key: cord-0827502-oqkjzgrv
authors: Blair, P. W.; Brown, D. M.; Jang, M.; Antar, A. A.; Keruly, J. C.; Bachu, V.; Townsend, J. L.; Tornheim, J. A.; Keller, S. C.; Sauer, L.; Thomas, D. L.; Manabe, Y. C.; Team, Ambulatory COVID Study
title: The clinical course of COVID-19 in the outpatient setting: a prospective cohort study
date: 2020-09-03
journal: nan
DOI: 10.1101/2020.09.01.20184937
sha: 2fea833ffd266e7eb5817a3e47928ae06163c3ed
doc_id: 827502
cord_uid: oqkjzgrv

Background: Outpatient COVID-19 has been insufficiently characterized. Objective: To determine the progression of disease and subsequent determinants of hospitalization. Design: A prospective outpatient cohort. Setting: Outpatients were recruited by phone between April 21 to June 23, 2020 after receiving outpatient or emergency department testing within a large health network in Maryland, USA. Participants: Outpatient adults with positive RT-PCR results for SARS-CoV-2. Measurements: Symptoms, portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected by participants on days 0, 3, 7, 14, 21, and 28 after enrollment. Baseline demographics, comorbid conditions were evaluated for risk of subsequent hospitalization using negative binomial, logistic, and random effects logistic regression. Results: Among 118 SARS-CoV-2 infected outpatients, the median age was 56.0 years (IQR, 50.0 to 63.0) and 50 (42.4%) were male. Among those reporting active symptoms, the most common symptoms during the first week since symptom onset included weakness/fatigue (67.3%), cough (58.0%), headache (43.8%), and sore throat (34.8%). Participants returned to their usual health a median of 20 days (IQR, 13 to 38) from the symptom onset, and only 65.5% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. Individuals at the same duration of illness had a 6.1 times increased adjusted odds of subsequent hospitalization per every percent decrease in home SaO2 (95% confidence interval [CI]: 1.41 to 31.23, p=0.02). Limitations: Severity and duration of illness may differ in a younger population. Conclusion: Symptoms often persisted but uncommonly progressed to hospitalization. Home SaO2 might be an important adjunctive tool to identify progression of COVID-19.

minute; CI, 0.58 to 1.88, p=0.90) were not. The AUROC for the initial SaO2 for predicting subsequent 191 hospitalization was 0.85 (CI, 0.71 to 0.89).

To further explore the utility of a resting SaO2, the performance characteristics of the individual-level 194 nadir of resting SaO2 were determined for those within the first week of illness (N=42). The AUROC was 195 found to be 0.84 (CI, 0.67 to 1.0) for predicting subsequent hospitalization. SaO2 values of 93% or below 196 in the first week of illness were specific (92.1%) but not sensitive (50%) for predicting subsequent 197 hospitalization with a 6.3 positive likelihood ratio. There was a negative likelihood ratio of zero for 198 subsequent hospitalization among those with a resting oxygen saturation that went no lower than 96% 199 (Appendix Table S3 ).

To evaluate for the association of oxygen saturation levels over time, a random effects logistic 202 regression model was fit adjusting for age. The model was more parsimonious according to a lower AIC 203 when including age as a covariate. Individuals at the same duration of illness were found to have a 6.6-204 fold increased crude odds (CI: 1.41 to 31.23, p = 0.02) and a 6.1-fold increased adjusted odds of 205 subsequent hospitalization per every SaO2 percent decrease (CI: 1.41 to 31.23, p=0.02). This may be the first study to prospectively characterize the incidence, intensity, and duration of 210 COVID-19 in an outpatient setting. Presenting symptoms were diverse, persistent, and uncommonly 211 required hospitalization, especially when high ambulatory blood oxygen concentration were sustained.

