Asymptomatic Hypoxemia as a Characteristic Symptom of Coronavirus Disease: A Narrative Review of Its Pathophysiology

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a pandemic and caused a huge burden to healthcare systems worldwide. One of the characteristic symptoms of COVID-19 is asymptomatic hypoxemia, also called happy hypoxia, silent hypoxemia, or asymptomatic hypoxemia. Patients with asymptomatic hypoxemia often have no subjective symptoms, such as dyspnea, even though hypoxemia is judged by objective tests, such as blood gas analysis and pulse oximetry. Asymptomatic hypoxemia can lead to acute respiratory distress syndrome, and the delay in making a diagnosis and providing initial treatment can have fatal outcomes, especially during the COVID-19 pandemic. Thus far, not many studies have covered asymptomatic hypoxemia. We present a review on the human response to hypoxemia, focusing on the respiratory response to hypoxemia rather than the pathophysiology of lung injury arising from SARS-CoV-2 infection. We have also discussed whether asymptomatic hypoxemia is specific to SARS-CoV-2 infection or a common phenomenon in lung-targeted viral infections.

Inhibiting SARS-CoV-2 infection in vitro by suppressing its receptor, angiotensin-converting enzyme 2, via aryl-hydrocarbon receptor signal.

Since understanding molecular mechanisms of SARS-CoV-2 infection is extremely important for developing effective therapies against COVID-19, we focused on the internalization mechanism of SARS-CoV-2 via ACE2. Although cigarette smoke is generally believed to be harmful to the pathogenesis of COVID-19, cigarette smoke extract (CSE) treatments were surprisingly found to suppress the expression of ACE2 in HepG2 cells. We thus tried to clarify the mechanism of CSE effects on expression of ACE2 in mammalian cells. Because RNA-seq analysis suggested that suppressive effects on ACE2 might be inversely correlated with induction of the genes regulated by aryl hydrocarbon receptor (AHR), the AHR agonists 6-formylindolo(3,2-b)carbazole (FICZ) and omeprazole (OMP) were tested to assess whether those treatments affected ACE2 expression. Both FICZ and OMP clearly suppressed ACE2 expression in a dose-dependent manner along with inducing CYP1A1. Knock-down experiments indicated a reduction of ACE2 by FICZ treatment in an AHR-dependent manner. Finally, treatments of AHR agonists inhibited SARS-CoV-2 infection into Vero E6 cells as determined with immunoblotting analyses detecting SARS-CoV-2 specific nucleocapsid protein. We here demonstrate that treatment with AHR agonists, including FICZ, and OMP, decreases expression of ACE2 via AHR activation, resulting in suppression of SARS-CoV-2 infection in mammalian cells.

Hypoxia-dependent signaling in perioperative and critical care medicine.

A critical goal of patient management for anesthesiologists and intensivists is to maintain oxygen homeostasis in patients admitted to operation theaters and intensive care units. For this purpose, it is imperative to understand the strategies of the body against oxygen imbalance-especially oxygen deficiency (hypoxia). Adaptation to hypoxia and maintenance of oxygen homeostasis involve a wide range of responses that occur at different organizational levels in the body. These responses are greatly influenced by perioperative patient management including factors such as perioperative drugs. Herein, the influence of perioperative patient management on the body's response to oxygen imbalance was reviewed with a special emphasis on hypoxia-inducible factors (HIFs), transcription factors whose activity are regulated by the perturbation of oxygen metabolism. The 2019 Nobel Prize in Physiology or Medicine was awarded to three researchers who made outstanding achievements in this field. While previous studies have reported the effect of perioperatively used drugs on hypoxia-induced gene expression mediated by HIFs, this review focused on effects of subacute or chronic hypoxia changes in gene expression that are mediated by the transcriptional regulator HIFs. The clinical implications and perspectives of these findings also will be discussed. Understanding the basic biology of the transcription factor HIF can be informative for us since anesthesiologists manage patients during the perioperative period facing the imbalances the oxygen metabolism in organ and tissue. The clinical implications of hypoxia-dependent signaling in critical illness, including Coronavirus disease (COVID-19), in which disturbances in oxygen metabolism play a major role in its pathogenesis will also be discussed.

Estimation of the Number of General Anesthesia Cases Based on a Series of Nationwide Surveys on Twitter during COVID-19 Pandemic in Japan: A Statistical Analysis.

Background and objectives: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread to more than 200 countries. In light of this situation, the Japanese Government declared a state of emergency in seven regions of Japan on 7 April 2020 under the provisions of the law. The medical care delivery system has been under pressure. Although various surgical societies have published guidelines on which to base their surgical decisions, it is not clear how general anesthesia has been performed and will be performed in Japan. Materials and Methods: One of the services provided by the social network service Twitter is a voting function-Twitter Polls-through which anonymous surveys were conducted. We analyzed the results of a series of surveys 17 times over 22 weeks on Twitter on the status of operating restrictions using quadratic programming to solve the mathematical optimizing problem, and public data provided by the Japanese Government were used to estimate the current changes in the number of general anesthesia performed in Japan. Results: The minimum number of general anesthesia cases per week was estimated at 67.1% compared to 2015 on 27 April 2020. The timeseries trend was compatible with the results reported by the Japanese Society of Anesthesiologists (correlation coefficient r = 0.69, p < 0.001). Conclusions: The number of general anesthesia was reduced up to two-thirds during the pandemic of COVID-19 in Japan and was successfully quantitatively estimated using a quick questionnaire on Twitter.

Critical Care Demand and Intensive Care Supply for Patients in Japan with COVID-19 at the Time of the State of Emergency Declaration in April 2020: A Descriptive Analysis.

Background and objectives: The coronavirus disease 2019 (COVID-19) pandemic is overwhelming Japan's intensive care capacity. This study aimed to determine the number of patients with COVID-19 who required intensive care and to compare the numbers with Japan's intensive care capacity. Materials and Methods: Publicly available datasets were used to obtain the number of confirmed patients with COVID-19 undergoing mechanical ventilation and extracorporeal membrane oxygenation (ECMO) between 15 February and 19 July 2020 to determine and compare intensive care unit (ICU) and attending bed needs for patients with COVID-19, and to estimate peak ICU demands in Japan. Results: During the epidemic peak in late April, 11,443 patients (1.03/10,000 adults) had been infected, 373 patients (0.034/10,000 adults) were in ICU, 312 patients (0.028/10,000 adults) were receiving mechanical ventilation, and 62 patients (0.0056/10,000 adults) were under ECMO per day. At the peak of the epidemic, the number of infected patients was 651% of designated beds, and the number of patients requiring intensive care was 6.0% of ICU beds, 19.1% of board-certified intensivists, and 106% of designated medical institutions in Japan. Conclusions: The number of critically ill patients with COVID-19 continued to rise during the pandemic, exceeding the number of designated beds but not exceeding ICU capacity.

[SARS-CoV-2 infection and the hyperinflammatory response/cytokine storm : what determines the outcome of the winner?]

The COVID-19 pandemic caused by SARS-CoV-2 infection is still sweeping the world, and the excessive inflammatory response induced by SARS-CoV-2 correlates with the severity of illness in infected patients. The resulting acute respiratory distress syndrome (ARDS) is a major cause of death. Acute pulmonary injury and ARDS associated with sepsis may be familiar to anesthesiologists and intensivists who are the readers of LiSA. At the time of writing, the date of this article is June 2020.