The final set contained 1,085 men, 142 (13·09%) of whom were infected with Toxoplasma and 131 (12·07%) diagnosed with Covid, and 3,414 women, 644 (18·86%) of whom were infected with Toxoplasma and 339 (9·93%) diagnosed with Covid. The incidence of other potential risk factors is shown in Table 1.
A significant difference in age between men (38·9, s.d. 10·9) and women (40·0, s.d. 10·5) (t4497 = -2·86, p = 0·0043) and between Toxoplasma-free (39·3, s.d. 10·5) and Toxoplasma-infected (42·7, s.d. 10·1) women (t3412 = -7·41, p < 0·0001), but not between Toxoplasma-free (38·7, s.d. 10·7) and Toxoplasma-infected (40·0, s.d. 11·8) men (t1083 = -1·25, p = 0·211) existed in the population under study. No association between age and Covid in either men or women (p > 0·38) was detected.
Table 1
Incidence of risk and protective factors for Covid-19 in men and women
|
Women
|
Men
|
|
|
|
|
no Covid
|
Covid
|
no Covid
|
Covid
|
OR
|
C.I.95
|
p
|
|
N
|
%
|
N
|
%
|
N
|
%
|
N
|
%
|
|
|
|
Toxoplasmosis
|
563
|
18·31
|
81
|
23·89
|
115
|
12·05
|
27
|
20·61
|
1·50
|
1·19–1·89
|
0·0007
|
Borreliosis
|
410
|
19·85
|
57
|
24·26
|
108
|
14·57
|
17
|
17·00
|
1·27
|
0·96–1·68
|
0·0881
|
Rh-positivity
|
1953
|
76·41
|
219
|
76·31
|
490
|
75·85
|
61
|
74·39
|
0·98
|
0·76–1·26
|
0·8854
|
A blood group
|
989
|
37·26
|
123
|
41·14
|
236
|
34·05
|
33
|
35·87
|
1·16
|
0·93–1·44
|
0·1795
|
B blood group
|
568
|
21·40
|
50
|
16·72
|
156
|
22·51
|
22
|
23·91
|
0·82
|
0·62–1·07
|
0·1368
|
AB blood group
|
247
|
9·31
|
34
|
11·37
|
91
|
13·13
|
13
|
14·13
|
1·19
|
0·86–1·65
|
0·2929
|
0 blood group
|
850
|
32·03
|
92
|
30·77
|
210
|
30·30
|
24
|
26·09
|
0·91
|
0·73–1·15
|
0·4396
|
Being overweight
|
739
|
35·11
|
90
|
31·03
|
258
|
42·64
|
35
|
33·02
|
0·74
|
0·57–0·95
|
0·0169
|
Diabetes
|
75
|
3·56
|
7
|
2·41
|
28
|
4·63
|
8
|
7·55
|
0·96
|
0·52–1·76
|
0·8921
|
Cardiovascular problems
|
131
|
6·22
|
16
|
5·52
|
65
|
10·74
|
9
|
8·49
|
0·81
|
0·50–1·30
|
0·3820
|
Asthma
|
1846
|
87·70
|
256
|
88·28
|
544
|
89·92
|
89
|
83·96
|
1·13
|
0·80–1·59
|
0·4908
|
Chronic obstructive pulmonary disease
|
49
|
2·33
|
5
|
1·72
|
16
|
2·64
|
1·89
|
0·67
|
0·27–1·63
|
0·3737
|
|
Immunosuppression
|
289
|
13·73
|
40
|
13·79
|
52
|
8·60
|
9
|
8·49
|
1·00
|
0·70–1·42
|
0·9929
|
Allergy
|
548
|
26·03
|
77
|
26·55
|
150
|
24·79
|
28
|
26·42
|
1·06
|
0·81–1·37
|
0·6798
|
Autoimmunity
|
168
|
14·35
|
25
|
11·57
|
26
|
8·72
|
6
|
9·09
|
0·75
|
0·45–1·24
|
0·2545
|
Living alone
|
285
|
9·30
|
28
|
8·28
|
160
|
16·91
|
23
|
17·56
|
0·96
|
0·70–1·32
|
0·8027
|
Tobacco smoking
|
415
|
19·71
|
54
|
18·62
|
148
|
24·46
|
23
|
21·70
|
0·89
|
0·66–1·19
|
0·4341
|
Marihuana consumption
|
56
|
2·66
|
6
|
2·07
|
40
|
6·61
|
14
|
13·21
|
1·49
|
0·88–2·53
|
0·1367
|
Daily alcohol consumption
|
126
|
5·99
|
16
|
5·52
|
97
|
16·03
|
14
|
13·21
|
0·86
|
0·55–1·33
|
0·4887
|
Frequent singing
|
269
|
12·78
|
39
|
13·45
|
50
|
8·26
|
14
|
13·21
|
1·21
|
0·87–1·70
|
0·2612
|
Sport
|
620
|
29·45
|
92
|
31·72
|
274
|
45·29
|
60
|
56·60
|
1·30
|
1·03–1·65
|
0·0300
|
Cold water swimming
|
205
|
9·74
|
37
|
12·76
|
102
|
16·86
|
19
|
17·92
|
1·32
|
0·95–1·84
|
0·0989
|
Frequent sauna use
|
94
|
8·03
|
20
|
9·26
|
37
|
12·42
|
8
|
12·12
|
1·16
|
0·70–1·93
|
0·5558
|
Vitamins and supplements
|
753
|
35·77
|
133
|
45·86
|
289
|
47·77
|
60
|
56·60
|
0·62
|
0·49–0·78
|
0·0001
|
Wearing glasses
|
1101
|
60·36
|
169
|
61·90
|
371
|
67·82
|
67
|
66·34
|
0·96
|
0·75–1·24
|
0·7723
|
Dog keeping
|
365
|
44·19
|
78
|
49·37
|
93
|
51·10
|
21
|
45·65
|
0·82
|
0·56–1·18
|
0·282
|
Cat keeping
|
381
|
46·13
|
82
|
51·90
|
82
|
45·05
|
17
|
36·96
|
1·16
|
0·80–1·68
|
0·4303
|
