Post-COVID-19 syndrome in outpatients: a cohort study

TL;DR: More than half of COVID-positive outpatients report persisting symptoms up to 10 months after infection and 21% seek medical care for this reason as mentioned in this paper, which suggests that post-COVID syndrome places a significant burden on society and especially healthcare systems.

Abstract: BackgroundSome patients experience long-term symptoms after COVID-19, but data on outpatients with mild-to-moderate COVID-19 are scarce. ObjectiveTo describe persisting symptoms more than 3 months after infection in PCR-confirmed COVID-19 in comparison to negative SARS-CoV-2 PCR outpatients and to identify predictors of long-term symptoms in COVID-19. SettingOutpatient clinics of a Swiss university center. Patients418 symptomatic outpatients with PCR-confirmed COVID-19 (COVID-positive) and 89 negative SARS-CoV-2 PCR (COVID-negative). DesignProspective cohort study. MeasurementsPredefined long-term symptoms were evaluated though a phone interview >3 to 10 months after diagnosis. Associations between long-term symptoms and PCR test result, as well predictors of persisting symptoms in COVID-positive were evaluated by multivariate logistic regression including potential confounders (age, sex, smoking, comorbidities, time of the phone survey). ResultsThe study population consisted mostly of young (median of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p=0.020) health care workers (67% versus 82%; p=0.006).. Persisting symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative (p=0.006). Overall, 21% COVID-positive and 15% COVID-negative (p=0.182) consulted a doctor for these symptoms. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio [aOR] 2.14, 95%CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16) and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (aOR 1.67, 95% CI 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persisting symptoms. LimitationsUndiagnosed SARS-CoV-2 infection in COVID-negative cannot be completely excluded. ConclusionMore than half of COVID-positive outpatients report persisting symptoms up to 10 months after infection and 21% seek medical care for this reason. These data suggest that post-COVID syndrome places a significant burden on society and especially healthcare systems.

Summary

1. INTRODUCTION

• In the area of optical fiber sensing, FBGs have been demonstrated to be the most promising mechanical probe for several research fields and applications.
• For this purpose, different interrogation systems have been developed so far, mostly based on broad-emission radiation sources combined to optical spectrum analyzers and filters.
• In most such cases, low-acoustic frequency detection is affected by temperature cross-sensitivity effects that may limit the ultimate measurement accuracy.
• That is particularly relevant for field applications where a robust and reliable operation is required.
• The authors describe the proposed methods, the experimental set-ups and the preliminary results obtained by a single FBG sensor and an in-fiber FabryPérot (FFP).

2. METHODOLOGY

• A scheme of the interrogation set-up used for a Panda FBG is shown in figure 1. Terms of Use: http://spiedl.org/terms generates two sideband frequencies at a relative distance from the carriers exactly equal to f1,2.
• A double-balanced mixer (DBM) demodulates the detector signals at frequency f1,2 and extracts a dispersive-like signal resulting from sideband-carrier frequency beating.
• Mixer output lineshapes around the PM FBG peaks for a 45° incident polarization.
• The Bragg mirrors are separated by about 50 cm and closed in aluminum cylinders to keep them mechanically insensitive.

3. RESULTS

• Measurements with the single sensor have been carried out so far applying longitudinal loads by the PZT.
• As a proof of the efficiency of the sensing method, simultaneous detection of AC strain and temperature changes is demonstrated in figure 5.
• It is worth noting, from figure 5a, how the system discriminates between slow longitudinal strain and temperature variations applied at different frequencies by the slow-axis (laser 1) and the fast-axis (laser 2) signals.
• Transverse strain as well as thermal stress effects on the PM sensor are still under study.

4. CONCLUSIONS

• The authors present recent results on a novel interrogation scheme, relying on a laser-frequency stabilization technique, which enables for active tracking of FBG-based sensors fabricated in HiBi fiber.
• Both, a single Panda-fiber Bragg grating sensor and an intrinsically highly-reflectivity-FBG resonator were used in demonstrating the capability to perform simultaneous interrogation of the two orthogonal polarisation axes of a HiBi FBG thereby opening up prospects for strain-temperature discrimination, given high measured resolution possible with laser-based spectroscopic methods.
• Based on a preliminary estimate, minimum detectable strain signals below 10 nε/√Hz and 60 pε/√Hz can be in principle achieved for the single sensor and the fiber resonator, respectively.
• Interrogation and test of the fiber resonator in a similar fashion for simultaneous high-sensitivity strain and temperature measurements are in progress.
• Furthermore, an experimental investigation of cross-sensitivity effects of transverse strain and longitudinal strain in a dynamic measurement regime is in progress.

