A few cases of coinfection with SARS-CoV-2 and DENV-2 have been reported in different countries for adult patients [4,5,6], yet this is the first case in a child. As described above, this 7-year-old boy under our care experienced many serious complications during these two infections.
According to previous reports [7,8,9,10], the clinical profiles of non-severe dengue disease in children include fever, myalgia, abdominal pain, petechiae, vomiting, retroorbital pain, and abdominal distension. In the case of severe dengue, platelets < 150,000 cells/mm3, leukopenia, positive tourniquet, myalgia/arthralgia, petechia, gastrointestinal bleeding, elevation in serum glutamic oxaloacetic transaminase (SGOT), hepatomegaly, fluid leak, and pleural effusion  are common symptoms; bilateral effusion, abdominal pain, abnormal prothrombin time (PT), activated partial thromboplastin time (aPTT), and neurological symptoms such as encephalopathy and convulsions are very rare. Some forms of atypical manifestations of severe dengue in children include acute respiratory distress syndrome (ARDS), persistent shock, and diastolic dysfunction. Another secondary clinical consequence of DENV disease is hemophagocytic lymphohistiocytosis (HLH). HLH is a life-threatening condition with severe hyperinflammation from uncontrolled proliferation of active lymphocytes and histiocytes that secrete high amounts of inflammatory cytokines; this condition can be inherited or acquired  and has been increasingly reported as a complication of dengue. An analysis of pediatric patients in Puerto Rico showed that dengue patients with HLH between 1 and 13 years old were more likely to be hospitalized; in addition, most cases had a coinfection (hepatitis B virus, Plasmodium vivax, Plasmodium falciparum, scrub typhus, invasive aspergillosis, herpes simplex virus, respiratory syncytial virus, or Epstein‐Barr virus ), longer duration of fever, lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases . It was also observed that severe dengue with HLH diagnosis has a higher rate of mortality . In the same way, another relevant yet unusual clinical symptom of DENV is that it can generate cardiomegaly because DENV can infect the heart, myocardial endothelium, and cardiomyocytes [16, 17]. Cardiomegaly was significantly related to elevated blood pressure [18, 19]. Likewise, cardiomegaly has been reported to be observed in patients with COVID-19, with the majority of patients having hypertension and other cardiovascular diseases . Both viruses can generate cardiomegaly mostly in adults with cardiac disease, and infection with both DENV and SARS-CoV-2 can exacerbate cardiovascular complications. In this case report, the patient presented cerebral edema, pericardial effusion, bilateral periorbital edema, edema in all four extremities, hepatomegaly, thrombocytopenia, long prothrombin time, cardiomegaly, and HLH, which are characterized by DENV, although not all symptoms.
In the case of COVID-19, clinical symptoms in pediatric patients are not well documented, although various studies report fever and cough as the main symptoms; others include rhinorrhea, sore throat, headache, fatigue/myalgia, and gastrointestinal symptoms. It was also shown that infants 0–1 years old are more likely to be affected . COVID-19 is characterized by low WBCs, marginally elevated lymphocytes in the early stages, and mild symptoms. In contrast, severe cases of COVID-19 may present with increased serum inflammatory markers, such as D dimer, procalcitonin, creatine kinase, and interleukin 6, as well as progressive lymphopenia [21, 22]. In the early days of the infection, our patient showed mild symptoms, which worsened each day. According to a systematic review  in which 7,780 pediatric patients with COVID-19 from 131 studies and 16 countries were evaluated, 19.3% of the children were asymptomatic, and only 3.3% required ICU admission. In contrast, immunosuppressed children or those with chronic cardiac or respiratory illness comprised children with underlying medical conditions (65%). The production of an inflammatory cascade causing multisystemic inflammatory syndrome in children (MIS-C) (11 patients) can create the need for respiratory assistance. The cause of MIS-C is still unclear, but it is disproportionately frequent among African American and Afro-Caribbean populations. The most common symptoms of MIS-C are fever, abdominal pain/diarrhea, and vomiting, while the common laboratory investigation findings are elevated mean neutrophil percentage and low lymphocytes, increased C-reactive protein, ferritin, and procalcitonin, and abnormal d-dimer [24,25,26].
COVID-19 has also been related neurological symptoms . One of these neurological manifestations is myoclonus. In a systematic review by Chan et al. , 51 cases were identified as myoclonus associated with COVID-19, with ages ranging from 26 to 88 years. Myoclonus usually onset within 1 month of COVID-19 symptoms and was multifocal or generalized with a duration from 1 day to 2 months. Treatments involved different medications from anti-epileptic (levetiracetam, clonazepam, valproic acid, and primidone), immunotherapy (methylprednisolone, intravenous immunoglobulin, and plasma exchange), sedative (midazolam, lorazepam, ketamine, and dexmedetomidine), or nonepileptic treatments, with 80% improvement. There has not been a case of a pediatric patient with myoclonus reported, although opsoclonus associated with myoclonus has been reported after COVID-19 in an infant treated with intravenous immunoglobulin and corticosteroids . In this case, the patient presented myoclonus after 1 week of onset of symptoms and was treated with phenytoin sodium. Phenytoin is helpful in only a minority of patients, it has also been related to exacerbated myoclonus seizures, and it only has value in the treatment of cortical myoclonus with motor seizures (palatal myoclonus) . In addition to myoclonus, COVID-19 has been demonstrated to cause cerebral edema by the direct invasion of SARS-CoV-2 to the central nervous system (CNS) . No case with simultaneous edema and myoclonus has been reported. Likewise, cerebral edema, limb stiffness, and limb paralysis are other neurological complications caused by COVID-19. In three different cases, a 66-year-old man, a 52-year-old man, and 61-year-old female with flaccid lower extremity paralysis were associated with acute flaccid myelitis related to COVID-19 [32,33,34]. In this case report, neither myelitis nor Guillain-Barré syndrome was detected in the pediatric patient, although the latter has been related to COVID-19 and affects myelin in the peripheral nerves, leading to paresis, muscle weakness, and even bilateral ascending paralysis . The limb stiffness and myoclonus in this case may have been generated by COVID-19 or as a consequence of brain edema .
