It has described a phenomenon called “beginning of the end” (BOTE) sign which refers to clinical erythema and swelling of an MC skin lesion when the regression phase begins (Figure 2). This phenomenon is likely due to an immune response towards the MC infection rather than a bacterial superinfection.1,25,31
It has been reported that the novel coronavirus disease (COVID‐19) may be associated with a papulovesicular skin eruption predominantly involving the trunk. We hereby present a case of COVID‐19–associated varicella‐like exanthem in an 8‐year‐old girl with mild systemic symptoms.
1 CASE REPORT
On March 21, 2020, an 8‐year‐old girl from Milan (Lombardy region, Italy) presented to our outpatient service for a 3‐day history of an asymptomatic papulovesicular skin eruption. On physical examination, there were about forty erythematous papules and few vesicles scattered bilaterally and symmetrically on the trunk. Limbs, face, and genitals as well as mucous membranes were spared. The lesions were initially erythematous papules (Figure 1A,B), some of which showed a tendency to superficial vesiculation leading to crust formation. Medical history revealed that she was in good health except for a 6‐day history of mild cough. She had a history of varicella infection a year earlier. Routine blood tests, including complete blood count, liver and kidney function, and C‐reactive protein, showed no abnormalities except for mild thrombocytopenia (platelet count: 105 000/μL; range: 150 000/μL–400 000/μL).
A and B, Scattered erythematous papulovesicles on the trunk in a suspected COVID‐19 patient
Based on the clinical findings, a diagnosis of viral exanthem was suspected. The patient's parents refused a skin biopsy. Two days later, the patient developed mild fever. On March 24, 2020, the patient's father, mother, and grandmother manifested fever and cough, and, on the same day, the patient and her family tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) via nasopharyngeal swab. The patient's grandmother was hospitalized for COVID‐19–associated pneumonia. The patient's skin lesions as well as systemic symptoms subsided without any therapy within 7 days, and platelet count reverted to normal. The patient was discharged to home isolation with her family, and no further systemic nor skin manifestations were reported.
2 DISCUSSION
COVID‐19, an infection due to SARS‐CoV‐2, arose in Wuhan (Hubei province), China, and quickly spread to Europe, becoming a public health emergency of global concern.1 The illness is characterized by a wide list of clinical manifestations, ranging from respiratory symptoms such as dry cough and dyspnea to non‐respiratory symptoms including myalgia and diarrhea.1 Loss of smell and taste has also been reported.2
Cutaneous manifestations associated with COVID‐19 have been recently reported in adults by Joob and coworkers,3 who described a patient from Thailand with a petechial rash initially misdiagnosed as dengue, and by Recalcati4 who reported on hospitalized patients in Italy with erythematous rash (n = 14), widespread urticaria (n = 3), and varicella‐like vesicles (n = 1). Two of the authors of the present paper (GG and AVM) have reported a series of 21 adult patients and one child (who is the case described here in detail) with COVID‐19 who developed a varicella‐like rash predominantly involving the trunk, including 7 cases in which histology was obtained and findings were compatible with viral infection.5
Herein, we describe this varicella‐like exanthem as a possible COVID‐19–associated skin manifestation in children. In our patient, the latency time of the development of rash after cough's onset was three days and the exanthem duration was seven days. Other skin manifestations and mucosal involvement as well as symptoms such as pruritus, pain, or burning were absent. Alternative diagnoses for such an eruption include varicella infection, which is unlikely based on prior infection, and insect bites, which are unlikely in the absence of pruritus.
Even though our data do not prove that this rash is caused by or definitively associated with COVID‐19, we suggest that papulovesicular eruptions be included in the spectrum of exanthems possibly associated with COVID‐19. Based on the features and early appearance, this varicella‐like exanthem could be a useful clue to suspect the diagnosis of COVID‐19 in asymptomatic and paucisymptomatic children, prompting microbiological investigation in these patients. Since COVID‐19 usually manifests without severe respiratory symptoms in children, the recognition of potential associated skin manifestations could avoid spreading of the infection in the population.
In 1969, archaeologist BK Thapar excavated Kalibangan (Rajasthan, India). They dug out a settlement which dates back to mature IVC phase (c. 2600 BC) along the banks of now extinct Sarasvati river.
But the archaeologist was shocked. He saw that the houses had tiled floors. And the tiled floors were painted with a design. 'This is exactly the design on the floor of my house'- the startled archaeologist exclaimed.
Supervising Editor: Zachary F. Meisel, MD, MPH, MSc.
