Table 2.
M12 anti-S1 and anti-N geometric mean concentrations by number and type of immune events.
| Determinants Cells contain mean (SD) | M12 Anti-S1 | M12 Anti-N | ||||
|---|---|---|---|---|---|---|
| Log10 Conc (IU/mL) |
GMC 1 (IU/mL) |
p 2 | Log10 Conc (IU/mL) |
GMC 1 (IU/mL) |
p 2 | |
| Overall mean | 1.55 (1.39) | 35.48 (24.55) | 0.73 (0.52) | 5.37 (3.31) | ||
| Intervention | 0.431 | 0.096 | ||||
| BCG | 1.51 (1.36) | 32.36 (22.91) | 0.71 (0.53) | 5.13 (3.38) | ||
| Placebo | 1.59 (1.41) | 38.90 (25.70) | 0.75 (0.52) | 5.62 (3.31) | ||
| Number of immune events 3 | <0.001 | <0.001 | ||||
| 0 | 0.25 (0.32) | 1.78 (2.09) | 0.54 (0.28) | 3.47 (1.91) | ||
| 1 | 2.02 (0.86) | 104.71 (7.24) | 1.12 (0.70) | 13.18 (5.01) | ||
| 2 | 2.98 (0.61) | 954.99 (4.07) | 0.65 (0.47) | 4.47 (2.95) | ||
| 3 | 3.36 (0.42) | 2290.87 (2.63) | 1.28 (0.51) | 19.05 (3.23) | ||
| Immunity type | <0.001 | <0.001 | ||||
| None | 0.25 (0.32) | 1.78 (2.09) | 0.54 (0.28) | 3.47 (1.91) | ||
| Infection only 4 | 1.90 (0.82) | 79.43 (6.61) | 1.42 (0.65) | 26.30 (4.47) | ||
| Vaccine 1 dose | 2.25 (0.88) | 177.83 (7.59) | 0.53 (0.26) | 3.39 (1.82) | ||
| Vaccine 2 doses | 2.90 (0.54) | 794.33 (3.47) | 0.54 (0.26) | 3.47 (1.82) | ||
| Infection + 1 dose | 3.60 (0.73) | 3981.07 (5.37) | 1.50 (0.75) | 31.62 (5.62) | ||
| Infection + 2 doses | 3.36 (0.42) | 2290.87 (2.63) | 1.28 (0.51) | 19.05 (3.24) | ||
| COVID-19 vaccine product and dose 5 | <0.001 | 0.956 | ||||
| None | 0.25 (0.32) | 1.78 (2.09) | 0.54 (0.28) | 3.47 (1.91) | ||
| mRNA 1 dose | 2.67 (0.76) | 467.73 (5.75) | 0.56 (0.28) | 3.36 (1.91) | ||
| mRNA 2 doses | 2.90 (0.54) | 794.33 (3.47) | 0.54 (0.26) | 3.47 (1.82) | ||
| Vector 1 dose | 1.80 (0.70) | 63.10 (5.01) | 0.51 (0.23) | 3.24 (1.70) | ||
| Infection severity 6 | 0.566 | 0.002 | ||||
| Asymptomatic | 2.54 (0.90) | 346.74 (7.94) | 1.14 (0.49) | 13.80 (3.09) | ||
| Very mild | 2.52 (1.03) | 331.13 (10.72) | 1.36 (0.66) | 22.91 (4.57) | ||
| Mild | 2.67 (1.13) | 467.73 (13.49) | 1.65 (0.52) | 44.67 (3.31) | ||
| Moderate | 3.36 (0.56) | 2290.87 (3.63) | 1.66 (1.41) | 45.71 (25.70) | ||
| Acute-episode duration 7 | 0.755 | 0.128 | ||||
| 0 days/no infection | 2.53 (0.92) | 33.84 (8.32) | 1.13 (0.48) | 13.49 (3.02) | ||
| 0–1 weeks | 2.45 (1.11) | 281.84 (12.88) | 1.37 (0.65) | 23.44 (4.47) | ||
| 1–2 weeks | 2.49 (1.04) | 309.03 (10.96) | 1.32 (0.64) | 20.89 (4.37) | ||
| 2–3 weeks | 2.80 (0.91) | 630.96 (8.13) | 1.56 (0.69) | 36.31 (4.90) | ||
| 3–4 weeks | 2.38 (0.97) | 239.88 (9.33) | 1.37 (0.67) | 23.44 (4.68) | ||
| 4+ weeks | 2.61 (1.28) | 407.38 (19.05) | 1.57 (0.53) | 37.15 (3.39) | ||
| Lingering | 2.80 (1.07) | 630.96 (11.75) | 1.49 (0.62) | 30.90 (4.17) | ||
| Ongoing/UNK | 2.63 (1.22) | 426.58 (16.60) | 1.46 (0.66) | 28.84 (4.57) | ||
| Long COVID 7,8 | 0.973 | 0.194 | ||||
| No | 2.59 (1.03) | 389.05 (10.72) | 1.36 (0.63) | 22.91 (4.27) | ||
| Yes | 2.57 (1.25) | 371.54 (17.78) | 1.53 (0.66) | 33.88 (4.57) | ||
| Unknown | 2.55 (1.07) | 354.81 (11.75) | 1.63 (0.54) | 42.66 (3.47) | ||
| Long-term loss taste/smell 7,9 | 0.572 | 0.541 | ||||
| No | 2.57 (1.04) | 371.54 (10.96) | 1.38 (0.63) | 23.99 (4.27) | ||
| Yes | 3.06 (1.11) | 1148.15 (12.88) | 1.30 (0.49) | 19.95 (3.09) | ||
| Unknown | 2.56 (1.25) | 363.08 (17.78) | 1.62 (0.74) | 41.69 (5.50) | ||
| Dyspnoea severity 10,11 | 0.938 | 0.239 | ||||
| 0 | 2.57 (1.07) | 371.54 (11.75) | 1.35 (0.61) | 22.39 (4.07) | ||
