key: cord-1018167-a3sich0o
authors: Navarra, J.; Ruiz-Ceamanos, A.; Moreno, J. J.; Garcia-Basterrechea, J. M.; de Haro-Licer, J.; Sinnett, S.; Spence, C.; Gallardo-Pujol, D.
title: Acute nasal dryness in COVID-19
date: 2020-11-19
journal: nan
DOI: 10.1101/2020.11.18.20233874
sha: 27554f5bd5241bd82a53eb196610fa1d88e80904
doc_id: 1018167
cord_uid: a3sich0o

One of the entry routes of SARS-CoV-2 is the nasal epithelium. Although mounting evidence suggests the presence of olfactory dysfunction, and even anosmia, in patients with COVID-19, it is not clear whether these patients also suffer from other 'nasal' symptoms that may influence their olfaction. A group of 35 patients with COVID-19 (and a control group matched in gender and age) were surveyed about the presence of a variety of nasal symptoms that may be associated to drastic perturbations experienced in the nasal cavity (e.g., 'excessive dryness' and/or a continual sensation of having had a 'nasal douche'). We used a cross-sectional, retrospective survey, targeted at the general population by means of non-quoted, non-random, snowball sampling. Symptoms were assessed with absence/presence responses. The possible association between two continuously distributed latent variables from categorical variables was estimated by means of polychoric correlations. More than 68% of the patients reported at least one 'nasal' symptom. The clinical group also experienced 'a strange sensation in the nose' and having excessive nasal dryness significantly more often than the control group. Fifty-two percent of the patients (but only 3% of the control group) reported a constant sensation of having had a strong nasal douche. Nasal symptoms predominantly co-occurred with anosmia/hyposmia, and ageusia/hypogeusia, appeared principally before or during the other symptoms of COVID-19, and lasted for twelve days, in average. The presence of these nasal symptoms, and their early occurrence, could potentially facilitate early diagnosis of COVID-19 and initial social distancing efforts.

In 2020, a new disease, known as COVID-19, caused by an infection of SARS-CoV-2, 27 has spread globally. Given the high percentage of patients with COVID-19 who are 28 asymptomatic or experience only mild symptoms (Kim et al., 2020) , the need to identify 29 (and isolate if necessary) possible carriers of the SARS-CoV-2 virus quickly and 30

inexpensively is crucial to helping reduce its spread. Recognizing and understanding all 31 of the possible symptomatic manifestations of COVID-19, including those that seem to 32 be less life-threatening, can be relevant for diagnostic, treatment, and mitigation efforts 33 (e.g., social distancing), especially in situations where RT-PCR tests cannot be 34 administered to all non-severe cases. Along these lines, we now know, for example, that 35 approximately 80% of COVID-19 patients in Europe report some loss of smell and taste 36 (Lechien, Chiesa-Estomba, De Siati, 2020; see also Moein, Hashemian, Mansourafshar, 37

Khorram-Tousi, Tabarsi, and Doty, 2020). 38

Evidence suggests that the virus adheres to angiotensin-converting enzyme 2 (ACE-2) 39 receptors in epithelial cells ( is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. ; https://doi.org/10.1101/2020.11.18.20233874 doi: medRxiv preprint imply a drastic change of the mucosa environment. As sudden changes in mucus density 51 could compromise the final adherence of the volatile chemical compounds to their 52 corresponding odorant receptors, olfaction may possibly be compromised in the process 53 (Hummel, Whitcroft, and Andrews, 2016) . 54

Most important for our purpose, an ostensible reduction of mucus could certainly lead 55 to strange sensations in the nasal cavity (Hildenbrand, Weber, Brehmer, 2011) . If 56 patients with COVID-19 do experience odd, and even unprecedented sensations in their 57 nasal cavity, we might be observing yet another warning sign of COVID-19 that has 58 been ignored so far, probably due to its being overshadowed by more severe symptoms 59 needing urgent intervention. 60

