Factors Associated with Long COVID-19 in a French Multicentric Prospective Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Study Population
2.3. Patients and Follow-up Visits
2.4. Definitions
2.5. Outcomes
2.6. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Prevalence of Clinical Symptoms at Follow-up Visits
3.3. Factors Associated with Persistent Clinical Symptoms at Follow-up
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | N = 189 (%) |
---|---|
Gender | |
Female | 76 (40.2) |
Male | 113 (59.8) |
Age, mean (min–max) | 63.4 (25–93) |
BMI (kg/m2), mean (min–max), n = 152 | 27.4 (16.4–44.4) |
Past medical history | 151 (79.9) |
Type of underlying diseases | |
Cardiac failure | 24 (12.7) |
Cardiovascular diseases | 84 (44.4) |
Diabetes mellitus | 36 (19) |
Hypertension | 68 (36) |
Hypothyroidism | 17 (9) |
Immunodeficiency | 10 (5.3) |
Liver diseases | 16 (8.5) |
Lung diseases | 12 (6.3) |
Malignancy | 21 (11.1) |
Neurological diseases | 9 (4.8) |
Renal diseases | 18 (9.5) |
Rheumatic diseases | 20 (10.6) |
Other | 100 (52.9) |
COVID-19 history | |
Delay (days) between onset of symptoms and hospital admission, mean (min–max) | 8.2 (0–31) |
Symptoms at hospital admission, N (%) | |
Ageusia | 25 (13.3) |
Anosmia | 26 (13.8) |
Cough | 150 (79.8) |
Diarrhea | 63 (33.5) |
Fatigue | 139 (73.9) |
Headache | 38 (20.2) |
Irritability | 6 (3.2) |
Nausea | 23 (12.2) |
Pain | 71 (37.8) |
Pain location | |
Abdominal | 14 (19.7) |
Chest | 10 (14.1) |
Joints | 6 (8.5) |
Muscular | 52 (73.2) |
Shortness of breath | 124 (66) |
Sore throat | 10 (5.3) |
Rhinorrhea | 29 (15.4) |
Other symptoms | 48 (25.5) |
Number of symptoms, mean (min–max) | 5.0 (1–9) |
Duration (days) of symptoms in symptomatic patients, mean (min–max) n = 164 | 24.5 (2–126) |
Signs at hospital admission, N (%) | |
Abnormal lung auscultation, n = 173 | 157 (83.1) |
Abnormal lung X-ray when realized, n = 162 | 157 (96.9) |
Coma, n = 173 | 1 (0.6) |
Dyspnea, n = 173 | 132 (76.3) |
Fever | 171 (91) |
Temperature (°C), mean (min–max) | 37.8 (35.5–40) |
Biological data (Reference Range) | |
Complete Blood Count | |
WBC (4–10 G/L), mean (min–max), n = 178 | 6.9 (1.5–22.8) |
Neutrophils (1.8–7.5 G/L), mean (min–max), n = 178 | 5.3 (1.1–17.8) |
Lymphocytes (1–4 G/L), mean (min–max), n = 178 | 1.1 (0.1–0.68) |
Monocytes (0.2–0.9 G/L), mean (min–max), n = 178 | 0.5 (0.0–1.6) |
Platelets (150–400 G/L), mean (min–max), n = 177 | 216.7 (71–618) |
RBC (4–6 G/L), mean (min–max), n = 178 | 4.7 (2.8–6.5) |
Hemoglobin (120–170 G/L), mean (min–max), n = 178 | 138.1 (70–199) |
Biochemistry tests | |
ALT (13–61 U/L), mean (min–max), n = 148 | 45.1 7–375) |
