key: cord-0770454-i7ikhbvn
authors: Özceylan, Gökmen; Altuntaş, Sibel Baktir
title: Relación entre los síntomas iniciales y el pronóstico de los pacientes con Covid-19
date: 2021-06-25
journal: Aten Primaria
DOI: 10.1016/j.aprim.2021.102146
sha: 7d593aa1192fa33b7ca43c1d5d86f13313008424
doc_id: 770454
cord_uid: i7ikhbvn

Objective: Aims to describe the initial symptoms most related to the prognosis of Covid-19. Design: This is a retrospective cross sectional, quantative, data analyzed study. Site: This study was made in the family medicine centers (n=82) of Çorlu distrinct of Tekirdağ provience, in Turkey. Participants: The study included patients (n=1.506) who had a positive PCR test for Covid-19 from March to September 2020. And we asked them their initial sympotoms which bring them to the family medicine centers before the test. Main measurements: The participants' age, gender, presence of chronic disease, and initial symptoms which they come to a healthcare facility were evaluated. These variables were analyzed in terms of length of hospital stay, intensive care unit admission and mortality rates. Results: The most common initial symptom in Covid-19 patients was cough. The presence of a chronic disease, the shortness of breath, malaise, the loss of smell and taste, and vomiting were found to be associated with an increased mortality rate. Advanced age, the presence of cough, malaise, the loss of smell and taste, and vomiting as the initial symptoms were found to have increased the likelihood of being admitted to the intensive care unit. Conclusions: The authors advise placing more attention on the initial symptoms of cough, malaise, the loss of smell and taste and vomiting in Covid-19 patients. Because these symptoms are related with severe prognosis indicators.

1 What is known on the topic 2 -Fever measurement is performed while entering common areas all over the world for the 3 purpose of screening -A common algorithm could not be created to suspect Covid-19 in health centers where PCR 5 testing cannot be performed. 6 -Although the symptoms seen in Covid-19 have been shown in many studies, there are not 7

enough studies showing what the initial symptoms are and the relationship of these symptoms 8 with prognosis. 9

What this study contributes 10 -This study shows that for covid-19 screening, the complaint of cough should be considered as 11 the first application complaint rather than fever control in common areas 12 -In health centers where Covid-19 PCR testing cannot be performed, Covid 19 provides 13

information to an algorithm to be created from initial symptoms. 14 -This study particularly reveals the frequency of initial symptoms of Covid 19, as well as their 15 relationship with prognosis. 16

Objetivo 19

Aims to describe the initial symptoms most related to the prognosis of Covid-19. 20 21 Diseño 22

Este es un estudio retrospectivo de análisis de datos transversales, cuantificativos. 23

Este estudio se realizó en los centros de medicina familiar (n=82) de Çorlu distrinct de la 25 proviencia de Tekirdağ, en Turquía. 26 27 Participantes 28 el estudio incluyó pacientes (n=1,506) que tuvieron una prueba de PCR positiva para de marzo a septiembre de 2020. Y les preguntamos sus simpotomas iniciales que los llevan a 30 los centros de medicina familiar antes de la prueba. 31

Se evaluaron la edad, el sexo, la presencia de enfermedad crónica y los 2 síntomas iniciales de los participantes que llegan a un centro de atención 3 médica. Estas variables se analizaron en términos de duración de la estancia 4 hospitalaria, ingreso a la unidad de cuidados intensivos y tasas de mortalidad. El síntoma inicial de presentación más común en los pacientes con Covid-19 8 fue la tos. La presencia de una enfermedad crónica, la falta de aliento, el 9 malestar, la pérdida de olor y sabor y los vómitos se asociaron a una mayor 10 tasa de mortalidad. La edad avanzada, la presencia de tos, malestar, la pérdida 11 de olor y sabor, y vómitos como los síntomas iniciales se encontraron para 12 haber aumentado la probabilidad de ser admitido en la unidad de cuidados 13 intensivos 14 15