Figures

Table 3. Factors associated with the presence of any long-term symptom during the phone survey in COVID-positive patients.

Table 2. Association between long-term symptoms (any and individualized symptoms) assessed at the time of phone survey and COVID positive status.

Figure 3: Factors associated with the presence of selected long-term symptoms (fatigue, smell or taste disorder, dyspnea and memory impairment) during the phone survey in COVID-positive patients.

Table 1: Characteristics of patients according to SARS-CoV-2 RT-PCR result (COVID-negative and COVID-positive).

Full text

1
Post‑COVID‑19 syndrome in outpatients: a cohort study
Florian Desgranges
1
, Eliana Tadini
1
, Aline Munting
1
, Jean Regina
1
, Paraskevas Filippidis
1
,
Benjamin Viala
1
, Eleftherios Karachalias
2
, Véronique Suttels
1
, David Haefliger
1
, Eleftheria
Kampouri
1,3
, Mathias Van Singer
1
, Jonathan Tschopp
1
, Laurence Rochat Stettler
1
, Siméon
Schaad
1
, Thomas Brahier
1
, Olivier Hugli
4
, Yolanda Mueller Chabloz
5
, Alexandre Gouveia
5
, Onya
Opota
6
, Pierre-Nicolas Carron
4
, Benoît Guery
1
, Matthaios Papadimitriou-Olivgeris
1
*, Noémie
Boillat-Blanco
1
*, the RegCOVID research group.
* Equal contribution to this work
Members of the RegCOVID group are listed in the acknowledgement section
1
Infectious Diseases Service, Lausanne University Hospital and University of Lausanne,
Switzerland;
2
Data Scientist, Cardiff, England;
3
Service of Hospital Preventive Medicine,
Lausanne University Hospital and University of Lausanne, Switzerland;
4
Emergency
Department, University Hospital of Lausanne and Lausanne University, Switzerland;
5
Department of Family Medicine, Center for Primary Care and Public Health (Unisanté),
University of Lausanne, Switzerland;
6
Institute of Microbiology, Lausanne University and
University Hospital of Lausanne, Switzerland
Word count:
 Abstract: 263
 Manuscript: 2986
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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 preprintthis version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255742doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

2
ABSTRACT
Background
Some patients experience long-term symptoms after COVID-19, but data on outpatients with
mild-to-moderate COVID-19 are scarce.
Objective
To describe persisting symptoms more than 3 months after infection in PCR-confirmed COVID-
19 in comparison to negative SARS-CoV-2 PCR outpatients and to identify predictors of long-
term symptoms in COVID-19.
Setting
Outpatient clinics of a Swiss university center.
Patients
418 symptomatic outpatients with PCR-confirmed COVID-19 (COVID-positive) and 89 negative
SARS-CoV-2 PCR (COVID-negative).
Design
Prospective cohort study.
Measurements
Predefined long-term symptoms were evaluated though a phone interview >3 to 10 months
after diagnosis.
Associations between long-term symptoms and PCR test result, as well predictors of persisting
symptoms in COVID-positive were evaluated by multivariate logistic regression including
potential confounders (age, sex, smoking, comorbidities, time of the phone survey).
Results
The study population consisted mostly of young (median of 41 versus 36 years in COVID-
positive and COVID-negative, respectively; p=0.020) health care workers (67% versus 82%;
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 preprintthis version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255742doi: medRxiv preprint

3
p=0.006).. Persisting symptoms were reported by 223 (53%) COVID-positive and 33 (37%)
COVID-negative (p=0.006). Overall, 21% COVID-positive and 15% COVID-negative (p=0.182)
consulted a doctor for these symptoms. Four surveyed symptoms were independently
associated with COVID-19: fatigue (adjusted odds ratio [aOR] 2.14, 95%CI 1.04-4.41),
smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16) and memory impairment
(5.71, 1.53-21.3). Among COVID-positive, female gender (aOR 1.67, 95% CI 1.09-2.56) and
overweight/obesity (1.67, 1.10-2.56) were predictors of persisting symptoms.
Limitations
Undiagnosed SARS-CoV-2 infection in COVID-negative cannot be completely excluded.
Conclusion
More than half of COVID-positive outpatients report persisting symptoms up to 10 months
after infection and 21% seek medical care for this reason. These data suggest that post-COVID
syndrome places a significant burden on society and especially healthcare systems.
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 preprintthis version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255742doi: medRxiv preprint

