To the editor
We have read with interest the recent paper of Chen Y et al., about antibody prevalence among healthcare workers (HCWs) exposed to COVID-19
1
. They found a significant incidence of asymptomatic HCWs previously exposed to COVID-19 patients. We have performed a cross-sectional descriptive study to assess the clinical and epidemiological characteristics of mildly symptomatic COVID-19 in a series of Spanish HCWs outpatients with reverse transcription polymerase chain reaction (RT-PCR)-confirmed disease. Nowadays, Spain has the highest number of confirmed cases of COVID-19 among its HCWs around the world. The study protocol was approved by the clinical research ethics committee of the Hospital Clinico San Carlos de Madrid and complied with the clinical research guidelines of the Declaration of Helsinki. Criteria for inclusion in our study were: age over 18 years, laboratory (RT-PCR)-confirmed COVID-19; clinical cure (lack of symptoms except olfactory and gustatory symptoms), healthcare worker (both hospital and community care staff) and reading comprehension of Spanish. Exclusion criteria were hospitalization, symptom persistence at the study outset or no laboratory confirmation of COVID-19 infection. Clinical and epidemiological data was collected though a voluntary, anonymous, self-administered online questionnaire, accessible from Google Docs. The questionnaire consisted of three general questions (about age, sex and occupation), two about general clinical issues (comorbidities and systemic treatments), and two about COVID-19 symptoms. Questionnaire data were transferred to an Excel database. Statistical analysis was performed using the Statistical Package for the Social Sciences for Windows (SPSS version 22,0; IBM Corp, Armonk, NY, USA). Categorical variables are provided as counts and percentages and continuous measurements as the mean, standard deviation (SD) and range. We compared means for continuous variables through independent group t tests. Proportions of categorical variables were compared using the χ2 test. Significance was set at P < 0.05.The final study population comprised 1177 patients fulfilling the inclusion and exclusion criteria. Mean patient age was 41.7 (11.6) years (range 19–68). There were 866 women (73.6%). There were no differences in age according to gender (p = 0.09). Most patients were physicians (62.2%) or nurses (29%). 405 patients (34.4%) had allergies (to pollens, dust mites, epithelia of animals, etc.). Most frequent concomitant diseases were arterial hypertension (6.9%), asthma (6.6%) and high blood cholesterol (5.7%).
Fever at some time during the disease course was reported by 842 patients (71.5%) (Table 1). Each patient described a mean of 7.88 (3.26) symptoms.
Table 1Symptom frequencies: overall and by sex.
| SIGNS AND SYMPTOMS | TOTAL (n = 1177) (%) | MEN (n = 310) (%) | WOMEN (n = 866) (%) | p |
| Fever | 842 (71.5) | 241 (78.5) | 600 (71.5) | 0.018 |
| < 37.5 °C | 192 (22.8)* | 34 (14.1)* | 158 (26.3)* | |
| 37.6–38 °C | 393 (46.7)* | 105 (43.6)* | 287 (47.8)* | <0.001 |
| 38.1–39 °C | 232 (27.6)* | 91 (37.8)* | 141 (23.5)* | |
| > 39 °C | 25 (3)* | 11 (4.6)* | 14 (2.3)* | |
| Fatigue | 878 (74.6) | 216 (69.7) | 662 (76.4) | 0.02 |
| Cough | 827 (70.3) | 216 (69.7) | 610 (70.4) | 0.8 |
| Myalgia | 822 (69.8) | 223 (71.9) | 599 (69.2) | 0.36 |
| Headache | 814 (69.2) | 186 (60.0) | 628 (72.5) | <0.001 |
| Anosmia | 625 (53.1) | 130 (41.9) | 495 (57.2) | <0.001 |
| Nasal congestion | 570 (48.4) | 117 (37.7) | 453 (52.3) | <0.001 |
| Sore throat | 552 (46.9) | 115 (37.1) | 436 (50.3) | <0.001 |
| Diarrhea | 511 (43.4) | 111 (35.8) | 399 (46.1) | 0.002 |
| Chills | 509 (43.2) | 129 (41.6) | 380 (43.9) | 0.49 |
| Ageusia | 405 (34.4) | 78 (25.2) | 327 (37.8) | <0.001 |
| Dysgeusia | 380 (32.3) | 106 (34.2) | 274 (31.6) | 0.41 |
| Nausea | 243 (20.6) | 29 (9.4) | 214 (24.7) | <0.001 |
| Stabbing chest pain | 240 (20.4) | 44 (14.2) | 196 (22.6) | 0.002 |
| Shortness of breath | 218 (18.5) | 38 (12.3) | 180 (20.8) | 0.001 |
| Hyposmia | 200 (17) | 59 (19) | 141 (16.3) | 0.27 |
| Abdominal pain | 167 (14.2) | 25 (8.1) | 142 (16.4) | <0.001 |
| Conjunctivitis | 104 (8.8) | 21 (6.8) | 82 (9.5) | 0.15 |
| Dizziness | 86 (7.3) | 9 (2.9) | 77 (8.9) | 0.001 |
| Mouth and tongue sores | 79 (6.7) | 12 (3.9) | 67 (7.7) | 0.02 |
| Vomiting | 55 (4.7) | 5 (1.6) | 50 (5.8) | 0.003 |
| Skin rash | 15 (1.3) | 2 (0.6) | 13 (1.5) | 0.25 |
| Asymptomatic | 23 (1.9) | 10 (3.2) | 13 (1.5) | 0.06 |
(* among patients with fever).
