COVID-19 enters cells via angiotensin-converting enzyme-2 receptors, replicates in the respiratory tract, and causes multi-organ injury. We know that angiotensin-converting enzyme-2 receptors exist in the lungs, heart, kidney, gastrointestinal tract, and vascular endothelium. Pediatric skin manifestations have been described as livedoid rash, purpuric lesions (Figure 2), macular or morbilliform rash (Figure 3), desquamation on extremities and/or buttocks (Figure 4), and occasionally targetoid lesions on the trunk or extremities. COVID toes (Figure 5) or chilblain-like lesions (reddish, purple skin discoloration) have been described in children as well. Studies from the United Kingdom, Italy, and Spain were first to describe case reports of children with chilblain noted on the extremities.7,8 Children’s ages ranged from 5 to 17 years, and they often presented with cough and rhinorrhea that developed a few days prior. Acral lesions were described as red, purple, blistery, and sometimes painful or itchy. Symptoms often progressed to fever, hypotension, and organ dysfunction. Similar to adults, some children had elevated D-dimer levels leading to coagulopathy evaluation.8 Biopsy specimens revealed dense lymphocytic perivascular cuffing and peri-adnexal infiltration. The Italian group suggested that the etiology was a vaso-occlusive phenomenon, supporting coagulation work-up in all children with acrovasculitis-like findings.7,8 Few children had a negative initial COVID-19 Prevention, Retention, and Contingency (PRC) test result; some had a positive follow-up test result, whereas others could have had a false-negative result because sensitivity of the real-time polymerase chain reaction (RT-PCR) depends on the quality of the sample. All children in the above studies healed.
Nonexudative conjunctivitis, mucositis, and cracked erythematous lips have also been noted. Initial presentation of COVID-related illness in children is often described as fever, rash, nonspecific weakness, extremity pain, and gastrointestinal symptoms.9 Many would consider a broad differential diagnosis at this point: common viral exanthems, streptococcal scarlet fever, or contact dermatitis (if only rash is present). With prolonged fever, desquamation, and erythroderma, staphylococcal scalded skin syndrome and toxic epidermal necrolysis should be considered in the differential diagnosis; mucosal membrane involvement adds toxic shock syndrome, Stevens-Johnson syndrome, and KD. Let us not forget SARS-CoV-2 in our differential diagnosis, as running an RT-PCR test may allow a practitioner to anticipate potential developments or complications seen with acute SARS-CoV-2 or 2- to 3-week post sequalae such as KD-like disease or MIS-C.
We do not know the etiology of KD, but we know that there is a triggering event. Could SARS-CoV-2 be that triggering event leading to atypical KD? Or can the infection cause cytokine storm (hyperexcitability of the immune system, release of pro-inflammatory interleukins [eg, IL-6], hypercoagulation, and hypoxia), resulting in the injury of multiple organs via inflammation following the acute phase of COVID-19? We do not know for sure, but what we do know at this point is as follows.
It does not seem that there is vertical transmission to neonates from COVID-19–positive mothers, but cases of COVID-positive children as young as 2 days have been reported.3–5 The transmission is likely from person-to-person exposure as there are no studies showing RT-PCR–positive tests of amniotic fluid, placenta, or cord blood.5 Neonates may present with respiratory symptoms, occasionally fevers, and cutaneous findings such as desquamation, erythematous or lacy purpuric rash, and purpuric macules (Figures 2–4). There are discussions in the literature questioning if there are transplacental transmissions via infected maternal cells passing to the fetal side of the cytotrophoblast or by transcytosis of free virus.11 If those mechanisms are viable, will SARS-CoV-2 infection become additional viral TORCH infections (ie, toxoplasmosis, other [syphilis, varicella-zoster, parvovirus B19], rubella, cytomegalovirus, and herpes infections)?12 Not enough data are available now, but animal studies have shown that previous SARS viruses did have such in utero transmission.
Young children present with fever, cough, rhinorrhea, diarrhea, vomiting, and weakness. Some have pharyngitis and tachypnea later. Children younger than 10 presenting with cardiorespiratory failure may have KD, atypical KD, or COVID-induced myocardial disease.9–11 They have the above-described rash and, in addition, may have COVID toes and mucosal membrane involvement. The feared cardiovascular complications of coronary artery aneurysm, myocarditis, and cardiomyopathy can be prevented or treated if recognized in a timely manner. Fever and rash might be the early clues.
Adolescents who had a simple rash and viral symptoms may present with complex heart failure symptoms 2–3 weeks later or acutely as SARS-CoV-2 progresses. In our system, all children who presented with this condition were either COVID PRC- or serology-positive. Heart failure and shock, as opposed to respiratory failure, can result in intensive care unit (ICU) admission, intubation, and use of vasopressors and extracorporeal membrane oxygenation (ECMO) support. Many believe that SARS-CoV-2 triggers immune dysregulation and hyperinflammation. Timely and appropriate treatment can be lifesaving. Immunoglobulins and steroids seem to restore cardiac function in children with MIS-C.12 Aspirin and immunoglobulin are traditional treatments of KD.9
Timely recognition is paramount not only for life-saving treatments, but for skin injuries seen in these children as the result of SARS-CoV-2 disease. Those in the ICU suffer from extravasations and pressure injuries. I have seen children with “purple” lesions that resemble deep tissue injury and are often in pressure-transmitting locations, such as the sacral area or buttocks, but it is not clear whether a pressure injury or COVID-related vasculitis is the etiology (Figure 6). Most do not become open wounds. I treat them as a stage 1 deep tissue injury by using protection with foam, repositioning, and frequent observation.