Modified respiratory rate oxygenation index: an early warning index for the need of intubation in COVID-19 patients with high-flow nasal cannula therapy

Background High-flow nasal cannula oxygen therapy (HFNC) is recommended for COVID-19 patients. However, the increasing use of HFNC brings a risk of delayed intubation. The optimal timing of switching from HFNC to invasive mechanical ventilation (IMV) remains unclear. An effective predictor is needed to assist in deciding on the timing of intubation. Respiratory rate and oxygenation (ROX) index, defined as (SpO2/FiO2)/respiratory rate, already show good diagnostic accuracy. Modified ROX (mROX) index, defined as (PaO2/FiO2)/respiratory rate, might be better than the ROX index in predicting HFNC failure. Objective The aim was to evaluate the predictive value of mROX for HFNC failure in COVID-19 patients. Methods Severe or critical COVID-19 patients treated with HFNC were enrolled in two clinical centers. Laboratory indicators, respiratory parameters, and mROX index at 0 h and 2 h after initial HFNC were collected. Based on the need of IMV after HFNC initiation, the patients were divided into the HFNC failure group and the HFNC success group. The predictive value of mROX index for IMV was evaluated by the area under the receiver operating characteristic curve (AUROC) and logistic regression analysis. We performed Kaplan–Meier survival analysis using the log-rank test. Results Sixty COVID-19 patients (mean age, 62.8 ± 14.1 years;42 males) receiving HFNC were evaluated, including 18 critical and 42 severe cases. A total of 33 patients had hypertension;14 had diabetes;17 had chronic cardiac disease;11 had chronic lung disease;13 had chronic kidney disease;and 17 had a history of stroke. The AUROC of mROX index at 2 h was superior than that of other respiratory parameters to predict the need of IMV (0.959;P < 0.001). At the mROX index cutoff point of 4.45, predicting HFNC failure reached the optimal threshold, with specificity of 94% and sensitivity of 92%. Logistic regression analysis showed that 2-h mROX index below 4.45 was a protective factor for IMV (OR 0.18;95% CI, 0.05 to 0.64;P = 0.008). In the HFNC failure group, the median time from HFNC to IMV was 22.5 h. The 28-day mortality of the late intubation patients (≥22.5 h) was higher than that of the early intubation patients (<22.5 h) (53.8% vs 8.3%, P = 0.023). Conclusion mROX at 2 h is a good early warning index for the need of IMV in COVID-19 patients after HFNC initiation. Early intubation may lead to better survival in patients with 2-h mROX index below 4.45.

Engineered soluble ACE2 receptor: Responding to change with change.

SARS coronavirus 2 (SARS-CoV-2) invades the human body by binding to major receptors such as ACE2 via its S-spike protein, so the interaction of receptor-binding sites has been a hot topic in the development of coronavirus drugs. At present, the clinical progress in monoclonal antibody therapy that occurred early in the pandemic is gradually showing signs of slowing. While recombinant soluble ACE2, as an alternative therapy, has been modified by many engineering methods, both the safety and functional aspects are approaching maturity, and this therapy shows great potential for broadly neutralizing coronaviruses, but its progress in clinical development remains stalled. Therefore, there are still several key problems to be considered and solved for recombinant soluble ACE2 to be approved as a clinical treatment as soon as possible.

Engineered soluble ACE2 receptor: Responding to change with change

SARS coronavirus 2 (SARS-CoV-2) invades the human body by binding to major receptors such as ACE2 via its S-spike protein, so the interaction of receptor-binding sites has been a hot topic in the development of coronavirus drugs. At present, the clinical progress in monoclonal antibody therapy that occurred early in the pandemic is gradually showing signs of slowing. While recombinant soluble ACE2, as an alternative therapy, has been modified by many engineering methods, both the safety and functional aspects are approaching maturity, and this therapy shows great potential for broadly neutralizing coronaviruses, but its progress in clinical development remains stalled. Therefore, there are still several key problems to be considered and solved for recombinant soluble ACE2 to be approved as a clinical treatment as soon as possible.

Adaptive Evolution of the Fox Coronavirus Based on Genome-Wide Sequence Analysis.

Purpose: To report the first complete fox coronavirus (CoV) genome sequence obtained through genome-wide amplifications and to understand the adaptive evolution of fox CoV. Methods: Anal swab samples were collected from 35 foxes to detect the presence of CoV and obtain the virus sequence. Phylogenetic analysis was conducted using MrBayes. The possibility of recombination within these sequences was assessed using GARD. Analysis of the levels of selection pressure experienced by these sequences was assessed using methods on both the PAML and Data Monkey platforms. Results: Of the 35 samples, two were positive, and complete genome sequences for the viruses were obtained. Phylogenetic analysis, using Bayesian methods, of these sequences, together with other CoV sequences, revealed that the fox CoV sequences clustered with canine coronavirus (CCoV) sequences, with sequences from other carnivores more distantly related. In contrast to the feline, ferret and mink CoV sequences that clustered into species-specific clades, the fox CoV fell within the CCoV clade. Minimal evidence for recombination was found among the sequences. A total of 7, 3, 14, and 2 positively selected sites were identified in the M, N, S, and 7B genes, respectively, with 99, 111, and 581 negatively selected sites identified in M, N, and S genes, respectively. Conclusion: The complete genome sequence of fox CoV has been obtained for the first time. The results suggest that the genome sequence of fox CoV may have experienced adaptive evolution in the genes replication, entry, and virulence. The number of sites in each gene that experienced negative selection is far greater than the number that underwent positive selection, suggesting that most of the sequence is highly conserved and important for viral survive. However, positive selection at a few sites likely aided these viruses to adapt to new environments.

Back Cover: Therapeutic antibodies under development for SARS-CoV-2 (View 2/2022)

Research on antibody therapy for SARS-COV-2 is in the ascendant, including single antibody therapy and multiple antibody combinations. The multi-drug combination is also called an antibody cocktail, which relies on different antibodies to target different epitopes so it can avoid immune escape caused by mutations in a better way and achieve a better curative effect. In article number 20200178, Shi Hu and co-workers have portrayed antibody cocktails as a kind of cocktails which is a mixture of different liqueurs in different colors. As the last drop of liquid is added, a cocktail specially tuned to hit the virus will be finished.

Therapeutic antibodies under development for SARS-CoV-2.

The world is experiencing one of the most difficult moments in history with COVID-19, which has rapidly developed into a worldwide pandemic with a significant health and economic burden. Efforts to fight the virus, including prevention and treatment, have never stopped. However, no specific drugs or treatments have yet been found. Antibody drugs have never been absent in epidemics such as SARS, MERS, HIV, Ebola, and so on in the past two decades. At present, while research on the SARS-CoV-2 vaccine is in full swing, antibody drugs are also receiving widespread attention. Several antibody drugs have successfully entered clinical trials and achieved impressive therapeutic effects. Here, we summarize the therapeutic antibodies against SARS-CoV-2, as well as the research using ACE2 recombinant protein or ACE2-Ig fusion protein.

Corrigendum: Identification of Diverse Bat Alphacoronaviruses and Betacoronaviruses in China Provides New Insights Into the Evolution and Origin of Coronavirus-Related Diseases.

[This corrects the article DOI: 10.3389/fmicb.2019.01900.].