Post-COVID functional limitations on daily living activities are associated with symptoms experienced at the acute phase of SARS-CoV-2 infection and internal care unit admission: A multicenter study.

Dear editor

Evidence supports that almost 60% of COVID-19 survivors will experience post-COVID symptom during the first 6-months following the infection. These symptoms lead to a decrease in health-related quality of life and decreased function. , In a letter to the editor in Journal of Infection, Taboada et al. found that female sex, age, length of hospital stance and internal care unit (ICU) admission were associated with limitations in functional status. These authors evaluated the Functional Status Scale (PCFS), a scale assessing global patient-functional limitation by using a 6-points scale. The PCFS did not differentiate on which daily life activity the limitation is present since it uses a global score. Due to the complexity of COVID-19, it is possible that functional limitations and their associated risk factors are different depending on the type e.g., social, occupational, basic or instrumental, of daily living activity. In addition, previous studies have included limited numbers of participants (n < 300) recruited from just one single center. – We describe a multicenter study investigating those risk factors associated with the presence of functional status differentiating occupational, leisure/social, basic or instrumental daily living activities in a sample of hospitalized COVID-19 survivors at a long-term follow-up period after hospital discharge.

This multicenter study included patients hospitalized in five hospitals of Madrid (Spain) with a diagnosis of SARS-CoV-2 infection during the first wave of the pandemic. A sample of 400 individuals from each hospital was randomly selected for this study. Local Ethics Committee of each participating hospital approved the study (HUFA 20/126, HCSC20/495E, HSO25112020, HUIL/092-20, HUF/EC1517). All participants provided their informed consent. Clinical features (i.e., gender, age, height, weight, medical co-morbidities), symptoms at hospital admission, and hospitalization data (days at hospital, ICU admission) were collected from medical records. Participants were scheduled for a telephone interview conducted by experienced healthcare professionals to evaluate the functional status of the patient. Participants were asked for self-perceived limitations in occupational, leisure/social activities, instrumental, and basic daily living activities. They s were asked for determining their functional status at the moment of the interview (post-COVID) in comparison with their previous status before hospitalization.

Mean and standard deviation (SD) or percentages were calculated. Missing values were imputed using median imputation. Multivariate logistic regressions were conducted to analyze associations between clinical and hospitalization variables with the presence of limitations in occupational, leisure/social activities, instrumental, and basic activities of daily living (dependent variables) using Python's library statsmodels 0.11.1. Adjusted odds ratio (OR) with their confidence intervals (95%CI) were calculated.

From 2000 patients randomly selected from the five hospitals and invited to participate, a total of 1969 (46% women, age: 61, SD: 16 years) were assessed a mean of 8.4 months (SD 1.5) after hospital discharge. Fever (74.6%), dyspnea (31.5%) and myalgia (30.7%) were the most prevalent symptoms at hospital admission (Table 1 ). The mean number of COVID-19 symptoms at hospital admission was 2.2. (SD 0.8). Almost 57.5% of patients (n = 1133) reported at least one comorbidity. The mean number of medical co-morbidities was 0.8 (SD 0.9). Hypertension (26.2%), diabetes (12.0%), and cardiovascular disorders (11.9%) were the most common medical comorbidities (Table 1). Between 20 and 30% of participants reported limitations during at least one daily living activity (Table 1).

Table1

Clinical, hospitalization and functional status data of the sample (n = 1969).

Age, mean (SD), years	61 (16)
Gender, male/female (%)	1054 (53.5%) / 915 (46.5%)
Weight, mean (SD), kg.	75 (15)
Height, mean (SD), cm.	165 (16.5)
Main Symptoms at hospital admission, n (%)FeverdyspneaMyalgiaCoughHeadachediarrhoeaAnosmiaThroat PainAgeusiaVomiting	1469 (74.6%)620 (31.5%)604 (30.7%)549 (27.9%)332 (16.9%)210 (10.7%)167 (8.5%)102 (5.2%)66 (33.5%)55 (2.8%)
Medical co-morbiditiesHypertensionDiabetesCardiovascular DiseaseAsmaObesityChronic Obstructive Pulmonary DiseaseStrokeRheumatological DiseaseOther (Cancer, Kidney Disease)	514 (26.1%)236 (12.0%)234 (11.9%)126 (6.4%)88 (4.5%)77 (3.9%)38 (2.0%)31 (1.6%)332 (16.9%)
Stay at the hospital, mean (SD), days	11.3 (11.4)
Intensive Care Unit (ICU) admissionYes/No, n (%)	130 (6.6%) / 1839 (93.4%)
Functional Limitations n (%)Limitation in Occupational ActivitiesLimitation in Leisure/Social ActivitiesLimitation in Basic Activities of Daily LifeLimitation in Instrumental Activities of Daily Life	418 (21.2%)604 (30.6%)542 (27.5%)389 (19.7%)

