key: cord-1031895-izbyhprv
authors: Motta, L. P.; Silva, P. P. F.; Borguezan, B. M.; Amaral, J. L. M.; Milagres, L. G.; Boia, M. N.; Ferraz, M. R.; Mogami, R.; Nunes, R. A.; Melo, P. L. d.
title: An emergency system for monitoring pulse oximetry, peak expiratory flow and body temperature of patients with COVID-19 at home: Development and preliminary application
date: 2020-12-11
journal: nan
DOI: 10.1101/2020.12.11.20247650
sha: a9fb1f2279bfd3460b673e546f9a9b1aacd2f421
doc_id: 1031895
cord_uid: izbyhprv

Background COVID-19 is characterized by a rapid change in the patients condition, with major changes occurring over a few days. Our aim was to develop and evaluate an emergency system for monitoring patients with COVID-19, which may be useful in hospitals where more severe patients stay in their homes. Methodology/Principal findings The system consists of the home-based patient unit, which is set up around the patient and the hospital unit, which enables the medical staff to telemonitor the patients condition and help to send medical recommendations. The home unit allows the data transmission from the patient to the hospital, which is performed using a cell phone application. The hospital unit includes a virtual instrument developed in LabVIEW environment that is able to provide a real-time monitoring of the oxygen saturation (SpO 2 ), beats per minute (BPM), body temperature (BT) and peak expiratory flow (PEF). Abnormal events may be fast and automatically identified. After the design details are described, the system is validated by a 30-day home monitoring study in 12 controls and 12 patients with COVID-19 presenting asymptomatic to mild disease. Patients presented reduced SpO 2 (p<0.0001) and increased BPM values (p<0.0001). Three patients (25%) presented PEF values between 50 and 80% of the predicted. Three of the 12 monitored patients presented events of desaturation (SpO 2 <92%). The experimental results were in close agreement with the involved pathophysiology, providing clear evidences that the proposed system can be a useful tool for the remote monitoring of patients with COVID-19. Conclusions An emergency system for home monitoring of patients with COVID-19 was developed in the current study. The proposed system allowed us to quickly respond to early abnormalities in these patients. This system may contribute to conserve hospital resources for those most in need, while simultaneously enabling early recognition of patients under acute deterioration, requiring urgent assessment.

We are experiencing a global pandemic due to COVID-19 of devastating consequences. 36

The highly infectious pathogen that causes COVID-19, SARS-CoV-2, has infected most 37 of the countries in the world, with over 62.7 million confirmed cases, and just under 38 1.460 .000 deaths as of December 1, 2020 [1] . 39

As the hospital environment becomes more crowded, the criteria for hospital 40 admission become progressively stricter and, as a consequence, more severe patients stay 41 in their homes awaiting improvement or worsening. It was pointed out previously that a 42 rapid clinical deterioration may occur in the initial phase of COVID-19, due to the 43 development of arterial hypoxemia without a concomitant increase in work of breathing 44

[2]. This can prevent an adequate perception by the patient of the real magnitude of the 45 problem. In this context, patients have emerged who silently and rapidly decompensate 46 respiratory function at home, progressing to death even before receiving specialized care. 47

Thus, it is essential to obtain severity markers, especially to predict and prevent the 48 evolution to hospitalization in ICU and death. In this emergency scenario, a consensus 49 has emerged in the literature on the need to institute home monitoring of these patients 50 [3] [4] [5] , enabling early identification of those who deteriorate acutely and require urgent 51 assessment. 52

In this context, our aim was to develop an emergency system for monitoring 53 patients with COVID-19, which may be useful in hospitals where more severe patients 54 stay in their homes. We hypothesized that an emergency system based on a smart phone 55 application and specific instruments that allows oxygen saturation, body temperature and 56 peak expiratory flow could be useful as a COVID-19 home-monitoring tool in clinical 57 practice. 58 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint Previous studies describing the physiological changes in COVID-19 have shown 109 rapid reductions in lung volumes in the presence of edema [8, 21] , which highlights the 110 importance of monitoring the PEF of these patients. However, there is no previous studies 111 concerning the use of PEF in COVID-19. 112 113