AST (15–37 U/L), mean (min–max), n = 148 | 58.4 (12–671) |
Creatinine (45–104 µmol/L), mean (min–max), n = 178 | 87.4 (30–669) |
C-Reactive Protein (< 5 mg/L), mean (min–max), n = 167 | 86.0 (0–367.6) |
LDH (87–241 U/L), mean (min–max), n = 62 | 362.2 (141–825) |
Potassium (3.5–5.1 mmol/L), mean (min–max), n = 177 | 4.1 (2.8–6.2) |
Prothrombin time (70–150 %), mean (min–max), n = 142 | 81.7 (18–126) |
Sodium (136–145 mmol/L), mean (min–max), n = 179 | 136.0 (125–146) |
Urea (2.5–9.2 mmol/L), mean (min–max), n = 178 | 6.9 (2.10–47.7) |
Prognosis | |
Admission to ICU | 64 (33.9) |
Development of complications during hospital stay | |
Respiratory | 46 (83.6) |
Bacterial pneumonia | 16 (29.1) |
Other infections | 11 (20) |
Cardiac | 8 (14.5) |
Other complications | 34 (20.5) |
Length of stay (days), mean (min–max) | 19.9 (1–184) |
First Visit | Second Visit | |
---|---|---|
Variables | N = 189 (%) | N = 178 (%) |
Delay between COVID-19 and first visit (months), mean (min–max) | 8.8 (6–11) | 12.1 (10–13) |
Patients with at least one persistent clinical symptom | 109 (57.7) | 103 (57.9) |
Persistent clinical symptoms | ||
Ageusia | 10 (9.2) | 5 (2.8) |
Anosmia | 12 (11) | 8 (4.5) |
Confusion | 4 (3.7) | 1 (0.6) |
Cough | 5 (4.6) | 9 (5.1) |
Diarrhea | 1 (0.9) | 1 (0.6) |
Dyspnea | 41 (37.6) | 44 (24.7) |
Fatigue | 37 (33.9) | 9 (5.1) |
Headache | 5 (4.6) | 6 (3.4) |
Nausea | 0 (0) | 2 (1.1) |
Pain | 26 (23.9) | 43 (24.2) |
Pain localization | 20 (11.2) | |
Abdominal | 1 (3.8) | 2 (10) |
Articular | 6 (23.1) | 11 (55) |
Muscular | 15 (57.7) | 11 (55) |
Respiratory | 6 (23.1) | 4 (20) |
Rhinorrhea | 5 (4.6) | 3 (1.7) |
Sore throat | 5 (4.6) | 4 (2.2) |
Other symptoms | 54 (49.5) | 50 (28.1) |
Readmission COVID-19 related | 4 (2.1) | 1 (0.6) |
New clinical symptoms reported | 27 (14.3) | 9 (5.1) |
Type of new reported clinical symptoms | ||
Cough | 0 (0) | 1 (0.6) |
Diarrhea | 4 (14.8) | 0 (0) |
Dyspnea | 5 (18.5) | 3 (1.7) |
Fatigue | 6 (22.2) | 5 (2.8) |
Fever | 5 (18.5) | 1 (0.6) |
Headache | 5 (18.5) | 2 (1.1) |
Nausea | 1 (3.7) | 0 (0) |
Pain | 6 (22.2) | 0 (0) |
Rhinorrhea | 2 (7.4) | 0 (0) |
Sore throat | 3 (11.1) | 0 (0) |
First Visit | Second Visit | |||
---|---|---|---|---|
Variables | Crude OR, (IC95%) | p | Crude OR, (IC95%) | p |
Gender (male) | 0.82 (0.46–1.48) | 0.52 | 0.73 (0.45–1.75) | 0.73 |
Age, years | 0.99 (0.97–1.01) | 0.36 | 0.99 (0.97–1.02) | 0.53 |
BMI > 30 kg/m2 | 2.91 (1.21–7.0) | 0.02 | 2.83 (1.03–7.74) | 0.04 |
At least one underlying disease | 0.78 (0.38–1.59) | 0.49 | 1.02 (0.44–2.32) | 0.97 |
Cardiac failure | 0.70 (0.30–1.65) | 0.42 | 0.67 (0.24–1.89) | 0.45 |
