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Paediatric patients comprise a small proportion of the SARS-CoV-2 infected population. They usually present with mild symptoms, however a small proportion of them may require intensive care due to shock and multi-organ failure related to Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS). This review article summarises the oral mucosal lesions in children with COVID-19 and PIMS-TS. The most common sites affected are the tongue and lips. Commonly reported lesions include cheilitis, dry and red lips, and tongue swelling. This article is of importance to all healthcare professionals involved in the multidisciplinary care for this group of patients.Copyright © 2021 The Authors
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CASE: A 22-year-old woman with h/o asthma initially presented to the hospital with lip swelling and sore throat. She tested positive for COVID-19 and received a casirivimab-imdevimab (monoclonal antibody) infusion. She returned a week later with worsening lip swelling, dysphagia and conjunctivitis. Physical exam revealed edematous lips with vesicular lesions, no tongue swelling, tonsillar exudate, 4+ conjunctival injection bilaterally with purulent discharge, and shallow clean based clitoral ulceration. She reports no history of allergic reactions, angioedema or exposure to new medications. Nasopharyngolaryngoscopy showed no laryngeal edema but visualized exudates throughout the supraglottis and glottis. C4, ANA, CMV, EBV, throat and blood cultures were negative. STI testing was trichomonas positive and gonorrhea/chlamydia negative. Respiratory virus panel remained positive for COVID-19. HSV swab of lip lesion, HSV 1/2 IgG and IgM were negative. Mycoplasma pneumoniae IgG was elevated (0.60, negative is ≤0.09), IgM equivocal (0.85, negative is ≤0.76), and nasopharyngeal PCR negative. Conjunctival culture showed rare bacteria (S. Aureus) and no leukocytes. She initially received methylprednisolone IV due to concern for angioedema, acyclovir for empiric HSV treatment and empiric antibacterial moxifloxacin eye drops. Given lack of infectious trigger, her presentation was concerning for reactive infectious mucocutaneous eruption (RIME) associated with SARSCoV-2 or Mycoplasma. Prednisone 1mg/kg daily was initiated followed by improvement in oral mucositis and conjunctivitis within days. IMPACT/DISCUSSION: A broad differential is important when evaluating oral swelling and mucositis. Her lack of cutaneous involvement, medication exposure or family history and negative infectious, autoimmune and inflammatory workup make other causes including Stevens-Johnson syndrome, erythema multiforme, angioedema, and HSV less likely. Our final diagnosis of RIME describes mucocutaneous eruptions likely due to an immune response triggered by bacterial or viral infection. Our patient's RIME may be due to COVID-19 or Mycoplasma given her equivocal Mycoplasma IgM. Eruptions generally involve two or more mucosal sites and occur mostly in children and adolescents. Common presentations include oral erosions and ulcers, purulent bilateral conjunctivitis, or urogenital lesions, which were all seen in our patient. As this is a relatively rare and new condition, no standard of care treatment exists for RIME but systemic steroids have been effective in case reports for initial treatment and subsequent flares. CONCLUSION: RIME is a rare, newly described condition in young patients who develop postinfectious mucocutaneous eruptions of two or more mucosal sites. It has been recently reported in association with COVID-19 and its association with Mycoplasma infection is important to evaluate. This condition is important to recognize and treat given the requirement for higher dose steroids than that used for angioedema.
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CASE: Our patient is a 52-year-old female with a history of gastroesophageal reflux and hypertension. 36 hours after receiving the second Pfizer COVID-19 vaccine, she developed lip and tongue swelling, mucosal ulcerations, and respiratory distress. There was no conjunctivitis or genital involvement. She denied taking any new medications, supplements, or food that might have led to the reactions. She initially presented to an outside hospital and required intubation prior to transfer to our facility. A bedside esophagogastroduodenoscopy (EGD) was performed noting extensive Grade D erosive esophagitis and gastric ulcerations with friability. When the endoscope was removed a 34cm section of necrotic esophageal tissue was removed from the airway. Despite intravenous steroid treatment, she continued to have esophageal scarring and was unable to tolerate food by mouth. Therefore, a gastrostomy tube was placed. Since that time, she has required several recurrent EGDs for esophageal dilation due to scarring. It has now been six months from her initial injury, and unfortunately, the patient is still unable to take PO and is dependent on tube feedings. IMPACT/DISCUSSION: The coronavirus pandemic began in December 2019. At the time of this report, SARS-CoV-2 infection has been the cause of 5.48 million deaths worldwide and 836,000 deaths in the United States alone. In addition, this global pandemic has had severe economic and social implications. There are currently three vaccines authorized by the United States Food and Drug Administration for emergency use. I report an extremely uncommon complication of the Pfizer COVID-19 vaccine: a case of Eryethema Multiforme Major that occurred after the second dose vaccine without exposure to any other drug. Eryethema Multiforme is divided into major and minor forms and is regarded as distinct from Stevens- Johnson syndrome and toxic epidermal necrolysis. It is related to infections, usually Herpes Simplex Virus, or less commonly, to medications. In Erythema Multiforme, mucous membrane involvement is absent or mild. Erythema Multiforme Major is an immune mediated skin reaction involving the oral cavity and mucosa that is serious and occasionally life threatening. There have been several reported cases of Erythema Multiforme following COVID-19 vaccination but only one other cases of Erythema Multiforme Major associated with the mRnA-1273 SARS-CoV-2 vaccine (Moderna.) CONCLUSION: This case highlights an extremely rare vaccine consequence. The benefits still greatly outweigh the risks of vaccination, and this case does not diminish the importance of COVID-19 vaccination to effectively control this pandemic.