The general architecture of the system is reported in Figure 1 . The system consists mainly 115 of two parts: 1) the home-based patient unit, which is set up around the patient to acquire 116 data and to receive medical recommendations, and 2) the hospital unit, which enables the 117 medical staff to telemonitor the patient's condition and help to send medical 118 recommendations. 119 120 Insert Figure 1  121 122 Considering the urgency of patient care, the home-based patient unit was 123 developed using readily available commercial instruments. In order to simplify the use of 124 the system by patients, easy-to-use instruments were selected. Thus, patients were 125 assessed using a portable pulse oximeter (finger type, BIC model YK-80A) together with 126 a disposable peak flow meter (Medicate, model 72000M). The used thermometer was the 127 one owned by the patients. 128

The home unit allows the data transmission from the patient to the hospital, which 129 is performed using a cell phone application. The application was developed in Java using 130 the integrated development environment Android Studio (version 3.6.3). It is based on a 131

form that is filled out and sent by the patient. To make clinical use easier for non-technical 132 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint personnel, a dedicated user-friendly front panel was developed in the smartphone 133 environment. This interface is shown in Figure 2 . 134 135 Insert Figure 2  136 137 After filled out, this form is sent from the application to an online script from 138

Google, the script saves the data in a worksheet according to the patient ID. To this end, 139 the application uses Google Sheets (spreadsheet where data is saved) and Google Scrips 140 (script that integrates the application and Google Spreadsheet). As a result, the application 141 creates an Excel file with one spreadsheet for each patient, which the maximum size is 5 142 million cells. 143

Additionally, the values obtained in these exams are also recorded by the patients 144 in a follow-up paper personal diary. These diaries are provided to patients at the beginning 145 of the monitoring. This redundancy is important in order to maintain the perfect 146 functioning of the system even in case of failures in the Internet or other system 147 component. 148

In the hospital environment, on the other hand, the hardware platform was 149 constituted by an Intel Core i7-8750H, 2.2 GHz computer with 16 GB of RAM, a hard 150 disk of 1 TB and Microsoft Windows 10 operating system. The software was developed 151 in the LABVIEW 2020 environment (National Instruments, Austin, TX). A user-friendly 152 front panel was also developed to be used in the hospital environment. This interface is 153 shown in Figure 3 . Its use is described in the flow diagram presented in Figure 4 , and the 154 basic LabVIEW program is described in Figure 5 . perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint EPF analyses are performed taking into account the measured absolute values 183 (blue trace in the EPF chart in Figure 9 ) and the percent of the predicted values [25] for 184 each monitored patient (yellow trace in the EPF chart in Figure 9 ). We are performing an 185 initial analysis adapting a methodology traditionally used in asthmatic patients [26] . A 186 zone scheme similar to a traffic light system (green-yellow-red zones) was used to 187 evaluate the predicted EPF values (EPFp) obtained by the patient. The green zone is 188 characterized by PEF readings between 100 to 80% of the EPFp, and signals "all clear". 189

The yellow zone includes reading from 80 to 50% of the EPFp, and signals "caution", 190 while the red zone (below 50% of the EPFp) signals "medical alert". The limits used in 191 the cited zones are probably not adequate for COVID-19 patients, and we hope that they 192 can be rapidly adjusted as the experience of using the system accumulates. After the first scan of patient results, the system automatically updates the results 202 whenever a patient reports new measurements ( Figure 4 ). This is an important feature as 203 it allows the real-time identification of adverse events, and, as a consequence, the 204 clinician may quickly implement the treatment plan. This can be very useful in COVID-205 19, since this disease is characterized by the presence of rapid deterioration in the patient 206 conditions. 207 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint

The biometric characteristics of the studied subjects are described in Table 1 , 259 while the past medical history and medication use of the patients with COVID-19 are 260 described in Table 2 preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in