The last four columns show the results of logistic regression with Covid-19 infection as a dependent variable, age, sex, size of the place of residence as covariates, and one of risk/protective factors listed in the first column as the independent variable. Results shown in bold were significant after correction for multiple tests.
The risk of acquiring toxoplasmosis depends on certain confounding factors, such as sex, age, and size of the place of residence. Therefore, the association between potential risk factors and protective factors was analysed using a logistic regression with binary variable Covid as a dependent variable, sex, age, size of place of residence as covariates, and one of the analysed factors as the independent variable. The results are shown in the last three columns of Table 1. Toxoplasmosis, with an odds ratio of 1·50 (C.I.95 = 1·19–1·89, p = 0·0007, risk ratio 1·40 (CI95: 1·05–1·80) for women and 1·91 (CI95: 1·20–3·05) for men, turned out to be the most serious risk factor for being diagnosed with Covid.
It is known that Rh-negative subjects are more prone to experiencing the negative effects of toxoplasmosis than Rh-positive subjects are.[38–40] Therefore, also a more complex model containing not only sex, age, size of the place of residence, and toxoplasmosis, but also the Rh factor and Rh–toxoplasmosis interaction was analysed. Logistic regression showed a significant effect of toxoplasmosis (OR = 1·45, CI95: 1·06–2·10, p = 0·046), but not Rh (p = 0·86) or Rh–toxoplasmosis interaction (p = 0·84).
Respondents who had been diagnosed with Covid-19 were asked to rate the course of their disease and indicate which symptoms they experienced during their illness. Figure 1 shows that Toxoplasma-infected subjects of both sexes had a more serious course of Covid. Partial Kendall correlation (Table 2) showed that toxoplasmosis represents a more pronounced risk factor for a severe course of Covid-19 than compromised autoimmunity, immunodeficiency, male sex, cat keeping, being overweight, borreliosis, higher age, or chronic obstructive pulmonary disease does.
One could speculate that keeping a cat could be just a proxy for being Toxoplasma-infected and indeed, the prevalence of toxoplasmosis in subjects who do keep a cat (24.6%) was markedly higher than in those who do not (15·5%) (Chi2 = 15·5, p < 0.0001). To test this hypothesis, the partial Kendall correlation tests was performed separately for Toxoplasma-free and Toxoplasma-infected subjects (Table 2, the last four columns). Existence of the cat-keeping effects (i.e. increased likelihood of contracting Covid-19 and of having a severe course of the disease in the cat-keepers) in the Toxoplasma-infected subpopulation suggests that keeping a cat is a real risk factor for Covid-19, not just a side-effect of a higher probability of having toxoplasmosis. In fact, the strength of the cat-keeping effect was twice higher in the Toxoplasma-infected (Tau = 0·153) than in Toxoplasma-free subjects (Tau = 0·084). One could speculate that a cat might be able to transmit Covid among family members. Members of one family could moreover be infected repeatedly and the virus could adapt to the similar genotype of (genetically related) members of the same family; both of the above scenarios could then result in a more severe course of the disease. Indeed, separate analyses for 194 respondents who lived in multi-member families showed that keeping a cat increases the risk of a severe course of Covid-19 (Tau = 0·116, p = 0·017). The same analysis for 22 respondents who lived alone showed no such increase; in fact, it showed a nonsignificant effect in the opposite direction (Tau = -0·028, p = 0·867).