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The aim is to determine oral manifestations in patients with COVID-19 disease and in the postcovid period. Methods: A special survey (questionnaire) was made in 424 people who had COVID-19 confirmed by RT-PCR, ELISA for specific IgM and IgG antibodies and Chest CT scan (168 people). 123 people had complaints and clinical symptoms in the oral cavity 2-6 months after the illness and they came to the University dental clinic. Laboratory tests have been performed (clinical blood test, blood immunogram, virus and fungal identification). Results: Survey results showed that 16,0% participants had asymptomatic COVID-19, 23,6% - mild and 48,1% moderate disease. 12,3% with severe COVID-19 were treated in a hospital with oxygen support. In the first 2 weeks 44,3% indicated xerostomia, dysgeusia (21,7%), muscle pain during chewing (11,3%), pain during swallowing (30,2%), burning and painful tongue (1,9%), tongue swelling (30,2%), catharal stomatitis (16,0%), gingival bleeding (22,6%), painful ulcers (aphthae) (8,5%) and signs of candidiasis - white plaque in the tongue (12,3%). After illness (3-6 months), patients indicated dry mouth (12,3%), progressing of gingivitis (20,7%) and periodontitis (11,3%). In patients who applied to the clinic we identified such diagnoses: desquamative glossitis - 16 cases, glossodynia (11), herpes labialis and recurrent herpetic gingivostomatitis (27), hairy leukoplakia (1), recurrent aphthous stomatitis (22), aphthosis Sutton (4), necrotising ulcerative gingivitis (13), oral candidiasis (14), erythema multiforme (8), Stevens-Johnson syndrome (2), oral squamous cell papillomas on the gingiva (4) and the lower lip (1). According to laboratory studies, virus reactivation (HSV, VZV, EBV, CMV, Papilloma viruces) was noted in 52 patients (42,3%), immunodeficiency in 96 people (78,0%), immunoregulation disorders (allergic and autoimmune reactions) in 24 people (19,5%). Conclusions: Lack of oral hygiene, hyposalivation, vascular compromise, stress, immunodeficiency and reactivation of persistent viral and fungal infections in patients with COVID-19 disease are risk factors for progression of periodontal and oral mucosal diseases.
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Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well described as an etiology to severe acute respiratory distress syndrome (ARDS). However, rare immunologic and allergic manifestations may also occur from this infection. We report a novel case of angioedema occurring in the setting of COVID-19 infection in a fully vaccinated patient. Case Report: A 61-yearold COVID-19 vaccinated female with hypertension presented to the emergency department with tongue and lip swelling, odynophagia, dysphonia, and difficulty breathing. She denied personal or family history of allergies, anaphylaxis, or angioedema. Her home medications included Aspirin, methadone, Seroquel, and Klonopin, with no recent changes reported. Physical exam was notable for significant lip and tongue edema, audible dysphonia, and bilateral end-inspiratory wheezing. She was hypoxemic and placed on nasal cannula. Laboratory findings revealed lymphopenia, elevated inflammatory proteins, including C-reactive protein (57), Lactate dehydrogenase (LDH) (238), and D-dimer (11.52). Functional C1 esterase inhibitor levels (>91) were normal. Nasal PCR swab returned positive for SARS-CoV-2. Ear, nose, and throat specialist was consulted given concern for angioedema, and flexible nasolaryngoscopy was performed revealing uvular, epiglottic, and bilateral arytenoid edema concerning for impending airway compromise. The patient was initiated on intravenous methylprednisolone, epinephrine, antihistamines, tranexamic acid and admitted to the medical intensive care unit (ICU). She was monitored closely in the ICU with subsequent improvement of the angioedema and resolution of the hypoxemia. She was discharged with an oral steroid regimen and scheduled for a follow-up appointment with an allergist. Discussion: There exists only a handful of case reports describing angioedema in patients with COVID-19 infection. In those reports, patients also had normal C1 esterase inhibitor levels and no personal or family history of inherited angioedema. Interestingly, our patient was vaccinated six months prior to her presentation. The association between SARS-CoV-2 and angiotensinconverting enzyme 2 (ACE-2), the primary receptor for viral entry into the epithelial cells of the lungs, could be a potential explanation for the occurrence of angioedema. ACE-2 plays a pivotal role in inhibiting a potent ligand of bradykinin receptor 1, Arginine bradykinin. It has been postulated that SARS-CoV-2 downregulation of ACE-2 leads to elevated angiotensin II levels and subsequent activation of the bradykinin pathway. Excessive bradykinin production generates high levels of nitric oxide and prostaglandins, resulting in vasodilation, increased vascular permeability, and angioedema. This case highlights the importance of recognizing atypical and rare presentations of COVID-19 infection, especially angioedema, given its sudden onset and life-threatening complications.
