General characteristics
In total, 209 participants were recruited for this study. After excluding participants with incomplete questionnaires, 173 participants were included in the study. The research population consisted of 130 college students (94.22%), 1 postgraduate (0.58%), 1 teacher (0.58%), 3 assistants (1.73%), and 5 staff members (2.89%). Of these, 116 individuals who were infected with SARS-CoV-2 were subdivided into a study group with an LC comprised of 32 (18.50%) individuals and a study group without an LC comprised of 84 (48.55%), while the remaining 57 individuals (32.95%) with no history of infection were selected as the control group. A few patients in the COVID-19 experienced group were hospitalized (2.6%). Seven patients have underlying diseases in post-COVID group, including one case of hypertension, one case of insensitive pulmonary tuberculosis, one case of pneumonia, one case of migraine, and two cases of rhinitis, whereas no underlying diseases were found in the control group.
The participants’ characteristics are presented in Table 1. To determine the long-term potential impacts of SARS-CoV-2 infection and further investigate the differences in HRV between patients recovering after COVID-19 infection and patients with long-term COVID-19, we subdivided the study group into two groups: Covid-19 experienced group without LCS and COVID-19 experienced group with LCS, based on the presence or absence of long-COVID symptoms, and made a comparison among all groups showed in Table 1. Correlations among the groups were observed regarding the ages and underlying diseases. The long-term COVID-19 group was older on average than the control group and no long-COVID symptoms group (p<0.001), implying that young adults were less likely to have LCS. In addition, this table also shows that the LC group had more patients with underlying diseases (p=0.044) than the control group.
Table 1. General characteristics among the research population with regards to long COVID-19 status (n=173).
Variable
|
Control group (group1)
|
COVID-19 experienced group without LCS (group2)
|
COVID-19 experienced group with LC (group3)
|
P1 (between group1-3)
|
P2 (between group1 and group3)
|
P3 (between group2 and group3)
|
n=57
|
n=84
|
n=32
|
Age
|
22.2±4.29
|
21.2±2.52
|
26.8±10.9
|
0.0342)
|
0.0506)
|
0.0406)
|
<25
|
49(86.0)
|
80(95.2)
|
22(68.8)
|
<0.0013)
|
0.0523)
|
<0.0013)
|
³25
|
8(14.0)
|
4(4.8)
|
10(31.2)
|
|
|
|
Gender
|
|
|
|
0.6763)
|
0.4203)
|
0.4033)
|
male
|
15(26.3))
|
22(26.2)
|
6(18.8)
|
|
|
|
female
|
42(73.7)
|
62(73.8)
|
26(81.2)
|
|
|
|
Vaccine
|
|
|
|
0.8464)
|
0.6304)
|
0.5304)
|
yes
|
53(93.0)
|
80(95.2)
|
30(93.8)
|
|
|
|
no
|
4(7.0)
|
4(4.8)
|
2(6.2)
|
|
|
|
Regular exercise
|
|
|
|
0.1853)
|
0.1853)
|
0.9663)
|
yes
|
35(61.4)
|
39(46.4)
|
15(46.9)
|
|
|
|
no
|
22(38.6)
|
45(53.6)
|
17(53.1)
|
|
|
|
Underlying disease
|
|
|
|
0.0514)
|
0.0444)
|
0.4394)
|
Yes
|
0(0.0)
|
4(4.8)
|
3(9.4)
|
|
|
|
no
|
57(100.0)
|
80(95.2)
|
29(90.6)
|
|
|
|
SBP*
|
120±14.6
|
118±12.6
|
116±12.3
|
0.1451)
|
0.0706)
|
0.5106)
|
DBP*
|
71.6±11.6
|
70.0±11.6
|
73.0±10.4
|
0.7612)
|
0.5575)
|
0.1785)
|
* SBP: systolic blood pressure; DBP: diastolic blood pressure. Statistic methods: 1) ANOVA test; 2) Kruskal-Wallis H test; 3) Pearson’s Chi-squared test; 4) Fisher’s exact test; 5) Student t-test; 6) Mann-Whitny U test.