These findings support early observations from hospitalized patients that symptoms may persist 213 long-term after acute COVID-19 illness (6, 7, 20, 21) . Despite outpatient COVID-19 being considered 214 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) 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 September 3, 2020. . https: //doi.org/10.1101 //doi.org/10. /2020 generally mild, we also found that respiratory and systemic symptoms persistent for weeks, notably shortness of breath were present among 43%, 35%, and 29%, respectively, among those that initially 219 reported symptoms(6). In comparison, participants in our cohort reported cough among 23.4%, 220 weakness or fatigue among 40.8%, and shortness of breath among 11.7% during the third week of 221 illness regardless of initial symptoms. Weakness or fatigue was the most pervasive symptom and almost 222 one-third of participants reported fatigue after 22-28 days of illness. Between 10-20 percent of 223 participants continued to have some degree of cough, headache, or anosmia as long as a month or more 224 after the onset of symptoms. The prolonged duration of loss of taste and smell has been previously 225 noted in the study using telephone surveys and is consistent with our prospective findings(6).

While hospitalization was uncommon in our outpatient cohort, low ambulatory or resting oxygen 228 saturation (<93%) were predictive for requiring subsequent hospitalization, suggesting a role for home 229 pulse oximetry in outpatient management of COVID-19. We found that the initial SaO2 value, a SaO2 230 nadir during the first week of illness, or any SaO2, adjusting for duration of symptoms, is predictive of 231 subsequent hospitalization. We found no major difference in the diagnostic yield between resting and 232 ambulatory SaO2 in this setting. The predictive value of outpatient oxygen saturation values have been 233 previously described (5, 22) . One study provided pulse oximeters to participants with COVID-19 who 234 presented to an ED or outpatient testing centers; 29% required subsequent hospitalization. Low oxygen Although in the present study pulse oximetry was predictive of hospitalization, the measure alone often 239 was not sufficient. Some persons needed hospitalization for non-respiratory symptoms (e.g. diarrhea) 240 that logically were not detected by lower oxygen saturation. In addition, no single oxygen saturation 241 reading alone predicted outcome as there was overlap in both the resting and ambulatory oxygen 242 saturations of those who remained at home and those who were hospitalized. Therefore, pulse oximetry 243 may be most useful as an adjunct to clinical monitoring of high risk populations such as those over 60 244 years of age, males, and persons with elevated body mass index (5, 23).

While this is the largest prospective outpatient cohort to characterize the clinical course of COVID-19, 247 the study has several limitations. First, this study predominantly included older individuals to increase 248 the statistical power for severe outcomes given the known association between age and 249 hospitalization(12). Symptoms including severity and duration of illness may differ considerably in 250 younger individuals and our results are more generalizable for persons of similar ages (24). Outpatients 251 have been previously found to be younger and have less comorbidities compared to hospitalized 252 patients(25). Second, the recruitment strategy may have skewed the study population. For instance, 253 participants with milder symptoms and those with altruistic professions (e.g. healthcare workers) could 254 have been more likely to participate in the study processes than others. A quarter of participants had 255 symptoms of onset 10 days prior to enrollment, and therefore a proportion of participants may have 256 been selected who had successfully passed a time window of disease severity. Additionally, due to 257 operational requirements, Spanish-speakers were not enrolled proportionate to cases early after study 258 initiation and individuals without active mobile phone access were not enrolled. Third, missing data 259 from loss to follow-up or withdrawals during the study period could have skewed the longitudinal 260 severity of results. For example, participants with milder illness could have been more likely to 261 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) 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 September 3, 2020. (which was not certified by peer review) 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 September 3, 2020. (which was not certified by peer review) 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 September 3, 2020. (which was not certified by peer review) 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 September 3, 2020. . https://doi.org/10.1101/2020.09.01.20184937 doi: medRxiv preprint (which was not certified by peer review) 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 September 3, 2020. (which was not certified by peer review) 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 September 3, 2020. . https://doi.org/10.1101/2020.09.01.20184937 doi: medRxiv preprint All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) 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 September 3, 2020. 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(which was not certified by peer review) 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 September 3, 2020. Severity of disease during first month of illness among those with symptomatic outpatient COVID-19 including (C) perception of disease, (D) perception of health, and (E) the effect on usual activities.

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(which was not certified by peer review) 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 September 3, 2020. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) 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 September 3, 2020. . https://doi.org/10.1101/2020.09.01.20184937 doi: medRxiv preprint

Clinical characteristics of 3,062 COVID-19 280 patients: a meta-analysis