Discussion
In this study, we found 41% of outpatients infected with SARS-CoV-2 had positive pulmonary findings by LUS. Our cohort was well balanced between men and women and racially and ethnically diverse. Patients presented with a broad range of symptoms, similar to that described in prior studies.25
Despite the high prevalence of positive LUS examinations, no patients in our study developed severe COVID-19 requiring mechanical ventilation or resulting in death through 8 weeks of follow-up. Only one patient required a brief overnight hospitalisation for SOB and fever. This suggests that the presence of pulmonary disease detectable by LUS at baseline is not a specific predictor of worse long-term clinical outcomes in this cohort of outpatients. This is in line with a study that looked at 30-day outcomes in 27 non-critical ER patients undergoing LUS, which did not find LUS to be prognostic of mortality or short-term complications but did predict likelihood of admission despite noncritical symptoms.26 Similarly, Colombi et al27 showed that while LUS sensitivity for COVID-19 pneumonia was similar to CT in emergency department patients, there was limited prognostic value. This is in contrast to studies that have shown LUS to be useful in hospitalised patients in predicting ICU admission, ventilation and mortality.28–30
Compared with CV(+)/LUS(−) patients, CV(+)/LUS(+) patients were older, more likely to be female, with a lower BMI. Given that the opposite (ie, male sex and increased BMI) are associated with more severe COVID-19, this further supports the notion that positive LUS findings early in the course of the disease likely do not portend worse outcomes. We did find increased and persistent pulmonary involvement with age, which parallels reports of more severe pulmonary disease in older patients with COVID-19.31–33
Although having a positive LUS was not a useful prognosticator, it did appear clinically meaningful. A higher LUS severity score was significantly associated with baseline SOB, after adjusting for patient age, sex, African-American and Hispanic race/ethnicity, smoking status and BMI. This suggests that disease detectable by LUS translates into relevant clinical symptoms.
Through longitudinal assessment of 24 CV(+)/LUS(+) patients, we demonstrated that the majority of patients had improvement in their LUS severity score at 1-week follow-up. Furthermore, nine patients had worsening LUS severity scores at follow-up, and yet still had favourable clinical outcomes, without developing severe illness. Notably, the patients with worse LUS scores at 1-week follow-up were significantly older than those who improved and had increased persistence of symptoms of cough and SOB. For longitudinal follow-up beyond 1 week, there was no relationship between persistent or resolved LUS findings and symptoms, providing no support for persistent LUS findings as a predictor of chronic COVID-19. An important unanswered question that remains is whether persistent LUS findings may ultimately predict long-term parenchymal lung disease.
This study has several limitations. First, patients with increased BMI were less likely to have a positive LUS, and this may reflect a decreased sensitivity of LUS technique due to reduced tissue penetration. Second, a subset of potential outpatient enrollees declined participation specifically because they felt too ill to participate (14 of 311 contacted patients, 5%), resulting in a potential selection bias. We imagine that including these patients would likely result in the prevalence of lung disease detected by LUS being higher than what we report here. Third, we were unable to determine the exact date of infection and its relationship to our baseline LUS examinations. The heterogeneity in the time between infection and LUS examination could theoretically lead to LUS findings resolving by the time of baseline examination, or LUS findings developing after baseline examination. We attempted to keep the time between SARS-CoV-2 testing and baseline LUS as short as possible but were limited by result turnaround time, time to patient being informed, and screening and scheduling factors. Taking into account our longitudinal LUS results, only one LUS(−) patient at baseline went on to develop LUS findings at week 1. Conversely, numerous LUS(+) patients had persistent findings at longitudinal follow-up. This suggests that the impact of variability in time between infection and baseline LUS examination is likely to be small. Fourth, we chose to perform only posterior LUS evaluations to minimise infection risks associated with the study. Dedicated studies assessing the sensitivity of posterior assessment compared with posterior and anterior assessment are not available; however, COVID-19 lung involvement is commonly found in the posterior and lateral aspects of the lungs.8 9 Lastly, patients did not undergo CT imaging for confirmation of LUS findings as part of the study, although two patients did have CT scans for clinical evaluation and those studies were concordant with their LUS. As recent studies have confirmed high sensitivity of LUS for COVID-19 pneumonia, this limitation unlikely has significant impact on disease prevalence, although we acknowledge that severity score concordance between CT and LUS vary.8
This study also has several strengths. This was the first study to investigate the prevalence of pulmonary findings in outpatients with SARS-CoV-2 infection using LUS, and the largest outpatient COVID-19 study of the general population to date. Our cohort was diverse and representative of the geographic region. While several LUS scoring systems have been outlined for COVID-19, none have been robustly validated. We developed a scoring system combining component severity and distribution throughout the lung zones, which resulted in a wide range of scores and excellent inter-rater reliability. In addition, we included 14 control CV(−) subjects, which were all read as LUS(−). Finally, we were able to provide longitudinal data on a subset of patients and describe the natural evolution of COVID-19 by LUS.