Acute Symptoms of Mild to Moderate COVID-19 Are Highly Heterogeneous Across Individuals and Over Time

Abstract

Background: The symptoms of coronavirus disease 2019 (COVID-19) appear to be heterogenous, and the typical course of these symptoms is unknown. Our objectives were to characterize the common trajectories of COVID-19 symptoms and to assess how symptom course predicts other symptom changes as well as clinical deterioration.

Methods: One hundred sixty-two participants with acute COVID-19 responded to surveys up to 31 times for up to 17 days. Several statistical methods were used to characterize the temporal dynamics of these symptoms. Because 9 participants showed clinical deterioration, we explored whether these participants showed any differences in symptom profiles.

Results: Trajectories varied greatly between individuals, with many having persistently severe symptoms or developing new symptoms several days after being diagnosed. A typical trajectory was for a symptom to improve at a decremental rate, with most symptoms still persisting to some degree at the end of the reporting period. The pattern of symptoms over time suggested a fluctuating course for many patients. Participants who showed clinical deterioration were more likely to present with higher reports of severity of cough and diarrhea.

Conclusions: The course of symptoms during the initial weeks of COVID-19 is highly heterogeneous and is neither predictable nor easily characterized using typical survey methods. This has implications for clinical care and early-treatment clinical trials. Additional research is needed to determine whether the decelerating improvement pattern seen in our data is related to the phenomenon of patients reporting long-term symptoms and whether higher symptoms of diarrhea in early illness presages deterioration.

Keywords: COVID-19; cough; humans; severe acute respiratory syndrome coronavirus 2; smell; taste.

Graphical Abstract

Figure 1.

Up to a 17-day course (median, 16) of symptoms for 10 randomly selected participants on a per-symptom basis. Each row includes data for 1 participant. Time points are ~12 hours apart on up to 17 days. Note the “saw tooth” pattern for many participants, indicating symptoms that wax and wane. An expanded version of this figure is available in Supplementary Data.

Figure 2.

Representative courses of coronavirus disease 2019 symptoms across up to 17 days (median, 16 days). Each time point represents the average of 3 days, except that Time 4 included up to 5 days, but more typically 3 or 4. The Average line represents the average trajectory across the entire data set. The Rapid improvement and Slower improvement lines are the average for the 10 participants, with the strongest linear slope in the improving and worsening directions. For diarrhea, the quadratic slope was used as the linear slope had no variance. A worsening linear slope did not always translate to symptoms being aggravated overall because trajectories were curvilinear. Slower improvement lines are not depicted for appetite or chills because too few participants experienced worsening in this symptom as indexed by the linear slope. The Deteriorated lines provide the slope for the single participant who deteriorated midway through the trial yet provided a full set of data.

Figure 3.

On the left, the average course of 5 common symptoms across up to 17 days (median number of days, 16). On the right, 9 randomly selected participants (of those who had all 5 symptoms) and their individual trajectories. Note that because the model fits a curve to data points, the curve can transiently go above the response scale. An expanded version of this figure is available in the Supplementary Data.