune response, causes the cytokine storm responsable for the most severe cases.²³

Elevated levels of IL-6 have been detected in these patients, but we are unable to determine them in our hospital. In any case, the elevated acute phase reactants found and the clinical manifestations support the suspected diagnosis.¹⁵

Congenital heart disease, asthma, obesity, diabetes or neurologic conditions seem to be risk factors for severe COVID-19 illness in children and adolescents.²⁴ Our patient has mild extrinsic asthma, well control under aerosol therapy (salmeterol/fluticasone twice per day). Some studies found asthma as a risk factor for hospitalization and respiratory support²⁵ and others²⁶^,²⁷ did not find association. Moreover there are very few data in childhood and more studies are needed.

During the COVID-19 pandemic, cases of cardiac involvement have been described. Arrhythmias have been observed as well. Although Sars-CoV-2 have been found in myocardial cells, it seems that the mechanism of myocardial damage it is secondary to cytokine storm, hypoxic conditions and not as a direct viral infection. Otherwise, the arrihythmia pathogenesis remains unclear, and an abnormal heart rhythm has been found in recovered patients.²⁸ In this case, cardiac failure contributed to the severity of the patient’s condition. Myocarditis is an inflammatory disease of the heart muscle caused by viruses mainly, although bacteria, toxic drugs and autoimmune diseases can produce it too. The exacerbation of the inflammatory response and its associated cardio-depressor and prothrombotic effects could be the cause of alterations in the coronary circulation (microcirculation and vasospasm), myocardial dysfunction, and increased oxygen consumption.²⁹ Cardiac magnetic resonance imaging is useful for diagnosis but only endomyocardial biopsy can establish the etiological diagnosis.³⁰ We did not perform an endomyocardial biopsy due to coagulopathy and the pandemic situation.

There were no official guidelines for the treatment of MIS-C. The individual intra-hospital protocols at that time were based on symptomatic and supportive treatment and on the use of some immunosuppressive drugs. We did not consider antiviral therapy since the patient had already passed the COVID-19 infection.

The patient was treated with adrenaline, diuretics, and levosimendan. He was also receiving dexamethasone that helped to suppress the cytokine storm and enoxaparin to prevent the risk of thrombosis. We did not use inmunoglobulins or monoclonal antibodies as anakinra because the response to corticosteroids was favorable.³¹

He was raised in a committee for extracorporeal life support if it had been necessary, but heart function recovered in a couple of days.

The benefits of levosimendan in infectious myocarditis have been endorsed by different studies. It has been shown to be superior over dobutamine in terms of mortality in patients with heart failure.³²^,³³ It is a novel drug to treat myocardial dysfunction due to sepsis,³⁴ myocardial infarction with left ventricular failure³⁵ or cardiac decompensation.³⁶ Its cardioprotective effects are because it causes coronary vasodilation, reduces preloading and postloading, and activates mitochondrial-K+ ATP channels. Its inotropic, coronary, antiplatelet, antiapoptotic, and anti-inflammatory effects increases cardiac output and decreases the ventricular filling pressure, pulmonary and systemic vascular resistance.³⁷ This was the reason we decided to use levosimendan, after not getting a full response to adrenaline and the progression of the patient was satisfactory.

When he was discharged to the Internal Medicine ward, he was improving. However, they repeated the stool culture again and it was positive for Salmonella species and treated with ciprofloxacin, although the patient remained asymptomatic. In subsequent check-ups the patient had no sequelae of the disease and cardiac magnetic resonance imaging was performed, which was normal. This makes us suspect that the Salmonella infection was probably acquired in hospital and it was not the cause of myocarditis, although we cannot completely rule it out.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

Consent

Written informed consent for publication of their clinical details was obtained from the patient.

