key: cord-0828698-rsj4l2me
authors: Odièvre, Marie‐Hélène; de Marcellus, Charles; Ducou Le Pointe, Hubert; Allali, Slimane; Romain, Anne‐Sophie; Youn, Jenny; Taytard, Jessica; Nathan, Nadia; Corvol, Harriet
title: Dramatic improvement after tocilizumab of severe COVID‐19 in a child with sickle cell disease and acute chest syndrome
date: 2020-05-16
journal: Am J Hematol
DOI: 10.1002/ajh.25855
sha: 28ab0ce3f0912cf7a433d9ffd171778abe40fa55
doc_id: 828698
cord_uid: rsj4l2me

nan

vaso-occlusive events. She had no history of ACS or pulmonary hypertension, and her respiratory function and chest radiography were previously normal. As recommended by the French authorities, because of the COVID-19 outbreak, she was confined to her home with her parents. One week after her parents developed COVID-19 symptoms (cough, fever and anosmia), she presented with an isolated fever treated by acetaminophen (without non-steroidal anti-inflammatory drugs). Seven days later, she developed an ACS characterized by an acute chest pain associated with a respiratory distress syndrome (SpO 2 85%, superficial tachypnea 80/min, tachycardia 140/min). Real-time reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs confirmed the SARS-Cov-2 infection. Levels of C-reactive protein (355 mg/L), LDH (446 U/L) and D-dimer (23 611 ng/mL) were increased. Given the tachycardia and elevation of D-dimer in a SCD patient with COVID-19, a pulmonary embolism was suspected, which is assumed to be more frequent in this context. Indeed, the computed tomography pulmonary angiography (CTPA) showed a bilateral pulmonary embolism complicating the ACS, and was compatible with COVID-19 (bilateral consolidations with a halo sign on the right side, Figure S1 ). The patient was admitted to an intensive care unit (ICU) and required non-invasive ventilation, red blood cell exchange transfusion followed by simple transfusion (hemoglobin nadir 6.4 g/dL), and anticoagulation. Because of the severity of the disease, and based on the experience of COVID-19 in SCD adult patients, 1-3 she also received one pulse of intravenous tocilizumab (TCZ, 8 mg/kg). 1 Plasma level of Interleukin (IL)-6 was extremely high (629 pg/mL; normal <8.5 pg/mL) and was even higher after TCZ (724 pg/mL), in line with IL-6 receptor blockade.

To a much less extent, Tumor Necrosis Factor (TNF)-α level was also elevated (32.5 pg/mL; normal <20 pg/mL); and, on the contrary, IL-1β level was normal. The patient improved rapidly after TCZ treatment. Non-invasive ventilation was stopped 4 days after TCZ, with no oxygen requirement thereafter, allowing the discharge from ICU. She was then referred to a medical unit where CTPA was repeated 5 days after TCZ. A dramatic improvement occurred with a disappearance on the right, and a decrease on the left of both the pulmonary embolism and the consolidation opacities, as previously described by Cellina et al. 4 (Figure S1 ). She was finally discharged from the hospital 11 days after admission, with an oral anticoagulant treatment to be continued for a total of 6 weeks.

To our knowledge, this is the first reported use of TCZ in a COVID-19 pediatric SCD patient. A single injection of the treatment was followed by a rapid improvement of the patient's respiratory status, together with a dramatic improvement of CTPA images. H1N1 strain) , and Erythrovirus. Besides, monocyte activation has been reported in SCD and is responsible for an enhanced production of pro-inflammatory cytokines such as IL-6,IL-1β and TNF-α, which contributes to vaso-occlusion by promoting endothelial activation. 5 Many cytokines are elevated during steady-state in SCD, and some of them, especially IL-6, are further increased during vaso-occlusive crises.

To date, SARS-Cov-2 infection has been reported to cause ACS in four adult patients with SCD. [1] [2] [3] We recently managed two teenage SCD patients with ACS and COVID-19, including the presented case.

Note, COVID-19 is characterized by an inflammatory storm enhanced by T cells and monocytes. Large amounts of IL-6 and TNF-α are found in the plasma of infected patients. Tocilizumab, that targets IL-6 receptors, was suggested to be effective on clinical evolution as well as on immune dysregulation. 6 After a single TCZ injection, serum IL-6 level first increases rapidly before decreasing. In the absence of significant clinical improvement with persistence of an elevated IL-6 level, a second and a third dose of TCZ can be administered after 12 and 24-36 hours respectively. A favorable CT evolution has been previously described in an adult patient 7 days after two TCZ injections at 12 hour intervals. 4 Cytopenia and increased transaminases have been reported and need to be monitored. No adverse effect of TCZ was observed in our patient.

In the context of the COVID-19 outbreak, this diagnosis has to be evoked in case of ACS in patients with SCD, as both ACS and COVID-19 pneumonia may present with similar features. The hyperinflammatory state caused by the SARS-Cov-2 infection may be enhanced by the pro-inflammatory state of SCD. In such patients, TCZ seems to be safe and effective in adults as well as in children, in association with the usual treatment of severe ACS, including noninvasive ventilation and blood exchange transfusion.

Rapid and severe Covid-19 pneumonia with severe acute chest syndrome in a sickle cell patient successfully treated with tocilizumab

COVID-19 pneumonia as a cause of acute chest syndrome in an adult sickle cell patient

Vasoocclusive crisis and acute chest syndrome in sickle cell disease due to 2019 novel coronavirus disease (COVID-19)

Favorable changes of CT findings in a patient with COVID-19 pneumonia after treatment with tocilizumab

Inflammation in sickle cell disease

Why tocilizumab could be an effective treatment for severe COVID-19?

The authors wish to thank Pr. Pablo Bartolucci (from the Sickle Cell Referral Center of Henri-Mondor University Hospital in Créteil, France) for his expert advice on this case.

The authors declare no potential conflict of interest.

This correspondence received no specific grant from any funding