SARS-CoV-2 from alpha to epsilon: As battles to contain the COVID-19 pandemic continue, attention is focused on emerging variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that have been deemed variants of concern because they are resistant to antibodies elicited by infection or vaccination or they increase transmissibility or disease severity. Three papers used functional and structural studies to explore how mutations in the viral spike protein affect its ability to infect host cells and to evade host immunity. Gobeil et al . looked at a variant spike protein involved in transmission between minks and humans, as well as the B1.1.7 (alpha), B.1.351 (beta), and P1 (gamma) spike variants; Cai et al . focused on the alpha and beta variants; and McCallum et al . discuss the properties of the spike protein from the B1.1.427/B.1.429 (epsilon) variant. Together, these papers show a balance among mutations that enhance stability, those that increase binding to the human receptor ACE2, and those that confer resistance to neutralizing antibodies. —VV

Critical COVID-19 is a life-threatening disease characterized by severe hypoxemia with complex pathophysiological mechanisms that are not yet completely understood. A pathological shift in the oxyhemoglobin curve (ODC) was previously described through the analysis of p50, intended as the oxygen tension at which hemoglobin is saturated by oxygen at 50%. The aim of this study was to analyze Hb-O₂ affinity features over time in a cohort of critically ill COVID-19 patients, through the analysis of ODC p50 behavior. A retrospective analysis was performed; through multiple arterial blood gas (ABG) analyses, each p50 was calculated and normalized according to PaCO₂, pH and temperature; patients’ p50 evolution over time was reported, comparing the first 3 days (early p50s) with the last 3 days (late p50s) of ICU stay. A total of 3514 ABG analyses of 32 consecutive patients were analyzed. The majority of patients presented a left shift over time (p = 0.03). A difference between early p50s and late p50s was found (20.63 ± 2.1 vs. 18.68 ± 3.3 mmHg, p = 0.03); median p50 of deceased patients showed more right shifts than those of alive patients (24.1 vs. 18.45 mmHg, p = 0.01). One-way ANOVA revealed a p50 variance greater in the early p50s (σ² = 8.6) than in the late p50s (σ² = 3.84), associated with a reduction over time (p < 0.001). Comparing the Hb-O₂ affinity in critically ill COVID-19 patients between ICU admission and ICU discharge, a temporal shift in the ODC was observed.

Introduction: Nasogastric tube (NGT) placement is a procedure commonly performed in mechanically ventilated (MV) patients. Chest X-Ray is the diagnostic gold-standard to confirm its correct placement, with the downsides of requiring MV patients’ mobilization and of intrinsic actinic risk. Other potential methods to confirm NGT placement have shown lower accuracy compared to chest X-ray; end-tidal CO₂ (ETCO₂) and pH analysis have already been singularly investigated as an alternative to the gold standard. Aim of this study was to determine threshold values in ETCO₂ and pH measurement at which correct NGT positioning can be confirmed with the highest accuracy. Materials & methods: This was a prospective, multicenter, observational trial; a continuous cohort of eligible patients was allocated with site into two arms. Patients underwent general anesthesia, orotracheal intubation and MV; in the first and second group we respectively assessed the difference between tracheal and esophageal ETCO₂ and between esophageal and gastric pH values. Results: From November 2020 to March 2021, 85 consecutive patients were enrolled: 40 in the ETCO₂ group and 45 in the pH group. The ETCO₂ ROC analysis for predicting NGT tracheal misplacement demonstrated an optimal ETCO₂ cutoff value of 25.5 mmHg, with both sensitivity and specificity reaching 1.0 (AUC 1.0, p < 0.001). The pH ROC analysis for predicting NGT correct gastric placement resulted in an optimal pH cutoff value of 4.25, with mild diagnostic accuracy (AUC 0.79, p < 0.001). Discussion: In patients receiving MV, ETCO₂ and pH measurements respectively identified incorrect and correct NGT placement, allowing the identification of threshold values potentially able to improve correct NGT positioning. Trial registration: NCT03934515 (www.clinicaltrials.gov).

We would like to thank Böning et al. for all the important issues raised in the present commentary

Introduction: The COVID-19 pandemic required careful management of intensive care unit (ICU) admissions, to reduce ICU overload while facing limitations in resources. We implemented a standardized, physiology-based, ICU admission criteria and analyzed the mortality rate of patients refused from the ICU. Materials and methods: In this retrospective observational study, COVID-19 patients proposed for ICU admission were consecutively analyzed; Do-Not-Resuscitate patients were excluded. Patients presenting an oxygen peripheral saturation (SpO₂) lower than 85% and/or dyspnea and/or mental confusion resulted eligible for ICU admission; patients not presenting these criteria remained in the ward with an intensive monitoring protocol. Primary outcome was both groups’ survival rate. Secondary outcome was a sub analysis correlating SpO₂ cutoff with ICU admission. Results: From March 2020 to January 2021, 1623 patients were admitted to our Center; 208 DNR patients were excluded; 97 patients were evaluated. The ICU-admitted group (n = 63) mortality rate resulted 15.9% at 28 days and 27% at 40 days; the ICU-refused group (n = 34) mortality rate resulted 0% at both intervals (p < 0.001). With a SpO₂ cut-off of 85%, a significant correlation was found (p = 0.009), but with a 92% a cut-off there was no correlation with ICU admission (p = 0.26). A similar correlation was also found with dyspnea (p = 0.0002). Conclusion: In COVID-19 patients, standardized ICU admission criteria appeared to safely reduce ICU overload. In the absence of dyspnea and/or confusion, a SpO₂ cutoff up to 85% for ICU admission was not burdened by negative outcomes. In a pandemic context, the SpO₂ cutoff of 92%, as a threshold for ICU admission, needs critical re-evaluation.

Introduction: nasogastric tube (NGT) placement is a common procedure performed in critical care setting. Chest X-Ray is the diagnostic gold-standard to confirm correct placement, with the downsides of both the need for critical care patients’ mobilization and intrinsic actinic risk. Other potential methods to confirm NGT placement have shown lower accuracy compared to chest X-ray; ETCO ₂ and pH analysis have singularly yet investigated as an alternative to the gold standard. Aim of this study was to determine thresholds in combine measurements of ETCO ₂ and pH values, at which correct NGT positioning can be confirmed with the highest accuracy. Material & Methods: a prospective, multicenter, observational trial; a continuous cohort of eligible patients was allocated to two arms, to identify clear cut-off threshold able to detect correct NGT tip positioning with the maximal accuracy. Patients underwent general anesthesia and orotracheal intubation; in the first group difference between tracheal and esophageal ETCO ₂ values were assessed. In the second group difference between esophageal and gastric pH values were determined. Results: from November 2020 to March 2021, 85 consecutive patients were enrolled: 40 in the ETCO ₂ group and 45 in the pH group. The ETCO ₂ ROC analysis for predicting NGT tracheal misplacement demonstrate an optimal ETCO ₂ cutoff value of 25.5 mmHg, where both sensitivity than specificity reach 1.0 (AUC 1.0, p < 0.001). The pH ROC analysis for predicting NGT correct gastric placement demonstrated the optimal pH cutoff value at 4.25, with a mild diagnostic accuracy (AUC 0.79, p < 0.001). Discussion: A device capable of combining the presence of a negative marker with a positive marker could be accurate enough in identifying the correct NGTs positioning. Further studies are required to validate the reproducibility of these results by a specific device, whose accuracy also ought to be compared with standard chest X-ray. Trial number: NCT03934515 ( www.clinicaltrials.gov )