History of COVID-19 increases risk of fatigue and other long COVID symptoms in adults and children

Many individuals who have recovered from acute infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop persistent symptoms collectively referred to as post-acute sequelae of the coronavirus disease 2019 (PASC) or long COVID. Some common long COVID symptoms include fatigue, cognitive impairment, diabetes, shortness of breath, mental health conditions, cardiovascular diseases, and adverse kidney conditions.

Study: Association between SARS-CoV-2 Infection and Select Symptoms and Conditions 31 to 150 Days After Testing among Children and Adults. Image Credit: fizkes /


The incidence of PASC is significantly higher among those who suffered severe infection, including COVID-19 patients who required hospital admission and invasive mechanical ventilation. Older COVID-19 survivors are also more likely to develop long COVID. The prevalence of long COVID emphasizes the importance of understanding the symptoms and conditions related to this condition to ultimately guide clinicians to manage PASC more effectively.

More research is required to better understand new symptoms and conditions after recovery from SARS-CoV-2 infection. Most studies related to PASC have focused on specific patient populations, such as Medicare patients or United States veterans. Other studies that targeted the general adult population did not have a well-defined control group, thus minimizing the significance of these studies. 

Very few studies related to PASC among children and non-hospitalized adults are available. However, a recent study published on the medRxiv* preprint server determines whether certain symptoms and conditions were linked with SARS-CoV-2 infection among adults and children. This observation was compared with a control group comprising individuals with negative SARS-CoV-2 tests.

About the study

In this study, the authors collected electronic health records (EHR) data from health systems associated with PCORnet. PCORnet is a network that consists of more than 60 participating sites related to the healthcare system.

Relevant patient data was acquired from PCORnet between March 1, 2020, and May 31, 2020. A total of 3,091,580 adults above 20 years of age and 675,643 children younger than 19 years of age, who met all inclusion criteria, were included in this study. About 88% of the patients in this study were male and were relatively older, with a mean age of 59 years.

Key findings

Adults who tested positive for SARS-CoV-2 were at a higher risk of being diagnosed with certain symptoms, including fatigue and shortness of breath. These individuals were also at an increased risk of developing new conditions, such as diabetes and hematologic disorders, as potential PASC between 31 and 150 days after testing positive. These conditions and symptoms were absent in the control group.

Children hospitalized with COVID-19 also experienced persistent symptoms, such as shortness of breath. The comprehensive EHRs helped researchers adjust for various patient symptoms and conditions before and after SARS-CoV-2 infection.

A significant difference in the prevalence of symptoms and incidence of conditions following COVID-19 was found between hospitalized and non-hospitalized groups. After adjusting for confounding factors, the hospitalized group with severe SARS-CoV-2 infection was at an increased risk of developing type 1 or 2 diabetes, hematologic disorders, and respiratory diseases. Notably, these outcomes were not observed among hospitalized patients who were negative for COVID-19. 

Compared to hospitalized children who tested negative for COVID-19, those who tested positive were more susceptible to developing at least one symptom, such as shortness of breath. This finding agrees with previous reports revealing that COVID-19 patients with acute infection were more likely to develop PASC conditions and symptoms.

Regression analyses that adjusted for confounding factors revealed that non-hospitalized COVID-19-positive adults were more likely to be diagnosed with shortness of breath, fatigue, and hematologic disorders than the SARS-CoV-2 negative group. However, non-hospitalized children with a history of COVID-19 and those who tested negative for this infection were not at an increased risk of experiencing any particular symptom. 

An increased prevalence of certain conditions was reported among hospitalized adults who were negative for COVID-19, including major cardiovascular events, neurologic disorders, and mental health conditions.

Compared to the control group, individuals with severe SARS-CoV-2 infection were more likely to experience memory difficulties, kidney injury, respiratory failure, fatigue, cardiac rhythm disorders, and hypercoagulability. 


The current study has several limitations, including using EHR data to ascertain symptoms and conditions, which might lead to an underestimation of true symptom prevalence. In addition, in this data system, the symptoms and conditions are defined in codes, which might reduce the specificity of the analysis. Another limitation of this study is the incomplete capture of vaccination data from EHRs.

Despite these limitations, the current study provided new insights into symptoms and conditions associated with PASC in adults and children. Moreover, the researchers observed that COVID-19 patients were at an increased risk of developing certain conditions, including nervous system diseases, cardiovascular diseases, mental health conditions, and respiratory conditions. Therefore, this study will help clinicians to monitor the development of persistent symptoms and conditions after SARS-CoV-2 infection.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Originally Posted Here

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