Analogical analyses of the risk of acquiring SARS-CoV-2 infection showed no significant effect of cat keeping neither in people who live in multi-member families nor in those who live alone. However, even here a positive non-significant effect of cat keeping in 3,983 respondents living in multi-member families (OR = 1·210, CI95: 0.82–1·78, p = 0·332) and a negative non-significant effect in 496 respondents living alone (OR = 0·692, CI95: 0·20–2·46, p = 0·568) were found.
The results also showed that many factors taken into consideration in this study had a much stronger effect on the risk of severe course of Covid in Toxoplasma-infected subjects than in those who were Toxoplasma-free: borreliosis (Tau = 0·212 vs. 0·010), being overweight (Tau = 0·140 vs. 0·089), cardiovascular diseases (Tau = 0·170 vs. 0·049), asthma (Tau = 0·133 vs. 0·039), chronic obstructive pulmonary disease (Tau = 0·219 vs. 0·013), allergy (Tau = 0·089 vs. 0·012), compromised autoimmunity (Tau = 0·254 vs. 0·074), and cat keeping (Tau = 0·153 vs. 0·0840). Conspicuous exceptions were male sex (Tau = 0·095 vs. 0·112) and immunodeficiency (Tau = 0·067 vs. 0·160). The protective effect of sport was also stronger in the Toxoplasma-free than in the Toxoplasma-infected subset (Tau = -1·16 vs. 0·028).
Table 2
Correlation between various risk/protective factors and severity of Covid-19 disease
|
All
|
Women
|
Men
|
Toxo-free
|
Toxo-infected
|
|
Tau
|
p
|
Tau
|
p
|
Tau
|
p
|
Tau
|
p
|
Tau
|
p
|
Sex
|
0·116
|
0·0002
|
NA
|
NA
|
NA
|
NA
|
0·112
|
0·0017
|
0·095
|
0·1713
|
Age
|
0·093
|
0·0032
|
0·124
|
0·0010
|
0·025
|
0·6763
|
0·066
|
0·0654
|
0·137
|
0·0494
|
Size of place of residence
|
0·009
|
0·7815
|
-0·002
|
0·9575
|
0·039
|
0·5093
|
0·000
|
0·9895
|
0·065
|
0·3477
|
Toxoplasmosis
|
0·146
|
0·0000
|
0·150
|
0·0001
|
0·123
|
0·0376
|
NA
|
NA
|
NA
|
NA
|
Borreliosis
|
0·094
|
0·0123
|
0·120
|
0·0088
|
0·030
|
0·6529
|
0·010
|
0·8146
|
0·212
|
0·0301
|
Rh-positivity
|
0·036
|
0·3097
|
0·035
|
0·3929
|
0·064
|
0·3950
|
0·022
|
0·5941
|
0·098
|
0·2112
|
A blood group
|
0·019
|
0·5892
|
0·000
|
0·9945
|
0·079
|
0·2715
|
0·032
|
0·4210
|
-0·052
|
0·4932
|
B blood group
|
-0·008
|
0·8101
|
-0·010
|
0·7940
|
0·009
|
0·8991
|
0·012
|
0·7680
|
-0·069
|
0·3606
|
AB blood group
|
0·021
|
0·5371
|
0·093
|
0·0210
|
-0·160
|
0·0254
|
-0·002
|
0·9586
|
0·080
|
0·2909
|
0 blood group
|
-0·028
|
0·4278
|
-0·050
|
0·2142
|
0·031
|
0·6694
|
-0·043
|
0·2834
|
0·048
|
0·5260
|
Being overweight
|
0·104
|
0·0012
|
0·107
|
0·0052
|
0·116
|
0·0558
|
0·089
|
0·0147
|
0·140
|
0·0505
|
Diabetes
|
0·004
|
0·8922
|
-0·021
|
0·5777
|
0·038
|
0·5301
|
0·019
|
0·5929
|
-0·022
|
0·7602
|
Cardiovascular problems
|
0·063
|
0·0514
|
0·063
|
0·0985
|
0·075
|
0·2194
|
0·049
|
0·1762
|
0·170
|
0·0174
|
Asthma
|
0·052
|
0·1055
|
0·036
|
0·3496
|
0·094
|
0·1233
|
0·039
|
0·2815
|
0·133
|
0·0630
|
Chronic obstructive pulmonary disease
|
0·072
|
0·0252
|
0·073
|
0·0583
|
0·080