Table 2 shows the HRV characteristics of each of the three groups, which suggested that individuals affected by long-COVID have lower SDNN (p=0.044), TP (p=0.034), and VLF values (p=0.015), but higher PSI (p=0.045), compared to the no long-COVID symptoms groups. Parasympathetic overtones, which were assessed as SDNN >60ms (16.4%) and RMSSD >40ms (32.7%), remained present in individuals who were convalescent from COVID-19 and those who experienced long-term COVID-19. In addition, compared to the control group, both the group2 and group3 showed a decrease in TP, with the group3 showing a much larger decrease (p=0.044). In contrast, the VLF increased in the group2, whereas those experiencing LC had a significant reduction, even below the control parameter (p=0.021).
Table 2. HRV-relevant test among research population with regards to long COVID-19 status (n=173).
parameters
|
Control group (group1)
|
COVID-19 experienced group without LCS (group2)
|
COVID-19 experienced group with LC (group3)
|
P1 (between group1-3)
|
P3 (between group1 and group3)
|
P4 (between group2 and group3)
|
|
n=57
|
n=84
|
n=32
|
|
|
|
Time domain
|
|
|
|
|
|
|
Mean RHT*
|
83.4±9.90
|
81.9±14.0
|
81.2±14.8
|
0.4082)
|
0.4556)
|
0.6777)
|
RMSSD[ms]*
|
31.5±16.5
|
35.2±19.2
|
32.4±19.9
|
0.5171)
|
0.8477)
|
0.4427)
|
SDNN[ms]*
|
40.0±16.0
|
43.9±16.4
|
37.7±18.8
|
0.0711)
|
0.4347)
|
0.0447)
|
Frequency domain
|
|
|
|
|
|
|
PSI*
|
60.2±57.6
|
61.6±103
|
86.0±98.8
|
0.0712)
|
0.5027)
|
0.0457)
|
TP[ms]*
|
7.88±7.27
|
7.13±0.995
|
6.65±1.07
|
0.0442)
|
0.1987)
|
0.0346)
|
VLF[ms]*
|
5.78±1.06
|
6.00±1.17
|
5.39±1.19
|
0.0212)
|
0.1266)
|
0.0156)
|
LF[ms]*
|
5.72±0.976
|
5.83±1.09
|
5.45±1.09
|
0.3731)
|
0.2436)
|
0.0966)
|
HF[ms]*
|
5.60±1.15
|
5.66±1.23
|
5.38±1.35
|
0.5031)
|
0.4297)
|
0.3066)
|
LF Norm
|
52.9±19.4
|
53.7±21.5
|
52.0±19.9
|
0.9202)
|
0.8217)
|
0.7417)
|
HF Norm
|
47.3±19.2
|
46.0±21.9
|
45.9±22.6
|
0.7321)
|
0.8477)
|
0.9916)
|
LF/HF
|
1.69±1.69
|
2.17±2.85
|
1.48±1.07
|
0.7922)
|
0.8617)
|
0.6027)
|
abnormal HR*
|
0.544±1.84
|
0.857±2.73
|
0.438±1.64
|
0.4602)
|
0.6817)
|
0.2727)
|
Stress survey
|
|
|
|
|
|
|
Autonomic neuroactivity
|
89.8±15.1
|
92.4±18.0
|
87.9±17.9
|
0.0802)
|
0.6267)
|
0.0966)
|
Degree of Autonomic neuroactivity
|
|
|
|
0.0633)
|
0.8513)
|
0.1113)
|
abnormal
|
35(61.4)
|
36(42.9)
|
19(59.4)
|
|
|
|
normal
|
22(38.6)
|
48(57.1)
|
13(40.6)
|
|
|
|
Autonomic neural balance diagram
|
51.9±33.8)
|
53.1±41.8
|
53.1±34.4
|
0.9392)
|
0.9287)
|
0.6887)
|
Degree of Autonomic neural balance diagram
|
|
|
|
0.8663)
|
0.6305)
|
0.6263)
|
imbalance
|
31(54.4)
|
43(51.2)
|
18(56.2)
|
|
|
|
balance
|
26(45.6)
|
41(48.8)
|
14(43.8)
|
|
|
|
Stress resistance
|
91.9±13.4
|
94.6±13.8
|
90.6±17.4
|
0.1672)
|
0.7657)
|
0.1337)
|
Degree of Stress resistance
|
|
|
|
0.3163)
|
0.9193)
