Neonatal immune dysfunction, as well as neonatal lung development is not fully developed, vulnerable to the invasion of external pathogens[13]. Pathogens can be transmitted to newborns through droplets and contact[14]. Because of the complexity of the community environment and the variation in regions and seasons, the distribution of pathogens would also be different. In addition, the incidence of disease increases rapidly, which is also the focus of current research[15].
In our study, the peak incidence of RSV pneumonia occurred during the winter and early spring. Similar results were reported in our previous study with a subtropical climate[16, 17], the peak of RSV activity is in winter and spring seasons[17].
The current research showed that RSV and PIV3 were the major viral pathogens in neonatal community-acquired viral pneumonia, especially RSV. Few patients were infected with InfA or InfB. RSV was the main virus in term newborns. While, PIV3 was the main virus in preterm infants. Preterm infants are more likely to co-infect with bacteria than term infants, especially gram-negative bacteria, such as Klebsiella pneumoniae. Therefore, in clinical work, we can preliminarily distinguish potential pathogens for newborns with community-acquired pneumonia according to different populations of preterm and term infants, and select the targeted treatment schemes.
In the present study, patients with PIV3 infection were more likely to be infected with bacteria than patients with RSV infection (60.0% vs. 33.0%). Meanwhile, patients with other virus (InfA, InfB) infection were more likely to be infected with bacteria than patients with RSV infection (80.0% vs. 33.0%). Among RSV infected patients, preterm infants were more likely to be complicated with bacterial infection than term infants, the same trend was found in PIV3 infected infants. It suggested that preterm infants are more susceptible to be co-infected with bacteria than term infants. Therefore, in the clinic, when treating patients with PIV3 and other virus (InfA, InfB) infection, or preterm infants, we should be alert to the possibility of combined bacterial infection and relax the indications for the use of antibiotics on the basis of support and symptomatic treatment. For patients with RSV infection, antibiotics should be used as soon as a concurrent bacterial infection is found.
Not everyone with neonatal viral pneumonia will have prodromal symptoms, the incidence of which usually varies between 30% and 65% depending on the pathogen[18]. In this study, mild patients only showed symptoms of mild cough and low fever, while severe patients had serious cough, high fever, apnea, cyanosis, tachypnea, refusal to feed, vomit or diarrhea, three concave signs, increased moist rales and wheezing in the lungs, even complicated with respiratory failure, heart failure and air leak syndrome.
This study also showed that preterm infants are more susceptible to co-infection, especially for bacteria, which is related to a relative lower immune function in preterm infants[19, 20]. The trachea of premature infants is narrow, and the wall of trachea is easy to collapse. The abundant capillaries and weak ciliary movement function provide a good environment for the attachment and reproduction of pathogenic bacteria[21]. Because the immune system of premature infants is not fully developed, the immune function is low[22, 23]. Neonatal immune function, and especially that of the local airway, is also under‑developed with lower levels of secretory IgA, which serves an anti‑infectious role[24]. Fetal immunoglobulins are mostly transmitted from the mother, but this physiological process mainly occurs in the middle and late stages of pregnancy. The IgG level of full-term newborns can reach the maternal level[25]. Respiratory virus infection is often accompanied by bacterial infection[26]. Because the humoral and cellular immunity of premature infants at small gestational age are at a low level[19], and the damaged respiratory mucosa and inhibited immune function by respiratory viruses induces the risk of bacterial infection.. So newborns are easier to be infected by a variety of pathogen. Therefore, targeted measures, such as perinatal detection and health care should be taken to reduce the birth of premature infants. When pneumonia occurs in premature infants, the corresponding treatment measures, including respiratory support, immune support, enteral nutrition, parenteral nutrition support and sodium supplements should be actively adopted.
Hyponatremia is relatively common in pneumonia with one large Italian series reporting a rate of 45%[27]. In our study, the overall incidence of hyponatremia was 30.9% (116/375), however, the hyponatremia was mild in majority of cases, from 130 mmol/l to 135 mmol/l. Studies in the developing countries have shown this to be associated with increasing severity of pneumonia and risk of death. Factors increasing the risk of dehydration and potentially hyponatremia include reduced nutrient/water intake and increased evaporative losses as a result of both increased respiratory rate and increased core temperature. Sometimes it may be as a result of additional losses from vomiting and diarrhea. Pneumonia is widely cited as a potential cause of syndrome of inappropriate antidiuretic hormone secretion (SIADH)[28], but no studies have examined the biochemistry and pathophysiology of hyponatremia in children with pneumonia with sufficient rigor to be able to differentiate adequately between SIADH and salt depletion, therefore, hyponatremia has frequently been ascribed to the SIADH is now being questioned. Some scholars suspect that hyponatremia principally occurs secondarily to dehydration in most children considered as having SIADH. This has major implications for acute patient management as SIADH is managed with fluid restriction and dehydration clearly requires rapid volume replacement. Further studies are urgently required to address this question in the future.
In all patients involved in this study, the main pathogens that co-infected were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Streptococcus viridans, which were similar to other reports[29]. In addition, this article also found that in term infants with concurrent bacterial infections the symptoms are more severe and more likely to have respiratory failure. Some of these patients require not only oxygen support but also CPAP-assisted ventilation. Therefore, term infants with viral and bacterial infections are more severe than pure viral infections[30] [31], and more attention should be taken for respiratory management[32, 33] and supportive care. Once the results of NPA culture are confirmed (before those of drug sensitivity testing are clear), appropriate antibiotics for common bacteria can be empirically selected. After the report of bacterial drug sensitivity test, the type of antibiotics should be adjusted according to the treatment effect.
Neutrophils play an important and active role in the body's nonspecific immunity. In the present study, the total number of leukocytes in preterm infants combined with bacterial infection was numerically higher than that in preterm patients with simple virus infection, although the difference was not statistically significant, the proportion of neutrophils to WBC is lower than that in patients with simple virus infection (p < 0.05). The hospital stay in preterm infants combined with bacterial infection is also longer than that in preterm patients with simple virus infection. When bacteria and other microbial pathogens invade and inflammatory reaction occurs, they can reach the inflammatory site under the influence of chemokines, devour bacteria and tissue fragments, and prevent the diffusion of pathogenic microorganisms in the body[34]. When the inflammatory reaction is strong, a large number of neutrophils stored in bone marrow are released into the blood, and the level of neutrophils increases. However, neutrophils were depleted in bone marrow when the infection was very serious, resulting in the decrease of neutrophil expression level[35]. Therefore, when the proportion of neutrophils to WBC is reduced in preterm infants, the risk of bacterial infection may increase and prolong the hospital stay.