Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)

Talaei, Mohammad; Faustini, Sian; Holt, Hayley; Jolliffe, David A.; Vivaldi, Giulia; Greenig, Matthew; Perdek, Natalia; Maltby, Sheena; Bigogno, Carola M.; Symons, Jane; Davies, Gwyneth A.; Lyons, Ronan A.; Griffiths, Christopher J.; Kee, Frank; Sheikh, Aziz; Richter, Alex G.; Shaheen, Seif O.; Martineau, Adrian R.

doi:10.1186/s12916-022-02286-4

Table 3 Minimally adjusted and fully adjusted geometric mean ratios of antibody titres in seropositive participants, with exploratory analysis of disease severity

From: Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)

	n (%)	Minimally adjusted model^a		Fully adjusted model^b		Fully adjusted model plus adjustment for disease severity^c
	n (%)	GMR (95% CI)	p value	GMR (95% CI)	p value	GMR (95% CI)	p value
Sociodemographic, occupational and lifestyle factors
Age (years)
< 30	50 (2.8%)	1.00		1.00		1.00
30 to < 40	124 (7.0%)	0.96 (0.80–1.15)	0.68	0.95 (0.78–1.16)	0.62	0.97 (0.81–1.16)	0.71
40 to < 50	257 (14.5%)	0.98 (0.83–1.16)	0.83	1.00 (0.82–1.22)	0.97	1.05 (0.88–1.25)	0.60
50 to < 60	445 (25.1%)	0.96 (0.82–1.12)	0.60	1.00 (0.82–1.22)	1.00	1.05 (0.88–1.25)	0.59
60 to < 70	575 (32.4%)	0.94 (0.80–1.10)	0.45	1.04 (0.84–1.27)	0.74	1.11 (0.92–1.33)	0.28
≥ 70	323 (18.2%)	0.94 (0.80–1.11)	0.46	1.05 (0.85–1.31)	0.64	1.14 (0.94–1.39)	0.18
p for trend			0.46		0.21		0.02
Sex
Female	1234 (69.6%)	1.00		1.00		1.00
Male	540 (30.4%)	1.00 (0.95–1.05)	0.93	0.95 (0.90–1.00)	0.07	0.94 (0.89–1.00)	0.03
Ethnicity
White	1672 (94.3%)	1.00		1.00		1.00
Black, African, Caribbean or Black British	11 (0.6%)	1.11 (0.96–1.28)	0.14	1.09 (0.93–1.27)	0.30	1.07 (0.92–1.25)	0.36
South Asian^d	35 (2.0%)	1.19 (1.01–1.40)	0.03	1.22 (1.04–1.44)	0.02	1.23 (1.04–1.47)	0.02
Mixed, multiple or other ethnic groups	56 (3.2%)	1.33 (0.93–1.91)	0.12	1.15 (0.78–1.71)	0.48	1.20 (0.81–1.77)	0.37
Housing
Owns own home	1021 (57.6%)	1.00		1.00		1.00
Mortgage	515 (29.0%)	1.12 (1.04–1.20)	0.002	1.08 (1.00–1.15)	0.05	1.06 (0.99–1.14)	0.08
Privately renting	112 (6.3%)	1.07 (0.96–1.20)	0.22	1.00 (0.89–1.13)	0.96	0.99 (0.89–1.10)	0.84
Renting from council	61 (3.4%)	1.05 (0.92–1.21)	0.47	1.00 (0.86–1.16)	1.00	1.01 (0.87–1.17)	0.90
Other	65 (3.7%)	1.17 (0.97–1.41)	0.09	1.14 (0.94–1.38)	0.19	1.13 (0.94–1.35)	0.20
Number of people per bedroom
≤ 0.5	611 (34.7%)	1.00		1.00		1.00
> 0.5 to < 1	521 (29.6%)	1.03 (0.97–1.09)	0.36	1.01 (0.95–1.07)	0.86	1.00 (0.94–1.05)	0.92
1 to < 2	593 (33.7%)	1.05 (0.99–1.12)	0.12	1.03 (0.96–1.10)	0.37	1.03 (0.96–1.09)	0.43
≥ 2	36 (2.0%)	1.26 (1.00–1.60)	0.05	1.20 (0.94–1.54)	0.15	1.22 (0.96–1.54)	0.10
p for trend			0.04		0.19		0.19
IMD rank
Quartile 1 (least wealthy)	432 (24.4%)	0.99 (0.93–1.06)	0.87	0.95 (0.88–1.02)	0.16	0.96 (0.90–1.03)	0.30
Quartile 2	428 (24.2%)	1.04 (0.97–1.12)	0.26	1.01 (0.94–1.08)	0.88	1.02 (0.95–1.09)	0.65