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Introduction: Circadian rhythms have critical roles in human health. We quantified the effect of time-of-day of COVID-19 vaccination and other covariates on self-reported side effects post vaccination. Methods: The dataset was created from MassGeneralBrigham (MGB) electronic health records and REDCap survey that collected self-reported symptoms for 1-3 days after each immunization. Variables are demographics (age, sex, race, and ethnicity), vaccine manufacturer, clock time of vaccine administration/appointment, any COVID-19 diagnosis/positive test prior to vaccination, any history of allergy, and any note of epinephrine self-injection (e.g., EpiPen) medication. Time of day groupings were morning (6 am10 am), midday (10 am2 pm), late afternoon (2 pm6 pm) or evening (6 pm10 pm). Side effects were classified as Allergic (Rash;Hives;Swollen lips, tongue, eyes, or face;Wheezing) and Non-Allergic (New Headache, New Fatigue, Arthralgias, Myalgias, Fever) symptoms. The study was approved by the MGB IRB.Machine learning (ML) techniques (e.g., extreme gradient boosting) were applied to the variables to predict the occurrence of side effects. Stratified k-fold cross validation was used to validate the performance of the ML models. Shapley Additive Explanation values were computed to explain the contribution of each of the variables to the prediction of the occurrence of side effects. Results: Data were from 54,844 individuals. On day 1 after the first vaccination, (i) females, people who received the Moderna vaccine, and those with any allergy history were more likely to report Allergic side effects;and (ii) females, people who received the Janssen vaccine, those who had prior COVID-19 diagnosis ,and those who received their vaccine in the morning or midday and were more likely to report Non-Allergic symptoms. Older persons had fewer side effects of any type. Conclusion: ML techniques identified demographic and time-ofday- of-vaccination effects on side effects reported on the first day after the first dose of a COVID-19 vaccination. We will use these techniques to test for changes on days 2 and 3 after the first dose, and the first 3 days after the second dose and for the influence of recent night or shiftwork. Future work should target underlying physiological reasons.
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Objective: To analyze the distribution characteristics of syndrome of TCM of the patients with COVID-19 in Kunming, China. Methods: To classify and summarize the TCM syndrome types of COVID-19 patients via Cluster analysis combining with tongue image, chest CT and clinical expertise of 36 Covid-19 patients in Kunming. Results: In the 36 cases of Kunming region confirmed COVID-19 patients, 17 cases had fever (47.2%), 18 cases had cough (50%), 16 cases felt bitter taste in the mouth (44.4%), 18 cases felt dry throat (50.0%), 17 cases had poor appetite (47.2%), 15 cases had nausea (41.7%);12 cases had diarrhea (33.3%), 15 cases had insomnia (41.7%);12 cases had chest tightness (33.3%);3 cases had dyspnea (8.3%);6 cases had nasal congestion and running nose (16.7%);15 cases had fatigue (41.7%);6 cases had headache and body pain (16.7%);5 cases had red tongue (13.9%);18 cases had pale red tongue (50%);8 cases had tongue with red edge and tip (22.2%);3 cases had dark red tongue (8.3%);2 cases had cyanosis (5.6%);3 cases had swollen tongue (8.3%);18 cases had dentate tongue (50%);4 cases had yellow tongue coating (11.1%);5 cases had yellow sticky tongue coating (13.9%);12 cases had white sticky tongue coating (33.3%);6 cases had thin white tongue coating (16.7%);2 cases had no tongue coating (5.6%). The chest CT results showed that: There were five cases without lesions. The lesions were located in the upper lobe of one lung in 13 cases located in the lower lobe of one lung in seven cases, located in the upper middle lobe in three cases, located in the lower lobe in five cases, and in the upper middle and lower lobes of double lung in 13 cases. There were 14 cases of Shaoyang syndrome, 17 cases of wet Resistance Tir-juao Syndrome. According to the time of onset, the disease was followed by Shaoyang Syndrome (1 day), the Wet blocked tri-jiao Syndrome (3 days), epidemic poison retention lung syndrome and syndrome of flaring heat in qifen and yingfen (5 days), and dampness-toxicity lung-stagnation syndrome (6 days). Conclusion: The TCM syndromes of COVID-19 in Kunming are mainly the Wet Resistance Tri-Jiao Syndrome and Shaoyang syndrome, followed by dampness-toxicity lung-stagnation syndrome, epidemic poison retention lung and syndrome of flaring heat in qifen and yingfen.