Abstract
The novel coronavirus, or COVID‐19, has rapidly become a global pandemic. A major cause of morbidity and mortality due to COVID‐19 has been the worsening hypoxia that, if untreated, can progress to acute respiratory distress syndrome (ARDS) and respiratory failure. Past work has found that intubated patients with ARDS experience physiological benefits to the prone position, because it promotes better matching of pulmonary perfusion to ventilation, improved secretion clearance, and recruitment of dependent areas of the lungs. We created a systemwide multi‐institutional (New York–Presbyterian Hospital enterprise) protocol for placing awake, nonintubated, emergency department patients with suspected or confirmed COVID‐19 in the prone position. In this piece, we describe the background literature and the approach we have taken at our institution as we care for a high burden of COVID‐19 cases with respiratory symptoms.
The novel coronavirus, or COVID‐19, has rapidly become a global pandemic. A major contributor to the morbidity and mortality of the illness is an acute viral pneumonitis, characterized by worsening hypoxia, eventually leading to acute respiratory distress syndrome (ARDS) and respiratory failure. Studies have shown that the prone position is physiologically beneficial in patients with ARDS. Proning (the maneuver of placing patients flat on their ventral surface) has been previously used as a strategy to promote better matching of pulmonary perfusion to ventilation, improved secretion clearance, and recruitment of dependent areas of the lungs in mechanically ventilated patients.1-3 It distributes lung stresses more homogeneously and so may prevent patients with hypoxemia from developing respiratory failure. Five major trials have compared the prone and supine positions in ARDS, examining survival advantage. All trials showed significant survival benefit in patients with a PaO2/FiO2 ratio lower than 100, specifically finding prone positioning offered a survival advantage of 10% to 17%.3 These findings are corroborated by the PROSEVA trial, which supports the early use of prone ventilation in patients with moderate to severe ARDS. Prone patients had an almost 50% reduction in both 28‐day and 90‐day mortality rates with an absolute mortality risk reduction of 17%. They also had increased rates of successful extubation.1 In a meta‐analysis of trials in critically ill intensive care unit (ICU) patients, prone positioning improved PaO2/FiO2 ratios by 25% to 36% in the first 3 days and more importantly had a mortality benefit, with an estimated number needed to treat of 11 to prevent one death.2 These positive effects have led to prone ventilation being recommended in international guidelines for the management of critically ill COVID‐19 patients.4, 5
The literature to date has largely focused on using this technique on intubated patients in ICU settings.2-6 However, it is postulated that adopting proning in nonintubated, awake COVID‐19 patients may have the same benefits in improving oxygenation and thus reducing the need for invasive ventilation. In a small study proning 20 nonintubated ARDS patients, 55% avoided intubation including patients with moderate and severe ARDS.7 Preliminary guidelines have been published for use on awake admitted patients both on the general floors and in the ICUs.5, 8
Based on the existing evidence of proning for respiratory management in critically ill patients we sought to create a protocol for the implementation of proning in the emergency department (ED) for awake, nonintubated patients with a new oxygen requirement.
PRONING GUIDELINES IN AWAKE ED COVID‐19 PATIENTS
Guidelines were developed based on review of the aforementioned studies as well as expert consensus of five of our board‐certified emergency medicine physicians with critical care training. These guidelines will be applied to ED patients with a supplemental oxygen requirement including nasal cannula (NC), nonrebreather, or high‐flow oxygen who remain hypoxic. We did not apply these guidelines to patients with normal oxygen saturations.
Inclusion criteria include the following patients:
Patients with suspected or confirmed COVID‐19 and an oxygen requirement of >4 L NC;
On a stretcher;
On continuous‐pulse oximetry monitor;
Awake with a normal mental status;
Able to follow instructions;
Able to tolerate changes in position;
Able to call for help or have call bell within reach;
Able to self‐prone or change position with minimal assistance.
Exclusion criteria include the following patients:
Normal oxygen saturation without need for supplemental oxygen source;
Altered mental status;
Inability to independently change position or tolerate positional changes;
Hemodynamic instability;
Inability to follow instructions or communicate with care team;
In a setting where patient is unable to be closely monitored.
Patients will be identified by emergency physicians (EP) as meeting criteria for proning. EPs will be responsible for assessing patient mobility and mental status as well as determining if the patient meets criteria for inclusion without any contraindications. EPs will collaborate with nursing staff to implement the protocol and reevaluate patients.
Prior to implementing the guidelines, patients should be made as comfortable as possible—that is, obtaining a pillow or using the restroom. They should be placed on the necessary level of supplemental oxygen as well as being on a continuous oxygen monitor. Ideally a call bell should be available within reach at bedside. The patient is placed on a stretcher in slight reverse Trendelenburg. They are provided with an instructional handout that includes a visual aid (Figure 1) explaining the proning guidelines and are walked through the process by a care provider. Patients will undergo a rotational change in position from prone to lying on each side to sitting up. Patients should change positions every 30 minutes as tolerated for as long as possible while awake. Patients are reassessed by care providers and/or nursing every 30 minutes for the first hour and every hour for the next 2 hours.