Conclusiones 16 los autores aconsejan prestar más atención a los síntomas iniciales de tos, malestar, pérdida 17 de olor y sabor y vómitos en pacientes con Covid-19. Porque estos síntomas están 18 relacionados con indicadores de pronóstico severos. 19

The initial symptoms and complaints of the participating the patients upon presenting to the 1 healthcare facilities were questioned. The symptoms were grouped as follows: fever, cough, 2 pain (muscle and joint pain, headache, sore throat, pain radiating to the back, and chest pain) , 3 malaise, the loss of smell and taste, diarrhea, nausea, vomiting, and expectoration. The initial 4 symptoms and complaints were taken from the family medicine center data records arranged at 5 the patients' first application to the health institution. 6

The length of hospital stay, the admission to the intensive care unit, and mortality data were 7 retrieved from the hospital records to evaluate prognosis, retrospectively. During this 8 evaluation, the patients were categorized into two groups as the patients with a length of 9 hospital stay of 14 days or shorter and the patients with a length of hospital stay of longer than 10 14 days, based on the official quarantine period of 14 days in Turkey. The statistical analysis 11 was performed using SPSS (Version 25.0, IBM, Chicago, IL, USA) software package. Basic 12 patient characteristics were expressed using descriptive statistics. A chi-square test was used in 13 the comparison of categorical variables. A binary logistic regression analysis was used to 14 determine the effects of symptoms on the admission to the intensive care unit, mortality, and 15 length of hospital stay. The variables that were found to be significant between the groups were 16 included in the multiple regression analysis. Multivariate regression analysis method was used 17

here. The odds ratio was given with a confidence interval (CI) of 95% on the regression table. A 18 p-value of less than 0.05 was considered statistically significant. 19

The mean age of the study participants was 38.6 ± 5.61 years (min: 1, max: 87). Of these 21 patients, 28.3% (n = 426) had one or more chronic diseases. Of the participating patients, 92.2% 22 had at least one or more symptoms (n = 1.389). Of all participating patients with positive Covid-23 19 PCR test, 3.1% (n = 46) were admitted to the intensive care unit, and 1.6% (n = 24) died. 24

The mean length of the hospital stay of the patients was 13.4 ± 5.9 (min: 1, max: 83) days. The analysis of sociodemographic features of the study patients is presented in Table 1 . According 1 to this table, Covid-19 most commonly occurred in adults aged 25-64 years whereas the disease 2 occurred in all age groups. The most common presenting symptom in Covid-19 patients was 3 cough (89.9%, n = 1.355). The frequency distribution of other symptoms is presented in Table  4 1. 5

The analysis of the distribution of the presenting symptoms and the complaints of the Covid-19 6 patients across the age groups was showed in Table 2 . According to this table cough was 7 uncommon in the 0-14 age group while the frequency of cough increased with increasing age (P 8 < 0.001). The frequency of fever was significantly higher in the 0-5 age group and the patients 9 aged 65 years and older compared to that in the other age groups (P < 0.001). The shortness of 10 breath was rarely observed in children aged 0-14 years while the frequency of this symptom 11 significantly increased with increasing age (P < 0.001). The presenting complaints of Covid-19 12 patients did not vary according to gender while only vomiting was more frequent in females ( 13 87,5 %) than in males (12,5%) (P = 0.017). 14 The frequency of cough, fever, shortness of breath, and malaise as the initial symptoms in 15

Covid-19 patients with a positive PCR test were significantly higher among patients with a 16 chronic disease than the other patients Cough was seen in 95.3% of patients with chronic 17 disease, while the rate of incidence in those without chronic disease was 87,9% (P<0,001).. 18

Fever was seen in 8.2% of patients with chronic disease, while the rate of incidence in others 19 was 3,7% (P<0,001). While the rate of shortness of breath as the initial symptom in patients 20 with chronic disease was 27.9%, it was 0,0% in those without chronic disease (P<0,001).. While 21 the rate of malaise as the initial symptom in patients with chronic disease was 3.1%, this rate 22 was 0.1% in those without chronic disease (P<0,001). 23

