Non-invasive evaluation of the endothelial and microvascular dysfunction induced by COVID-19
SARS-CoV-2 is the respiratory pathogen causing the infectious disease COVID-19. Common mild symptoms are dry coughing, fatigue and fever but in more severe appearances shortness of breath, persistent chest pain, confusion, loss of appetite and high temperatures can be experienced.
Please seek professional medical care immediately if you feel affected by any of these symptoms [1].
Four out of five diagnosed COVID-19 patients recover without hospital treatment but approximately 20% becomes seriously ill and will require oxygen, an estimated 5% will need an admission to the intensive care unit [2]. Respiratory failure and Acute Respiratory Distress Syndrome (ARDS) are among others associated complications that may lead to death.
To provide professional intensive care specifically fit to cure COVID-19, hospitals need the appropriate space and equipment. Not only breathing devices, but also computers, educated staff and logistical organization is needed to save the lives of patients. Health care professionals have been working with limited resources in extreme environments but knowledge and experience is rapidly expanding.
To increase chances of survival and reduce the negative long-term effects like fatigue and shortness of breath, appropriate healthcare in the form of respiratory management and hemodynamics support is essential [3]. Several institutes have been implementing Near InfraRed Spectroscopy to study the endothelial and microvascular dysfunction to support the development of targeted and individualized therapies. Non-invasively evaluating the oxygenation can provide answers related to the prognosis of the disease and efficiently managing the respiratory support.
The paper: ‘Microvascular reactivity is altered early in patients with acute respiratory distress syndrome’ by Vincent et al., 2016 [4], sparkled the interest of Dr. Marco Pagliazzi, a postdoctoral fellow at ICFO Medical Optics group. During a brainstorm session, the link between the oxygenation of the microvasculature and the acute respiratory distress syndrome was addressed resulting in the start of the hemocovid-19 project [5].
This video created by ICFO (Spain) introduces the HEMOCOVID-19 project, an international initiative led by ICFO and Hospital Parc Taulí testing the efficiency of personalized treatments targeting the health of the smallest blood vessels [6].
Vincent et al. found that the severity of ARDS directly relates to an altered peripheral microvascular reactivity. A Vascular Occlusion Test (VOT) was performed with a NIRS probe attached to the thenar eminence. During three minutes of occlusion baseline TSI, minimum and maximum TSI values, total hemoglobin and the ascending and descending slopes were measured for 27 healthy volunteers and 32 ARDS patients.
Figure 1 shows the significant differences in the slope of the ascent in TSI derived from NIRS during a vascular occlusion. During a vascular occlusion, no oxygen is provided to the tissue by the arteries or conveyed away by the veins, the decrease in TSI thus results from the oxygen uptake by the muscle. Desaturation reflects the local oxygen uptake and upon releasing the cuff resaturation can be studied to quantify the post occlusive microcirculatory vascular hyperemia. With NIRS being able to non-invasively monitor the existence, severity and predictive implications of early microcirculatory alterations it shows to be a valuable tool in the assessment of COVID-19 patients.
Figure 1, Ascending slope in TSI % per minute during VOT in healthy subjects and patients with ARDS. Figure 1a, visualizing 27 healthy volunteers and according to evolution 16 good and 16 poor evolving patients. Figure 1b visualizing 27 healthy volunteers and according to survival status 24 survivors and 8 non survivors (this graph is based on the data derived from Vincent et al., 2016 [4]).
With research on the microvascular involvement in COVID-19 expanding and being widely accepted as one of the key elements, the next step is assessing how Near InfraRed Spectrocopy can help in finding answers.
Figure 2 shows how NIRS can be, and already is, implemented during several stages over the course of the disease and care.
Figure 2, Schematic overview of NIRS implementation throughout ICU admission, image from the hemocovid-19 project.
The initial check by the triage nurse upon arrival in the hospital includes evaluation of the endothelial dysfunction and heart-lung interaction to assess the urgency of the situation. The main decision at this time is whether mechanical ventilation (MV) will improve the patient’s wellbeing. If decided to move to the Intensive Care Unit (ICU) under MV, NIRS was used to study the effectiveness of protective ventilatory strategies and therapy selection. Yang et al. [7] showed that approximately 11% of the patients undergoing MV require prone positioning. NIRS can be included to quantify the position-related oxygen deficiencies and quickly adjust the patient’s position if needed [8]. During the third stage implementation of NIRS during the winding down of the ICU ventilator is addressed. In general ICU patients, extubation failure is common symptom experienced by 1 out of 5 patients. The expected prevalence in COVID 19 is even higher since not all ICU patients experienced respiratory difficulties. With NIRS one can monitor the tolerance to spontaneous breathing, which if done appropriately, can eventually decrease the prevalence of extubation failure. In the follow-up of ICU COVID 19 patients, NIRS can be potentially used as a guide and assessment tool in determining which daily activities can be reperformed without limitations.
