In a recent study published in the journal Emerging Infectious Diseases, researchers analyzed and compared pre‒ and post‒COVID-19 diagnostic codes to identify symptoms that had higher encounter incidence in the post‒COVID-19 period as sequelae. COVID-19 sequelae and future emerging diseases can be generated and monitored using this method.
Study: Longitudinal Analysis of Electronic Health Information to Identify Possible COVID-19 Sequelae. Image Credit: p.ill.i / Shutterstock
SARS-CoV-2 is the causative agent of coronavirus disease 2019, which may result in several post-infection health conditions, including a broad spectrum of long-lasting sequelae. Previous studies have described symptoms experienced in the post-acute phase of COVID-19, including chest pains, malaise, fatigue, and conditions such as kidney failure, cardiomyopathy, venous thromboembolism, and lung diseases.
Clinical experiences have been documented to identify probable sequelae of emerging diseases; however, the approach may miss rare sequelae or those in which an increase in parameters is not very obvious. Large electronic medical record databases could help detect early warning signs, especially if the events leading to probable sequelae are dispersed over time.
About the study
The study aimed to identify possible COVID-19 sequelae in a nationwide database of healthcare encounters in the United States (US) by comparing pre-COVID-19 diagnosis codes with post-acute COVID-19 diagnosis codes.
The PHD-SR (premier healthcare database, special coronavirus disease 2019 release) database released on February 4, 2021, was used for the analysis. In addition, variables for the type of healthcare encounter (outpatient, inpatient, outpatient, and emergency encounters) and variables for the sequence of encounter dates were analyzed.
The encounter date variables included hospitalization date, duration of hospitalization, duration between healthcare encounters, the month of hospital discharge), and ICD-10-CM (international classification of diseases, 10th revision, clinical modification) codes at discharge. Individuals with an initial outpatient or inpatient encounter due to COVID-19 (i.e., ICD-10-CM codes for discharge after COVID-19-associated hospitalization), who received hospital discharge between January 1, 2019, and December 31, 2020, were analyzed. Pregnant women were excluded from the analysis.
The index date of COVID-19 considered was the date of the initial healthcare encounter. Healthcare encounters in the pre-SARS-CoV-2 infection period comprised encounters a year prior to an individual's initial healthcare encounter due to COVID-19. Healthcare encounters in the post-SARS-CoV-2 infection period comprised the initial healthcare encounter due to COVID-19 and the subsequent health encounters.
RR (relative rate) of post-SARS-CoV-2 infection diagnoses to pre-SARS-CoV-2 infection diagnoses were calculated in the period after acute COVID-19, stratified as 60 days to 89 days, 90 days to 119 days, and 120 days to 149 days, wherein day 0 represented the index date. Diagnoses with significantly higher rates of healthcare encounters >60.0 days post the index date from the pre-SARS-CoV-2 infection period was defined as probable post-acute SARS-CoV-2 infection sequelae.
A total of 385,067 eligible individuals were considered for the analysis, most (59%) of whom were women with a median age of 54. The median values for healthcare encounters per COVID-19 patient were two pre-SARS-CoV-2 infection encounters and one post-SARS-CoV-2 infection encounter. Most (87%) of the encounters were in outpatient settings, and the median duration of hospitalization for encounters in inpatient settings was 4.0 days.
Healthcare encounters associated with parasitic and infectious disease sequelae were greater after ≥149.0 days of the index COVID-19 dates (RR 12 for 120 days to 149 days). In addition, many months after the post-acute COVID-19 period, physicians encountered more cases of headache, fatigue, pneumonia, and ARDS (acute respiratory distress syndrome).
Sequelae of intensive care unit treatment were identified, including myopathy (RR of 5.0 at 60 days to 89 days), polyneuropathy (RR of 9.1 in the 90-day to 119-day period), pressure-type ulcers (third and fourth stage, RR of 1.6 to 1.7 at 60 days to 89 days) and non-scarring loss of hair (RR of 2.3 to 3.5 at several intervals after 60 days). Codes for sepsis and cardiomyopathy (RR of 9.8 in the 60-day to 89-day period) were increased only in the initial 90 days post-index date.
The rates for non-follicular diffuse lymphoma were elevated at 60 days to 119 days (RR of 273 to 411), but most healthcare encounters had been reported for a single COVID-19 patient. The healthcare encounters for third-stage chronic renal disease [glomerular filtration rate (GFR) values of 30 to 59 mL/min/1.7 m2] with RR of 2.5 to 6.4 after two months and for elevated hepatic aminotransferase values (RR of 4.8 to 6.5 after 60.0 days) were increased for many months post-index date through the 120-day to 149-day period post-acute COVID-19.
Infective myocarditis encounters (RR of 13) were more significant in the 90-day to 119-day period. The probable respiratory, cardiac, hepatic, and renal COVID-19 sequelae identified in the present study were concordant with previously published studies' findings. In the post-SARS-CoV-2 infection period, there were more cases of third-stage renal disease than in the pre-SARS-CoV-2 infection period.
Overall, the study findings showed a hypothesis-generating approach that could aid in identifying the initial signals of probable sequelae of novel emerging diseases and inform studies for identifying, characterizing, and refining probable sequelae for COVID-19 and other diseases. The study findings were consistent with the results of other studies that used different methods for identifying probable COVID-19 sequelae, such as directly surveying individuals with or without previous COVID-19 test results.