ABSTRACT
Background and Aims: Prone positioning increases oxygenation by recruiting dorsal lung regions and draining airway secretions and improves gas exchange and survival in ARDS. We describe the efficacy of prone positioning in awake non-intubated spontaneously breathing COVID-19 positive patients with hypoxemic acute respiratory failure. Methods: We studied 26 awake non-intubated spontaneously breathing patients with hypoxemic respiratory failure treated with prone positioning. Patients were kept in prone position for two hours in each session and four such sessions were given to patients in 24 hours. SPO2, PaO, 2RR and haemodynamics were measured before prone positioning (PRE), 60 minutes of prone positioning (PRONE), and one hour after the completion of each session (POST). Results: 26 patients (12 males and 14 females) non-intubated spontaneously breathing with SPO2 <94% on 0.4 FiO2 were treated with prone positioning. One patient required intubation and was shifted to ICU, the rest (25 patients) were discharged from HDU. Mean hours of prone positioning were 19.4 ± 2.06 hr. There was significant improvement in oxygenation (increase in PaO2 from 53.15 ± 6.0 mmHg to 64.23 ± 6.96 mmHg in PRE and POST sessions respectively, likewise there was increase in SPO2). No complications were noted with various sessions. Conclusion: Prone positioning was feasible and improved oxygenation in awake non-intubated, spontaneously breathing COVID-19 patients with hypoxemic acute respiratory failure.
ABSTRACT
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading fast worldwide. There is a pressing need to understand how the virus counteracts host innate immune responses. Deleterious clinical manifestations of coronaviruses have been associated with virus-induced direct dysregulation of innate immune responses occurring via viral macrodomains located within nonstructural protein-3 (Nsp3). However, no substantial information is available concerning the relationship of macrodomains to the unusually high pathogenicity of SARS-CoV-2. Here, we show that structural evolution of macrodomains may impart a critical role to the unique pathogenicity of SARS-CoV-2. Using sequence, structural, and phylogenetic analysis, we identify a specific set of historical substitutions that recapitulate the evolution of the macrodomains that counteract host immune response. These evolutionary substitutions may alter and reposition the secondary structural elements to create new intra-protein contacts and, thereby, may enhance the ability of SARS-CoV-2 to inhibit host immunity. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection-driven epistasis in protein evolution. Our findings warrant further characterization of macrodomain-specific evolutionary substitutions in in vitro and in vivo models to determine their inhibitory effects on the host immune system.