The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint To the best of our knowledge, this is the first study to provide a detailed description 293 of an emergency remote monitoring system for individuals with COVID-19. The system 294 is able to provide a real-time monitoring of oximetry, BPM, body temperature and peak 295 expiratory flow. The preliminary results obtained in the 30-day validation study showed 296 that patients with COVID-19 presented reduced SpO2 and PEF values, as well as 297

increased BPM values. This was also the first study to investigate the use of PEF in 298 COVID-19. The proposed system allowed us to quickly respond to early abnormalities in 299 patients with COVID-19. 300

During the 30-days period of the initial tests of the proposed system, 720 data-points 301 regarding SpO2 were remotely obtained, resulting in a total of 16 alerts among the 12 302 monitored patients (Figure 6 ). It was observed that these alerts resulted from an abrupt 303 drop in SpO2 rather than a gradual decline. This is consistent with previous results [23], 304 and is probably associated with the rapid deterioration caused by a surge in 305 proinflammatory molecules in the "cytokine storm" phase of COVID-19 [27] . 306

The values of SpO2 were reduced in patients with COVID-19 in comparison with 307 controls ( Figure 8A ). This finding is consistent with the observation that in the initial 308 phase of COVID-19 there is an increase in V/Q mismatch and thus persistence of 309 pulmonary arterial blood flow to non-ventilated alveoli. The current understanding is that 310 this results from the infection, which leads to a modest local interstitial edema and loss 311 of surfactant. These factors are associated with alveolar collapse and intrapulmonary 312

shunting [2] . The results observed in Figure 6 are in line with that obtained by O'Carroll 313 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint and collaborators [28] investigating the remote monitoring of SpO2 in individuals with 314

It was pointed out previously that data are lacking for young adults who often 316 present with mild or asymptomatic disease, a part of the population considered to be 317 perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint processes would be similar to that observed in restrictive diseases in which the volumes 339 exhaled are reduced [32] . These effects may explain, at least in part, the decrease in PEF 340 presented in three of the studied patients, as well as the transient values below 50% of the 341 predicted values observed in two patients, as described in Figure 9A . It is noteworthy that 342 one of the patients who had EPF <50% also had desaturation <92%. 343

There is general agreement in the literature that, given the severity of the ongoing 344 global pandemic, the ability to remotely monitor patients who do not require 345 hospitalization is essential for optimal utilization of health care resources This procedure hold the potential to increase bed availability without compromising safe 360 patient care. 361

We acknowledge the limitations of our study, including unknown methods of 362 temperature measurement. Nevertheless, a clear trend in increased mortality among the 363 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint patients with poor temperature control highlights the usefulness of this noninvasively and 364 easily obtained parameter for evaluating patients' prognoses. 365

Secondly, one could argue that the study presents a small sample size, and 366 additional studies, including a more significant number of subjects are necessary. These 367 studies would allowed us to perform a detailed investigation concerning the utilization of 368 home pulse oximetry, body temperature and peak expiratory flow monitoring to identify 369 robust predictors of hospitalization. 370 Finally, the system validation was performed in subjects from a Brazilian 371 population at a single practice site, which affects the study's generalizability. Therefore, 372 multicenter studies are necessary in the future to expand the generalizability of these 373 findings. The study used broad inclusion criteria and was performed in a typical setting 374 under usual clinical procedures, which enhanced its generalizability. 375 376 Conclusion 377 An emergency system for home monitoring of SpO2, body temperature and PEF in 378 patients with COVID-19 was developed in the current study. This was the first study to 379 propose such a system and to evaluate the use of PEF in COVID-19. Using this system, 380 the acquisition and analysis of the cited signals can be performed remotely through the 381

Internet. The ability of the system to detect abnormal events was initially validated by a 382 30-day monitoring study in normal subjects and patients with COVID-19. In close 383 agreement with previous results and physiological fundamentals, the presence of COVID-384 19 resulted in reduced values of SpO2, increased BPM, fever events in 41.7% of the 385 patients and decreased PEF in 33% of the studied patients. 386