A visual graphic guide is provided to both care providers and patients for improved instruction. Data Supplement S1 (available as supporting information in the online version of this paper, which is available at http://onlinelibrary.wiley.com/doi/10.1111/acem.14035/full) summarizes the inclusion and exclusion criteria as well as providing more directions. Along with a QRS code linking to this document, this allows for easier printing and share among providers as well as patients.
Frequent position changes will be discontinued if the patient cannot tolerate them due to discomfort or they develop hemodynamic instability or worsening respiratory status. Proning guidelines will also be discontinued if the patient is transferred out of the ED including transfer to the floor or ICU.
DISCUSSION
Proning of the awake COVID‐19 patient has become an increasingly popular intervention deployed in EDs for assisting suspected COVID‐19 patients and a major focus of discussion in emergency medicine free online open‐access medical education (FOAMed).9, 10 It was formally described in one protocol from China, and since then there have been small studies reporting success in proning awake, nonintubated COVID‐19 and non–COVID‐19 patients.7, 11-13 These studies were small and included patients with various clinical heterogeneity as well as varied approaches for respiratory support. Early preliminary work has been encouraging with laboratory, radiographic, and/or clinical improvement.7, 9, 12, 13
Initial data from more than 600 COVID‐19 patients found that the awake prone position had “significant effects in improving oxygenation and pulmonary heterogeneity.”9 Scaravilli et al.12 evaluated 15 patients almost entirely with pneumonia who underwent two proning sessions. Proning led to an increase in patients' P:F ratio as well as an increase in PaO2 and HgbO2 while in the prone position. Furthermore, the study by Ding et al.7 showed that proning may have larger clinical implications in staving off intubation. They evaluated 20 patients on noninvasive support of at least PEEP of 5 and an FiO2 of 0.5 or more. Patients were escalated from high‐flow nasal cannula (HFNC) to HFNC + proning to noninvasive ventilation (NIV) to NIV + proning to maintain SpO2 >90%. While effects must be interpreted with caution due to this being a small, nonrandomized study, intubation rates decreased to 45% from a predicted rate of 75%.
There are potential harms to placing patients in the prone position. Some patients may not be able to tolerate positioning due to body habitus or discomfort. Others may also experience anxiety or require light sedation to tolerate the appropriate position. With these factors in mind, care providers must ensure the patient does not fall asleep and is turning at appropriate time intervals to ensure no secondary complications such as pressure ulcers or hemodynamic instability and should monitor them closely for worsening hypoxia.
Early evidence on the efficacy of proning in awake, nonintubated patients is encouraging. Our protocol can be safely and easily deployed in many EDs. While outcome data need to be collected, it may lead to guidelines that could improve patient outcomes and prevent need for increased respiratory support and even invasive ventilation.
CONCLUSION
Proning may prove to be of great clinical benefit to the large number of COVID‐19 patients with severe hypoxemia. Emergency physicians should be aware of appropriate inclusion and exclusion criteria for safe and effective use of this technique. While further studies need to be conducted, we hope to encourage the adoption of prone positioning of awake COVID‐19 patients in the ED, as a noninvasive treatment that may prevent worsening hypoxemia and respiratory failure.
The spectrum of clinical manifestations of coronavirus disease 2019 in children is yet to be fully elucidated. We report the case of an infant who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and developed mild cardiovascular inflammation, a novelty for patients of very young age, that contributes to defining the puzzling nature of this disease in pediatric patients. The potential cardiovascular involvement of SARS‐CoV‐2 in children should always be taken into account.
Abbreviations
ACE2
angiotensin‐converting enzyme 2
COVID‐19
coronavirus disease 2019
SARS‐CoV‐2
severe acute respiratory syndrome coronavirus 2
1 CASE REPORT
Coronavirus disease 2019 (COVID‐19) is milder in children, with much fewer reported severe and critical cases (around 6%) than in adult patients (18.5%). This proportion appears to be slightly more elevated in infants (<1 10.6="" age="" of="" reaching="" span="" style="box-sizing: border-box;" year="">1
COVID‐19 may indeed have cardiac complications, including myocarditis,2 and up to 31% of children have myocardial enzyme elevation, mainly creatine kinase MB, despite no specific sign or symptom of clinical cardiac disease. Nevertheless, correlation between D‐dimer and myocardial enzymes elevation (particularly creatine kinase MB) and disease severity has been described.3
No specific morphological and functional cardiac assessment has yet been performed in COVID‐19 children with elevated myocardial enzymes.
For the first time, we report the case of an infant affected by COVID‐19 with documented mild cardiac involvement.
A full term, formula‐fed, 38‐day old male presenting with mild fever (37.6°C), rhinitis and modest hyporeactivity was admitted on 27th March for clinical evaluation. The pregnancy had been unremarkable, and the mother had been vaccinated against influenza. Both parents were diagnosed with COVID‐19 and household contagion was presumed. History was otherwise irrelevant and the infant did not show any sign or symptom of acute respiratory distress. A full workup was performed.
