Subclinical multi-organ affection after recovery from mild to moderate COVID-19
Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme
Introduction and methods
In severely ill and deceased COVID-19 patients, impairment of pulmonary, cardiac and renal function have been reported, as well as thromboembolism and serious neurological complications [1-4]. Most reports on long term symptoms are from hospitalized cohorts  and data on subclinical changes of multi-organ structure and function are lacking.
In this cross-sectional study, the intermediate-term impact of mild to moderate COVID-19 (defined as not requiring intensive care unit treatment) on organ-specific function was determined.
Multi-organ function was assessed by deep phenotyping patients ~9 months after mild to moderate COVID-19 recovery and comparing data with those of age-, sex-, and education-matched subjects from a population-based cohort study.
The cohort of 443 recovered COVID-19 patients consisted of individuals from Hamburg, Germany, with a positive PCR test for SARS-CoV-2 at least 4 months prior to enrollment (median enrollment was 9.6 months after the positive test). 92.8% Of these subjects were managed as outpatients. The population-based Hamburg City Health Study (HCHS) served a as the control cohort. Controls were eligible for this study if they had been enrolled prior to being at risk of SARS-CoV-2 infection; 1328 controls were enrolled.
Both patients recovered from COVID-19 and matched controls underwent the same standardized 7h assessment at the same center .
Surrogates of biological parameters in the respiratory, cardiac, vascular, renal, metabolic and inflammatory, and neurological systems, and of neurocognition and psychosocial outcomes were assessed.
- Total lung capacity was lower in recovered COVID-19 subject compared with controls (99.1% of the predictive value vs. 102.3%, regression coefficient -3.24, 95%CI:-5.57 to -0.91, adjusted=0.0014)
- Specific airway resistance was higher in patients after SARS-CoV-2 infection than matched controls (77.3% of the predicted value vs. 69.8%, regression coefficient 8.11, 95%CI: 3.56 to 12.65, adjusted P=0.001).
- Left ventricular ejection fraction derived from transthoracic echocardiography was decreased in patients after SARS-CoV-2 infection compared with controls (57.9 vs. 59.1%, regression coefficient -0.93, 95%CI: -1.54 to -0.32, adjusted P=0.015).
- Right ventricular systolic function, quantified by TAPSE using transthoracic echocardiography, was significantly reduced in patients after SARS-CoV-2 infection (23.0 vs. 23.9 mm, regression coefficient -0.72, 95%CI:-1.24 to -0.21, adjusted P=0.031).
- In patients after SARS-CoV-2 infection, the cardiac biomarkers NT-proBNP and high-sensitivity cardiac troponin were higher compared with matched controls (NT-proBNP: 87.84 vs. 62.76 ng/L, multiplicative regression coefficient 1.41, 95%CI:1.29 to 1.55, adjusted P<0.001; high-sensitivity cardiac troponin I: 2.07 vs. 1.90 ng/L, multiplicative regression coefficient 1.14, 95%CI:1.05 to 1.24, adjusted P=0.010).
- NT-proBNP ≥125 ng/L were more frequent in patients after SARS-CoV-2-infection than matched controls (33.2 vs. 18.2%, OR 2.39, 95%CI:1.82 to 3.12, adjusted P<0.001).
- Sonographically non-compressible common femoral veins were more frequently observed in individuals after SARS-CoV-2 infection than in matched controls (43.2 vs. 22.2%, OR 2.68, 95%CI: 1.77-5.05, adjusted P<0.001)
- Individuals after SARS-CoV-2 infection presented more often with atherosclerotic plaques (36.9 vs. 23.4%, OR 2.27, 95%CI: 1.76-2.93, adjusted P<0.001).
- eGFR based on creatinine measurements was reduced in patients after SARS-CoV-2 infection by 2.35 mL/min/1.73m2 (95%CI: -4.04 to -0.67, adjusted P=0.019).
- Patients after SARS-CoV-2 infection had higher mean cortical thickness compared to controls (2.65 vs. 2.63 mm, regression coefficient 0.03, 95%CI: 0.01-0.05, adjusted P=0.002).
Subclinical multi-organ involvement related to thrombotic function and pulmonary, cardiac and renal systems was observed in mainly non-hospitalized patients who recovered ~9 months ago from mild to moderate COVID-19. There were no signs of structural brain damage, impairment in cognitive function or quality of life.
The take-home message of the authors is that a standardized exam of these conditions after recovery from COVID-19 is recommended to identify individuals at risk and initiate preventive strategies.