Long COVID in Children: A Multidisciplinary Review

Abstract

Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by Long COVID, with potential clinical issues in different fields, including problems in school performance and daily activities. Yet, the pathophysiologic bases of Long COVID in children are largely unknown, and it is difficult to predict who will develop the syndrome. In this multidisciplinary clinical review, we summarise the latest scientific data regarding Long COVID and its impact on children. Special attention is given to diagnostic tests, in order to help the physicians to find potential disease markers and quantify impairment. Specifically, we assess the respiratory, upper airways, cardiac, neurologic and motor and psychological aspects. Finally, we also propose a multidisciplinary clinical approach.

Keywords: Long COVID; autonomic dysfunction; children; gastrointestinal; lung function; neuroCOVID; otorhinolaryngology; psychological well-being.

Figure 1

SARS-CoV-2 main pathogenic pathways. The virus binds to ACE2 receptor, dampening its anti-thrombotic and anti-atherosclerotic action and inducing vascular damage. Once inside the cell it replicates and viral RNA is recognised by PAMPs (pathogen-associated molecular patterns) receptor, such as Toll-like receptors (TLRs) [12,16]. Activated TLRs induce pro-inflammatory cytokines release, triggering a cascade of events that leads to cell apoptosis (pyroptosis). Cellular debris and cytokines in the bloodstream induce the activation of the innate and immune system, sustaining the inflammatory process [12]. Importantly, SARS-CoV-2 can bind to cell proteins different from ACE2 receptor, thus explaining why cells not expressing ACE2 receptor can also be infected by the virus [17,18,19,20]. Abbreviations: ACE2 = angiotensin-converting enzyme 2; PAMPs = pathogen-associated molecular patterns; DAMPS = damage-associated molecular patterns; TLR = toll-like receptor; IL = interleukin; TNF-a = tumour necrosis factor α; MIP1a = macrophage inflammatory protein 1 α; G-CSF = granulocyte-colony-stimulating factor.

Figure 2

Clinical approach to paediatric Long COVID. Abbreviations: 6MWT = six-minute walking test; DLCO = diffusion lung capacity for carbon monoxide; LUS = lung ultrasound; CT = computed tomography; EMG = electromyography; CPK = creatine phosphokinase; EEG = electroencephalogram; MRI = magnetic resonance; ECG = electrocardiograph; TTE = transthoracic echocardiography; BNP = brain-derived natriuretic peptide; US = ultrasound; AST = aspartate aminotransferase; ALT = alanine aminotransferase; GGT = gamma-glutamyl transpeptidase.