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

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18. Crayne C, Cron RQ: Pediatric macrophage activation syndrome, recognizing the tip of the Iceberg. Eur J Rheumatol [Internet].2019 Feb 3 [cited 2022 Dec 10];7(Suppl 1): 13–20. PubMed Abstract
19. Wang W, Gong F, Zhu W, et al.: Macrophage activation syndrome in Kawasaki disease: more common than we thought? Semin Arthritis Rheum [Internet].2015 [cited 2022 Dec 10];44(4): 405–410. PubMed Abstract
20. Xiao F, Tang M, Zheng X, et al.: Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology [Internet].2020 May 1 [cited 2022 Dec 10];158(6): 1831–1833.e3. PubMed Abstract
21. Feldstein LR, Rose EB, Horwitz SM, et al.: Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med [Internet].2020 Jul 23 [cited 2022 Nov 27];383(4): 334–46. PubMed Abstract
22. Jakovac H: The Pathophysiology of COVID-19 and SARS-CoV-2 Infection: COVID-19: is the ACE2 just a foe? PMC [Internet].2022 [cited 2022 Nov 26]. pp. 1025–1026. Free Full Text
23. Varga Z, Flammer AJ, Steiger P, et al.: Endothelial cell infection and endotheliitis in COVID-19. Lancet (London, England) [Internet].2020 May 2 [cited 2022 Dec 10];395(10234): 1417–1418. PubMed Abstract
24. Richardson S, Hirsch JS, Narasimhan M, et al.: Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 Apr; 323: 2052. Publisher Full Text
25. Graff K, Smith C, Silveira L, et al.: Risk Factors for Severe COVID-19 in Children. Pediatr Infect Dis J [Internet].2021 [cited2022 Dec 10];40(4): E137–E145. PubMed Abstract
26. Castro-Rodriguez JA, Forno E: Asthma and COVID-19 in children - a systematic review and call for data. medRxiv Prepr Serv Heal Sci [Internet].2020 May 8 [cited 2022 Nov 26]. PubMed Abstract
27. Kompaniyets L, Agathis NT, Nelson JM, et al.: Underlying Medical Conditions Associated with Severe COVID-19 Illness among Children. JAMA Netw Open. 2021; 4(6): e2111182. PubMed Abstract | Publisher Full Text | Free Full Text
28. Jakovac H, Ferenčić A, Stemberger C, et al.: Detection of SARS-CoV-2 Antigens in the AV-Node of a Cardiac Conduction System—A Case Report. Trop Med. Infect Dis. 2022 Mar 1; 7(3). Publisher Full Text
29. Dominguez F, Kühl U, Pieske B, et al.: Update on Myocarditis and Inflammatory Cardiomyopathy: Reemergence of Endomyocardial Biopsy. Rev Esp Cardiol (Engl Ed). 2016 Feb; 69(2): 178–187. PubMed Abstract | Free Full Text
30. Friedrich MG, Sechtem U, Schulz-Menger J, et al.: Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009; 53: 1475–1487. PubMed Abstract | Publisher Full Text | Free Full Text
31. Belhadjer Z, Méot M, Bajolle F, et al.: Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic. Circulation [Internet]. 2020 Aug 4 [cited 2022 Dec 10];142(5): 429–436. PubMed Abstract | Publisher Full Text
32. Cleland JGF, Ghosh J, Freemantle N, et al.: Clinical trials update and cumulative meta-analyses from the American College of Cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-LIPIDS and cardiac resynchronisation therapy in heart failure. Eur J Heart Fail. 2004; 6: 501–508. PubMed Abstract | Publisher Full Text
33. Follath F, Cleland JGF, Just H, et al.: Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): A randomised double-blind trial. Lancet. 2002 Jul 20; 360(9328): 196–202. PubMed Abstract | Publisher Full Text
34. Gong B, Li Z, Yat Wong PC: Levosimendan Treatment for Heart Failure: A Systematic Review and Meta-Analysis. J Cardiothorac Vasc Anesth. 2015 Dec 1; 29(6): 1415–1425. PubMed Abstract | Publisher Full Text
35. Moiseyev VS, Põder P, Andrejevs N, et al.: Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction: A randomized, placebo-controlled, double-blind study (RUSSLAN). Eur Heart J. 2002 Sep; 23(18): 1422–1432. PubMed Abstract | Free Full Text
36. Packer M, Colucci W, Fisher L, et al.: Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. JACC Hear Fail. 2013 Apr; 1(2): 103–111. PubMed Abstract | Publisher Full Text
37. Orriach Guerrero JL, Ramirez Fernandez A, Iglesias P, et al.: Preoperative Levosimendan. A New Way for Organoprotection. Curr Pharm Des. 2014 Sep 15; 20(34): 5476–5483. PubMed Abstract | Publisher Full Text

