This report describes an interesting case of SARS-CoV-2 infection that presented with fever, pallor, and purpura as the initial presentation in the absence of any respiratory symptoms or signs. COVID-19 presents in children usually with milder manifestations than in adults [4]. However, young children, especially infants, were found to be vulnerable to SARS-CoV-2 infection with a higher proportion of severe cases than any other pediatric age groups [5]. COVID-19 most commonly presents with a spectrum of signs and symptoms ranging from completely asymptomatic to symptoms of acute upper respiratory tract infection such as fever, cough, sore throat, rhinorrhea, and shortness of breath. In more severe cases, patients can have respiratory failure, shock, coagulopathy, and renal injury [5]. Regarding our patient’s clinical presentation, it was non-specific, having no respiratory symptoms or signs all during the period of hospitalization. However, this case had principally features of aplastic anemia with acute onset of pallor and purpura following fever and vomiting. Cai et al. [10] described five cases of COVID-19 in children that also presented non-respiratory manifestations as the first manifestation.
The finding of pancytopenia with reticulocytopenia and hypocellular bone marrow in this case was the guide toward a diagnosis of aplastic anemia (AA). Drug intake, viral infection, HLH, malignancy, bone marrow infiltration by a storage disorder, and inherited bone marrow failure syndromes (IBMFS) were the main suspected causes of AA in this case. Serology markers of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were negative. There was no history of drug intake prior to the presentation apart from paracetamol. Similarly, there were no features to suggest IBMFS (as there were no any developmental delay, family history of cytopenias or congenital anomalies, osteopetrosis, short stature, limb anomalies, or any other anomalies). Features suggestive of HLH in this patient were markedly elevated ferritin, high triglycerides, and pancytopenia in addition to clinically detected hepatosplenomegaly and fever. So, a diagnosis of AA secondary to HLH was considered.
Neither the Italian CONFIDENCE study [7] nor Lu et al. [6] in China reported COVID-19 cases with pancytopenia. Both studies reported only leukopenia and/or thrombocytopenia in some cases. A cytokine profile resembling sHLH is found to be associated with COVID-19 in some cases which is characterized by increased interleukin (IL)-2, IL-7, granulocyte colony stimulating factor, interferon-γ inducible protein 10, and many other factors [8]. This may indicate that sHLH could be triggered by COVID-19. It was reported that viral infections may trigger secondary forms of HLH [11]. Pancytopenia represents a great challenge for the diagnosis of COVID-19 because the clinical manifestations of respiratory affection were absent.
As regards the CT chest findings, this case report suggests that infants with SARS-CoV-2 infection may not exhibit respiratory symptoms and signs even in the presence of radiological findings of pneumonia. Similarly, Lu et al. [6] reported that out of 171 children with confirmed SARS-CoV-2 infection, only 12 had radiologic findings of pneumonia without having any symptoms of infection. Cai et al. [10] also reported five children with COVID-19 who had radiological findings of pneumonia in chest CT without having any respiratory symptoms or signs.
This case highlights that aplastic anemia due to sHLH can be the initial and the principal presenting feature of COVID-19. Reliance on respiratory symptoms and signs only for testing will easily miss cases in whom these symptoms and signs are absent while fever alone or symptoms of other organ system affection are the first presenting features. As the predominant clinical manifestations of COVID-19 can vary from one patient to another, one should keep a high index of suspicion, especially in the setting of increasing incidence of COVID-19 cases.