Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study

Figures & data

Table 1. Clinical features of included patients during follow-up.

Variable	Persistent PASC Median (IQR) N = 13	Non persistent PASC Median (IQR) N = 89	p Value
At COVID-19 diagnosis
Mild disease	20.00 (19.41)	26.00 (25.24)	.55
Severe disease	13.00 (12.62)	17.00 (16.50)	.55
Critical disease	15.00 (14.56)	12.00 (11.65)	.55
Type 2 Diabetes Mellitus	8.00 (7.76)	16.00 (15.53)	.13
Hypertension	10.00 (9.70)	18.00 (17.47)	.17
Obesity	21.00 (20.38)	25.00 (24.27)	.86
Cardiovascular disease	0.00 (0.00)	3.00 (2.91)	.04
Fever	28.00 (27.18)	31.00 (30.09)	.84
Headache	31.00 (30.09)	37.00 (35.92)	.77
Dysgeusia	14.00 (13.59)	10.00 (9.70)	.18
Conjunctivitis	5.00 (4.80)	2.00 (1.90)	.16
Diarrhea	8.00 (7.76)	7.00 (6.79)	.57
Arthralgias	30.00 (29.12)	27.00 (26.21)	.17
Myalgias	31.00 (30.09)	30.00 (29.12)	.30
Pharyngodynia	19.00 (18.44)	18.00 (17.47)	.46
Rhinorrhea	12.00 (11.65)	9.00 (8.73)	.27
Anosmia	19.00 (18.44)	13.00 (12.62)	.08
Cough	35.00 (33.98)	36.00 (34.95)	.41
One month after COVID-19 onset or hospital discharge
Confusion	4.00 (3.80)	0.00 (0.00)	.01
Fatigue	30.00 (29.12)	3.00 (2.91)	<.001
Cough	1.00 (0.90)	1.00 (0.94)	.92
Dyspnoea	11.00 (10.67)	1.00 (0.94)	<.001
Headache	13.00 (12.62)	1.00 (0.94)	<.001
Wheezing	4.00 (3.80)	1.00 (0.94)	.11
Fever	1.00 (0.90)	0.00 (0.00)	.21
Joint pain	7.00 (6.70)	0.00 (0.00)	<.001
Joint inflammation	2.00 (1.94)	1.00 (0.90)	.47
Inability to dress	0.00 (0.00)	0.00 (0.00)	.49
Inability to walk	0.00 (0.00)	0.00 (0.00)	.01
Inability to open jars	4.00 (3.80)	0.00 (0.00)	.02
Chest pain	6.00 (5.80)	0.00 (0.00)	.001
Orthopnea	1.00 (0.90)	0.00 (0.00)	.21
Peripheral edoema	3.00 (2.91)	1.00 (0.90)	.23
Myalgia	11.00 (10.67)	1.00 (0.90)	<.001
Dermatosis	0.00 (0.00)	1.00 (0.90)	.26
Paresthesia	10.00 (9.70)	0.00 (0.00)	<.001
Decreased visual acuity	8.00 (7.76)	0.00 (0.00)	<.001
Decreased concentration	2.00 (1.94)	0.00 (0.00)	.07
Memory impairment	6.00 (5.80)	2.00 (1.94)	.08
Alopecia	7.00 (6.70)	2.00 (1.94)	.04
Back pain	1.00 (0.90)	0.00 (0.00)	.21
Anosmia	0.00 (0.00)	0.00 (0.00)	.49
Dysgeusia	0.00 (0.00)	0.00 (0.00)	.49
Three months after COVID-19 onset or hospital discharge
Confusion	3.00 (2.91)	1.00 (0.90)	.23
Fatigue	27.00 (26.21)	3.00 (2.91)	<.001
Cough	0.00 (0.00)	0.00 (0.00)	.49
Dyspnoea	10.00 (9.70)	2.00 (1.94)	.005
Headache	14.00 (13.59)	4.00 (3.88)	.002
Wheezing	2.00 (1.94)	0.00 (0.00)	.07
Fever	0.00 (0.00)	0.00 (0.00)	.49
Joint pain	5.00 (4.85)	2.00 (1.94)	.16
Joint inflammation	1.00 (0.90)	0.00 (0.00)	.21
Inability to dress	1.00 (0.90)	2.00 (1.94)	.21
Inability to walk	2.00 (1.94)	0.00 (0.00)	.07
Inability to open jars	2.00 (1.94)	0.00 (0.00)	.07
Chest pain	4.00 (3.80)	0.00 (0.00)	.01
Orthopnea	0.00 (0.00)	0.00 (0.00)	.49
Peripheral edoema	1.00 (0.90)	1.00 (0.90)	.92
Myalgia	11.00 (10.67)	3.00 (2.91)	<.001
Dermatosis	0.00 (0.00)	0.00 (0.00)	.49
Paresthesia	6.00 (5.80)	2.00 (1.94)	.08
Decreased visual acuity	3.00 (2.91)	1.00 (0.90)	.23
Decreased concentration	3.00 (2.91)	0.00 (0.00)	.03
Memory impairment	5.00 (4.85)	0.00 (0.00)	.004
Alopecia	16.00 (15.53)	6.00 (5.80)	.005
Back pain	5.00 (4.85)	1.00 (0.90	.05
Anosmia	0.00 (0.00)	0.00 (0.00)	.49
Dysgeusia	0.00 (0.00)	0.00 (0.00)	.49
Six months after COVID-19 onset or hospital discharge
Confusion	1.00 (0.13)	1.00 (0.89)	.182
Fatigue	8.00 (1.04)	15.00 (13.35)	.177
Cough	0.00 (0.13)	2.00 (1.78)	.511
Dyspnoea	1.00 (1.04)	9.00 (8.01)	.413
Headache	2.00 (0.26)	6.00 (5.34)	.436
Wheezing	0.00 (0.13)	1.00 (0.89)	.222
Fever	0.00 (0.13)	2.00 (1.78)	.180
Joint pain	4.00 (0.52)	2.00 (1.78)	.790
Joint inflammation	0.00 (0.13)	2.00 (1.78)	.166
Inability to dress	0.00 (0.13)	2.00 (1.78)	.466
Inability to walk	0.00 (0.13)	2.00 (1.78)	.920
Inability to open jars	1.00 (1.04)	0.00 (0.00)	.691
Chest pain	1.00 (1.04)	0.00 (0.00)	.322
Orthopnea	0.00 (0.13)	2.00 (1.78)	.888
Peripheral edoema	0.00 (0.13)	11.00 (0.89)	.476
Myalgia	3.00 (0.39)	10.00 (8.90)	.244
Dermatosis	0.00 (0.13)	2.00 (1.78)	.542
Paresthesia	3.00 (0.39)	3.00 (2.67)	.095
Decreased visual acuity	2.00 (0.26)	2.00 (1.78)	.533
Decreased concentration	1.00 (1.04)	2.00 (1.78)	.186
Memory impairment	3.00 (0.39)	2.00 (1.78)	.597
Alopecia	4.00 (0.52)	20 (17.80)	.487
Back pain	2.00 (0.26)	11.00 (0.89)	.466
Anosmia	0.00 (0.13)	11.00 (0.89)	.143
Dysgeusia	0.00 (0.13)	2.00 (1.78)	.237