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Author details Author details

¹ ANESTHESIA-CARDIOLOGY DEPARTMENT, Malaga, Spain
² Department of Anaesthesia, Virgen de la Victoria University Hospital, Malaga, Spain
³ Department of Pharmacology and Pediatrics, School of Medicine, University of Malaga, Malaga, Spain
⁴ Department of Cardiology, Virgen de la Victoria University Hospital, Malaga, Spain

Veronica Rodriguez-Garcia
Roles: Investigation, Methodology, Supervision, Validation, Writing – Original Draft Preparation

Jose Luis Guerrero Orriach
Roles: Investigation, Methodology

Daniel Ariza Villanueva
Roles: Investigation, Methodology

Jose Manuel Garcia Pinilla
Roles: Investigation

Ainhoa Robles Mezcua
Roles: Conceptualization

Manuel Rubio Navarro
Roles: Methodology

Jose Cruz Mañas
Roles: Writing – Original Draft Preparation

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

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https://doi.org/10.12688/f1000research.50782.2

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https://doi.org/10.12688/f1000research.50782.1

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Rodriguez-Garcia V, Guerrero Orriach JL, Ariza Villanueva D et al. Case Report: COVID-19 with cytokine storm in a 16-year-old patient: if heart failures comes think about levosimendan [version 2; peer review: 1 approved, 3 approved with reservations]. F1000Research 2023, 10:244 (https://doi.org/10.12688/f1000research.50782.2)

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ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested

Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.

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Version 2

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PUBLISHED 07 Feb 2023

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Reviewer Report 27 Mar 2024

Srikanth Umakanthan, Pathology unit, Department of Paraclinical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago

Approved with Reservations

https://doi.org/10.5256/f1000research.142079.r255464

1. Introduction: Do not start the introduction by stating " our case is unique," which should be added, if necessary, in the conclusion.
2. Indicate the parameters of diagnosis done for concluding multi-organ failure.
3. The patient presenting ... Continue reading

1. Introduction: Do not start the introduction by stating " our case is unique," which should be added, if necessary, in the conclusion.
2. Indicate the parameters of diagnosis done for concluding multi-organ failure.
3. The patient presenting complaints need to be elaborated, keeping in mind the possible differential diagnosis.
4. The first diagnosis of lymphoproliferative syndrome with those presenting complaints sounds skeptical in this case.
5. The report lacks images and a proper flow chart.

Is the background of the case’s history and progression described in sufficient detail?

Partly
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly
Is the case presented with sufficient detail to be useful for other practitioners?

Partly

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Histopathology, Molecular genetics, COVID19

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Reviewer Report 26 Mar 2024

Zhongheng Zhang, Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

Approved with Reservations

https://doi.org/10.5256/f1000research.142079.r255461

This is generally an interesting case but I have several comments:
1. Since COVID-19 is a pandemic there are many such cases that COVID-19 with cytokine storm accompanied by heart failure. Some of them have myocarditis. The case does not ... Continue reading

This is generally an interesting case but I have several comments:
1. Since COVID-19 is a pandemic there are many such cases that COVID-19 with cytokine storm accompanied by heart failure. Some of them have myocarditis. The case does not add causal relationship between drug intervention and outcome. I would suggest discussion on this point in the context of causal inference (https://doi.org/10.1016/j.lers.2022.10.002) since the causal association can have significant impact on clinical management.
2. "Fortunately, the response to levosimendan and corticosteroids was adequate and he recovered favorably until discharge."--we actually do not have evidence to prove these drugs are responsible for the recovery, COVID-19 is self-limited even if no treatment is provided.
3. The temporal changes of cytokines and other important myocardial markers can be illustrated with plot.
4. "A new TTE that was performed four hours after levosimendan was initiated showed a moderate improvement in left ventricular function and a slight improvement in right ventricular function. "-----such minor improvement can be caused by normal variation and variations between operators/interpretators of the cardiography.

