Symptoms persisting after hospitalization for COVID-19: 12 months interim results of the COFLOW study

Abstract

IntroductionA large proportion of patients experiences a wide range of sequelae after acute COVID-19 infection, especially after severe illness. The long-term health sequelae need to be assessed. Our objective was to longitudinally assess persistence of symptoms and clusters of symptoms up to 12 months after hospitalization for COVID-19, and to assess determinants of the main persistent symptoms.MethodsIn this multicenter prospective cohort study patients with COVID-19 are followed up for 2 years with measurements at 3, 6, 12, and 24 months after hospital discharge. Here, we present interim results regarding persistent symptoms up to 12 months. Symptoms were clustered into physical, respiratory, cognitive and fatigue symptoms.ResultsWe included 492 patients; mean age was 60.2±10.7 years, 335 (68.1%) males, median length of hospital stay 11 (6.0-27.0) days. At 3 months after discharge 97.0% of the patients had at least 1 persisting symptom, this declined to 95.5% and 92.0% at 6 and 12 months, respectively (p=0.010). Muscle weakness, exertional dyspnea, fatigue, and memory and concentration problems were the most prevalent symptoms with rates over 50% during follow-up. Over time, muscle weakness, hair loss, and exertional dyspnea decreased significantly (p<0.001), while other symptoms, such as fatigue, concentration and memory problems, anosmia, and ageusia persisted. Symptoms from the physical and respiratory cluster declined significantly over time, in contrast to symptoms from the fatigue and cognitive clusters. Female gender was the most important predictor of persistent symptoms and co-occurrence of symptoms from all clusters. Shorter hospital stay and treatment with steroids were related with decreased muscle weakness; comorbidity and being employed were related with increased fatigue; and shorter hospital stay and comorbidity were related with memory problems.ConclusionThe majority of patients experienced COVID-19 sequelae up to 12 months after hospitalization. Whereas physical and respiratory symptoms showed slow gradual decline, fatigue and cognitive symptoms did not evidently resolve over time. This finding stresses the importance of finding the underlying causes and effective treatments for post-COVID condition, beside adequate COVID-19 prevention.

Symptoms persisting after hospitalisation for COVID-19: 12 months interim results of the CO-FLOW study

“…The COvid-19 Follow-up care paths and Long-term Outcomes Within the Dutch health care system (CO-FLOW) study is an ongoing multicenter prospective cohort study following COVID-19 patients discharged from hospitals in the Rotterdam-Rijnmond-Delft region in the Netherlands. Detailed description of its protocol can be found elsewhere (14). In short, up to 2 years after hospitalization patients with COVID-19 are evaluated at 3, 6, 12, and 24 months after hospital discharge.…”

Severe fatigue as symptom of long COVID is characterized by increased expression of inflammatory genes in monocytes, increased serum pro-inflammatory cytokines, and increased CD8+ T-lymphocytes: A putative dysregulation of the immune-brain axis, the coagulation process, and auto-inflammation to explain the diversity of long COVID symptoms

“…Among patients who had been hospitalized for acute COVID-19, proportions of up to 41% to 60% have been reported for patients that still suffer from fatigue one year after hospital discharge, without evident improvement beyond 6 months. 5,10,11 Furthermore, the fatigue has been shown to negatively affect quality of life.…”

Puzzling persisting symptoms after COVID-19

“…These sequelae are currently termed “post-COVID-19 condition” by a World Health Organization consensus definition concerning symptoms present 3 months beyond the onset of COVID-19, persisting for ≥2 months, that may fluctuate and relapse over time, and cannot be explained by an alternative diagnosis [ 2 ]. The most frequent post-COVID-19 symptoms reported include fatigue, shortness of breath, muscle problems and cognitive dysfunction [ 3 , 4 ].…”

“…Likewise, radiological abnormalities gradually improve over time and are rarely severe [ 11 ]. Despite the improvement in pulmonary function over time, more and more studies indicate that patient-reported symptoms do not improve [ 3 , 12 ].…”