The COVID-19 pandemic in a paediatric population: A health care perspective

During the COVID-19 pandemic, transmission from individuals has been significant. Virus incubation time and serial interval time are understood to be five to six days and eight days, respectively. These numbers are similar to the SARS and MERS outbreaks. The case fatality for COVID-19 is understood to be in the range of 0.9% to 3% [49], which is significantly less compared with SARS-CoV and MERS-COV, which ranged from 6% to 17% and 20% to 40%, respectively.

Several studies suggested that younger individuals, especially the paediatric population, have a milder severity of infection compared with relatively older individuals. COVID-19–positive paediatric population has been mostly asymptomatic. Moreover, the percentage of the paediatric population having a mild or moderate illness is 5.9%, which is significantly less compared with that of the adults, for which the corresponding percentage is 18.5%. Probable causes for younger individuals having lower infection rates and severity could be limited virus exposure, higher seclusion by staying at home, and relatively less exposure to cigarette smoke and pollution (thereby leading to better respiratory health). A diminished immune response is one factor that renders senior citizens more vulnerable to COVID-19. Interaction between infected individuals could potentially trigger lesser replication of the virions due to rivalry. Additionally, the working, expression, and other aspects of viral receptors, such as Angiotensin-Converting Enzyme-2 (ACE2) could be the determinants of age-specific vulnerability to severe forms of COVID-19 infection. [27,50,51,52]

Relatively fewer cases of severe COVID-19 illness in children are a challenge to precisely determining the clinical aspects of illness, which is compounded by an absence of biomarkers to ascertain disease severity. [53] Dong Y et al. [37] examined 2,143 children, of whom 13% were determined to be COVID-19 positive were asymptomatic. Epidemiological extrapolation is challenging since the likelihood of asymptomatic individuals being tested is lower, which is one reason that potentially promotes the spread of the disease. Children could also be suffering from other infections, which may render the detection of COVID-19 inconsequential from a clinical standpoint. The COVID-19 infection prognosis could be worsened by weight gain and cigarette smoke exposure. [53]

COVID-19 infection originated from a wet market in Wuhan, China, having passed from a bat to a person via an intermediary host, such as a pangolin. The most common mode of human-to-human transmission is direct or indirect contact with virus-laden respiratory droplets circulated by infected persons while sneezing or coughing.

COVID-19 has a similar mode of transmission, in which a person comes into contact with fomites, such as an infected patient's clothes or hands, dining utensils, door handles, counter surfaces, and other objects touched, soiled, or used by the infected person, causing respiratory droplets to be spread. SARS-CoV-2 is not thought to be able to penetrate the keratin layer of healthy human skin, but it is thought to enter the body through mucosal surfaces when contaminated hands come into contact with the eyes, nose, or mouth.

According to observations, it is expected that C0VID-19–positive paediatric populations are secondary cases infected through contact with any COVID-19 positive adult. There is a major scope for intra-family spread. [42] It is yet to be found whether COVID-19 infection can be transmitted through contact with infected stools. [54–55] According to a study, 80% of children who were COVID-19 positive per tests done through nasopharyngeal swabs continued to show repeat positive results for Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) of rectal swabs, even after their nasopharyngeal swabs turned out to be negative. [36] However, it cannot be claimed with certainty that the identification of virus by RT-PCR in faecal waste characterized by viral genomic components or lively viral replication is a characteristic symptom for COVID-19. However, it does imply that viral shedding from the stomach lasts longer and is of more significance than that from the lungs.

Three series of COVID-19 cases were reported for paediatric patients in Wuhan, where 171, 20, and 10 patients became symptomatic after an incubation period ranging from 2 to 14 days. [34,42,56] Positive diagnosis was made using the RT-PCR test on 171 children, where the reported symptoms were dry cough (48.5%), sore throat (46.2%), fever (41.5%), tachypnoea (28.7%), diarrhoea (8.8%), runny nose (7.6%), tiredness (7.6%), and vomiting (6.4%). This study revealed that 15.8% of the paediatric patients were asymptomatic, while 19.3% and 64.9% of the patients were found to have disorders of the upper respiratory tract, and pneumonia, respectively. [42]