Is the background of the case’s history and progression described in sufficient detail?

Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Yes
Is the case presented with sufficient detail to be useful for other practitioners?

Partly

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: intensive care medicine; critical care

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

CITE

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6

Reviewer Report 21 Feb 2023

Hrvoje Jakovac, University of Rijeka, Rijeka, Croatia

Approved

https://doi.org/10.5256/f1000research.142079.r162660

Authors improved manuscript according reviewers' comments. I don't have ... Continue reading

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Version 1

VERSION 1

PUBLISHED 26 Mar 2021

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11

Reviewer Report 03 Nov 2022

Hrvoje Jakovac, University of Rijeka, Rijeka, Croatia

Approved with Reservations

https://doi.org/10.5256/f1000research.53866.r154671

The authors bring an interesting case of a 16-year-old boy with severe COVID-19. Although the authors claim the cytokine storm was an underlying mechanism, there is no clear evidence that this was the scenario in described patients (the authors did ... Continue reading

The authors bring an interesting case of a 16-year-old boy with severe COVID-19. Although the authors claim the cytokine storm was an underlying mechanism, there is no clear evidence that this was the scenario in described patients (the authors did not measure plasma cytokine concentration).

The following sentence in the Introduction section is not clear: "The myocardial depressant effect of cytokines, an oxygen deficit generated by a prothrombotic state and coronary vasospasms could cause cardiac injury and dysfunction in other organs". Can SARS-CoV-2 directly infect the cardiac conduction system and cause arrhythmias? (See and refer to: https://doi.org/10.3390/tropicalmed7030043 ¹)

The patient's asthma had been treated with corticosteroids and aerosols occasionally. Please provide the treatment regimen and doses in more detail. Could asthma (and corticosteroids) have been a risk factor for the patient described? Please discuss.

Was SpO2 measured by pulse oximetry immediately at admission?
Please provide data on the patient's state of consciousness at admission.
Were there any physical signs of dehydration in the patient upon admission (skin turgor, dry mucous membranes)?
Please describe the patient's diarrhea (duration, stool frequency, number of stools).
Please show normal laboratory values in parentheses for each parameter.
Please provide data on the kit/device used for RT-PCR.

The lack of nasopharyngeal RT-PCR positivity with rectal swabs being positive is the most intriguing detail, but the authors did not discuss it. Please include it in the discussion. What are the potential causes of such findings? Is there any role of ACE2 distribution (see and refer to: https://doi.org/10.1152/ajplung.00119.2020 ²)

The discussion section should be more comprehensive, including consideration of the mechanisms of cardiac affection and arrhythmias described (see above).

Is the background of the case’s history and progression described in sufficient detail?

Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly
Is the case presented with sufficient detail to be useful for other practitioners?

Yes

References

1. Jakovac H, Ferenčić A, Stemberger C, Mohar Vitezić B, et al.: Detection of SARS-CoV-2 Antigens in the AV-Node of a Cardiac Conduction System—A Case Report. Tropical Medicine and Infectious Disease. 2022; 7 (3). Publisher Full Text
2. Jakovac H: COVID-19: is the ACE2 just a foe?. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2020; 318 (5): L1025-L1026 Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: COVID-19, heat shock proteins, oncogenesis, autoimmunity, neuroscience

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

CITE

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30

Reviewer Report 09 Dec 2021

Cecilia Bonazzetti, Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy

Approved with Reservations

https://doi.org/10.5256/f1000research.53866.r97530

This case report is well described, at times almost redundant. The description of the clinical case is interesting and complete in all information. However, the discussion should be revised because it lacks a very important etiological entity talking about this ... Continue reading

This case report is well described, at times almost redundant. The description of the clinical case is interesting and complete in all information. However, the discussion should be revised because it lacks a very important etiological entity talking about this topic which is the MIS-C and the most important works regarding this topic are not even mentioned: Feldstein et al., 2020¹, Jiang et al., 2020².