These are several examples how the endothelial and microvascular dysfunction can be evaluated with Near infrared Spectroscopy. Published work with NIRS in COVID is scarce, going from alternative approaches as for example the publication by Schober et al. [9] who studied the effect of MV on the viability of lingual tissue with aid of a NIRS probe on the tongue, to editorial letters as for example by Marco Ferrari and Valentina Quaresima who recently openly replied [10] on the exhaustive review ‘happy’ hypoxemia in COVID-19 by Dhont et al. published in BMC Respiratory Research [11]. They advocated to implement cerebral oximetry as an approach which to the best of their knowledge has not been implemented yet in COVID 19, although this could serve as an early warning indicator.
As Artinis we are proud to be able to contribute our devices to be used by the researchers who effortlessly work to expand the knowledge base of COVID-19. We wish everyone well and hope this pandemic is under control quickly. If you want to know more about how we as Artinis deal with the COVID-19 measures, please visit our COVID webpage.
References:
[1] Rijksinstituut voor Volksgezondheid en Milieu (RIVM), COVID-19 (nieuwe coronavirus), 2020 https://www.rivm.nl/coronavirus-covid-19 consulted at 14-12-20 website last modified 11-12-2020 | 10:40
[2] World Health Organization (WHO), Coronavirus disease (COVID-19) pandemic, 2020 https://www.who.int/emergencies/diseases/novel-coronavirus-2019 Consulted at 14-12-20 website last modified 14-12-2020 | 10:25
[3] Fan E., Beitler J.R., Brochard L., Calfee C.S., Ferguson N.D., Slutsky A.S., Brodie D., (2020) COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted?, The Lancet Respiratory Medicine, 8(8), 816-821, https://doi.org/10.1016/S2213-2600(20)30304-0.
[4] Orbegozo Cortés, D., Rahmania, L., Irazabal, M., Santacruz, C., Fontana, V., De Backer, D., Creteur, J., & Vincent, J. L. (2016). Microvascular reactivity is altered early in patients with acute respiratory distress syndrome. Respiratory research, 17(1), 59. https://doi.org/10.1186/s12931-016-0375-y (Visualized data (fig. 1) is in compliance with http://creativecommons.org/publicdomain/zero/1.0/)
[5] Hemocovid-19 http://hemocovid19-project.org/ Consulted at 14-12-20 Website last modified 2-12-20 | 13:08
[6] HEMOCOVID-19 – ICFO, (2020) https://vimeo.com/432453723. Video uploaded 25-6-2020 | 6:40
[7] Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H., Wu Y., Zhang L., Yu Z., Fang M., Yu T., Wang Y., Pan S., Zou X., Yuan S., Shang Y., (2020) Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study, The Lancet Respiratory Medicine, 8 (5), 475-481, https://doi.org/10.1016/S2213-2600(20)30079-5.
[8] Pelosi P., Brazzi L., Gattinoni L., (2002),Prone position in acute respiratory distress syndrome. European Respiratory Journal, 20 (4) 1017-1028; DOI: 10.1183/09031936.02.00401702
[9] Schober, P., Lust, E. J., Heunks, L. M. A., & Schwarte, L. A. (2020). Thinking Out-of-the-Box: A Non-Standard Application of Standard Pulse-Oximetry and Standard Near-Infrared Spectroscopy in a COVID-19 Patient. Journal of Intensive Care Medicine. https://doi.org/10.1177/0885066620965167
[10] Ferrari, M., Quaresima, V. Hypoxemia in COVID-19: cerebral oximetry should be explored as a warning indicator for mechanically ventilated adults with COVID-19. Respir Res 21, 261 (2020). https://doi.org/10.1186/s12931-020-01530-w
[11] Dhont, S., Derom, E., Van Braeckel, E. et al. The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respir Res 21, 198 (2020). https://doi.org/10.1186/s12931-020-01462-5
