By Stuart H. Ditchek, MD, FAAP
As we all know, with the exception of high-risk children with underlying serious medical conditions, children have been spared from the terrible deadly outcomes seen in adult COVID-19 victims. The same infection that has ravaged adults of all ages has been virtually unnoticed in children including newborns. I have cared for several COVID-19 positive newborns born to mothers who had the disease at the time of birth. None have had any sequelae of the infection, not even a fever or a cough.
This clinical peculiarity should not go unnoticed by those of us who are caring for seriously sick COVID-19 patients. By definition, newborns are at-risk for ALL infections at birth and for six weeks post-natal. If is for this reason that we take great care in not exposing newborns to even the most benign viral infections such as colds. Pregnant mothers are given a whooping cough booster and an influenza vaccine prior to delivery to protect the newborn for the first three months. Babies who develop fever under one month of age are always urgently assessed and tested for possible infections that can threaten their lives. Newborns by definition are immune compromised. Despite that compromise, they seem to have little or no sequelae of the potentially deadly COVID-19 infection. Certainly these newborns benefit from the mothers immune response to COVID-19 but is that the entire story?
In recent days, I have constructed a position statement that we need to revisit initial emergency respiratory protocols regarding COVID-19 seriously sick patients. The focus has been to redefine the current assumption that COVID-19 patients suffer from classical ARDS (Adult Respiratory Distress Syndrome). My research and contention is that the early stage critically ill COVID-19 patients resemble the more classical neonatal ARDS seen in premature infants. This is a different disease with dramatically different management. I now refer to this as COVID-19 ARDS or CARDS, a distinctly different radiological and management scenario than the current classical ARDS assumptions.
Serial X-rays and CT scans on CARDS patients are much more similar to premature neonatal lung disease both in appearance and in clinical behavior. My contention is now being adopted by some is that the initial ventilator management of high pressure ventilation is in fact causing damage to these very sick patients. The emergency and urgent intubation and ventilation in the minutes following respiratory failure have demonstrated clues and shortfalls in the current care. Under normal circumstances, the X-ray of respiratory failure with pneumonia and classical ARDS pre-intubation show many areas of atelectatsis (collapsed portions of the lung) and poor air entry. In almost every normal intubation scenario, the first X-ray done after inserting an endotracheal tube shows improvement of the previously collapsed areas reflecting better oxygenation of the lungs. In COVID-19 patients, many ICU clinicians have observed the post-intubation X-ray as being worse than the pre-intubation film. This is a critical observation which should immediately lead us to question why that paradoxical observation is occurring so frequently. In addition, as previously demonstrated, many X-rays then show very rapid appearance of multi-focal peripheral opacities post-intubation. It is believed that these opacities represent the areas now known as “cytokine storms” where the patient’s own immune system attacks itself or inflammatory overreaction. It is very likely that the high pressures used both intentionally and inadvertently during urgent intubation are forcing oxygen to areas of the lung which are just not ready or able to accept it. These areas that are unable to accept high pressures are likely being damaged during this process. In the years before we understood the role of surfactant deficiency in premature babies, similar errors were made in ventilation protocols. Today, premature neonates are ventilated gently and meticulously via high-frequency oscillatory ventilation (HFOV) which prevents areas of the lung from being damaged inadvertently. In essence, we have to start viewing the COVID-19 adult lungs as similar to premature neonatal lung disease.
How does that possible mechanism work and why does this have the unique relationship to COVID-19 infection never previously experienced? The answer lies in the infection mechanism and the resulting damage to critical alveolar cells called penumocytes. COVID-19 enters the human body through the respiratory tract. The virus transits towards the alveolar penumocyte cells where it “hijacks” the cell. It uses the pneumocyte to reproduce and wreak havoc at the alveolar areas of the lung or the gas exchange sites where respiration occurs. Once infected, the pneumocyte cell is damaged and can no longer function. The primary function of the pneumocyte cell is to produce a phospholipid called surfactant which is critical for the exchange of oxygen and carbon dioxide. Pulmonary surfactant reduces surface tension at the air-liquid interface of the alveolus preventing its collapse during end- exhalation. In addition, surfactant participates and is primarily linked to host defenses against inhaled pathogens (Nkadi et al). This is specifically why COVID-19 is so successful at attacking humans. It’s a near perfect killing machine that destroys both the immune function of the surfactant producing pneumocyte as well as the oxygen exchange activity of the alveoli. It is surely no coincidence that Hydroxychloroquine which has possible beneficial effects in these patients increases surfactant production in lungs in addition to its direct effect reducing the viral load.
For many years, premature infants have been treated with two very successful modalities to overcome this surfactant challenge, HFOV and inhaled surfactant therapy. My statement remains that centers treating seriously sick COVID-19 patients consider immediate live trials utilizing minimal pressure intubation strategies followed by HFOV ventilator settings. In addition, centers should consider immediate research submissions for treatment with surfactant therapy for both the intubated patient as well as via nebulization for those not yet intubated but moderately sick. These are not radical nor farfetched conclusions and should be taken seriously as we are losing so many patients under the current established ICU protocols.
The clues needed to improve COVID-19 survival might very well lie with the children who have been spared of this deadly virus. It would not be the first time in my career that I have learned important lessons from children. Let’s look to them now.
Stuart H. Ditchek, MD, FAAP
Board Certified Pediatrician