|
0·1853
|
0·013
|
0·7220
|
0·219
|
0·0022
|
Immunodeficiency
|
0·135
|
0·0000
|
0·141
|
0·0002
|
0·116
|
0·0558
|
0·160
|
0·0000
|
0·067
|
0·3472
|
Allergy
|
-0·015
|
0·6453
|
-0·011
|
0·7829
|
-0·025
|
0·6809
|
-0·028
|
0·4376
|
0·025
|
0·7235
|
Autoimmunity
|
0·137
|
0·0004
|
0·146
|
0·0011
|
0·112
|
0·1590
|
0·074
|
0·0874
|
0·254
|
0·0048
|
Living alone
|
0·034
|
0·2794
|
0·092
|
0·0151
|
-0·061
|
0·2999
|
0·030
|
0·3960
|
0·073
|
0·2990
|
Tobacco smoking
|
0·061
|
0·0576
|
0·045
|
0·2454
|
0·090
|
0·1364
|
0·082
|
0·0239
|
0·006
|
0·9351
|
Marihuana consumption
|
-0·001
|
0·9777
|
-0·082
|
0·0330
|
0·081
|
0·1800
|
0·057
|
0·1207
|
-0·195
|
0·0065
|
Daily alcohol consumption
|
-0·039
|
0·2311
|
-0·094
|
0·0138
|
0·067
|
0·2677
|
-0·055
|
0·1279
|
0·035
|
0·6289
|
Frequent singing
|
-0·032
|
0·3162
|
-0·060
|
0·1153
|
0·056
|
0·3553
|
-0·053
|
0·1459
|
-0·001
|
0·9861
|
Sport
|
-0·092
|
0·0044
|
-0·112
|
0·0036
|
-0·056
|
0·3543
|
-0·116
|
0·0015
|
-0·028
|
0·6944
|
Cold water swimming
|
-0·047
|
0·1447
|
-0·041
|
0·2851
|
-0·055
|
0·3614
|
-0·062
|
0·0883
|
-0·041
|
0·5691
|
Frequent use of sauna
|
-0·036
|
0·3550
|
-0·040
|
0·3731
|
-0·037
|
0·6432
|
-0·009
|
0·8280
|
-0·177
|
0·0491
|
Vitamins and supplements
|
-0·047
|
0·1425
|
-0·029
|
0·4437
|
-0·087
|
0·1499
|
-0·068
|
0·0628
|
0·034
|
0·6329
|
Wearing glasses
|
-0·033
|
0·3244
|
0·005
|
0·9037
|
-0·131
|
0·0346
|
-0·003
|
0·9346
|
-0·069
|
0·3559
|
Current dog keeping
|
0·004
|
0·9321
|
0·015
|
0·7737
|
-0·042
|
0·6694
|
0·049
|
0·3497
|
-0·120
|
0·2637
|
Current cat keeping
|
0·107
|
0·0203
|
0·123
|
0·0194
|
0·058
|
0·5549
|
0·084
|
0·1052
|
0·153
|
0·1544
|
The table shows effect size and significance, i.e. partial Kendall Taus and p values. The effect of sex was controlled for age, and size of place of residence, the effect of age for sex, and size of place of residence, and size of place of residence for sex and age; all other effects were controlled for all three covariates. Positive Tau means a more severe course of Covid in subjects reporting the factor listed in the first column. The results in bold were significant after correction for multiple tests. In less numerous men, all factors lost their significance after correction for multiple tests but observed Tau values show that the effects in men are mostly stronger than in women.
Logistic regression controlled for age, sex, and size of the place of residence showed that Toxoplasma-infected participants reported having more symptoms during Covid, but only the presence of chest pain or pressure (OR = 1·96) and higher sexual appetence (OR = 2·68) were statistically significant after correction for multiple tests (Table 3). On the other hand, even the effects that did not reach the formal level of statistical significance tended to show a higher frequency of symptoms in Toxoplasma-infected than in Toxoplasma-free subjects and were nearly always stronger in men than in women.
