According to earlier studies, the incubation period of COVID-19 infections varies from 1 to 14 days, frequently in the range of 3 to 7 days (approximately 5.2 days) (
19,
34,
46). Age of onset in children is estimated to range from 1.5 months to 17 years, with most cases having familial transmission (
49). Accordingly 93.5% of infected children were reported in family clusters (
38). At the onset of the disease, the most common symptoms are fever, fatigue, dry cough and diarrhea (
28,
46,
50). Most of the pediatric cases represent low to moderate fever, and in some cases no fever (
50). Other symptoms include headache, sputum production, dyspnea, lymphopenia, and hemoptysis (
45,
51-
53). Chest CT scans reveal clinical features presented as pneumonia, and in more severe cases, abnormal features such as acute respiratory distress syndrome (ARDS) (
52). As the infection progresses, after about 1 week, dyspnea, cyanosis and other related symptoms can appear, and they can be accompanied by systemic toxic symptoms such as restlessness (malaise), loss of appetite and reduced activity (
50). The disease progression in some children might be rapid and result in respiratory failure. In these severe cases, even, irreversible bleeding (and coagulation dysfunction), metabolic acidosis and septic shock are possible (
50). Muscle ache, headache, confusion, rhinorrhea, sore throat, sputum production, nausea (and vomiting) and chest pain have been reported as symptoms of COVID-19 infection (
28,
39,
52).
According to guidelines for diagnosis and treatments for COVID-19 published by the National Health Commission of China, based on the severity of symptoms, COVID-19 is classified to 4 levels (
28):
6.3. Severe
Patients with severe symptoms may represent one of the following criteria (
28):
1) Dyspnea, RR > 30 times/min (In children: RR ≥ 70/min (in children with younger than 1 year), RR ≥ 50/min (in children older than 1 year) (
50));
2) Oxygen saturation < 93% in ambient air (< 90% in premature infants (
50));
3) PaO2/FiO2 < 300 mmHg.
In another article, some other criteria have been attributed to this stage of disease (
50), such as:
1) Intercostal, subcostal and suprasternal retractions, nasal flaring, apnea, cyanosis and etc.
2) Blood gases: PaCO2 > 50 mmHg, PaO2 < 60 mmHg.
3) Consciousness impairment: lethargy, restlessness, convulsion, coma, etc.
4) Nourishment problems: Poor appetite, poor feeding, and even dehydration.
5) Myocardial damage: Increased level of myocardial enzyme, cardiomegaly, electrocardiogram ST-T changes and even cardiac insufficiency in severe cases.
6) Other manifestations: coagulation disorders (prolonged prothrombin time (PT) and elevated level of d-dimer), gastrointestinal dysfunction, rhabdomyolysis and raised levels of liver enzymes.
6.4. Critical
Critical patients may exhibit one or more of the following conditions (
28):
1) Respiratory failure (patients represent acute respiratory distress syndrome (ARDS) and refractory hypoxemia, which is irresponsible to conventional oxygen therapy, such as oxygen mask or nasal catheter (
50));
2) Septic shock;
3) Multiple organ failure;
There have been a few reports about COVID-19 infection in newborns as well. According to Shen et al. (
19) no newborns delivered from infected mothers have been shown to be COVID-19 positive (
19). There were no infections among newborns until the publication of their work in until January 29th 2020. However, by March 1st, 2020, Lu et al. (
2) reported three newborns with COVID-19 mainly as part of family cluster cases. A 17 days old newborn diagnosed with COVID-19 showed cough, fever and milk vomiting. His mother was infected as well (
55). The second (birth to 1 month) presented with fever on 5th day after birth. In this case the mother was infected as well (
45). The third case whose mother was infected, was silent and diagnosed 30 hours after birth by the viral nucleic acid test (
54). From these, we understand that milk vomiting, shortness of breath, fever and cough are symptoms of COVID-19 infection in neonates (birth to 1 month). The vital signs of these neonates were found to be stable. There have also not been any severe emergency cases (
49,
55-
57). On the other hand, maternal hypoxemia as a result of severe infection could cause premature delivery, intrauterine asphyxia and other further risks. Neonates, specifically preterm newborns, may represent non-specific symptoms, which requires careful observation (
50).
It has been found that most pediatric cases show mild symptoms, without any sign of pneumonia or fever. They mostly have good prognosis and, within 1 - 2 weeks after disease onset, they recover fully (
58). Only a few cases have presented infections in their lower respiratory tract (
19). According to Shen et al. (
19) despite the generally mild cases in children, the probable risk of death in pediatric population must not be ignored. During epidemics of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), ARDS and death happened among pediatric patients as well (
12,
59-
61). It is also important to know that the data from these studies have been conducted based on a limited number of patients, and therefore, continuous observation of further cases is recommended. (
Table 1).
| Chen et al. | Henry et al. | Cai Jiehao et al. | Wei Xia et al. | Zheng et al. (58) |
|---|
| Fever, % | 45.2 | 68.0 | 70.0 | 60.0 | 40.4 |
| Cough, % | 41.9 | 36.0 | 60.0 | 65.0 | 48.1 |
| Nasal congestion, % | 9.7 | | 30.0 | | |
| Pharyngitis, % | 6.5 | 12.0 | 40.0 | 5.0 | 5.8 |
| Rhinorrhea, % | 6.5 | 8.0 | 20.0 | 15.0 | |
| Fatigue, % | 6.5 | | | 5.0 | 9.6 |
| Diarrhea, % | | 4.0 | | 15.0 | 1.9 |