Significant differences emerged between both sexes in the frequencies of most of the symptoms listed (15 of 21).
In Table 2 we provide symptom frequencies by age group.
Table 2Symptom frequencies: overall and by age group.
| SIGNS AND SYMPTOMS | TOTAL (n = 1177) (%) | < 30 years (n = 278) (%) | 31–40 years (n = 285) (%) | 41–50 years (n = 296) (%) | 51–60 years (n = 246) (%) | > 60 years (n = 72) (%) | p |
| Fever < 37.5 °C 37.6–38 °C 38.1–39 °C > 39 °C | 842 (71.5) 192 (22.8)* 393 (46.7)* 232 (27.6)* 25 (3)* | 168 (62.9) 35 (20.8)* 83 (49.4)* 46 (27.4)* 4 (2.4)* | 212 (76.5) 50 (23.6)* 97 (45.8)* 58 (27.4)* 7 (3.3)* | 228 (78.1) 59 (25.9)* 102 (44.7)* 58 (25.4)* 9 (3.9)* | 176 (73) 33 (18.8)* 85 (48.3)* 53 (30.1)* 5 (2.8)* | 58 (82.9) 15 (25.9)* 26 (44.8)* 17 (29.3)* 0 | <0.001 0.86 |
| Fatigue | 878 (74.6) | 196 (70.5) | 214 (75.1) | 227 (76.7) | 188 (76.4) | 53 (73.6) | 0.46 |
| Cough | 827 (70.3) | 177 (63.7) | 207 (72.6) | 216 (73) | 174 (70.7) | 53 (73.6) | 0.09 |
| Myalgia | 822 (69.8) | 180 (64.7) | 186 (65.3) | 220 (74.3) | 186 (75.6) | 50 (69.4) | 0.01 |
| Headache | 814 (69.2) | 201 (72.3) | 209 (73.3) | 215 (72.6) | 147 (59.8) | 42 (58.3) | 0.001 |
| Anosmia | 625 (53.1) | 163 (58.6) | 179 (62.8) | 148 (50) | 105 (42.7) | 30 (41.7) | <0.001 |
| Nasal congestion | 570 (48.4) | 158 (56.8) | 160 (56.1) | 130 (43.9) | 96 (39) | 26 (36.1) | <0.001 |
| Sore throat | 552 (46.9) | 123 (44.2) | 145 (50.9) | 148 (50) | 105 (42.7) | 31 (43.1) | 0.21 |
| Diarrhea | 511 (43.4) | 107 (38.5) | 126 (44.2) | 131 (44.3) | 115 (46.7) | 32 (44.4) | 0.4 |
| Chills | 509 (43.2) | 93 (33.5) | 117 (41.1) | 154 (52) | 111 (45.1) | 34 (47.2) | <0.001 |
| Ageusia | 405 (34.4) | 121 (43.5) | 110 (38.6) | 95 (32.1) | 62 (25.2) | 17 (23.6) | <0.001 |
| Dysgeusia | 380 (32.3) | 76 (27.3) | 94 (33) | 98 (33.1) | 89 (36.2) | 23 (31.9) | 0.29 |
| Nausea | 243 (20.6) | 29 (9.4) | 62 (21.8) | 61 (20.6) | 53 (21.5) | 11 (15.3) | 0.8 |
| Stabbing chest pain | 240 (20.4) | 51 (18.3) | 58 (20.4) | 73 (24.7) | 47 (19.1) | 11 (15.3) | 0.24 |
| Shortness of breath | 218 (18.5) | 50 (18) | 54 (18.9) | 55 (18.6) | 47 (19.1) | 12 (16.7) | 0.99 |
| Hyposmia | 200 (17) | 45 (16.2) | 41 (14.4) | 45 (15.2) | 54 (22) | 15 (20.8) | 0.13 |
| Abdominal pain | 167 (14.2) | 32 (11.5) | 39 (12.7) | 45 (15.2) | 41 (16.7) | 10 (13.9) | 0.53 |