Quartile 3	444 (25.1%)	0.93 (0.87–0.99)	0.03	0.91 (0.86–0.97)	0.004	0.93 (0.87–0.99)	0.02
Quartile 4 (most wealthy)	465 (26.3%)	1.00		1.00		1.00
p for trend			0.41		0.62		0.84
Frontline worker
No	1402 (79.0%)	1.00		1.00		1.00
Health or social care	166 (9.4%)	1.33 (1.20–1.48)	< 0.001	1.24 (1.11–1.39)	< 0.001	1.19 (1.07–1.33)	0.001
Other	206 (11.6%)	1.08 (0.99–1.17)	0.07	1.05 (0.97–1.14)	0.26	1.03 (0.95–1.11)	0.51
Highest educational level attained
Primary or secondary	209 (11.8%)	1.00		1.00		1.00
Higher or further education (A levels or BTEC)	255 (14.4%)	0.93 (0.84–1.03)	0.16	0.95 (0.86–1.05)	0.29	0.97 (0.89–1.06)	0.53
College or university	805 (45.4%)	0.93 (0.85–1.01)	0.09	0.95 (0.88–1.04)	0.29	0.97 (0.90–1.06)	0.51
Postgraduate degree	504 (28.4%)	0.94 (0.85–1.02)	0.15	0.96 (0.87–1.05)	0.36	0.97 (0.89–1.06)	0.46
p for trend			0.22		0.50		0.53
Tobacco smoking status
Never-smoker	969 (54.6%)	1.00		1.00		1.00
Ex-smoker	728 (41.0%)	1.06 (1.01–1.12)	0.02	1.06 (1.00–1.11)	0.03	1.04 (0.99–1.09)	0.12
Current smoker	77 (4.3%)	0.97 (0.86–1.09)	0.59	0.90 (0.80–1.02)	0.09	0.91 (0.82–1.02)	0.10
Actual sleep (hours per night)
≤ 5	169 (9.5%)	1.14 (1.03–1.26)	0.01	1.09 (0.98–1.22)	0.10	1.05 (0.95–1.16)	0.36
6	419 (23.6%)	1.01 (0.96–1.07)	0.80	1.00 (0.94–1.06)	0.99	1.00 (0.94–1.06)	0.99
7	728 (41.1%)	1.00		1.00		1.00
≥ 8	457 (25.8%)	1.03 (0.97–1.09)	0.42	1.02 (0.96–1.08)	0.60	1.01 (0.95–1.07)	0.74
p for trend			0.03		0.30		0.70
Vigorous physical exercise (hours per week)
0	714 (40.3%)	1.00		1.00		1.00
1–3	635 (35.9%)	0.94 (0.89–0.99)	0.03	0.98 (0.92–1.04)	0.43	0.98 (0.93–1.04)	0.49
≥ 4	422 (23.8%)	0.97 (0.91–1.04)	0.38	1.01 (0.94–1.08)	0.87	1.01 (0.95–1.08)	0.72
p for trend			0.26		0.95		0.79
Light physical exercise (hours per week)
0–4	659 (37.2%)	1.00		1.00		1.00
5–9	631 (35.6%)	0.93 (0.88–0.98)	0.01	0.96 (0.91–1.02)	0.24	0.98 (0.93–1.04)	0.58
≥ 10	483 (27.2%)	1.00 (0.93–1.06)	0.90	1.03 (0.96–1.10)	0.44	1.03 (0.97–1.10)	0.34
p for trend			0.70		0.51		0.38
Lower-impact physical activity (hours per week)
0	1048 (59.2)	1.00		1.00		1.00
1	331 (18.7)	0.95 (0.89–1.01)	0.11	0.97 (0.91–1.03)	0.29	0.97 (0.92–1.04)	0.42
≥ 2	390 (22.0)	0.95 (0.89–1.00)	0.07	0.98 (0.92–1.05)	0.53	0.99 (0.93–1.05)	0.69
p for trend			0.04		0.44		0.60
Number of visits to shops and other indoor public places (per week)
0	237 (13.4)	1.00		1.00		1.00
1–2	591 (33.3)	1.02 (0.94–1.11)	0.57	1.06 (0.98–1.16)	0.16	1.05 (0.97–1.14)	0.22
2–4	428 (24.1)	1.08 (0.99–1.18)	0.07	1.12 (1.02–1.22)	0.02	1.12 (1.03–1.22)	0.01
≥ 5	518 (29.2)	1.12 (1.02–1.22)	0.02	1.12 (1.02–1.23)	0.02	1.12 (1.02–1.22)	0.01
p for trend			0.004		0.01		0.01
Number of public transport journeys per week
0	1569 (88.7)	1.00		1.00		1.00
1–5	139 (7.9)	1.05 (0.97–1.15)	0.24	1.04 (0.95–1.13)	0.44	1.02 (0.94–1.11)	0.60
≥ 6	60 (3.4)	1.15 (1.00–1.31)	0.05	1.09 (0.95–1.26)	0.21	1.05 (0.93–1.18)	0.44