A few cases of COVID-19 and dengue have been reported. In a study of 178 adult patients (> 18 years of age) in Brazil, 63% were diagnosed as positive for SARS-CoV-2 after RT-qPCR confirmation; from this percentage, 38.4% of patients were also positive for dengue coinfection by a dengue IgM test. A higher rate of pulmonary impairment and hospitalization were demonstrated in coinfection. The patients also showed lower levels of blood lymphocytes (30.52% vs 26.37%) and monocytes (7.76% vs 6.99%) .
Neither COVID-19 nor DENV disease has been shown to cause coronary artery ectasia (CAE). Degradation of the medial arterial layer by activation of serine proteinase in addition to matrix metalloproteinase (MMP) in the arterial smooth muscle cells generates CAE ; a study by Shi et al.  measured the levels of matrix metalloproteinase 3 in serum, comparing noninfected and infected patients with COVID-19, and found a significant difference in serum MMP3. Patients with COVID-19 have an increase in this enzyme, although a laboratory analysis of MMP3 in this case report was not available. COVID-19-induced elevations of MMP3 causing CAE is a hypothesis worth exploring.
Other relevant points are the high values of white blood cells (WBCs), as DENV disease causes leukopenia according to diverse studies [40, 41]. In the case of COVID-19, leukopenia and lymphopenia have been associated with severe COVID-19 and a negative outcome, mostly in adults [42, 43], although other studies confirmed that high white blood cells (WBCs) in patients with a medical history of myocardial infarction had higher leucocyte counts. Both lymphopenia and high WBC count have been correlated with increased C-reactive protein and mortality .
Infection caused by SARS-CoV-2 has been a major challenge for physicians due to its wide range of clinical manifestations. Diverse clinically approved drugs have been tested as potential anti-SARS-CoV-2 candidates . Antiviral drugs such as lopinavir/ritonavir (LPV/RTV) , remdesivir (RDV) , acyclovir ribavirin, umifenovir, azithromycin, and oseltamivir have been employed to treat SARS-CoV-2, although it is not yet clear whether the use of these antiviral agents is beneficial in improving the outcome of COVID-19 patients [45, 48]. In this case report, the patient was treated with acyclovir. Acyclovir is an agent with antiviral activity against herpes simplex virus (HSV). In a review of 90 articles, 11 articles reported laboratory-confirmed COVID-19 and HSV in 28 patients (7–28 age range) with HSV reactivation. Patients received antiviral therapy against HSV and COVID-19 management, with no mortality reported. The authors concluded that acyclovir could be considered a potential add-on treatment to the COVID-19 treatment regimen, although further clinical trials should be done . On the other hand, bacterial pathogens are an important cause of morbidity and mortality in viral respiratory tract infections. The prevalence, incidence, and characteristics of bacterial infection in patients with SARS-CoV-2 are not well understood and documented. As antibiotics are infective against SARS-CoV-2, they are prescribed in patients with COVID-19 due to the difficulty of ruling out bacterial coinfection or the possibility of bacterial secondary infection during the illness. The broad-spectrum antibiotics used are fluoroquinolones and third-generation cephalosporins in most cases . The pediatric patient in this case report was treated with third-generation cephalosporin and clindamycin to avoid coinfection or secondary infection with pathogenic bacteria.
It is worthwhile to address contraindications of nonsteroidal anti-inflammatory agents (NSAIDs), as these drugs can potentially increase bleeding risk . The patient received high doses after hospitalization. During hospitalization, the patient was prescribed acetylsalicylic after thrombocytopenia was stopped on day 16 of illness, although dengue results weren´t available at that moment and the medication was stopped as soon the positive result was received; the previous doses of acetylsalicylic (after and during hospitalization) might have triggered bleeding. These drugs could have been avoided if rapid tests for DENV had been done on time; unfortunately, hospital and laboratory capacity was limited due to the COVID-19 pandemic with a surplus of patients admitted, so rapid tests were not available.
The patient in this case report did not have all the symptomatology required for MIS-C caused by SARS-CoV-2, and he presented a coinfection with DENV-2, which may have aggravated the severity in both diseases resulting in effects not usually seen in children.
As the COVID-19 vaccine is still in trials and DENV is a national public health concern in Mexico, we may see more cases of coinfection of SARS-CoV-2 and DENV in pediatric patients in the near future; thus, the intention of this paper is to yield insight on behavior, management, and preparation for coinfection. As observed in this case report, not all medication given to this patient was appropriate, thus some symptoms could have been avoided. As clinicians, it is our duty to research the best options for our patients and their wellbeing, especially with a novel virus that is not well characterized in different scenarios. We hope that this case report will help physicians better treat coinfection between DENV and SARS-CoV-2 in pediatric patients.