|
0.2883)
|
abnormal
|
22(38.6)
|
23(27.4)
|
12(37.5)
|
|
|
|
normal
|
35(61.4)
|
61(72.6)
|
20(62.5)
|
|
|
|
Stress index
|
104±13.9
|
101±16.9
|
106±20.1
|
0.1731)
|
0.9227)
|
0.1557)
|
Degree of stress index
|
|
|
|
0.7893)
|
0.8543)
|
0.5363)
|
abnormal
|
15(26.3)
|
19(22.6)
|
9(28.1)
|
|
|
|
normal
|
42(73.3)
|
65(77.4)
|
23(71.9)
|
|
|
|
Fatigue
|
108±20.2
|
105±21.4
|
110±19.1
|
0.2802)
|
0.7687)
|
0.1797)
|
Degree of fatigue
|
|
|
|
0.1243)
|
0.8513)
|
0.1733)
|
abnormal
|
35(61.4)
|
38(45.2)
|
19(59.4)
|
|
|
|
normal
|
22(8.6)
|
46(54.8)
|
13(40.6)
|
|
|
|
Average HR
|
83.3±9.79
|
82.1±14.1
|
81.7±14.6
|
0.5371)
|
0.5796)
|
0.8916)
|
Degree of average HR
|
|
|
|
0.4394)
|
0.2333)
|
0.5344)
|
abnormal
|
4(7.0)
|
12(14.3)
|
4(12.5)
|
|
|
|
normal
|
53(93.0)
|
72(85.7)
|
28(87.5)
|
|
|
|
Cardiac stability
|
94.7±18.4
|
97.4±21.7
|
94.3±22.4
|
0.8162)
|
0.9366)
|
0.5637)
|
Degree of Cardiac stability
|
|
|
|
0.8933)
|
0.6353)
|
0.7493)
|
abnormal
|
22(38.6)
|
34(40.5)
|
14(43.8)
|
|
|
|
normal
|
35(61.4)
|
32(59.5)
|
14(66.3)
|
|
|
|
* LC: long-COVID; LCS: long-COVID symptoms; P1: p-value for comparison among the control group, the study group without long-term COVID-19 symptoms and the study group in whom experienced long-COVID-19; P2: p-value for comparison between the control group and the study group with long-COVID symptoms; P3: p-value for comparison between two study groups; Mean HRT: mean heart rate; RMSSD: root mean square of the successive normal; SDNN: standard deviation of normal-to-normal; PSI: psychology stress index; TP: total power; VLF: very low frequency; LF: low frequency; HF: low frequency; HR: heart rate. Statistical methods:1) ANOVA; 2) Kruskal-Wallis H test; 3) Pearson’s chi-squared test; 4) Fisher’s exact test; 5) Chi-squared test with Yates’ continuity correction; 6) Student’s t-test; and 7) Mann-Whitney U test.
To exclude age-related differences, we counted the HRV characteristics of those aged <25 years and those aged ≥25 years in the autonomic balance survey population, as shown in Table 3 and Table 4, respectively. Table 3 demonstrates that there was still a significant difference in the VLF between the groups of study subjects under 25 years of age (p=0.031), as shown by an increase in the VLF value in the convalescent population, and a significant decrease in the LC group compared to the COVID-19 experienced group without any LCS (p=0.012), which is in line with the results of the previous table. The results also suggest more abnormal autonomic activity in the group3 than in the group2. In contrast, there were no significant differences in HRV between groups among study participants aged ≥25 years, as shown in Table 4.
Table 3. HRV-related test among research population under 25 years old with regards to long COVID-19 status (n=151).