| Conjunctivitis | 104 (8.8) | 24 (8.6) | 18 (6.3) | 31 (10.5) | 23 (9.3) | 8 (11.1) | 0.44 |
| Dizziness | 86 (7.3) | 34 (12.2) | 17 (6) | 16 (5.4) | 14 (5.7) | 5 (6.9) | 0.01 |
| Mouth and tongue sores | 79 (6.7) | 24 (8.6) | 28 (9.8) | 15 (5.1) | 6 (2.4) | 6 (8.3) | 0.005 |
| Vomiting | 55 (4.7) | 11 (4) | 12 (4.2) | 15 (5.1) | 17 (6.9) | 0 | 0.14 |
| Skin rash | 15 (1.3) | 4 (1.4) | 4 (1.4) | 4 (1.4) | 1 (0.4) | 2 (2.8) | 0.58 |
| Asymptomatic | 23 (1.9) | 8 (2.9) | 3 (1.1) | 4 (1.4) | 5 (2) | 3 (4.2) | 0.3 |
(* among patients with fever).
So, while the symptoms most frequently reported were similar to those described in hospitalized patients (fatigue, fever and cough)
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, other symptoms appeared with greater frequency (myalgia, headache, nasal congestion, sore throat, diarrhea or chills). In fact, in several studies regarding hospitalized patients, several symptoms that are common in outpatients with mild infection have been reported as infrequent- Goyal P.
- Choi J.J.
- Pinheiro L.C.
- Schenck E.J.
- Chen R.
- Jabri A.
- Satlin M.J.
- Jr Campion TR
- Nahid M.
- Ringel J.B.
- Hoffman K.L.
- Alshak M.N.
- Li H.A.
- Wehmeyer G.T.
- Rajan M.
- Reshetnyak E.
- Hupert N.
- Horn E.M.
- Martinez F.J.
- Gulick R.M.
- Safford M.M
Clinical Characteristics of Covid-19 in New York City.
N Engl J Med. 2020; (Apr 17)
4
: myalgia (21.2–36.2%), headache (9.9–18.6%), nasal congestion (0.4–3.9%) or diarrhea (4.8–12.6%). Similarly, other common symptoms in mildly symptomatic patients seen here and in other studies were not mentioned in hospitalized patients, even in the larger series- Fu L.
- Wang B.
- Yuan T.
- Chen X.
- Ao Y.
- Fitzpatrick T.
- Li P.
- Zhou Y.
- Lin Y.F.
- Duan Q.
- Luo G.
- Fan S.
- Lu Y.
- Feng A.
- Zhan Y.
- Liang B.
- Cai W.
- Zhang L.
- Du X.
- Li L.
- Shu Y.
- Zou H
Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis.
J Infect. 2020; (Apr 10)
2
,3
, like anosmia and ageusia, which have been reported with similar incidence to the present study (71.6%) in a study among 202 mildly symptomatic outpatients from Italy (64.4%).- Goyal P.
- Choi J.J.
- Pinheiro L.C.
- Schenck E.J.
- Chen R.
- Jabri A.
- Satlin M.J.
- Jr Campion TR
- Nahid M.
- Ringel J.B.
- Hoffman K.L.
- Alshak M.N.
- Li H.A.
- Wehmeyer G.T.
- Rajan M.
- Reshetnyak E.
- Hupert N.
- Horn E.M.