The regression model revealed that the number of COVID-19 symptoms at hospital admission (occupational activities: OR1.51, 95%CI 1.14–2.01, P = 0.004; leisure/social activities: OR1.59, 95%CI 1.25–2.03, P < 0.001; basic daily live activities: OR1.61, 95%CI 1.21–2.13, P < 0.001; instrumental daily live activities: OR1.57, 95%CI 1.22–2.01, P < 0.001) and ICU admission (occupational activities: OR1.79, 95%CI 1.16–2.78, P = 0.009; leisure/social activities: OR1.83, 95%CI 1.22–2.73, P = 0.003; basic daily living activities: OR3.30, 95%CI 2.16–5.05, P < 0.001; instrumental daily living activities: OR2.37, 95%CI 1.57–3.58, P < 0.001) were significantly with limitations in all activities. Additionally, age was also associated with limitation in leisure/social activities (OR1.009, 95%CI 1.003–1.016, P = 0.006), limitations basic daily living activities (OR1.016, 95%CI 1.008–1.024, P < 0.001), and limitations in instrumental daily living activities (OR1.020, 95%CI 1.013–1.028, P < 0.001). Female sex was only associated with limitations in leisure and social activities (OR1.46, 95%CI 1.13–1.89, P = 0.003) and limitations instrumental daily living activities (OR1.66, 95%CI 1.28–2.16, P < 0.001).

Our multicenter study found that at least 20% of COVID-19 survivors self-reported limitations on daily living activities eight months after hospitalization. Current data agree with previous studies – ; nevertheless, we differentiated the type of activity perceived as limited, a distinction that is not commonly conducted in former post-COVID literature. Identification of risk factors is needed for an early identifying and monitoring of patients at a high risk of developing post-COVID sequelae. This multicenter study found that a higher number of symptoms at hospital admission and ICU admission were associated with functional limitations at all daily living activities. Our findings the assumption that a higher symptom load at the acute phase of the infection leads to a greater likelihood of suffering long-term functional disability at least in hospitalized COVID-19 survivors.

We also observed that other risk factors, e.g., female sex and age, which have been associated with post-COVID symptoms, were associated with the limitations of daily living activities, although clinical relevance of age could be questioned due to their lower adjusted OR. Our findings agree with those found by Taboada et al. except for the longer hospital stay. Increasing evidence suggests that post-COVID fatigue, probably one of the symptoms most associated with functional status, is not associated with the severity of the initial infection or damage in lung function at 3- and 6-month after. It would be probably that hospitalization data can exert less influence on the development of post-COVID sequelae than expected.

Although our study provides further evidence to the current literature about post-COVID functional status with a large, multicenter design evaluating specific daily living activities, potential weaknesses should be considered. First, only hospitalized COVID-19 patients participated. Second, the number of patients requiring ICU admission was small.

Third, the cross-sectional design did not permit to determine cause -and-effect association between suffering COVID-19 and functional status. Fourth, we did not collect objective data of COVID-19 disease and measures of lung damage, although these factors seem to be not related to post-COVID sequelae. ,

CRediT authorship contribution statement

César Fernández-de-las-Peñas: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Validation, Visualization, Writing – original draft, Writing – review & editing. José D. Martín-Guerrero: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing – original draft, Writing – review & editing. Esperanza Navarro-Pardo: Conceptualization, Data curation, Investigation, Methodology, Resources, Validation, Visualization, Writing – original draft, Writing – review & editing. Jorge Rodríguez-Jiménez: Conceptualization, Data curation, Investigation, Methodology, Validation, Visualization, Writing – original draft, Writing – review & editing. Oscar J. Pellicer-Valero: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing.

Declaration of Competing Interest

None.