Is the background of the case’s history and progression described in sufficient detail?

Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

No
Is the case presented with sufficient detail to be useful for other practitioners?

Yes

References

1. Feldstein L, Rose E, Horwitz S, Collins J, et al.: Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. New England Journal of Medicine. 2020; 383 (4): 334-346 Publisher Full Text
2. Jiang L, Tang K, Levin M, Irfan O, et al.: COVID-19 and multisystem inflammatory syndrome in children and adolescents. The Lancet Infectious Diseases. 2020; 20 (11): e276-e288 Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Infectious Disease

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

CITE

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Version 2

VERSION 2 PUBLISHED 26 Mar 2021

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Version 1 26 Mar 21	read	read

Cecilia Bonazzetti, Luigi Sacco University Hospital, Milan, Italy
Hrvoje Jakovac, University of Rijeka, Rijeka, Croatia
Zhongheng Zhang, Zhejiang University School of Medicine, Hangzhou, China
Srikanth Umakanthan, The University of the West Indies, St. Augustine, Trinidad and Tobago

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27 Mar 2024 | for Version 2

Srikanth Umakanthan, Pathology unit, Department of Paraclinical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago

0 Views Cite this report Responses(0)

Approved With Reservations

1. Introduction: Do not start the introduction by stating " our case is unique," which should be added, if necessary, in the conclusion.
2. Indicate the parameters of diagnosis done for concluding multi-organ failure.
3. The patient presenting complaints need to be elaborated, keeping in mind the possible differential diagnosis.
4. The first diagnosis of lymphoproliferative syndrome with those presenting complaints sounds skeptical in this case.
5. The report lacks images and a proper flow chart.

Is the background of the case’s history and progression described in sufficient detail?

Partly
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly
Is the case presented with sufficient detail to be useful for other practitioners?

Partly

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Histopathology, Molecular genetics, COVID19

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Respond to this report

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Reviewer Report

4 Views

26 Mar 2024 | for Version 2

Zhongheng Zhang, Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

4 Views Cite this report Responses(0)

Approved With Reservations

This is generally an interesting case but I have several comments:
1. Since COVID-19 is a pandemic there are many such cases that COVID-19 with cytokine storm accompanied by heart failure. Some of them have myocarditis. The case does not add causal relationship between drug intervention and outcome. I would suggest discussion on this point in the context of causal inference (https://doi.org/10.1016/j.lers.2022.10.002) since the causal association can have significant impact on clinical management.
2. "Fortunately, the response to levosimendan and corticosteroids was adequate and he recovered favorably until discharge."--we actually do not have evidence to prove these drugs are responsible for the recovery, COVID-19 is self-limited even if no treatment is provided.
3. The temporal changes of cytokines and other important myocardial markers can be illustrated with plot.
4. "A new TTE that was performed four hours after levosimendan was initiated showed a moderate improvement in left ventricular function and a slight improvement in right ventricular function. "-----such minor improvement can be caused by normal variation and variations between operators/interpretators of the cardiography.

Is the background of the case’s history and progression described in sufficient detail?

Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Yes
Is the case presented with sufficient detail to be useful for other practitioners?

Partly

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

intensive care medicine; critical care

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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6 Views

21 Feb 2023 | for Version 2

Hrvoje Jakovac, University of Rijeka, Rijeka, Croatia

6 Views Cite this report Responses(0)

Approved

Authors improved manuscript according reviewers' comments. I don't have any comments and I consider the article suitable for indexing.

