Figure 1
Countries participating in WHF COVID-19 Long-term Follow-up Study.
Table 1
Participants’ socio-demographic characteristics, COVID-19 symptoms and vital signs at baseline by survival status.
| OVERALL | NON-SURVIVORS | SURVIVORS | p-VALUE | |
|---|---|---|---|---|
| N = 2535 | N = 382 (15%) | N = 2153 (85%) | ||
| Sex | 0.006 | |||
| Male | 1408 (55.5%) | 236 (61.8%) | 1173 (54.5%) | |
| Female | 1125 (44.4%) | 146 (38.2%) | 979 (45.5%) | |
| Age, mean (SD) | 59.5 (20.0) | 76.2 (13.9) | 56.6 (19.4) | <0.001 |
| Age, category | <0.001 | |||
| <50 years | 812 (32.0%) | 23 (6.0%) | 789 (36.6%) | |
| 51–60 years | 422 (16.6%) | 20 (5.2%) | 402 (18.7%) | |
| 61–70 years | 496 (19.6%) | 57 (14.9%) | 439 (20.4%) | |
| >70 years | 805 (31.8%) | 282 (73.8%) | 523 (24.3%) | |
| Ethnic Origin | <0.001 | |||
| Caucasian | 17 (0.7%) | 1 (0.3%) | 16 (0.7%) | |
| Hispanic | 168 (6.6%) | 64 (16.8%) | 104 (4.8%) | |
| Black | 69 (2.7%) | 14 (3.7%) | 55 (2.6%) | |
| Middle Eastern | 101 (4.0%) | 13 (3.4%) | 88 (4.1%) | |
| Asian | 1951 (77.0%) | 265 (69.4%) | 1686 (78.3%) | |
| Other | 229 (9.0%) | 25 (6.5%) | 204 (9.5%) | |
| WHO Region (Total sites = 26) | <0.001 | |||
| Europe (n = 2) | 106 (4.2%) | 18 (4.7%) | 88 (4.1%) | |
| Asia Pacific (n = 4) | 576 (22.7%) | 59 (15.4%) | 517 (24.0%) | |
| Latin America (n = 4) | 223 (8.8%) | 67 (17.5%) | 156 (7.2%) | |
| Middle East (n = 1) | 100 (3.9%) | 13 (3.4%) | 87 (4.0%) | |
| Southeast Asia (n = 10) | 1378 (54.4%) | 205 (53.7%) | 1173 (54.5%) | |
| SSA (n = 5) | 152 (6.0%) | 20 (5.2%) | 132 (6.1%) | |
| World Bank Income Groups (Total sites = 26) | 0.011 | |||
| LIC (n = 1) | 20 (0.8%) | 4 (1.0%) | 16 (0.7%) | |
| LMIC (n = 15) | 1610 (63.5%) | 232 (60.7%) | 1378 (64.0%) | |
| UMIC (n = 7) | 525 (20.7%) | 101 (26.4%) | 424 (19.7%) | |
| HIC (n = 3) | 380 (15.0%) | 45 (11.8%) | 335 (15.6%) | |
| Body Mass Index (kg/m2), mean (SD) | 24.5 (4.2) | 24.2 (4.7) | 24.5 (4.1) | 0.32 |
| Body Mass Index (kg/m2) categories | 0.11 | |||
| Underweight (<18) | 77 (3.0%) | 16 (4.2%) | 61 (2.8%) | |
| Normal weight (18–24) | 1275 (50.3%) | 170 (44.5%) | 1105 (51.3%) | |
| Overweight (25–29) | 596 (23.5%) | 67 (17.5%) | 529 (24.6%) | |
| Obese (≥30) | 187 (7.4%) | 23 (6.0%) | 164 (7.6%) | |
| Unknown | 400 (15.8%) | 106 (27.7%) | 294 (13.7%) | |
| Confirmed case of COVID-19 infection | 2528 (99.7%) | 379 (99.2%) | 2149 (99.8%) | 0.040 |
| Diagnosed by using RT-PCR | 2212 (87.3%) | 313 (81.9%) | 1899 (88.2%) | 0.002 |
| Laboratory test confirmation (antigen test or molecular test- Positive result | 2259 (89.1%) | 332 (86.9%) | 1927 (89.5%) | 0.31 |
| Presence of signs and symptoms suggestive of COVID-19 | 2360 (93.1%) | 354 (92.7%) | 2006 (93.2%) | 0.69 |
| A history of self-reported fever | 1875 (74.0%) | 269 (70.4%) | 1606 (74.6%) | 0.081 |
| Cough | 1955 (77.1%) | 283 (74.1%) | 1672 (77.7%) | 0.12 |
