Main finding of this study

Our results indicate that loss of taste or smell was present in three of the four combinations of symptoms associated with positive cases of COVID-19. Although most settings related to positive cases of COVID-19 contain the symptom "loss of taste or smell", in cases that did not test positive for COVID-19, this symptom also appears in a smaller portion, but in this case, it does not is associated with fever. Respiratory distress was present both in positive and negative cases, although to a lesser extent in negative cases. The isolated symptom of fatigue was not able to configure a positive case of Sars-Cov-2, but when this presented in combination with the loss of smell or taste, it configured a combination of symptoms associated with the presence of the infection.

What is already known on this topic

There is a wide range of symptoms reported by people who have had COVID-19. Anyone can have mild or severe symptoms of the disease, even if they do not belong to any specific risk group. The period of onset of symptoms is between two to 14 days after exposure to the virus. Fever, chills, cough, difficulty breathing, fatigue, body aches, headache, loss of taste or smell, sore throat, nasal congestion, nausea, diarrhea, appetite loss, and chills are some of these reported symptoms19,20.

The sudden and isolated loss of smell or taste, in the absence of inflammatory diseases of the upper airways, such as allergic rhinitis, chronic rhinosinusitis, nasal polyposis, and other conditions, seems to be a warning sign to health professionals of the suspicion of COVID-1921. Our results showed that the loss of taste or smell in the absence of the headache would be a configuration of symptoms associated with the presence of COVID-19. Headache, unlike fever, has been reported less frequently in scientific articles describing the manifestations of COVID-1922. On the other hand, headache is among the most common symptoms reported in inflammatory disorders of the upper respiratory tract and is often confused with migraines23.

An important health surveillance strategy to reduce disease transmission is its rapid detection as early as possible so that cases can be isolated and treated24. The investigation of a possible case of COVID-19 is usually based on a combination of clinical parameters that the patient presents (e.g., fever, shortness of breath, and loss of smell and taste). It is from the observed clinical parameters that the search and infection control policies are triggered25. Given the scarcity of resources in many countries, testing, in most cases, is only performed if the patient's clinical parameters lead to suspicion of the disease.

Considering the scarce information about studies to identify a set of symptoms for diagnosing COVID-19 cases in the Primary Care Service, this study intends to contribute to the clinical diagnosis of COVID-19 in this scenario. In our results, loss of taste or smell was present in three of the four combinations of symptoms associated with positive cases of COVID-19, which were similarly reported in several studies21,26, however, most of them were carried out in different settings like hospitals, outpatients clinics or symptoms tracker apps27,28 and a small part, in Primary Care29. Altered taste perception (dysgeusia) in Sars-Cov-2 patients is widely reported in studies and can be found in up to 44% of cases30.

Both positive and negative cases of COVID-19 contain the symptom "loss of taste or smell", although, in the last, it appears in a smaller portion and is not associated with fever. What could explain the "loss of taste or smell" appearing in both positive and negative patients for COVID-19 would be the duration of the symptom, which usually remains for a few weeks after the patient becomes negative31.

Respiratory distress was present both in positive and negative cases, although to a lesser extent in negative cases. The isolated symptom of fatigue was not able to configure a positive case of Sars-Cov-2, but when this presented in combination with the loss of smell or taste, it configured a combination of symptoms associated with the presence of the infection. Fatigue is a common symptom in those with symptomatic COVID-19 and also persists after COVID-1932. Perhaps the fact that both respiratory distress and fatigue are associated not only with Sars-Cov-2 but also with other diseases, like, cardiopulmonary, renal, gastrointestinal, oncology, and infectious diseases33,34,35,36, may explain why these symptoms are not associated solely with positive cases of Sars-Cov-2.

In this study, Qualitative Comparative Analysis Method was chosen due to its capacity to analyze the combinations of signs and symptoms to evaluate the clinical presentation of COVID-19 and model these relationships to obtain subsets that explain a given outcome. It is a usual method applied for social and political research but more recently, it is utilized to respond to some questions related to public health37,38.

What this study adds

Our results may be useful to guide the diagnosis of Sars-Cov-2 in scenarios where testing is not possible, contributing to increasing knowledge about which sets of symptoms could predict the disease. More comprehensive studies, involving different locations, using other analysis techniques could contribute to improving access to the diagnosis of COVID-19.

Limitations of this study

As a limitation, it was not possible to obtain reliable information on the duration of symptoms in the cases at the time of performing the diagnostic test, so part of the tests may have been performed outside the indicated period for testing, which may have compromised the result. Another issue that was not considered was the type of virus variant, given that the different variants have specific peculiarities, the symptoms may have varied during the collection period. However, despite these limitations, these results can contribute to diagnostic guidance in locations that do not have access to diagnostic tests.

The symptoms used in this study were self-reported by the participants, so they present a certain degree of subjectivity. Loss of taste or smell, for example, despite its subjectivity, was reported in a National Survey in the United States by about 38% of suspected COVID-19 patients and was included by the CDC as one of the main symptoms associated with the disease39.

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