Is It Possible to Predict Respiratory Evolution in COVID-19 Patients?

COVID-19, the disease caused by the SARS-CoV-2 virus, is characterized by acute respiratory failure like ARDS with endothelial dysfunction and micro- and macrovascular involvement, requiring invasive mechanical ventilation in about 5–23% of the cases [1, 2, 3] with high mortality [3, 4]. Most of hospitalized patients have hypoxemic respiratory failure, are old, or have comorbidities [3]. The capability of preventing serious illness with early interventions or managing severe disease could be essential to improve the patients' outcomes. Better understanding of patients who will progress to acute respiratory insufficiency could help to better monitoring, correct time for possible medications, and choosing the best progressive respiratory support [5, 6]. Early detection of parameters that can predict poor prognosis of COVID-19 patients as old age, multiple comorbidities, high neutrophil-lymphocyte ratio, and severe hypoxemia at admission [7] can help to improve intensive assistance and monitoring.

COVID-19 patients that are hospitalized because of acute respiratory failure (20–40% patients) have viral pneumonia that can improve along time or evolve to ARDS, multiple organ failure, and death. These patients can also have complications as pulmonary embolism and secondary infections that must be diagnosed and treated [1, 2].

Monitoring of COVID-19 acute respiratory failure patients includes the following parameters: level of consciousness, capacity to protect the airways, respiratory drive and inspiratory muscles strength and endurance, respiratory rate, arterial gases with emphasis to PaO/FIO2 ratio, PaCO2 and pH, and respiratory imaging in COVID-19; a thoracic angiotomography can evaluate the lungs parenchyma as well as the pulmonary vascular bed, and a dual-energy tomography can also evaluate the lungs perfusion [8]. Systemic parameters such as arterial pressure, cardiac function (especially cardiac ischemia and arrhythmias), renal function, and hydric balance can be important parameters in specific patients.

In COVID-19 patients with acute respiratory failure, a new respiratory situation named happy or silent hypoxemia that has an atypical clinical presentation was reported. The patient is awake, alert, and comfortable, but present with hypoxemia (desaturation) without dyspnea and with near-normal lung compliance [9].

The role of different levels of hypoxemia, respiratory rate, and PaCO2 at admission as well as their evolution during hospital stay is not well understood. In this issue of Respiration, Maraziti and Bacattini [10] retrospectively analyzed 100 consecutive COVID-19 patients hospitalized because of acute respiratory failure regarding respiratory index (RI: SpO2/RR), ROX index (ROX: SpO2/FIO2/RR), PaO2/FIO2 ratio, and standard PaO2/FIO2 (ST P/F: 1.66 × PaCO2 + PaO2 − 66.4 mm Hg) at admission and during hospital stay before ICU admission. The authors analyzed the association among the RI, ROX, PaO2/FIO2 ratio, and ST P/F with hospital death as primary outcome and with death at 7 days or ICU admission as secondary outcome. The authors observed that 37 out of the 100 patients (37%) died during hospital stay, 25 out of the 100 patients (25%) were admitted to the ICU, 18 of whom died during ICU stay. The authors showed that RI, ROX, and PaO2/FIO2 at admission were independent predictors for death or ICU admission at 7 days, while ST P/F was not. They also observed that the decrease of RI, ROX, PaO2/FIO2 ratio, and ST P/F during hospital stay was independently associated with hospital death or ICU admission at 7 days. It is worthwhile to mention that the study also showed that older age was independently associated with hospital death.

What are the results of this paper by Maraziti and Bacattini [10] that could change our clinical practice trying to better monitoring the COVID-19 patients hospitalized with acute respiratory failure? First, it is important to measure and follow respiratory indexes like RI, ROX, and PaO2/FIO2 ratio at admission and their variation during hospital stay of COVID-19 patients with respiratory failure because their results at admission and their variation during hospital stay can predict the risk of ICU admission and death. Second, their results suggest that patients with ROX less than 3.85, RI less than 3.8, and PaO2/FIO2 less than 100 at admission could be admitted to intensive care unit for the best monitoring and respiratory support (early noninvasive ventilation? Early intubation and protective ventilation?), early measurement of viral load (low CT) and possible administration of antiviral drugs, measurement of inflammatory mediators like Il-6, C-reactive protein that can detect hyperinflammatory states and possible early administration of anti-inflammatory drugs. Finally, recently, the Recovery-RS randomized clinical trial [11] revealed that among COVID-19 patients with acute hypoxemic respiratory failure, an initial strategy of CPAP significantly reduced the risk of tracheal intubation and invasive mechanical ventilation or mortality compared with conventional oxygen therapy. Early initiation of NIV according to stratification based on admission respiratory indexes of severity of acute respiratory failure is worth of testing in COVID-19 patients as in other types of acute respiratory failure.

Limitations of the study included its retrospective nature that included only 100 consecutive patients with different ages (a well-known prognostic factor, older the age, worse the prognostic of the COVID-19 patient with acute respiratory failure). The authors included 25 out of 100 (25%) of do-not-resuscitate order patients that can per se have a poor prognosis that was confirmed by the authors' analysis that revealed a 54% of death of these patients compared with only 8% of survivors. Another issue that can be addressed was the choosing of the primary outcome (in hospital death) and the secondary outcomes (ICU admission or death at 7 days) that was not directly related to the acute respiratory failure itself and may be related to other factors such as infection, shock, and multiple organ failure. An outcome as necessity of intubation and invasive mechanical ventilation should be a better outcome to analyze the association of respiratory indexes and respiratory prognosis [6].

The novelty and one of the strengths of the study were the validation of the prognostic value of the RI index for COVID-19 patients with acute respiratory failure at admission and during hospitalization. (RI index was validated for pulmonary embolism [12, 13].) The other strength was the longitudinal evaluation of the indexes along the hospital stay. In the clinical practice, it is crucial to stratify the respiratory severity of the COVID-19 patient and other acute respiratory failure patients in order to admit the patient to the right place (ICU, intermediary care or ward), with the adequate monitoring and allocation of respiratory equipment. The best monitoring of patient's respiratory evolution inside the hospital is of uppermost importance to early detection of patient's deterioration and activation of the hospital multidisciplinary team response to adequate the best treatment and proceed to escalation of respiratory support [14]. In the future, it will be important to prospectively test the role of the measurement of the respiratory indexes and evaluate their evolution during hospital stay according to the possible intervention in the prognosis of COVID-19 patients with acute respiratory failure.

Conflict of Interest Statement

The authors have no conflict of interests regarding this commentary.

Funding Sources

The authors received no funding for this commentary.

Author Contributions

Carmen Silvia Valente Barbas and Bruno Franco Mazza planned and wrote the commentary.