The goal of the present study was to obtain diagnostic-valuable data regarding the 61 presence of these non-olfactory nasal symptoms in patients with COVID-19. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. ; https://doi.org/10.1101/2020.11.18.20233874 doi: medRxiv preprint regarding the presence/absence of other symptoms previously described in the literature 78 (e.g., fever, cough, smell and taste loss, etc.), was obtained from a group of patients 1) capture the main demographics of respondents, 2) ask whether they were COVID-82 tested or COVID-suspected (as suspicion without a PCR test result was considered an 83 exclusion criterion), and 3) collect information about COVID-19 symptoms. 84

The survey questionnaire comprised a total of 69 items in four different languages 85 (Catalan, Spanish, Italian, and French) and were administered depending on the 86 participants' responses (i.e., some questions appeared only in cases where a specific 87 response to a particular item was provided by the participant). Snowball sampling was 88 used to recruit the sample of participants (Goodman, 1961) . 89

Only those participants who provided a copy of their positive result for SARS-CoV-2 in 91 a PCR test were included in the patient group. The survey was conducted from 92 03/30/2020 to 04/06/2020 and a total of 414 people took part. 93

The vast majority of respondents were from Spain (86%), followed by Italy (9%) and 94

France (1.5%). Responses from the survey were used to classify respondents as either 95 patients (with demonstrable positive results in a PCR test), controls, or those with an 96 uncertain status. Data from the latter were removed from the analyses. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. ; https://doi.org/10.1101/2020.11.18.20233874 doi: medRxiv preprint vs. 19 female, respectively; see Table 1 for basic demographic information). However, 107 the groups were not completely matched in terms of smoking habits (p=.004), given that 108 no patients (but 8 participants from the control group) reported smoking. The 109 distribution of overall symptoms for both groups can be found in Table 2 . 110 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. ; https://doi.org/10.1101/2020.11.18.20233874 doi: medRxiv preprint symptoms were tested with an unpaired 2-tailed Welch's t test, and 95% CIs are 117 reported. The possible co-occurrence of symptoms was calculated on the basis of 118 correlations for categorical variables. These correlations were computed via the 119 "polychoric" function of the psych package using frequencies as input data. The 120 significance level was set at p < .05, and uncertainty estimates are given as confidence 121 intervals. 122 123 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. ; https://doi.org/10.1101/2020.11.18.20233874 doi: medRxiv preprint

The participants' responses revealed that 68.6% of the patients experienced at least one 126 of these "nasal" symptoms ( Figure 1A) . Further analyses showed that the clinical group 127 reported having experienced excessive nasal dryness significantly more often than the 128 control group (21 (61.8%) vs. 5 (15%); odds ratio, 8.7; 95% CI, 2.5-36.5 p<.001; see 129 Figure is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. ; https://doi.org/10.1101/2020.11.18.20233874 doi: medRxiv preprint imply the addition of roughly 8-9 more participants with positive result in PCR test in 181 our full sample, or 1-2 in the subsample, which would not alter the results significantly. 182

Considering that nasal dryness could easily be related to some initial damage caused by We would like to thank all of the participants that volunteered to answer the survey used 189 to obtain the data reported in the present study. 190 . CC-BY-ND 4.0 International license It is made available under a perpetuity.

is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. ; https://doi.org/10.1101/2020.11.18.20233874 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 19, 2020. ; https://doi.org/10.1101/2020.11.18.20233874 doi: medRxiv preprint

Snowball Sampling

Rhinitis sicca, dry nose and atrophic rhinitis: a 201 review of the literature

Causes and classification of olfactory 204 loss. Position paper on olfactory dysfunction

Clinical characteristics of 206 asymptomatic and symptomatic patientswith mild COVID-19

Olfactory and gustatory 209 dysfunctions as a clinical presentation of mild to moderate forms of the 210 coronavirus disease (COVID-19): A multicenter European study

Alterations in smell or taste in mildly 219 symptomatic outpatients with SARS-CoV-2 infection

SARS-CoV-2 entry factors are highly 222 expressed in nasal epithelial cells together with innate immune genes

Receptor recognition by the novel 225 coronavirus from Wuhan: an analysis based on decade-long structural studies of 226 SARS coronavirus

SARS-CoV-2 Receptor ACE2 is an 228