The analysis of the relationship between initial symptoms of Covid-19 patients and the length of 24 hospital stay, the admission to the intensive care unit, and mortality revealed that the length of hospital stay was longer than 14 days in the patients with fever, pain, malaise, and diarrhea (P < 1 0.001, P < 0.001, P = 0.042, and P = 0.007, respectively). In contrast, the patients with a cough 2 had a hospital stay shorter than 14 days (P = 0.002) (Table 3) . 3

The length of intensive care unit stay was longer among Covid-19 patients with a positive PCR 4 test who presented with fever, pain, malaise, and the loss of smell and taste (P = 0.011, P = 5 0.009, P < 0.001, and P < 0.001, respectively) ( Table 3) . 6

Among Covid-19 patients with a positive PCR test, the mortality rate was significantly higher in 7 those with fever and malaise as the presenting symptoms (P = 0.008 and P < 0.001, 8 respectively). The relationship between the prognostic factors and initial symptoms is presented 9

in Table 3 . 10

When the relationship between prognostic factors (the length of hospital stay, admission to 11 intensive care unit, mortality) and age, the presence of chronic disease and initial symptoms 12 was evaluated in Covid-19 patients with a positive PCR test using logistic regression analysis, 13 the presence of a chronic disease (OR=0.26, p=0.045) the shortness of breath (OR=5.68, 14 p=0.048), malaise (OR=729.44, p<0.001), the loss of smell and taste (OR=86.98, p=0.018), and 15 vomiting (OR=58.93, p=0.049) were found to be associated with an increased mortality rate 16 ( 

In the present study, approximately nine out of ten Covid-19 patients with a positive PCR test 2 were symptomatic upon admission to the hospital, and cough was the most common presenting 3

The study found that advanced age, presence of a chronic disease, shortness of breath, malaise, 5 loss of smell and taste, and nausea upon initial admission were associated with an increased 6 mortality rate. At the same time, admission to the intensive care unit was associated with 7 advanced age and the presence of cough, the shortness of breath, malaise, the loss of smell and 8 taste, and nausea on initial admission. Advanced age and the presence of malaise and nausea on 9 admission were associated with a length of hospital stay of longer than 14 days. 10

The hospitals in the provinces and towns and the Family Health Centers (FHCs) located in the 11 districts have taken important tasks in fighting against the coronavirus pandemic in Turkey. The 12 diagnostic tests were not performed in the FHCs. As per the Public Health Guidelines of the 13 Scientific Committee, the family physicians referred patients, suspected of having coronavirus 14 infection for diagnostic tests to be performed in the test centers. PCR testing for Covid-19 is 15 performed in the hospitals located in the towns and provinces in Turkey. The reason for 16

avoiding Covid-19 testing in the FHCs is that healthy individuals often present to the FHCs for 17 routine follow-up visits, and by avoiding Covid-19 testing in these facilities intends to minimize 18 the disease spread among these healthy individuals and to maintain preventive healthcare 19 services safely (5). 20

The initial symptoms of coronavirus infection are heterogeneous. In a study of 138 patients 21 admitted to the Covid-19 pneumonia in Wuhan city, the most common clinical symptoms were 22 fever (99%), malaise (70%), non-productive cough (59%) (6). Different from the literature data, 23 the most common presenting symptom was cough and not fever. Uncommon occurrence of an 24 alarming symptom as fever may complicate the diagnosis of Covid-19. In a study of 1.099 patients from Wuhan city and other districts in China, the rate of fever (axillary body 1 temperature above 37.5° C) was 44% on initial admission and 89% among the hospitalized 2 patients (7). In the present study, the rate of respiratory symptoms increased with age, and fever 3 was the most common presenting symptom in the 0-6 age group. The rate of chronic diseases 4 increases with age, and the authors consider this change presenting symptoms in Covid-19 5 patients. The relation of age with fever in the 0-6 age group and with cough in adults should not 6 be overlooked. The reason for the low frequency of fever as the initial symptom in the older 7 people can be explained by the easy access of these patients to paracetamol-containing 8 medications, reserve paracetamol pills are found at most homes, and that these patients have 9

made a habit of taking paracetamol pills without seeing a doctor when they have a fever. 10