Parameters
|
Control group(group1)
|
COVID-19 experienced group without LCS (group2)
|
COVID-19 experienced group with LC (group3)
|
P1(between group1-3)
|
P3(between group1 and group3)
|
P4(between group2 and group3)
|
|
N=49
|
N=80
|
N=22
|
|
|
|
Time domain
|
|
|
|
|
|
|
Mean RHT*
|
83.7±9.95
|
81.5±13.9
|
82.0±14.9
|
0.5521)
|
0.7166)
|
0.8386)
|
RMSSD[ms]*
|
31.7±16.7
|
36.0±19.3
|
33.6±21.4
|
0.6722)
|
0.9755)
|
0.4875)
|
SDNN[ms]*
|
40.2±16.1
|
44.6±16.3
|
40.5±20.1
|
0.2332)
|
0.5835)
|
0.3446)
|
Frequency domain
|
|
|
|
|
|
|
PSI*
|
60.5±58.5
|
58.0±99.0
|
78.7±92.9
|
0.1592)
|
0.4625)
|
0.0915)
|
TP[ms]*
|
7.92±7.40
|
7.18±0.977
|
6.76±1.11
|
0.1402)
|
0.2795)
|
0.0986)
|
VLF[ms]*
|
5.79±1.08
|
6.06±1.16
|
5.38±1.27
|
0.0312)
|
0.0606)
|
0.0125)
|
LF[ms]*
|
5.75±0.93
|
5.86±1.08
|
5.59±1.10
|
0.4562)
|
0.5495)
|
0.2736)
|
HF[ms]*
|
5.60±1.15
|
5.71±1.23
|
5.55±1.32
|
0.6931)
|
0.6565)
|
0.6556)
|
LF Norm
|
53.1±19.0
|
53.2±21.6
|
51.1±18.5
|
0.9371)
|
0.7706)
|
0.5156)
|
HF Norm
|
19.0±47.1
|
21.6±46.5
|
18.5±46.0
|
0.6501)
|
0.7446)
|
0.9506)
|
LF/HF
|
1.70±1.71
|
2.16±2.90
|
1.36±0.920
|
0.6102)
|
0.7235)
|
0.4285)
|
abnormal HR*
|
0.564±1.87
|
0.888±2.80
|
0.565±1.93
|
0.4962)
|
0.9975)
|
0.4525)
|
Stress survey
|
|
|
|
|
|
|
Autonomic neuroactivity
|
89.8±15.4
|
95.0(±17.8
|
88.0±19.2
|
0.0722)
|
0.4155)
|
0.1276)
|
Degree of Autonomic neuroactivity
|
|
|
|
0.0563)
|
0.6073)
|
0.0483)
|
abnormal
|
28(57.1)
|
32(40.0)
|
14(63.6)
|
|
|
|
normal
|
21(42.9)
|
48(60.0)
|
8(36.4)
|
|
|
|
Autonomic neural balance diagram
|
51.3±33.4
|
54.7±42.0
|
34.2±34.2
|
0.9821)
|
0.8235)
|
0.8965)
|
Degree of Autonomic neural balance diagram
|
|
|
|
0.9553)
|
0.9653)
|
0.8653)
|
imbalance
|
27(55.1)
|
42(52.5)
|
12(54.5)
|
|
|
|
balance
|
22(44.9)
|
38(47.5)
|
10(45.5)
|
|
|
|
Stress resistance
|
91.8±13.7
|
95.2±13.6
|
91.9±18.4
|
0.9301)
|
0.7376)
|
0.4506)
|
Degree of Stress resistance
|
|
|
|
0.4863)
|
0.9763)
|
0.4193)
|
abnormal
|
18(36.7)
|
22(27.5)
|
8(36.4)
|
|
|
|
normal
|
31(63.3)
|
58(72.5)
|
14(63.6)
|
|
|
|
Stress index
|
104±14.1
|
100±16.4
|
106±20.5
|
0.2012)
|
0.5805)
|
0.1265)
|
Degree of stress index
|
|
|
|
0.8863)
|
0.6603)
|
0.6403)
|
abnormal
|
11(22.4)
|
18(22.5)
|
6(27.3)
|
|
|
|
normal
|
38(77.6)
|
62(77.5)
|
16(72.7)
|
|
|
|
Fatigue
|
108±20.4
|
105±21.6
|
111±19.1
|
0.2802)
|
0.5385)
|
0.1465)
|
Degree of fatigue
|
|
|
|
0.1243)
|
0.9943)
|
0.1673)
|
abnormal
|
29(59.2)
|
34(42.5)
|
13(59.1)
|
|
|
|
normal
|
20(40.8)
|
46(57.5)
|
9(40.9)
|
|
|
|
Average HR
|