| 1–3 | 2.63 (0.99) | 426.58 (9.77) | 1.42 (0.68) | 26.30 (4.79) | ||
| 4–5 | 2.55 (0.99) | 354.81 (9.77) | 1.54 (0.60) | 34.67 (3.98) | ||
| Dyspnoea duration (days) 11 | 0.373 | 0.280 | ||||
| 0 | 2.59 (1.08) | 389.05 (12.02) | 1.36 (0.62) | 22.91 (4.17) | ||
| 1–3 | 2.72 (0.94) | 524.81 (8.71) | 1.28 (0.58) | 19.05 (3.80) | ||
| 4–7 | 2.32 (0.96) | 208.93 (9.12) | 1.38 (0.73) | 23.99 (5.37) | ||
| Week+ | 2.84 (0.94) | 691.83 (8.71) | 1.62 (0.54) | 41.69 (3.47) | ||
| Resp. symptoms severity 10,12,13 | 0.240 | 0.003 | ||||
| 0 | 2.48 (0.97) | 302.00 (9.33) | 1.12 (0.55) | 13.18 (3.55) | ||
| 1–3 | 2.42 (1.11) | 263.03 (12.88) | 1.38 (0.65) | 23.99 (4.47) | ||
| 4–5 | 2.73 (0.97) | 537.03 (9.33) | 1.54 (0.61) | 34.67 (4.07) | ||
| Resp. symptoms duration (days) 12,14 | 0.641 | 0.006 | ||||
| 0 | 2.46 (0.96) | 288.40 (9.12) | 1.12 (0.55) | 13.18 (3.55) | ||
| 1–3 | 2.56 (1.13) | 363.08 (13.49) | 1.42 (0.62) | 26.30 (4.17) | ||
| 4–7 | 2.37 (1.15) | 234.42 (14.13) | 1.29 (0.68) | 19.50 (4.79) | ||
| Week+ | 2.65 (1.02) | 446.68 (10.47) | 1.52 (0.62) | 33.11 (4.17) | ||
| Fever 10,15 | 0.845 | 0.029 | ||||
| No | 2.57 (1.06) | 371.54 (11.48) | 1.31 (0.61) | 20.42 (4.07) | ||
| Yes | 2.60 (1.01) | 398.11 (10.23) | 1.50 (0.63) | 31.62 (4.27) | ||
| Fever duration (days) 10,15 | 0.781 | 0.024 | ||||
| 0 | 2.57 (1.06) | 371.54 (11.48) | 1.31 (0.61) | 20.42 (4.07) | ||
| 1–3 | 2.63 (1.09) | 426.58 (12.03) | 1.29 (0.53) | 19.50 (3.39) | ||
| 4–7 | 2.48 (0.93) | 302.00 (8.51) | 1.51 (0.68) | 32.36 (4.79) | ||
| Week+ | 2.74 (1.07) | 549.54 (11.75) | 1.69 (0.60) | 48.98 (3.98) | ||
| Non-resp. symptoms severity 10,16,17 | 0.225 | 0.002 | ||||
| 0 | 2.35 (1.07) | 223.87 (11.75) | 1.13 (0.54) | 13.48 (3.47) | ||
| 1–3 | 2.73 (0.95) | 537.03 (8.91) | 1.38 (0.59) | 23.99 (3.89) | ||
| 4–5 | 2.55 (1.05) | 354.81 (11.22) | 1.50 (0.65) | 31.62 (4.47) | ||
Abbreviations: BCG = Bacillus Calmette–Guerin; conc = concentration; GMC = geometric mean concentration; IU = international units; M = month; resp = respiratory; SD = standard deviation. p-values in bold indicate p < 0.05. 1 Antilog 10x of the log10-transformed mean concentration. 2 Kruskal–Wallis p-values for comparisons of mean log10-transformed concentrations in IU/mL after adding a pseudocount of 1. 3 One immune event (N = 187): 123 (65.8%) had an infection and 64 (34.2%) received one dose of a COVID-19 vaccine. Two immune events (N = 260): 30 (11.5%) had an infection and received one dose of a COVID-19 vaccine, while 230 (88.5%) received two doses of a COVID-19 vaccine. All participants with three immune events (N = 70) had an infection and received two COVID-19 vaccine doses. 4 No-one in this dataset experienced more than one infection. 5 Denominator is 747 because participants with infections were excluded as well as an additional participant, due to missing vaccine type. The number of COVID-19 vaccine doses was calculated as the total number of doses received by the participant during follow-up, regardless of whether the primary vaccination series consisted of one or two doses. The COVID-19 vaccines available during the study period in The Netherlands are listed in the methods. 6 Denominator is 199 because only participants who experienced an infection were included and 24 participants with unknown infection severity were removed. We also performed Jonckheere’s tests for trend with an a priori ordering of infection severity for mean anti-S1 log10-transformed concentrations (p-value = 0.367) and mean anti-N log10-transformed concentrations (p-value < 0.001). 