key: cord-1025821-otuxjh5e
authors: Dominguez-Nicolas, S. M.; Manjarrez, E.
title: Low-field thoracic magnetic stimulation increases peripheral oxygen saturation levels in coronavirus disease (COVID-19) patients: a single-blind, sham-controlled, crossover study
date: 2021-05-25
journal: nan
DOI: 10.1101/2021.05.21.21256456
sha: d8e427e9c042ec8d0f2bdac50ea14a64597a9816
doc_id: 1025821
cord_uid: otuxjh5e

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause low oxygen saturation (SpO2) and respiratory failure in coronavirus disease (COVID-19) patients. Hence the increase of SpO2 levels could be crucial for the quality of life and recovery of these patients. Here we introduce an electromagnetic device termed low-field thoracic magnetic stimulation (LF-ThMS) system. This device was designed to non-invasively deliver a pulsed magnetic field from 100 to 118 Hz and 10.5 to 13.1 mT (i.e., 105 to 131 Gauss) to the dorsal thorax. We show that these frequencies and magnetic flux densities are safe for the patients. We also present a proof-of-concept that a single session of LF-ThMS applied for 30 minutes to the dorsal thorax of 17 COVID-19 patients significantly increases their SpO2 levels. We designed a single-blind, sham-controlled, crossover study on 5 COVID-19 patients who underwent two sessions of the study (real and sham LF-ThMS) and 12 COVID-19 patients who underwent only the real LF-ThMS. We found a statistically significant correlation between magnetic flux density, frequency, or temperature associated with the real LF-ThMS and SpO2 levels in all COVID-19 patients. However, the five patients of the sham-controlled study did not exhibit a significant change in their SpO2 levels during sham stimulation. All the patients did not present adverse events after the LF-ThMS intervention.

Although recent studies about the structure and function of SARS-CoV-2 may 70 help develop new targeted treatments against COVID-19, there is still not a universally 71 approved treatment for this sickness [1, 2] . For instance, some pharmacological 

Study design 125 We designed a single-blind, sham-controlled, crossover study on 5 COVID-19 126 subjects who underwent two sessions of the study (sham or real LF-ThMS) and 12 employed an electronic circuit in our LF-ThMS device to limit the temperature and 163 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) To generate the magnetic field, we used alternating current from 100 to 118 Hz and physically with a magnetic field sensor (475 DSP Gaussmeter, Lakeshore). We also 176 used a thermocouple sensor (model NTC 10k) for monitoring temperature changes due 177 to the LF-ThMS. Both the Gaussmeter and thermocouple sensors were helpful to 178 calibrate magnetic flux densities and temperatures in a safe range (Table 1) .

The main electronic components of the LF-ThMS device consist of a power relay 180 RL of two poles, a 12 Vcc coil, silver alloy contacts of Vcc/10A or 250 Vca/10A, Q NPN 181 2N2222 transistor, 10 kΩ resistance at 0.25 Watts, and a D IN4007 semiconductor 182 diode. We also employed a PCI-DAS6031 board to energize the RL at 10 Vcc and a 183 virtual instrument developed in Delphi Borland 7. Figure 1 shows the electronic circuit of 184 our LF-ThMS device, and Table 1 shows the frequency, magnetic flux density, and 185 temperature associated with the LF-ThMS during a 30 minutes single session.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) 187 The LF-ThMS was locally applied on the dorsal thorax while the patients were 188 kept in a prone position. The LF-ThMS intensity was successively increased every 5 min 189 during a single session of 30 min, following the values of frequency, magnetic flux 190 density, and temperature indicated in Table 1 Figure 2A illustrates anatomical landmarks and coordinates of the LF-ThMS rings. 198 We positioned the center of these LF-ThMS rings using palpable skeletal landmarks. We 199 employed the spinous process of C7 (i.e., vertebra prominens) as zero landmarks (see a 200 gray circle in Figure 2A ). The center of these rings was positioned 8.5 cm below this 201 landmark and bilaterally ± 6 cm on the dorsal thorax (see black arrows in Figure 2A ).

The device allowed a gradual increase in the frequency, magnetic flux density, 203 and temperature, as illustrated in Figure 2B , 2C, and 2D, respectively. The patients 204 rested for three hours after the session, and they did not report any discomfort during or 205 after the magnetic stimuli. In contrast, they felt more comfortable, mainly because the CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 25, 2021. ; https://doi.org/10.1101/2021.05.21.21256456 doi: medRxiv preprint Sham stimulation 211 The coils were positioned in the same coordinates for sham exposure, but the 212 pulse generator was not turned on. Subjects were blinded for the real LF-ThMS or sham 213 stimulation conditions. were obtained per subject. In this way, we were able to quantify the repeatability of 221 effects of LF-ThMS through the study in different patients.