All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint

The proposed system may contribute to conserve hospital resources for those most 387 in need, while simultaneously enabling early recognition of patients under acute 388 deterioration, requiring urgent assessment. 389

Based on these promising results, future work includes a clinical trial in which we 390 will perform a follow up in well-defined groups of patients with COVID-19. This will 391 provide a detailed evaluation of the clinical contribution of the home monitoring approach 392 in improving the patient's care and outcomes. 393 perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint The top and the bottom of the box plot represent the 25th-to 75th-percentile values while 556 the circle represents the mean value, and the bar across the box represents the 50th-557 percentile value. 558 559 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 11, 2020. ; https://doi.org/10.1101/2020.12.11.20247650 doi: medRxiv preprint

WHO Coronavirus Disease (COVID-19) Dashboard 2020

The 399 pathophysiology of 'happy' hypoxemia in COVID-19

Telemedicine in the Era of COVID-19. The journal 403 of allergy and clinical immunology In practice

Telemedicine and 407 the COVID-19 Pandemic, Lessons for the Future. Telemedicine journal and e-health 408 : the official journal of the American Telemedicine Association

Home monitoring for patients with ILD 411 and the COVID-19 pandemic. The Lancet Respiratory medicine

Systematic review of home telemonitoring for chronic 415 diseases: the evidence base

Clinical features of patients 419 infected with 2019 novel coronavirus in Wuhan

Management of COVID-19 Respiratory Distress

Why COVID-19 Silent Hypoxemia Is Baffling to 425 Physicians. American journal of respiratory and critical care medicine

Covid-19: Patients to use pulse oximetry at home to spot deterioration

Body temperature correlates with 431 mortality in COVID-19 patients

Report of the WHO-China Joint Mission on Coronavirus Disease

Measurement of body 436 temperature to prevent pandemic COVID-19 in hospitals in Taiwan: repeated 437 measurement is necessary. The Journal of hospital infection

Response to "Body temperature correlates with 441 mortality in COVID-19 patients

World Health Organization WHO. GINA -Global Initiative for

Correlation of airway obstruction and patient-reported 447 endpoints in clinical studies. The European respiratory journal

Can peak expiratory 450 flow measurements estimate small airway function in asthmatic children?

Objective measures of lung function

Asthma self-management education 455 program by home monitoring of peak expiratory flow

Daily 459 peak flow monitoring can be a useful tool in identifying COPD patients predisposed 460 to worse outcomes

COVID-19 pneumonia: different respiratory treatments for different phenotypes? 463 Intensive Care Med

A multicentre 465 prospective observational study comparing arterial blood gas values to those obtained 466 by pulse oximeters used in adult patients attending Australian and New Zealand 467 hospitals

Novel Use 470 of Home Pulse Oximetry Monitoring in COVID-19 Patients Discharged From the 471 Emergency Department Identifies Need for Hospitalization

Guyton and hall textbook of medical physiology. 14

Use as a Clinical Test of Ventilatory 476

The American review of respiratory disease

Peak expiratory flow monitoring in asthma2019 Accessed on 479

The pathogenesis and treatment of the `Cytokine Storm' in 482 COVID-19

Remote monitoring of oxygen saturation in individuals with COVID-19 pneumonia

The European respiratory journal

Body 490 temperature screening to identify SARS-CoV-2 infected young adult travellers is 491 ineffective. Travel medicine and infectious disease

Cardiovascular complications in 495 COVID-19. The American journal of emergency medicine

Covid-19: a remote assessment in primary care

Pulmonary Function Tests in Clinical 501 Practice

Home telemonitoring for 503 patients with severe respiratory illness: the Italian experience

Telemedicine--the way ahead for medicine in the developing world

A 509 telemanagement system for home follow-up of respiratory patients

Efficacy of multiparametric 512 telemonitoring on respiratory outcomes in elderly people with COPD: a randomized 513 controlled trial