Table 3
Symptoms of Covid-19 in Toxoplasma-infected and Toxoplasma-free subjects
|
All
|
Women
|
Men
|
|
|
|
|
|
|
Toxo-
|
Toxo+
|
Toxo-
|
Toxo+
|
Toxo-
|
Toxo+
|
OR
|
C.I.95
|
p
|
ORW
|
ORM
|
Fever > 38°C (100·4°F)
|
0·38
|
0·39
|
0·34
|
0·37
|
0·47
|
0·45
|
1·07
|
0·67–1·7
|
0·789
|
1·09
|
0·99
|
Fatigue
|
0·74
|
0·81
|
0·79
|
0·90
|
0·57
|
0·57
|
1·19
|
0·45–3·14
|
0·729
|
1·30
|
1·22
|
Dry cough
|
0·42
|
0·53
|
0·44
|
0·50
|
0·38
|
0·64
|
1·40
|
0·89–2·2
|
0·141
|
1·16
|
2·97
|
Shortness of breath
|
0·32
|
0·39
|
0·33
|
0·41
|
0·31
|
0·32
|
1·19
|
0·74–1·91
|
0·466
|
1·30
|
1·04
|
Sore throat
|
0·36
|
0·36
|
0·37
|
0·40
|
0·34
|
0·23
|
1·00
|
0·63–1·61
|
0·985
|
1·08
|
1·36
|
Headache
|
0·70
|
0·78
|
0·74
|
0·84
|
0·60
|
0·59
|
1·37
|
0·82–2·29
|
0·225
|
1·71
|
0·90
|
Chest pain or pressure
|
0·32
|
0·51
|
0·35
|
0·53
|
0·24
|
0·45
|
1·96
|
1·24–3·13
|
0·004
|
1·79
|
2·73
|
Other pains
|
0·31
|
0·38
|
0·33
|
0·41
|
0·26
|
0·27
|
1·20
|
0·74–1·93
|
0·453
|
1·16
|
1·18
|
Diarrhoea
|
0·28
|
0·36
|
0·29
|
0·36
|
0·25
|
0·36
|
1·40
|
0·86–2·26
|
0·171
|
1·17
|
2·26
|
Conjunctivitis
|
0·08
|
0·12
|
0·09
|
0·14
|
0·05
|
0·05
|
1·28
|
0·6–2·72
|
0·522
|
1·22
|
1·84
|
Loss of smell
|
0·71
|
0·72
|
0·73
|
0·74
|
0·66
|
0·64
|
0·99
|
0·61–1·59
|
0·954
|
0·99
|
0·94
|
Loss of taste
|
0·58
|
0·55
|
0·62
|
0·59
|
0·49
|
0·45
|
0·88
|
0·56–1·39
|
0·593
|
0·89
|
0·87
|
Middle ear pain
|
0·12
|
0·22
|
0·14
|
0·25
|
0·06
|
0·14
|
1·95
|
0·68–5·56
|
0·209
|
1·67
|
5·11
|
Problems speaking and walking
|
0·03
|
0·05
|
0·03
|
0·06
|
0·04
|
0·05
|
1·72
|
0·6–4·98
|
0·313
|
1·32
|
2·18
|
Skin rash
|
0·08
|
0·10
|
0·10
|
0·09
|
0·02
|
0·14
|
1·31
|
0·6–2·87
|
0·492
|
0·77
|
6·00
|
Changes in pigmentation
|
0·03
|
0·05
|
0·04
|
0·06
|
0·01
|
0·05
|
1·81
|
0·64–5·09
|
0·262
|
1·29
|
4·05
|
Higher sexual appetence
|
0·03
|
0·08
|
0·03
|
0·06
|
0·04
|
0·14
|
3·40
|
1·42–8·17
|
0·006
|
2·53
|
4·50
|
Other symptoms
|
0·27
|
0·25
|
0·29
|
0·27
|
0·22
|
0·18
|
0·93
|
0·56–1·55
|
0·778
|
0·90
|
0·99
|
Columns 2–7 show reported incidence of particular symptoms (in percents); the last five columns show results logistic regression with a particular symptom as the dependent variable, age, sex, size of place of residence as covariates, and toxoplasmosis as the independent variable. The last two columns show OR computed separately for women and men. The results in bold were significant after correction for multiple tests.