In a Spanish study, respiratory symptoms such as cough and shortness of breath were less 11 common in Covid-19 patients older than 65 years than in young adults (8). In a study by Machhi 12 et al., cough was identified as the most common symptom in the first 14 days in the patients 13 with a mild disease course (9). Cough being the most common presenting symptom and its more 14 frequent occurrence in young adults are thought to be an important factor in rapid disease spread 15 in the study area. Thus, the presence of this symptom on initial presentation should suggest 16

Covid-19. Cough is an essential symptom in air-borne infections because bodily fluids spilled 17 by cough are important in the transfer and spread of an infection. 18

In a study in China, malaise was reported to be one of the most common symptoms of Covid-19 19, and the rate of malaise was 37% in the patients with a mild disease and 39% in the patients 20 with a severe disease course (10). Malaise, as a disease symptom, was often observed as from 21 the disease onset and has been the most intractable symptom depending on the clinical course of 22 the disease (11). In the present study, the frequency of malaise, as the initial presenting 23 symptom, was lower than those reported in the literature; however, it was more common in the 24 patients older than 65 years. This finding suggests that the presence of this non-specific symptom that can accompany many disease conditions should raise the suspicion of Covid-19 1 in the patients older than 65 years. 2

In the first cohort studies conducted in China, the loss of smell and taste (anosmia and 3 dysgeusia) was reported as common symptoms in . In a study of 59 4 patients in Italy, 34% of the patients had loss of smell or taste, and 19% had loss of both 5 sensations(10). They suggested that loss of smell could be an independent risk factor and used it 6 as a marker for detecting the patients with a mild disease presentation (13). It is unclear whether 7 this symptom could be a distinctive feature of Covid-19. It is, however, considered that this 8 symptom occurs in the coming days in the disease course. There is also no evidence as to 9

whether it leaves permanent damage (14). In the present study, the loss of smell and taste was 10 rare as the initial presenting symptom. Although it is considered a distinctive feature, this 11 symptom's rare occurrence on initial presentation poses another diagnostic challenge. 12

One study reported that only 16% of Covid-19 patients present with gastrointestinal symptoms, 13 including anorexia, nausea, vomiting, diarrhea, and abdominal pain (15). Gastrointestinal 14 symptoms such as nausea, vomiting, and diarrhea were found to be more common in patients in a study conducted in Turkey (16). It remains unknown whether coronavirus is 16 transmitted through the fecal-oral route; however, fecal-oral transmission was reported during 17 the SARS outbreak (17). Gastrointestinal symptoms in the present study were diarrhea, nausea, 18 and vomiting. Although the rate of these symptoms as the initial presenting symptoms was 19 lower than that reported in the literature, they were more common in the 0-14 age group. The 20 presence of gastrointestinal symptoms in pediatric patients should raise the flag for possible 21 diagnosis of Covid-19. 22

In a study examining disease prognosis, 13.8% of the patients required hospitalization, and of 23 these patients, 6.7% required admission to the intensive care unit (18). Covid-19 has a more 24 severe course in older people and those with a chronic disease (19). A modeling study related to the disease prognosis based on the data of Covid-19 patients in China reported that the rate of 1 hospitalization increased with age, and a hospitalization rate of 1% was reported in the 20-29 2 age group, a rate of 4% was reported in the 50-59 age group, and a rate of 18% was reported in 3 the patients aged older than 80 years. Advanced age was found to be associated with an 4 increased mortality rate (20). 5 It becomes apparent in recent studies that the presence of an accompanying chronic disease, 6 apart from advanced age, is another factor affecting prognosis. In a study involving 1.139 7