- Martinez F.J.
- Gulick R.M.
- Safford M.M
Clinical Characteristics of Covid-19 in New York City.
N Engl J Med. 2020; (Apr 17)
5
Besides, in another recent study, anosmia was strongly and independently associated with outpatient care in a trial designed to identify risk factors for hospital admission, suggesting that this factor could be a marker of milder manifestations of COVID-19.6
The results of our study indicate that loss of smell is even more frequent in mildly symptomatic patients under 40 years of age. Rates of asymptomatic patients from 1.4% to 11.6% of patients have been provided.4
In our study, this rate was 1.9%, thus, within the lower range of reported prevalence. However, the purpose of our study was not to detect asymptomatic patients. Besides, diagnostic tests for healthcare staff in the initial stages of the epidemic in our country were practically restricted to symptomatic cases, so these asymptomatic patients were HCWs in contact with confirmed COVID-19 cases who were tested because of epidemiological or occupational health risks (and have positive RT-PCR, unlike the HCWs in Chen Y at al´s study). Finally, differences emerged between men and women in the presentation of most symptoms [just like Chen Y et al. study,- Fu L.
- Wang B.
- Yuan T.
- Chen X.
- Ao Y.
- Fitzpatrick T.
- Li P.
- Zhou Y.
- Lin Y.F.
- Duan Q.
- Luo G.
- Fan S.
- Lu Y.
- Feng A.
- Zhan Y.
- Liang B.
- Cai W.
- Zhang L.
- Du X.
- Li L.
- Shu Y.
- Zou H
Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis.
J Infect. 2020; (Apr 10)
1
the proportion of females in our study was high (73.6%) and may be attributed to the inclusion criteria (HCWs, 70% of which in Spain are women)]. Some symptoms were also more frequent depending on patient age.Our study has several obvious limitations. First, data were self-reported, so recall biases are likely. However, our study was conducted mid-pandemic and participants had just recovered. In addition, it was based on a cross-sectional survey, although only recovered patients with no active symptoms were included to obtain data for the whole disease course. The only exception was that we accepted patients with persisting olfactory and gustatory alterations, because has been reported that 56% of patients show persistent olfactory dysfunction over the days following resolution of the general clinical manifestations of COVID-19
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. Finally, to avoid possible infections, this was an online-based voluntary study, so the possibility of selection bias exists.- Lechien J.R.
- Chiesa-Estomba C.M.
- De Siati D.R.
- Horoi M.
- Le Bon S.D.
- Rodriguez A.
- Dequanter D.
- Blecic S.
- El Afia F.
- Distinguin L.
- Chekkoury-Idrissi Y.
- Hans S.
- Delgado I.L.
- Calvo-Henriquez C.
- Lavigne P.
- Falanga C.
- Barillari M.R.
- Cammaroto G.
- Khalife M.
- Leich P.
- Souchay C.
- Rossi C.
- Journe F.
- Hsieh J.
- Edjlali M.
- Carlier R.
- Ris L.
- Lovato A.
- De Filippis C.
- Coppee F.
- Fakhry N.
- Ayad T.
- Saussez S
Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.
Eur Arch Otorhinolaryngol. 2020; (Apr 6)
To the best of our knowledge, this is the largest described clinical case series of mildly symptomatic HCWs COVID-19 disease outpatients. Their particular clinical spectrum could help physicians make a correct diagnosis and thus help avoid infection spread, as a health priority in most countries.
References
- High SARS-CoV-2 antibody prevalence among healthcare workers exposed to COVID-19 patients.J Infect. 2020; (Jun 4:S0163-4453(20)30344-3)
- Clinical Characteristics of Coronavirus Disease 2019 in China.N Engl J Med. 2020; (Feb 28)
- Clinical Characteristics of Covid-19 in New York City.N Engl J Med. 2020; (Apr 17)
- Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis.J Infect. 2020; (Apr 10)
- Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection.JAMA. 2020; (Apr 22)
- Self-reported olfactory loss associates with outpatient clinical course in Covid-19.Int Forum Allergy Rhinol. 2020; (Apr 24)
- Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.Eur Arch Otorhinolaryngol. 2020; (Apr 6)
Article info
Publication history
Published online: July 02, 2020
Accepted:
July 1,
2020
Identification
Copyright
© 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