Cardiovascular diseases | 1.05 (0.59–1.88) | 0.87 | 1.13 (0.59–2.21) | 0.72 |
Chronic pulmonary diseases | 1.03 (0.32–3.37) | 0.96 | 1.05 (0.28–3.89) | 0.94 |
Diabetes mellitus | 0.68 (0.33–1.41) | 0.30 | 0.79 (0.33–1.91) | 0.61 |
Immunodeficiency | 0.72 (0.20–2.58) | 0.62 | 0.68 (0.19–2.46) | 0.56 |
Hypertension | 0.98 (0.54–1.79) | 0.95 | 1.02 (0.52–2.03) | 0.95 |
Hypothyroidism | 1.86 (0.63–5.50) | 0.26 | 3.39 (0.71–16.29) | 0.13 |
Liver diseases | 1.68 (0.56–5.05) | 0.35 | 1.64 (0.48–5.58) | 0.43 |
Malignancy | 1.22 (0.48–3.10) | 0.68 | 0.86 (0.32–2.31) | 0.76 |
Neurological diseases | 0.35 (0.09–1.44) | 0.15 | 0.21 (0.04–1.10) | 0.07 |
Renal diseases | 0.71 (0.27–1.88) | 0.49 | 0.78 (0.27–2.27) | 0.64 |
Rheumatic diseases | 1.41 (0.54–3.72) | 0.49 | 2.27 (0.70–7.42) | 0.18 |
Delay (days) between onset of symptoms and hospital admission | 1.04 (0.98–1.11) | 0.22 | 1.06 (0.98–1.14) | 0.15 |
Admission to ICU | 2.03 (1.08–3.83) | 0.03 | 2.48 (1.19–5.17) | 0.02 |
Complications during hospital stay | 2.51 (1.27–5.0) | 0.008 | 2.51 (1.14–5.52) | 0.02 |
Length of hospital stay (days) | 1.01 (1.0–1.03) | 0.05 | 1.01 (1.0–1.03) | 0.11 |
Duration of initial symptoms (days) | 1.02 (1.0–1.04) | 0.04 | 1.03 (1.0–1.05) | 0.04 |
Number of initial symptoms | 1.12 (0.94–1.33) | 0.20 | 1.21 (0.98–1.48) | 0.08 |
Abnormal lung osculation | 1.16 (0.41–3.28) | 0.78 | 1.41 (0.41–4.89) | 0.56 |
Ageusia | 0.83 (0.39–2.13) | 0.83 | 0.81 (0.34–2.02) | 0.65 |
Anorexia | 0.84 (0.36–1.92) | 0.67 | 0.53 (0.21–1.31) | 0.17 |
Anosmia | 2.17 (0.87–5.45) | 0.10 | 2.22 (0.82–6.01) | 0.12 |
Cough | 1.15 (0.56–2.35) | 0.70 | 1.44 (0.64–3.26) | 0.38 |
Diarrhea | 0.86 (0.47–1.59) | 0.63 | 0.97 (0.49–1.93) | 0.94 |
Dyspnea | 0.83 (0.41–1.69) | 0.61 | 1.13 (0.49–2.59) | 0.78 |
Fatigue | 1.05 (0.54–2.02) | 0.89 | 1.02 (0.49–2.13) | 0.96 |
Fever | 2.78 (0.98–7.86) | 0.05 | 15 (1.85–121.88) | 0.01 |
Headache | 1.0 (0.48–2.05) | 0.99 | 1.26 (0.55–2.89) | 0.58 |
Irritability | 0.72 (0.14–3.65) | 0.69 | 0.45 (0.07–2.79) | 0.39 |
Nausea | 1.15 (0.47–2.80) | 0.76 | 1.05 (0.40–2.76) | 0.92 |
Pain | 1.30 (0.71–2.38) | 0.39 | 1.58 (0.80–3.14) | 0.19 |
Rhinorrhea | 0.87 (0.39–1.94) | 0.74 | 1.16 (0.45–2.99) | 0.76 |
Short of breath | 1.81 (0.98–3.33) | 0.06 | 2.05 (1.0–4.22) | 0.05 |
Sore throat | 0.71 (0.20–2.55) | 0.60 | 0.93 (0.20–4.30) | 0.90 |
Other symptoms | 1.20 (0.52–2.81) | 0.67 | 1.23 (0.45–3.33) | 0.67 |
Laboratory data | ||||
ALT (≥55 U/L) | 1.15 (0.52–2.54) | 0.74 | 1.34 (0.56–3.27) | 0.52 |
AST according to quartiles (ref < 31) | 0.10 | |||
31–42 | 3.49 (1.33–9.12) | 0.01 | 2.95 (1.03–8.45) | 0.04 |