p for trend			0.03		0.17		0.38
Travel to place of work or study in past week
No	697 (39.6%)	1.00		1.00		1.00
Yes	1064 (60.4%)	1.07 (1.01–1.12)	0.01	1.02 (0.97–1.08)	0.44	1.03 (0.98–1.08)	0.24
Travel outside of the UK between November 2019, and February 2021^e
No	955 (53.8%)	1.00		1.00		1.00
Yes	602 (33.9%)	1.08 (1.02–1.13)	0.004	1.11 (1.05–1.16)	< 0.001	1.09 (1.04–1.15)	0.001
Diet and supplemental micronutrient intake
Multivitamin supplement
No	1377 (77.6%)	1.00		1.00		1.00
Yes	397 (22.4%)	1.08 (1.02–1.16)	0.01	1.08 (1.01–1.15)	0.02	1.09 (1.02–1.16)	0.009
Iron (only) supplement
No	1713 (96.6%)	1.00		1.00		1.00
Yes	61 (3.4%)	1.17 (0.99–1.38)	0.07	1.16 (0.99–1.37)	0.07	1.15 (0.98–1.35)	0.09
Zinc (only) supplement
No	1673 (94.3%)	1.00		1.00		1.00
Yes	101 (5.7%)	0.91 (0.83–1.00)	0.06	0.94 (0.85–1.03)	0.18	0.92 (0.84–1.02)	0.10
Selenium (only) supplement
No	1754 (98.9)	1.00		1.00		1.00
Yes	20 (1.1)	0.87 (0.73–1.03)	0.10	0.86 (0.72–1.03)	0.11	0.86 (0.74–1.01)	0.07
Fruit, vegetable, or salad intake per day
0–2	266 (15.1%)	1.00		1.00		1.00
3–4	559 (31.7%)	0.94 (0.87–1.02)	0.12	0.94 (0.86–1.02)	0.12	0.94 (0.87–1.01)	0.11
5	374 (21.2%)	0.93 (0.86–1.02)	0.11	0.92 (0.85–1.01)	0.07	0.92 (0.85–1.00)	0.06
≥ 6	567 (32.1%)	0.92 (0.86–1.00)	0.05	0.91 (0.84–0.99)	0.03	0.90 (0.84–0.98)	0.01
p for trend			0.09		0.05		0.02
Portions of dairy products or calcium-fortified alternatives per day
0–1	491 (27.8%)	1.00		1.00		1.00
2	485 (27.4%)	1.07 (1.00–1.14)	0.04	1.08 (1.01–1.15)	0.02	1.09 (1.02–1.16)	0.01
3–5	407 (23.0%)	1.10 (1.03–1.19)	0.01	1.12 (1.04–1.20)	0.002	1.10 (1.03–1.18)	0.01
≥ 6	386 (21.8%)	1.06 (0.99–1.14)	0.08	1.09 (1.01–1.17)	0.03	1.08 (1.00–1.16)	0.04
p for trend			0.04		0.01		0.02
Medical conditions and medication use
Self-reported general health
Excellent	341 (19.2%)	1.00		1.00		1.00
Very good	701 (39.5%)	1.03 (0.96–1.10)	0.42	0.99 (0.93–1.06)	0.83	0.99 (0.93–1.06)	0.80
Good	474 (26.7%)	1.02 (0.95–1.09)	0.67	0.98 (0.91–1.06)	0.61	0.97 (0.90–1.05)	0.46
Fair	198 (11.2%)	1.07 (0.97–1.18)	0.18	1.01 (0.91–1.12)	0.80	0.99 (0.90–1.09)	0.86
Poor	59 (3.3%)	1.18 (1.00–1.39)	0.05	1.14 (0.95–1.36)	0.17	1.05 (0.87–1.27)	0.62
p for trend			0.07		0.47		0.96
BMI, kg/m²
< 25	764 (43.2%)	1.00		1.00		1.00
25–30	626 (35.4%)	1.05 (1.00–1.11)	0.07	1.04 (0.98–1.10)	0.19	1.03 (0.98–1.09)	0.28
> 30	379 (21.4%)	1.11 (1.04–1.19)	0.003	1.10 (1.02–1.19)	0.01	1.07 (1.00–1.15)	0.06
p for trend			0.002		0.008		0.05
Diabetes or pre-diabetes
No diabetes	1636 (92.3%)	1.00		1.00		1.00
Pre-diabetes	52 (2.9%)	1.03 (0.89–1.19)	0.70	0.97 (0.85–1.11)	0.65	0.99 (0.87–1.13)	0.88
Type 1	12 (0.7%)	1.00 (0.77–1.30)	0.99	0.95 (0.71–1.27)	0.73	0.99 (0.73–1.34)	0.96
Type 2	72 (4.1%)	1.14 (0.98–1.32)	0.09	0.97 (0.82–1.15)	0.71	0.96 (0.82–1.12)	0.59
Asthma/atopy
No/no	1178 (66.4)	1.00		1.00		1.00
No/yes	305 (17.2)	0.95 (0.89–1.01)	0.10	0.95 (0.89–1.01)	0.09	0.95 (0.90–1.00)	0.07