Statistical analysis 223 We analyzed the statistical differences among the SpO2 levels related to each Moreover, a Pearson's product-moment correlation coefficient was employed to 232 examine whether there is a statistically significant linear correlation between SpO2 233 levels and frequency, magnetic flux density, and temperature changes during the LF-234 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

We measured the SpO2 level for all the patients before the LF-ThMS intervention. 242 We found that COVID-19 patients presented similar symptoms. On the first day of 243 magnetic stimulation, we found that the patients experienced difficulty breathing with a 244 low SpO2 level of 86.6 ± 2.2 % (N=17 patients), consistent with COVID-19 signs and 245 breathlessness symptoms. However, we found that during the LF-ThMS, the patients 246 exhibited a gradual increase in their SpO2 levels. No adverse events or discomfort 247 sensations were reported during or after the LF-ThMS. 250 In the controlled study, we observed no statistically significant changes in SpO2 251 levels during sham stimulation (five subjects, Figure 3A ). We performed parametric one- 

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 25, 2021. ; https://doi.org/10.1101/2021.05.21.21256456 doi: medRxiv preprint However, during the real LF-ThMS, we observed statistically significant changes 258 in SpO2 levels in response to real LF-ThMS in 5 COVID-19 subjects who previously 259 underwent sham stimulation (green triangles and green line; Figure 3B ) and in the other 260 12 COVID-19 subjects who underwent only the real LF-ThMS (orange circles and gray 261 line; Figure 3B ). We performed parametric one-way repeated-measures ANOVA to 262 examine statistical significance between groups: "control SpO2 levels" and "SpO2 levels 274 In the controlled study, we also examined whether SpO2 levels exhibited Adverse events 293 We did not find adverse effects during or after the LF-ThMS intervention. We also 294 made a follow-up on the health conditions of all the patients. We found that five days 295 after successive LF-ThMS sessions, the mean SpO2 level was 98.3 ± 0.7 % for 17 296 patients (Table 3) . We also found a mean SpO2 level of 98.4 ± 0.8 %, for 11 patients, six 297 months after the LF-ThMS intervention (Table 3) . Such normal SpO2 levels indicate that 298 the LF-ThMS did not produce adverse events in the oxygen saturation. In the follow-up 299 on the general health conditions after five days or six months, the physicians confirmed 300 that the patients did not exhibit any adverse event or secondary effect after the LF- 370 Finally, because the inflammation and cytokine storm are the main factors 371 contributing to breathing, ventilation, and oxygenation, in COVID-19 patients, it will be 372 necessary to examine in future studies whether the LF-ThMS has an impact on these 373 factors.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 25, 2021. ; https://doi.org/10.1101/2021.05.21.21256456 doi: medRxiv preprint 375 The first potential advantage of the thoracic LF-ThMS is that the subjects did not 376 require oxygen therapy with face masks, mainly because during the LF-ThMS session, 377 the patients significantly increased their SpO2 levels 20 minutes after the LF-ThMS 378 (p<0.001, Table 2 ). The second advantage is that the device for LF-ThMS is easy to 379 reproduce, and the electronic components are not expensive. It may be possible that Another limitation of our study is that it will be necessary to know the real Table 1 . Variables associated with the LF-ThMS (frequency, magnetic flux density, 594 temperature) and the mean SpO2 levels in 17 COVD-19 patients. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 25, 2021. ; https://doi.org/10.1101/2021.05.21.21256456 doi: medRxiv preprint CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 25, 2021. ; https://doi.org/10.1101/2021.05.21.21256456 doi: medRxiv preprint

Review of registered 447 clinical trials for the treatment of COVID-19

Novel immunogenomic insights of corona virus 450 disease (COVID-19): Available potential immunotherapeutics, current challenges, 451 immune cell recognition and ongoing managerial strategies

Therapeutic management of patients 454 with COVID-19: a systematic review. Infection Prevention in Practice

COVID-19): Therapeutic repurposing and unmet 458 clinical needs

 703 We declare that all relevant ethical guidelines have been followed and ethics committee 704 approval has been obtained. All necessary patient/participant consent has been 705 obtained. SPIRIT-Checklist was included as a supplementary file.