In an evaluation of 2,143 paediatric individuals, 34% had COVID-19, which was confirmed through laboratory tests, while the remaining individuals were only suspected to be ill. [37] Among the paediatric patients, 12.9% were asymptomatic. On the other hand, 43.1% of the patients had mild illness compared with 41% who were moderately ill. Of the patient pool, 2.5% had a severe illness, while 0.4% were critical. Paediatric subjects having a confirmed COVID-19 diagnosis exhibited slower progression compared with the suspected population, which indicates that the illness caused by COVID-19 could be less severe compared with other respiratory disorders. The minimum time between infection onset and the confirmed diagnosis was 48 hours. For paediatric patients having a severe or critical form of the illness, the incidence was 10.6% for infants less than 12 months of age, while it was 7.3%, 4.2%, and 4.1% for children of 1–5 years, 6–10 years, and 11–15 years, respectively. Individuals over 15 years of age had an incidence of 3.0%. These numbers suggest that infants are more susceptible to COVID-19 infection when compared with older children. The individuals considered as having a severe form of the illness had complaints of hypoperfusion and hypoxemia after seven days of onset. Common symptoms of COVID-19 in the paediatric population include liver dysfunction, septic shock, myocarditis, disseminated intravascular coagulation, Acute Respiratory Distress Syndrome (ARDS), and acute kidney injury. [57] In the context of Chinese paediatric patients, the predicted mortality rate was 0% for children up to 9 years of age, while for those of 10–19 years of age, the mortality rate was 0.18%, both of which are very low compared with the 2.3% for adults in the 70–79 years age bracket. [49]

The oral cavity is the first interaction point between the human body and the external environment. Viral colonization of the oral cavity has a significant role in catching a viral infection. The mucosa of the tongue has a high expression of ACE-2.

In the context of COVID-19 infection, oral health is affected indirectly, though it is multi-directional and manifests itself as an immune response. Acute COVID-19 infection and the associated treatment may potentially affect oral health due to the highly susceptible oral mucosa and the compromised immune response of the body. It is crucial to know that the cytokine storm created as a result of the dysregulation of humoral and cellular processes could lead to autoimmune disorders in the oro-pharyngeal region. Health deterioration due to infection and side effects of treatment could lead to oral lesions by way of opportunistic infection.

Decreased ability to taste is a common symptom of COVID-19. The changes in taste could be attributed to the viral interaction with the ACE-2 receptors through which the virions enter the cells. The epithelial cells of the oral mucosa have a strong presence of ACE-2 receptors. Other oral symptoms include xerostomia and chemosensory disturbance. Paediatric patients are reported to have ulcers in the oral cavity due to COVID-19; however, the pathogenesis remains unknown. Therefore, it is crucial to investigate oral alterations using oral examination on COVID-19–positive paediatric patients. [58–59]

Nasopharyngeal RT-PCR tests and the throat swab tests are proposed as diagnostic tests for determining the presence of COVID-19 nucleic acid, which confirms COVID-19 infection. [28] Samples for RT-PCR testing may also be obtained by using bronchoalveolar lavage and endotracheal secretions.

The paediatric population has lesser lymphocytopenia and an increase in inflammatory markers compared with COVID-19–positive adults; however, there are inadequate data to ascertain the reasons for such observations. Henry BM and team [28] evaluated 12 studies and reported that 69.2% of COVID-19 positive children had normal leucocyte levels. On the other hand, 6% had reduced neutrophils, 4.6% had increased neutrophils, and 3% of the population had reduced lymphocytes. Among paediatric patients, about 13.6% were observed to have elevated C-reactive protein (CRP) levels, while 10.6% had higher levels of procalcitonin. Therefore, lymphocytes, CRP, and procalcitonin are important markers of severe COVID-19 illness and their levels must be ascertained to make a positive diagnosis of COVID-19 and other infections.

While chest x-rays are nonspecific for the paediatric population, those suffering from a mild form of COVID-19 should not be subjected to Computed Tomography (CT) of the chest because of the risks of radiation exposure. [60] CT scans reveal ground-glass opacity for about one-third of the paediatric population. There have also been reports of peripherally distributed lung lesions with multilobar involvement [61] COVID-19 positive children exhibit consolidation with an associated halo, as observed on the CT images. It is challenging for clinicians to use chest CT images as conclusive evidence of COVID-19 infection since several illnesses have similar radiological indications. Plasma levels of IL-2, IL-7, and IL-10 are shown to be elevated in paediatric patients with serious COVID-19 disease. In addition, levels of interferon-gamma-inducible protein 10 (IP10), granulocyte colony-stimulating factor (GCSF), tumour necrosis factor (TNF), alpha monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1 alpha (MIP1A) are higher in COVID-19 patients.

Until now, there has been no concrete proof of the efficacy and safety of particular medications against COVID-19. In one case study, 36 children were given interferon twice a day via aerosol and 14 of them were also given lopinavir-ritonavir syrup. It was impossible to infer the influence of the antiviral drug since this was an observational trial with no monitoring arm and all of the children had mild-to-moderately severe disease. [38] Various antivirals and immunomodulatory medications, such as chloroquine, azithromycin, remdesivir, tocilizumab, and convalescent plasma therapy, were attempted in a recent report on children admitted to the ICU with COVID-19. [36]

In the initial course of infection, antiviral therapy is expected to be successful. Since there is currently insufficient evidence, immunomodulatory therapy may be recommended only where there is strong evidence of hyperinflammation or in the second step of the disease. On a case-by-case basis, compassionate off-label care can be offered. Off-label treatment of antivirals, immunomodulatory agents, immunoglobulins, and even convalescent plasma therapy have been reported anecdotally. [36,38]