Yes/no	145 (8.2)	1.00 (0.91–1.10)	0.98	0.97 (0.88–1.07)	0.55	0.95 (0.87–1.05)	0.33
Yes/yes	146 (8.2)	0.99 (0.91–1.08)	0.82	0.99 (0.90–1.09)	0.87	1.00 (0.91–1.10)	0.97
COPD
No	1728 (97.4%)	1.00		1.00		1.00
Yes	46 (2.6%)	1.22 (1.01–1.49)	0.04	1.12 (0.93–1.35)	0.23	1.08 (0.91–1.29)	0.39
Reported feeling anxious or depressed at baseline
No	1294 (73.0%)	1.00		1.00		1.00
Yes	479 (27.0%)	0.95 (0.90–1.00)	0.07	0.92 (0.87–0.97)	0.003	0.91 (0.87–0.97)	0.002
Anticholinergics
No	1685 (95.0%)	1.00		1.00		1.00
Yes	89 (5.0%)	1.16 (1.01–1.34)	0.04	1.15 (0.99–1.32)	0.06	1.16 (1.00–1.33)	0.04
Beta blockers
No	1659 (93.5%)	1.00		1.00		1.00
Yes	115 (6.5%)	1.12 (1.01–1.25)	0.04	1.09 (0.98–1.22)	0.10	1.12 (1.01–1.24)	0.03
Metformin
No	1720 (97.0%)	1.00		1.00		1.00
Yes	54 (3.0%)	1.23 (1.04–1.47)	0.02	1.13 (0.91–1.42)	0.28	1.17 (0.95–1.43)	0.14
Statins
No	1487 (83.8%)	1.00		1.00		1.00
Yes	287 (16.2%)	1.07 (0.99–1.15)	0.07	1.04 (0.96–1.13)	0.31	1.04 (0.97–1.13)	0.28
Follow-up duration (days)		0.001 (0.001–0.001)	< 0.001	0.001 (0.001–0.002)	< 0.001	0.001 (0.001–0.001)	< 0.001
COVID-19 severity^g
Asymptomatic	1242 (70.6%)	1.00				1.00
Symptomatic, not hospitalised	473 (26.9%)	1.29 (1.22–1.36)	< 0.001			1.25 (1.18–1.33)	< 0.001
Hospitalised	44 (2.5%)	2.13 (1.70–2.67)	< 0.001			1.92 (1.54–2.40)	< 0.001
p for trend			< 0.001				< 0.001

Minimally adjusted models included 1774 participants, except for a few items that included sample sizes were slightly lower (ranged from 1759 to 1773) because of missing values. The fully adjusted analyses included 1707 participants with data available for all factors, and 1694 participants after adjustment for COVID-19 severity
BMI body mass index, BTEC Business and Technology Education Council, COPD chronic obstructive pulmonary disease, GMR geometric mean ratio, IMD index of multiple deprivation
^aAdjusted for age, sex and duration of follow-up
^bAdjusted for duration of follow-up and all factors shown except symptom severity
^cAdjusted for duration of follow-up and all factors shown
^dSouth Asian indicates people who self-identified their ethnic origin as Indian, Pakistani or Bangladeshi
^eThe 217 participants with unknown or missing travel status were included in the analysis as a separate category to ensure greater power
^gCOVID-19 severity was classified as ‘asymptomatic’ (non-hospitalised participants who either did not report any symptoms of acute respiratory infection, or whose symptoms were classified as having <50% probability of being due to COVID-19), ‘symptomatic, not hospitalised’ (non-hospitalised participants reporting symptoms of acute respiratory infection that were classified as having ≥50% probability of being due to COVID-19) and ‘hospitalised’ (participants hospitalised for treatment of COVID-19)

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