83.6±9.84
|
81.7±14.0
|
82.5±15.0
|
0.6801)
|
0.8366)
|
0.7916)
|
Degree of average HR
|
|
|
|
0.6894)
|
0.7764)
|
0.6477)
|
abnormal
|
4(8.2)
|
11(13.8)
|
3(13.6)
|
|
|
|
normal
|
45(91.8)
|
69(86.3)
|
19(86.4)
|
|
|
|
Cardiac stability
|
94.7±18.7
|
98.2±21.8
|
94.8±22.7
|
0.9021)
|
0.7746)
|
5786)
|
Degree of Cardiac stability
|
|
|
|
0.6873)
|
0.3883)
|
0.5703)
|
abnormal
|
17(34.7)
|
31(38.8)
|
10(45.5)
|
|
|
|
normal
|
32(65.3)
|
49(61.2)
|
12(54.5)
|
|
|
|
* LC: long-COVID; LCS: long-COVID symptoms; P1: p-value for comparison among the control group, the study group without long-term COVID-19 symptoms and the study group in whom experienced long-COVID-19; P2: p-value for comparison between the control group and the study group with long-covid symptoms; P3: p-value for comparison between two study groups; Mean HRT: mean heart rate; RMSSD: root mean square of the successive normal; SDNN: standard deviation of normal-to-normal; PSI: psychology stress index; TP: total power; VLF: very low frequency; LF: low frequency; HF: low frequency; HR: heart rate. Statistical methods: 1) ANOVA test; 2) Kruskal-Wallis H Test; 3) Pearson’s chi-squared test; 4) chi-squared test with Yates’ continuity correction; 5) Mann-Whitney U test; 6) Student’s t-test; and 7) Fisher’s exact test.
Table 4. HRV-related test among research population over 25 years old with regards to long COVID-19 status (n=22).
Time domain
|
Control group (group1)
|
COVID-19 experienced group without LCS (group2)
|
COVID-19 experienced group with LC (group3)
|
P1(between group1-3)
|
P3(between group1 and group3)
|
P4(between group2 and group3)
|
|
N=8
|
N=10
|
N=4
|
|
|
|
Mean RHT
|
76.0±5.66
|
90.5±14.7
|
79.1±15.2
|
0.5051)
|
0.5024)
|
0.2374)
|
RMSSD[ms]
|
25.4±6.08
|
19.5±7.08
|
29.3±15.9
|
0.1471)
|
0.1574)
|
0.1334)
|
SDNN[ms]
|
35.6±15.2
|
29.4±11.4
|
30.4±13.4
|
0.9082)
|
0.6284)
|
0.6905)
|
Frequency domain
|
|
|
|
|
|
|
PSI
|
51.6±29.4
|
134.0±169
|
104±117
|
0.7282)
|
0.9575)
|
0.7015)
|
TP[ms]
|
6.57±0.796
|
6.15±0.959
|
6.39±0.988
|
0.9212)
|
0.6324)
|
0.5755)
|
VLF[ms]
|
5.57±0.003
|
4.97±1.03
|
5.42±1.01
|
0.2281)
|
0.2314)
|
0.3774)
|
LF[ms]
|
4.95±2.30
|
5.28±1.18
|
5.10±1.04
|
0.9362)
|
0.9574)
|
0.9125)
|
HF[ms]
|
5.70±1.38
|
4.63±0.72
|
4.94±1.39
|
0.9101)
|
0.9324)
|
0.5564)
|
LF Norm
|
46.5±37.6
|
64.5±16.0
|
54.3±24.3
|
0.6221)
|
0.6564)
|
0.4644)
|
HF Norm
|
53.5±37.7
|
16.0±35.5
|
24.3±45.7
|
0.6211)
|
0.6554)
|
0.4644)
|
LF/HF
|
1.48±1.74
|
2.34±1.66
|
1.80±1.41
|
0.8702)
|
0.5505)
|
0.6504)
|
abnormal HR