4
INTRODUCTION
1
More than one year after the first cases of Coronavirus disease 2019 (COVID-19) (1), the
2
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic remains a constant
3
threat challenging the capacity of healthcare systems and affecting well-being of many
4
individuals. The clinical presentation and outcome of acute COVID-19 is well described, most
5
patients presenting with mild disease and only a minority needing hospital admission (2).
6
While most affected people experience complete resolution of their symptoms after two to
7
six weeks (3,4), symptoms lasting more than 3 months have been reported in social media (5–
8
7) and in observational studies (8–13). Three studies reported that a large number of patients
9
have persisting symptoms for more than 6 months after COVID-19: one study including adults
10
discharged from hospital (14) and two studies including outpatients with mild-to-moderate
11
disease (15,16). Recent guidelines defined post-COVID-19 syndrome as the persistence of
12
signs and symptoms for more than 3 months after infection in the absence of an alternative
13
diagnosis (17).
14
Although they represent the vast majority of cases, data on long-term consequences in
15
outpatients with mild-to-moderate COVID-19 are still scarce. To the best of our knowledge,
16
no study compared the prevalence of persisting symptoms among patients screened for
17
similar symptoms, between those tested positive for SARS-CoV-2 and those tested negative.
18
Therefore, the association between PCR-confirmed COVID-19 and long-term symptoms is not
19
well established. Furthermore, no study explored the factors associated with persisting
20
symptoms in outpatients. These data are crucial as they may modify patients’ follow-up after
21
their infection and influence public health vaccination strategies by identifying additional
22
population groups that should be prioritized.
23
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 preprintthis version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255742doi: medRxiv preprint

5
We aimed to compare the prevalence of symptoms persisting for more than 3 months
24
between SARS-CoV-2 PCR-confirmed (COVID-positive)
and PCR-negative (COVID-negative)
25
patients in outpatient clinics, and to identify predictors of persisting symptoms in COVID-
26
positive.
27
28
METHODS
29
Study design, setting and participants
30
This cohort study recruited consecutive PCR-confirmed COVID-19 patients (COVID-positive
31
group) during their initial visit in the emergency department (ED) or in the SARS-CoV-2
32
screening center of the University hospital of Lausanne, as well as in the two outpatient clinics
33
of the University of Lausanne, Switzerland, between February 26
th
and April 27
th
2020. During
34
the study period, SARS-CoV-2 screening was restricted to symptomatic patients (i.e.
35
symptoms of acute respiratory tract infection, anamnestic fever or sudden loss of smell or
36
taste) with at least one risk factor for severe COVID-19 (i.e. ≥ 65 years old or presence of a
37
comorbidity such as hypertension, diabetes, cancer, chronic cardiac or respiratory disease,
38
immunosuppression) and to symptomatic health workers (18). Validated nucleic acid
39
amplification tests were used and a dedicated trained medical team performed the
40
nasopharyngeal swabs (19).
41
We included a control group of outpatients attending the same health facilities during the
42
same period with symptoms suggestive of COVID-19 (cough and/or dyspnea) at presentation,
43
but a negative PCR SARS-CoV-2 result in nasopharyngeal swab (COVID-negative group). This
44
group was part of a prospective cohort of patients with acute respiratory infections previously
45
described (20,21).
46
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 preprintthis version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255742doi: medRxiv preprint

Frequently asked questions

Q1. What are the contributions in "Post‐covid‐19 syndrome in outpatients: a cohort study" ?

Florian Desgranges1, Eliana Tadini1, Aline Munting1, Jean Regina1, Paraskevas Filippidis1, Benjamin Viala1, Eleftherios Karachalias2, Véronique Suttels1, David Haefliger1, Eleftheria Kampouri1,3, Mathias Van Singer1, Jonathan Tschopp1, Laurence Rochat Stettler1, Siméon Schaad1, Thomas Brahier1, this paper 

Q2. What tests were performed when comparing proportions?

Two-sided chi-squared or Fisher tests were performed when comparing proportions, and Mann–Whitney U tests were performed for continuous variables. 

Q3. What is the name of the study?

BMI: body mass index; SpO2: oxygen saturation; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; RT-PCR: real time reverse transcriptase polymerase chain reaction.