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A 60-year-old woman presents to hospital in St. Petersburg, Russia, with symptoms of SARS-CoV-2 infection for the previous 14 days, including persistent dry cough, weakness, and intermittent fever. She also notes that she has been urinating much less than usual.

Clinicians confirm SARS-CoV-2 infection by a reverse-transcription polymerase chain reaction (nasal swab) test. Physical examination findings are unremarkable, except for dry mucous membranes, sinus tachycardia, prolonged capillary refill time, and the oliguria. Comorbidities include obesity and arterial hypertension, with blood pressure of 158/90 mm Hg.

The patient is admitted to the hospital and after a laboratory workup, the medical team starts the standard treatment for COVID-19 according to the hospital protocols in use at that time, including low molecular weight heparin, hydroxychloroquine, and azidothymidine/zidovudine.

Her symptoms continue to worsen, however -- she is increasingly short of breath, her dry cough becomes more frequent, and she reports abdominal pain and loose stool.

Two days after being admitted (on day 16 of infection onset), the patient's decreasing peripheral oxygen saturation (SPO₂) falls to 92% on room air. At this point, clinicians order the first of a series of computerized tomography (CT) scans to be performed at 5-day intervals.

SpO₂ follow-up scan performed 21 days after the onset of infection shows a steady increase in lung lesions with evidence of bilateral lung consolidations.

On day 23, in response to the patient's declining clinical status – indicated by her permanent need for high-flow supplemental oxygen via facial mask and imminent respiratory failure – clinicians initiate high-frequency percussive ventilation (HFPV) therapy, which combines mechanical ventilation with high-frequency oscillatory ventilation.

The patient receives HFPV at 8-hour intervals for 1 week. After 3 days, her clinical status shows improvement, and her need for supplemental oxygen decreases. On day 27 after infection onset, a CT scan shows significant resolution of the previously severe lung lesions.

At 29 days after initial symptoms, the patient's SPO₂ on room air is 97%-99%. Clinicians discontinue her supplemental oxygen, and 4 days later, she is discharged from the ward, without ever requiring admission to the intensive care unit (ICU).

Discussion

This case is included in a of three cases showing that intermittent adjunctive treatment with HFPV in patients with severe COVID-19 pneumonia not only improved lung function but also appeared to prevent further clinical deterioration.

Cases 2 and 3 were men ages 65 and 72 who were admitted to the hospital 10 days after the onset of SARS-CoV-2 infection symptoms. All three patients presented with clinical deterioration accompanied by worsening lung lesions shown on CT scans about 3 weeks after symptom onset. The patients also had impending respiratory failure when intermittent HFPV therapy was initiated, and showed significant clinical improvement and visible decreases in lung lesions on follow-up CT scans 4-6 days later.

COVID-19 is an important novel cause of acute respiratory distress syndrome (ARDS) characterized by hypoxemic respiratory failure, most commonly due to pneumonia, sepsis, and aspiration. The distinct time course, imaging, and laboratory features from the time of infection to hypoxemic respiratory failure may allow prior to or at earlier stages of ARDS, the case authors explain.

Research describing the stages of COVID-19 pneumonia and patterns observed on lung CT scan has identified ground-glass opacities, intralobular and/or interlobular septal thickening, reticular pattern, consolidation, and linear opacities as occurring most frequently, with these variations occurring separately or in combination as the disease runs its course.

The authors note that lung involvement generally increases rapidly during the first 8-9 days after initial symptoms start, with lung lesions reaching a peak within approximately 14-21 days. The following week (21-28 days from disease onset) – the absorption phase – is typically characterized by gradual reduction in the extent and intensity of lung lesions, in cases with favorable outcomes.

Conversely, patients with worsening lung lesions along with clinical deterioration about 4 weeks after disease onset are at risk for respiratory failure and ICU admittance. Thus, particularly in these high-risk patients, the focus is on of respiratory failure and ARDS, as well as cardiac injury and coagulopathies.

The prevalence of hypoxic respiratory failure in patients with COVID-19 is 19%. suggest that adults suffering from COVID-19-related acute hypoxemic respiratory failure despite conventional oxygen therapy would benefit more from high-flow nasal cannula than conventional oxygen therapy, the case authors note.

The guidelines panel issued a strong recommendation against using oxygen to target SpO₂ over 96%, as well as avoiding lower values (SpO₂ less than 90%). Therefore, a reasonable SpO₂ range for patients receiving oxygen is 92-96%.

The recommendations stress the importance of timely treatment when patients show clinical deterioration and are at high risk of imminent respiratory failure, with elevated inflammatory markers and expanding areas of lung damage.

Therapeutic measures are therefore vital to reduce interstitial and intra-alveolar edema and recruitment of collapsed alveoli, to decrease intrapulmonary right-to-left shunting, and to improve oxygenation without causing lung over-distention, the authors state.

They note that this may be effectively achieved with a treatment that uses low volumes of oxygen with high frequency to prevent sharp increases in pressure, high flow to reach peripheral lung areas, and low pressure (to prevent barotrauma) to reach heterogeneously damaged lung areas.

As viral pneumonia moves through its stages, the lungs are affected by heterogeneous lesions and areas with different compliance, the case authors explain. Standard ventilator strategies using positive end expiratory pressure recruit non-aerated alveoli and help promote homogeneity of lung volume distribution. There is a risk, however, of over-distention of normal alveolar spaces leading to barotrauma.

All three patients in the report received HFPV using the IPV-2C Percussionaire Intrapulmonary Percussive Ventilation device. In addition, as the authors explain, HFPV using the Phasitron® device allows the recruitment of collapsed alveoli by delivering the optimal volume and pressure of air required by the alveolar space without over-distention of compartments with normal compliance -- "a very important issue to consider in mechanically heterogeneous lungs."

While the patients were in hospital when HFPV therapy was initiated, they were still dependent on oxygen and showing signs of clinical deterioration and impending respiratory failure -- i.e., evidence of clinical decline -- and findings of repeated lung CT scans indicated the need for more aggressive treatment, including HFPV therapy.

After the HFPV sessions were initiated, the patients were able to breathe more easily and there were clear signs of improved gas exchange, along with evidence of fewer lung lesions on CT scans. This stopped respiratory deterioration and hence, the need for admission to the ICU, while allowing these still severely ill patients to be managed on the ward, the authors stated.

"HFPV was beneficial in our patients because it allowed the recruitment of collapsed alveoli using high flow and frequency and accommodating the optimal volume and pressure of air required by the alveolar space," the authors wrote. "Due to the associated risk of aerosol spreading, HFPV was performed in a single room with the minimum number of required healthcare workers wearing adequate personal protection equipment to minimize staff exposure."

Conclusions

The authors conclude that the use of HFPV led to clinical improvement in all three patients in the report, showing that the use of intermittent adjunctive treatment with HFPV in patients with severe COVID-19 pneumonia may have prevented clinical deterioration. In the current context of pandemic-related ICU bed shortages, avoiding ICU admission by using adjunctive therapies on the ward is extremely important.

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