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

COVID-19, heat shock proteins, oncogenesis, autoimmunity, neuroscience

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

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11 Views

03 Nov 2022 | for Version 1

Hrvoje Jakovac, University of Rijeka, Rijeka, Croatia

11 Views Cite this report Responses(0)

Approved With Reservations

The authors bring an interesting case of a 16-year-old boy with severe COVID-19. Although the authors claim the cytokine storm was an underlying mechanism, there is no clear evidence that this was the scenario in described patients (the authors did not measure plasma cytokine concentration).

The following sentence in the Introduction section is not clear: "The myocardial depressant effect of cytokines, an oxygen deficit generated by a prothrombotic state and coronary vasospasms could cause cardiac injury and dysfunction in other organs". Can SARS-CoV-2 directly infect the cardiac conduction system and cause arrhythmias? (See and refer to: https://doi.org/10.3390/tropicalmed7030043 ¹)

The patient's asthma had been treated with corticosteroids and aerosols occasionally. Please provide the treatment regimen and doses in more detail. Could asthma (and corticosteroids) have been a risk factor for the patient described? Please discuss.

Was SpO2 measured by pulse oximetry immediately at admission?
Please provide data on the patient's state of consciousness at admission.
Were there any physical signs of dehydration in the patient upon admission (skin turgor, dry mucous membranes)?
Please describe the patient's diarrhea (duration, stool frequency, number of stools).
Please show normal laboratory values in parentheses for each parameter.
Please provide data on the kit/device used for RT-PCR.

The lack of nasopharyngeal RT-PCR positivity with rectal swabs being positive is the most intriguing detail, but the authors did not discuss it. Please include it in the discussion. What are the potential causes of such findings? Is there any role of ACE2 distribution (see and refer to: https://doi.org/10.1152/ajplung.00119.2020 ²)

The discussion section should be more comprehensive, including consideration of the mechanisms of cardiac affection and arrhythmias described (see above).

Is the background of the case’s history and progression described in sufficient detail?

Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Partly
Is the case presented with sufficient detail to be useful for other practitioners?

Yes

References

1. Jakovac H, Ferenčić A, Stemberger C, Mohar Vitezić B, et al.: Detection of SARS-CoV-2 Antigens in the AV-Node of a Cardiac Conduction System—A Case Report. Tropical Medicine and Infectious Disease. 2022; 7 (3). Publisher Full Text
2. Jakovac H: COVID-19: is the ACE2 just a foe?. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2020; 318 (5): L1025-L1026 Publisher Full Text

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

COVID-19, heat shock proteins, oncogenesis, autoimmunity, neuroscience

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Respond to this report

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Reviewer Report

30 Views

09 Dec 2021 | for Version 1

Cecilia Bonazzetti, Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy

30 Views Cite this report Responses(0)

Approved With Reservations

This case report is well described, at times almost redundant. The description of the clinical case is interesting and complete in all information. However, the discussion should be revised because it lacks a very important etiological entity talking about this topic which is the MIS-C and the most important works regarding this topic are not even mentioned: Feldstein et al., 2020¹, Jiang et al., 2020².

Is the background of the case’s history and progression described in sufficient detail?

Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

No
Is the case presented with sufficient detail to be useful for other practitioners?

Yes

References

1. Feldstein L, Rose E, Horwitz S, Collins J, et al.: Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. New England Journal of Medicine. 2020; 383 (4): 334-346 Publisher Full Text
2. Jiang L, Tang K, Levin M, Irfan O, et al.: COVID-19 and multisystem inflammatory syndrome in children and adolescents. The Lancet Infectious Diseases. 2020; 20 (11): e276-e288 Publisher Full Text

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Infectious Disease

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Respond to this report

Responses (0)

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Case Report: COVID-19 with cytokine storm in a 16-year-old patient: if heart failures comes think about levosimendan

Abstract

Keywords

Revised Amendments from Version 1

Introduction

Case presentation

Patient information

Clinical findings

Table 1. Sepsis parameters.

Diagnostic assessment

Table 2. Echocardiographic parameters.

Therapeutic intervention

Outcomes

Table 3. Timeline with information from the current episode of care.

Discussion

Data availability

Consent

Competing interests

Grant information

References

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