Complete blood count showed fluctuations during the hospital stay, but lymphocytopenia was never observed (min, 7100/μL); mild thrombocytosis (max, 525 000 /μL) was present, with normal values of hemoglobin. C‐reactive protein and erythrocyte sedimentation rate were confirmed negative throughout the hospital stay, while a persistent increase in procalcitonin levels was observed (max, 3.28 ng/mL; nv < 0.5). Electrolytes were in normal range and lactate dehydrogenase was mildly increased. Liver transaminases were normal.
Nasal and pharyngeal swab specimens tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleic acid by using real‐time reverse‐transcriptase polymerase chain reaction assay on 28th March, while Allplex Seegene Respiratory Panel for 18 viruses resulted negative.
Blood culture, urine culture, and pharyngeal swab for S. pyogenes were also negative.
Chest X‐ray showed mild thickening of bronchovascular markings, but no pulmonary parenchymal opacities. The chest computed tomograpghy scan was not performed, thus avoiding the exposure to ionizing radiations in an infant without overt respiratory involvement.
An increase in troponin T was observed (max, 8.2 ng/dL; reference range for age <5 9.8="" a="" as="" creatine="" elevated="" g="" kinase="" max="" range="" reference="" slightly="" span="" style="box-sizing: border-box;" well="">4
Pro‐brain natriuretic peptide (208 pg/mL) was normal. INR and partial thromboplastin time were normal, while D‐dimer was found to be increased (max, 13.3 μg/mL, reference range <0 .87="" and="" consecutive="" diminished="" fibrinogen="" g="" in="" measurements="" nv="" resolution.="" spontaneous="" subsequent="" transiently="" two=""> 1.5) without associated platelet consumption. A graphical representation of laboratory tests trends is shown in Figure 1.
Time course of relevant cardiac and vascular biomarkers. Maximum and minimum values are reported next to the corresponding symbol
Continuous monitoring of vital parameters documented resting heart rate of 140/min, with peak frequency of 200/min. Serial electrocardiograms and a 24‐hour Holter electrocardiogram confirmed only mild sinus tachycardia and a first cardiac ultrasonography was normal (Figure 2, panel A). A cardiac magnetic resonance was also performed with the “feed and sleep” approach, which excluded edema of the myocardium and showed a minimal amount of pericardial effusion (Figure S1).
A, Four chamber view of the heart taken during the first cardiological evaluation shows normal structure and dimensions of cardiac chambers, without pericardial effusion. B, Four chamber view of the heart four days after the previous one shows a 2 to 3 mm pericardial effusion in the lateral‐posterior pericardial space (arrow)
Three days after the first cardiac ultrasound, a new sonographic evaluation documented a 2 mm pericardial effusion which did not evolve during follow‐up (Figure 2, panel B).
The patient remained asymptomatic with normal vital parameters, thus no specific treatment was undertaken. Serological tests ruled out other common causes of viral myopericarditis (Coxsackie virus, echovirus, cytomegalovirus, and Epstein‐Barr virus).
In consideration of the altered D‐dimer and fibrinogen, and given the recent reports of SARS‐CoV‐2 associated coagulopathy and cerebral infarcts,5 the infant underwent a brain MR angiography with the “feed and sleep” approach which resulted normal. Lupus‐like anti coagulants, anti‐nuclear, and anti‐cardiolipin antibodies were undetectable.
Hospital stay was unremarkable; no oxygen or antiviral therapy was administered. After 14 days the child was discharged in good health and he tested negative for SARS‐CoV‐2 on 16th and 17th April. He was thus enrolled in a cardiological follow‐up to monitor the long‐term evolution of the clinical picture.
SARS‐CoV‐2 enters the cells through the angiotensin‐converting enzyme 2 (ACE2) receptor, which is displayed by a range of tissues, including the endothelium and the respiratory epithelium.2 The reason why COVID‐19 is milder in children is unknown. Cardiac involvement by SARS‐CoV‐2 may be directly virus‐dependent, and/or secondary to inflammatory response. Given the immaturity of the immune system of our patient, we speculate that the former may be more relevant, at least in infants and neonates. The ubiquity of the ACE2 receptor may explain the cardiac and vascular involvement that have been observed in our case.
To the best of our knowledge this is the first report of cardiac involvement in an infant with SARS‐CoV‐2 infection, with comprehensive clinical, biochemical and multimodal imaging characterization. We suggest that SARS‐CoV‐2 cardiac involvement should always be taken into account also in children; while our case was mild, it might be of concern especially in patients with other underlying conditions. Follow‐up is necessary to detail the long‐term outcomes of cardiac involvement in affected patients.
