SARS-CoV-2 / COVID-19 Research
Sincere thanks to the international community of scientists working to advance our understanding of SARS-CoV-2 and COVID-19. We appreciate your contribution in the global fight toward developing treatments that will save lives everywhere.
To increase translatability of in vitro COVID research, researchers must correct the discrepancy between oxygen conditions routinely provided for cell-based assays (room air) and O2 levels actually measured within the human body. In healthy pulmonary alveoli, oxygen levels are reported at around 12% O2. In pulmonary blood, oxygen tensions exist over the range: 5-12% O2. In pathologic situations such as COVID, where air exchange is compromised due to pneumonia or ARDS, tissue oxygen levels will be far lower. Both physiologic oxygen (physioxia) and pathophysiologic hypoxia occur at levels far below those assessed for room air (21% O2).
Why cell culture O2 levels impact COVID data relevance:
- ACE2 Expression is modified by in vitro Oxygen Levels and HIF-1a
- Cytokine Storm Interleukins, like IL-1 and IL-6, are regulated by Hypoxia and HIF Signaling
- Room Air Oxygen adds Artifact to in vitro Toxicity Assays in Airway Cells
- In vitro O2 Levels affect Oxidative Stress Response to common COVID Treatments like Acetaminophen
To complement cell-based research, scientists use animal models to gain further insight. In vivo hypoxic (or hyperoxic) exposures help provide understanding about coronavirus disease progression or to simulate ventilator-induced injury. Therapeutic models with nitric oxide and carbon dioxide (hypercapnia) are useful for exploring potential COVID-19 treatment options.
Better physiologic simulation always results in better data.
The ProOx C21 & C-Chamber system permits researchers to control static levels of O2/CO2 in subchambers that insert within existing cell culture incubators. Use two or more ProOx C21 & C-Chamber subchamber systems in a single incubator for comparison studies at multiple oxygen levels.
OxyCycler C42 & C-Chamber
Carry out cell-based models of dynamic hypoxia (or hyperoxia) with OxyCycler C42 & C-Chamber system in any existing CO2 incubator. Configure OxyCycler C42 & C-Chamber with up to two incubator subchambers for different O2 experiments at the same time.
The Xvivo System X2 combines bio-containment with simultaneous control of physiological or pathophysiologic conditions throughout your entire cell workflow. Protect people from infectious pathogens while also protecting in vitro assays from environmental disruptions that routinely occur in biosafety facilities where CO2 incubators open/close to room air and samples are transported to/from BSCs. Xvivo System X2 operates independent of facility HVAC and provides uninterrupted control of O2, CO2, Temp, pH, and RH through interconnecting incubators and cabinets that exhaust to a controlled remote destination.
Control static levels of either hypoxia or hyperoxia for in vivo modeling with the ProOx 360 & A-Chamber. Select from standard-size chambers or ask about custom sizes designed to meet your throughput needs or fit within precious vivarium space.
The OxyCycler A84XOV & A-Chamber precisely controls intermittent hypoxia profiles in COVID-19 research studies. Configure with 1-4 chambers to perform multiple, individually controlled protocols simultaneously. Optional Monitor Pod for OxyCycler A84XOV & A-Chamber detects and records environmental conditions (CO2 ppm, RH, & Temp) within one of the chambers.
Deliver precise nitric oxide levels for in vivo therapeutic models with OxyCycler AT42N & A-Chamber. Reproducibly carry out nitric oxide exposures with OxyCycler AT42N & A-Chamber over the range 1-300 parts per million (PPM).
Li Y, et al. Physiological and pathological regulation of ACE2, the SARS-CoV-2 receptor. Pharmacol Res. 2020 Apr 14:104833. [Epub ahead of print]
Joshi S, et al. Hypoxic regulation of angiotensin-converting enzyme 2 and Mas receptor in human CD34(+) cells. J Cell Physiol. 2019 Nov;234(11):20420-20431.
Zhang R, et al. Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):L631-40.
Mason RJ. Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J. 2020 Apr 16;55(4).
Kumar A, et al. Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiological levels. FEBS Lett. 2016 Jan;590(2):258-69.
Interview with Cytocentric Visionary: Ian Mudway, Lecturer – Respiratory Toxicology Lung Biology Group , King’s College London, Part One: What Are the Fundamental Things That We Absolutely Have To Get Right?
*new* Mini-review – Pivoting to COVID-19 Lung Research