As shown in Table 1, patients with persistent PASC at 6 months had a higher prevalence of fatigue, dyspnoea, headache and myalgia 1 and 3 months after the acute infection.

Significant differences between groups are shown in bold.  

Scheme 1. Variables that predispose to the development of persistent post-COVID-19 syndrome. (A) The expression of CD57 in CD8+ T cells. (B) Obesity. (C) History of acute-Post-COVID-19 syndrome. (D,E) Increased serum levels of IP-10 and MIP-1α.

Table 2. Variables associated with persistent PASC at 6 months.

Variable	OR	95% CI	p Value	Cut-off point	Score
History of post-COVID-19 syndrome 3 months after disease onset	6.77	1.38–52.11	.032	Present	5
Obesity	5.08	1.19–28.45	.039	Present	4
MIP-1α /CCL3 (pg/mL)	1.10	0.97–1.26	.114	5.28	3
IP-10/CXCL10 (pg/mL)	1.00	0.99–1.00	.112	2309.38	2
MFI of CD57 in CD8 + T cells	1.00	1.00–1.00	.051	32600	1

Scheme 2. Statistical Model of persistent post-COVID-19 syndrome. (A) Area under the curve (AUC) with 95% CI using a cut-off point >_12. (B) Calibration plot showing a good capacity of the model for persistent post-COVID-19 syndrome features.

Table 3. Optimism-corrected accuracy parameters of the model.

Parameter	Original model	Training	Test	Optimism corrected	Optimism
AUC	0.757	0.753	0.757	0.762	−0.004
c-statistics	0.758	0.753	0.757	0.762	−0.004
Somer’s D	0.516	0.506	0.514	0.524	−0.008
Emax	0.000	0.000	0.018	0.018	0.018
Brier	0.070	0.069	0.072	0.073	−0.003

Data availablity statement

All data generated or analysed during this study are included in this published article.