Distinguishing between COVID-19 and the common cold in a primary care setting - comparison of patients with positive and negative SARS-CoV-2 PCR results.

Background: Combating the COVID-19 pandemic is a major challenge for health systems, citizens and policy makers worldwide. Early detection of affected patients within the huge population of patients with common cold symptoms is an important element of this effort but often hindered by limited testing resources. We aimed to identify predictive risk profiles for a positive PCR result in primary care. Methods: Multi-center cross-sectional cohort study on predictive characteristics over a period of 4 weeks in primary care patients in Germany. We evaluated age, sex, reason for testing, risk factors, symptoms, and expected PCR result for their impact on the test result. Results: In total, 374 patients in 14 primary care centers received SARS-CoV-2 PCR swab testing and were included in this analysis. A fraction of 10.7% (n=40) tested positive for COVID-19. Patients who reported anosmia had a higher odds ratio (OR: 4.54; 95%-CI: 1.51-13.67) for a positive test result while patients with a sore throat had a lower OR (OR: 0.33; 95%-CI: 0.11-0.97). Patients who had a first grade contact with an infected persons and showed symptoms themselves also had an increased OR for positive testing (OR: 5.16; 95% CI: 1.72-15.51). This correlation was also present when they themselves were still asymptomatic (OR: 12.55; 95% CI: 3.97-39.67). Conclusion: The reported contact to an infected person is the most important factor for a positive PCR result, independent of any symptoms of illness in the tested patient. Those persons with contact to an infected person should always get a PCR test. If no contact is reported and testing material is scarce, anosmia should increase the likelihood of performing a test, while a sore throat should decrease it.

Background: Combating the COVID-19 pandemic is a major challenge for health 38 systems, citizens and policy makers worldwide. Early detection of affected patients 39 within the huge population of patients with common cold symptoms is an important 40 element of this effort but often hindered by limited testing resources. We aimed to 41 identify predictive risk profiles for a positive PCR result in primary care. The COVID-19 pandemic is a major challenge for health systems, citizens and policy 69 makers worldwide (1). The early political implementation of individual distancing has 70 slowed down the reproduction rate of the virus in Germany significantly (2) is the question of how far positive and negative patients differ in their initial clinical 83 presentation. The more precisely physicians use SARS-CoV-2 PCR testing, the more 84 efficient it is. Statistically, this is reflected in Baye's theorem: The quality of a test is not 85 only determined by specificity and sensitivity, but also depends on the pre-test 86 probability of the event to be tested. Thus, if the pre-test probability for COVID-19 is 87 higher, the probability that a SARS-CoV-2 PCR-positive patient is actually ill (positive-88 predictive value = PPV) is increased (4). 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 5, 2020. In this multi-center, cross-sectional study, the characteristics of patients who tested 98 positive and negative for COVID-19 were assessed. A total of 26 office-based 99 specialists for internal and/or general medicine with a full primary care mandate from 14 100 different locations participated in the study. 101 All locations collected patient-related data based on a uniform quality standard in the 102 documentation of COVID-19 suspect cases that we provided. 103 Each site reported anonymous data on all SARS-CoV-2 PCR swabs taken. These In order to ensure that there was no excessive distortion in the patient collective due to 125 the convenience sampling of practices, age and sex of the tested persons were 126 compared with demographic data from a large national sample. 127 128 . 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 5, 2020. . https://doi.org/10.1101/2020.04.27.20081877 doi: medRxiv preprint Data entry was performed twice and the data sets were compared digitally, any 129 deviations were checked and a plausibility check of the data entered was performed. 130 The statistical evaluation was carried out with the statistics program R. In addition to the 131 descriptive statistics, initial chi-square tests were performed for different potential    is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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(which was not certified by peer review)
The copyright holder for this preprint this version posted May 5, 2020. The most frequent symptoms at the presentation of patients who later tested positive for 174 COVID-19 were cough, fever, anosmia and muscle pain. 175 The most common symptoms at presentation of patients who later tested negative for 176 COVID-19 were cough, sore throat, fatigue and fever.  p-value . 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)
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(which was not certified by peer review)
The copyright holder for this preprint this version posted May 5, 2020. Chi-square test. The odds ratio (OR) for a positive COVID-19 PCR was increased in 184 patients who had contact with an infected person who were older and in patients with 185 anosmia and decreased in patients suffering from a sore throat.  . 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 5, 2020. Factors that were associated with a negative test result 226 Negative tests were associated with the symptom "sore throat". This result is consistent 227 with the low prevalence of the symptom "sore throat" in confirmed COVID-19 cases (6). 228 The correlation found between age and test results is marginal (younger people were 229 tested negative more often) and may be explained by local outbreaks in nursing homes. 230 This effect will most likely dissolve due to diffusion processes during the course of the 231 pandemic and may not be present in countries with a more homogenous spreading 232 pattern.

234
Factors that were associated with a positive test result 235 Positive tests were associated with confirmed contact. This was to be expected, but it 236 was surprising that this also applied to asymptomatic patients. He et al. concluded that 237 45% of infections occur in the pre-symptomatic phase of the patient, i.e. the patient is 238 still asymptomatic but already has large amounts of virus replicated in the throat and is 239 highly contagious (9). This result underlines the particular relevance of contact 240 anamnesis for the test decision, but also the relevance of early isolation of potentially 241 affected contacts. 242 Of particular clinical importance is the observed association between the symptom 243 anosmia and a positive PCR result. Anosmia has already been described as a relevant 244 COVID-19 symptom in other studies, but this is the first study to show that anosmia may 245 be a useful discriminator between COVID-19 and other, endemic respiratory tract 246 infections (8,10,11). Since the examined patients mainly presented with fever, cough, 247 muscle pain and other cold symptoms, which are common with endemic respiratory 248 . 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 5, 2020. . 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 5, 2020. . https://doi.org/10.1101/2020.04.27.20081877 doi: medRxiv preprint