Covid-19 patients, the disease was found to be more common and had a high mortality rate in 8 the patients with cardiovascular disease, hypertension, chronic obstructive pulmonary, and 9 diabetes (21). In a study examining 355 patients who died of Covid-19 in Italy, only three 10 patients did not have an underlying comorbid condition (22). In the present study, one of every 11 three patients had an accompanying chronic disease. Similar to that in the literature, the 12 presence of a chronic disease is one of the factors affecting prognosis in the present study. Thus, 13 older patients presenting to the healthcare facilities during the pandemic must be questioned for 14 the presence of a chronic disease and referred to test centers without any further delay in case of 15 high suspicion index for The studies examining the relationship between disease symptoms, the patient complaints, and 17 disease prognosis reported that the presence of fever and the shortness of breath increases the 18 rate of admission to the intensive care unit. A meta-analysis study found that cough, nausea, 19 headache, sore throat, expectoration, diarrhea, myalgia, and fatigue are not associated with the 20 admission to the intensive care unit and prognosis (23). A Turkish study found a low rate of 21 admission to the intensive care unit and a low mortality rate in Covid-19 patients with COPD 22 and asthma if there is a cough. The reason for this finding was suggested to be high 23 pneumococcal vaccination rates among patients with chronic pulmonary disease aged 65 years 24 and older in Turkey (24). These neurological symptoms were associated with a severe disease course (25). In a Turkish 3 study, the patients with the loss of smell and taste were reported to have a low hospitalization 4 rate. A possible explanation for this finding is the occurrence of these symptoms in the early 5 disease stage (26). In the present study, the loss of smell and taste uncommon as an initial 6 presenting symptom although this symptom was one of the factors affecting mortality. 7

Therefore, the authors of the present study consider that spotting these symptoms may not ease 8 disease diagnosis, but their presence should be taken as an alarming sign for poor prognosis. 9

In conclusion, running diagnostic tests in every individual is the most crucial tool in combating 11 coronavirus infection, for which there is no known definitive therapy and preventive vaccine 12 despite its widespread occurrence. The authors advise physicians working in healthcare 13 facilities without testing facilities should place more attention on the initial presenting 14 complaints of cough, fever, malaise, and nausea in the patients suspected of having coronavirus 15 infection if they are to be referred to advanced healthcare facilities. It is essential to consider 16 that these symptoms are associated with poor prognosis and deserve an approach accordingly. 17

The authors recommend evaluating cough together with other possible factors, and the isolation 18 of the patients without a further delay in case of a high index of suspicion for Covid-19, and the 19 administration of antitussive therapy to relieve cough. Reducing the additional contribution of 20 cough to the contagiousness of infection may be necessary. 21

Fever in children, unlike in adults, is associated with disease prognosis, and the authors suggest 22

that Covid-19 should be added to the algorithmic approach to the children with fever. 23

It is essential to know that loss of smell and taste, a distinctive clinical finding for Covid-19, is 24 among uncommon presenting symptoms, but this symptom affects prognosis. Therefore, the 1 should be made even if this symptom is absent on initial admission. 2

Keeping in mind that age above 65 years, the presence of a comorbid chronic condition, 3 malaise, and nausea as the presenting symptoms could be a marker of poor prognosis in the 4 patients with a high index of suspicion for Covid-19, the patients presenting to the primary 5 healthcare facilities with these features must be referred to an advanced healthcare facility 6 without further delay. medRxiv. 2020; 15 2020 .02.22.20026500. doi:10.1101 Avci 

-This study shows that for covid-19 screening, the complaint of cough should be considered as the first application complaint rather than fever control in common areas -In health centers where Covid-19 PCR testing cannot be performed, Covid 19 provides information to an algorithm to be created from initial symptoms.

-This study particularly reveals the frequency of initial symptoms of Covid 19, as well as their relationship with prognosis. 

Critical care ütilization for the COVID-19 Outbreak in 5

Don't overlook digestive symptoms in patients with

COVID-19)

Covid-19 patients with negative computed tomography 10 findings; Evaluation of epidemiological, clinical and laboratory results

The SARS epidemic in Hong Kong

Baseline characteristics and outcomes of 1591 15 patients infected with SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy

Features of 20 133 UK patients in hospital 18 with covid-19 using the ISARIC WHO clinical characterisation protocol: Prospective 19 observational cohort study

Risk factors sssociated with acute respiratory distress 21 syndrome and death in patients with Coronavirus Disease 2019 pneumonia in Wuhan