>42 | 2.16 (0.95–4.88) | 2.32 (0.91–5.88) | 0.08 | |
Creatinine (>104 µmol/L) | 0.71 (0.3–1.68) | 0.44 | 0.74 (0.29–1.88) | 0.52 |
CRP (mg/L) | 0.76 (0.21–2.70) | 0.67 | 0.68 (0.16–2.83) | 0.59 |
LDH (>400 U/L) | 0.86 (0.30–2.47) | 0.78 | 1.26 (0.36–4.42) | 0.72 |
Potassium (>4.5 mmol/L) | 1.00 (0.41–2.42) | 1.0 | 1.06 (0.38–2.96) | 0.92 |
Prothrombin (<70%) | 0.92 (0.38–2.19) | 0.85 | 0.53 (0.20–1.40) | 0.20 |
Urea (>9.2 mmol/L) | 0.92 (0.40–2.10) | 0.84 | 1.02 (0.40–2.58) | 0.97 |
Monocytes (>0.9 G/L) | 1.13 (0.38–3.32) | 0.83 | 1.06 (0.29–3.94) | 0.93 |
Neutrophils (>7.5G/L) | 1.29 (0.53–3.14) | 0.57 | 1.41 (0.52–3.79) | 0.50 |
WBC (>10 G/L) | 1.35 (0.54–3.41) | 0.52 | 1.48 (0.52–4.20) | 0.46 |
First Visit | Second Visit | |||
---|---|---|---|---|
Variables | Adjusted OR (95% CI) | p | Adjusted OR (95% CI) | p |
Personal history | ||||
BMI > 30 kg/m2 | 3.52 (1.25–9.91) | 0.02 | 3.80 (0.97–14.91) | 0.06 |
Rheumatic diseases | - | - | 5.25 (0.75–36.84) | 0.09 |
Factors related to acute COVID-19 | ||||
Ageusia | - | - | 0.17 (0.03–0.92) | 0.04 |
Anosmia | - | - | 13.34 (2.07–86.21) | 0.006 |
AST according to quartiles (ref < 31) | 0.003 | 0.03 | ||
31–42 | 8.68 (2.41–31.28) | 0.001 | 10.27 (1.88–56.29) | 0.007 |
>42 | 3.69 (1.32–10.31) | 0.01 | 2.52 (0.60–10.68) | 0.21 |
Delay (days) between onset of clinical symptoms and hospital admission | - | - | 1.14 (1.01–1.29) | 0.04 |
Pain | - | - | 4.31 (1.23–15.05) | 0.02 |
ICU stay | - | - | 5.43 (1.39–21.25) | 0.02 |
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Khanafer, N.; Henaff, L.; Bennia, S.; Termoz, A.; Chapurlat, R.; Escuret, V.; Proriol, M.; Duvert, F.; Mena, C.; Planckaert, C.; et al. Factors Associated with Long COVID-19 in a French Multicentric Prospective Cohort Study. Int. J. Environ. Res. Public Health 2023, 20, 6678. https://doi.org/10.3390/ijerph20176678
Khanafer N, Henaff L, Bennia S, Termoz A, Chapurlat R, Escuret V, Proriol M, Duvert F, Mena C, Planckaert C, et al. Factors Associated with Long COVID-19 in a French Multicentric Prospective Cohort Study. International Journal of Environmental Research and Public Health. 2023; 20(17):6678. https://doi.org/10.3390/ijerph20176678
Chicago/Turabian StyleKhanafer, Nagham, Laetitia Henaff, Sabrina Bennia, Anne Termoz, Roland Chapurlat, Vanessa Escuret, Mathilde Proriol, Florence Duvert, Camille Mena, Catherine Planckaert, and et al. 2023. "Factors Associated with Long COVID-19 in a French Multicentric Prospective Cohort Study" International Journal of Environmental Research and Public Health 20, no. 17: 6678. https://doi.org/10.3390/ijerph20176678