7 Denominator is 223 because only participants who experienced an infection were included. 8 Long COVID was defined as continuing to report symptoms other than standalone loss of smell/taste for at least 60 days after the end of the acute infection episode. “Unknown” includes participants who were reporting symptoms past the end of the acute infection episode but had not yet reached 60 days at the time the diary app was discontinued. There were 23 cases but 4 were excluded from the total-analysis population for being in the seroconversion window of the first COVID-19 vaccine dose. Of the remaining 19 cases, 5 had the infection in the first period and 14 in the second period; 8 received at least one COVID-19 vaccine dose in the first period and 11 were never vaccinated. 9 Long-term loss of smell/taste was defined as continuing to report standalone loss of smell/taste for at least 60 days after the end of the acute infection episode. “Unknown” includes participants who were reporting loss of smell/taste past the end of the acute infection episode but had not reached 60 days at the time the diary app was discontinued. There were nine cases but three were excluded from the total-analysis population for being in the seroconversion window of the first COVID-19 vaccine dose. When excluding the unknown category from the analysis, p = 0.290. 10 Symptoms were reported on a scale of 0–5: 0 for not present and 1–5 for present, with increasing severity. Fever was reported as present or not and was defined as having a temperature above 38 °C. 11 Denominator is 218 because only participants who experienced an infection were included and five additional participants were removed due to unknown dyspnoea severity and/or duration. 12 Respiratory symptoms exclude dyspnoea. Most participants reported more than one type of respiratory symptom during an infection episode; we took the highest severity reported for any respiratory symptom. The duration was calculated from the day on which the first respiratory symptom was reported until the day a respiratory symptom was reported. 13 Denominator is 205 because only participants who experienced an infection were included and 18 additional participants were removed due to unknown respiratory symptom severity. 14 Denominator is 200 because only participants who experienced an infection were included and 23 additional participants were removed due to unknown or ongoing respiratory-symptom duration. 15 Denominator is 217 because only participants who experienced an infection were included and six additional participants were removed due to unknown presence of fever or unknown fever duration. 16 Non-respiratory symptoms exclude fever. Most participants reported more than one type of non-respiratory symptom during an infection episode; we took the highest severity reported for any non-respiratory symptom. The duration was calculated from the day on which the first non-respiratory symptom was reported until the last day a non-respiratory symptom was reported. 17 Denominator is 205 because only participants who experienced an infection were included and 18 additional participants were removed due to unknown non-respiratory symptom severity.