|
0.0
|
0.25±0.5
|
0.11±0.33
|
0.6082))
|
0.2285)
|
0.607
|
Stress survey
|
|
|
|
|
|
|
Autonomic neuroactivity
|
89.0±2.83
|
77.8±10.7
|
87.4±14.9
|
0.1971)
|
0.2044)
|
0.1764)
|
Degree of Autonomic neuroactivity
|
|
|
|
0.1233)
|
0.1203)
|
0.1263)
|
bad
|
7(87.5)
|
4(100)
|
5(50.0)
|
|
|
|
normal
|
1(12.5)
|
0
|
5(50.0)
|
|
|
|
Autonomic neural balance diagram
|
69.0±56.6
|
22.2±24.6
|
62.3±35.1
|
0.4091)
|
0.4594)
|
0.0574)
|
Degree of Autonomic neural balance diagram
|
|
|
|
0.6503)
|
0.5203)
|
0.2803)
|
imbalance
|
4(50.0)
|
1(25.0)
|
6(60.0)
|
|
|
|
balance
|
4(50.0)
|
3(75.0)
|
4(40.0)
|
|
|
|
Stress resistance
|
94.0±2.83
|
83.8±14.5
|
87.3±14.9
|
0.5912)
|
0.5064)
|
0.6095)
|
Degree of Stress resistance
|
|
|
|
0.8583)
|
0.5203)
|
0.5453)
|
bad
|
4(50.0)
|
1(25.0)
|
4(40.0)
|
|
|
|
normal
|
4(50.0)
|
3(75.0)
|
6(60.0)
|
|
|
|
Stress index
|
97.0±1.41
|
114.0±23.7
|
107.0±20.3
|
0.3512)
|
0.4714)
|
0.5285)
|
Degree of stress index
|
|
|
|
0.6163)
|
0.3513)
|
0.6893)
|
bad
|
4(50.0)
|
1(25.0)
|
3(30.0)
|
|
|
|
normal
|
4(50.0)
|
3(75.0)
|
7(70.0)
|
|
|
|
Fatigue
|
114.0±18.4
|
118.0±12.6
|
108.0±20.1
|
0.7642)
|
0.3524)
|
0.2845)
|
Degree of fatigue
|
|
|
|
0.4033)
|
0.4373)
|
0.2103)
|
bad
|
1(50.0)
|
4(100.0)
|
6(66.7)
|
|
|
|
normal
|
1(50.0)
|
0(0.0)
|
3(33.3)
|
|
|
|
Average HR
|
76.0±5.66
|
90.5±14.7
|
79.8±14.2
|
0.5531)
|
0.5534)
|
0.2544)
|
Degree of average HR
|
|
|
|
0.4593)
|
0.3576)
|
0.5053)
|
Un-normal
|
0(0)
|
1(25.0)
|
1(10.0)
|
|
|
|
normal
|
8(100)
|
3(75.0)
|
9(90.0)
|
|
|
|
Cardiac stability
|
96.0±1.41
|
81.8±9.5
|
93.1±22.7
|
0.2111)
|
0.2364)
|
0.2074)
|
Degree of Cardiac stability
|
|
|
|
0.6243)
|
0.3193)
|
0.2803)
|
unnormal
|
5(62.5)
|
3(75.0)
|
4(40.0)
|
|
|
|
normal
|
3(37.5)
|
1(25.0)
|
6(60.0)
|
|
|
|
* LC: long-COVID; LCS: long-COVID symptoms; P1: p-value for comparison among the control group, the study group without long-term COVID-19 symptoms and the study group in whom experienced long-COVID-19; P2: p-value for comparison between the control group and the study group with long-covid symptoms; P3: p-value for comparison between two study groups; Mean HRT: mean heart rate; RMSSD: root mean square of the successive normal; SDNN: standard deviation of normal-to-normal; PSI: psychology stress index; TP: total power; VLF: very low frequency; LF: low frequency; HF: low frequency; HR: heart rate. Statistic methods:1) ANOVA test; 2) Kruskal-Wallis H test; 3) Fisher’s exact test;4) Student t-test;5) Mann-Whitney U test; 6) Pearson’s Chi-squared test.