| Dyspnoea (shortness of breath) OR Tachypnoea | 1316 (51.9%) | 261 (68.3%) | 1055 (49.0%) | <0.001 |
| Clinical suspicion of ARI despite not meeting criteria above | 252 (9.9%) | 49 (12.8%) | 203 (9.4%) | 0.037 |
| Median time from symptom onset to admission (IQR) in days | 2 (2, 4) | 3.0 (2.0, 5.0) | 2.0 (2.0, 4.0) | 0.009 |
| Heart rate (beats/min), mean (SD) | 90.2 (16.7) | 91.2 (17.5) | 90.1 (16.6) | 0.23 |
| Bradycardia (HR <60 bpm), mean (SD) | 52.7 (5.5) | 54.4 (4.0) | 52.3 (5.8) | 0.35 |
| Tachycardia (HR >100 bpm), mean (SD) | 114.8 (12.8) | 116.2 (12.4) | 114.6 (12.8) | 0.29 |
| Oxygen, first reading (mmHg), mean (SD) | 77.5 (46.2) | 78.1 (34.1) | 77.2 (52.1) | 0.90 |
| SpO2 level%, mean (SD) | 94.9 (4.9) | 93.1 (6.7) | 95.2 (4.4) | <0.001 |
| Oxygen therapy | 631 (24.9%) | 181 (47.4%) | 450 (20.9%) | <0.001 |
| Systolic BP (mmHg), mean (SD) | 125.8 (21.4) | 124.6 (22.1) | 126.0 (21.3) | 0.24 |
| Diastolic BP (mmHg), mean (SD) | 76.6 (12.4) | 74.7 (12.7) | 76.9 (12.3) | 0.001 |
| Respiratory rate (breaths/min), mean (SD) | 20.5 (4.1) | 21.4 (4.3) | 20.2 (4.1) | <0.001 |
| Shortness of Breath (SOB) | <0.001 | |||
| SOB <100 m | 329 (13.0%) | 79 (20.7%) | 250 (11.6%) | |
| SOB 100–500 m | 95 (3.7%) | 29 (7.6%) | 66 (3.1%) | |
| SOB >500 m | 26 (1.0%) | 4 (1.0%) | 22 (1.0%) | |
| Unknown | 955 (37.7%) | 157 (41.1%) | 798 (37.1%) | |
| AVPU: responsiveness scale | <0.001 | |||
| Alert | 1694 (66.8%) | 215 (56.3%) | 1479 (68.7%) | |
| Responsive to verbal stimulation | 258 (10.2%) | 44 (11.5%) | 214 (9.9%) | |
| Responsive to painful stimulation | 548 (21.6%) | 114 (29.8%) | 434 (20.2%) | |
| Unresponsive | 35 (1.4%) | 9 (2.4%) | 26 (1.2%) | |
| Length of hospital stay (Mean, SD) | 11.3 (25.1) | 15.4 (33.7) | 10.9 (23.9) | 0.006 |
| Length of hospital stay (Median, IQR) | 8 (5, 11) | 10 (7, 15) | 7 (5, 11) | <0.001 |
| ICU admission | 309 (12.2%) | 94 (24.6%) | 215 (10.0%) | <0.001 |
Table 2
Clinical outcomes, Long COVID symptoms, and new onset diseases since discharge over the follow-up period.
| 1 MONTH FOLLOW-UP | 3 MONTH FOLLOW-UP | 6 MONTH FOLLOW-UP | 9–12 MONTH FOLLOW-UP | |
|---|---|---|---|---|
Outcomes at follow-up visits | N = 2070 | N = 1974 | N = 1998 | N = 1916 |
| Alive | 1808 (87.3%) | 1786 (90.5%) | 1725(86.3%) | 1683 (87.8%) |
| Re-hospitalized | 22 (1.1%) | 12 (0.6%) | 20 (1.0%) | 11 (0.6%) |
| Death | 28 (1.4%) | 41 (2.1%) | 98 (4.9%) | 87 (4.5%) |
| Unknown/Loss-to-follow-up | 210 (10.1%) | 133 (6.7%) | 151 (7.6%) | 124 (6.5%) |
| Causes of Deaths | ||||
| Sudden cardiac death | 8 (0.4%) | 9 (0.5%) | 65 (3.3%) | 31 (1.6%) |
| Other cardiovascular cause | 7 (0.3%) | 12 (0.7%) | 16 (0.8%) | 24 (1.2%) |
| Non-cardiovascular cause | 13 (0.6) | 20 (1.0%) | 16 (0.8%) | 32 (1.7%) |
| Persistent long COVID symptoms | ||||
| At least one long COVID symptom | 1154 (55.7%) | 724 (36.7%) | 908 (45.4%) | 471 (24.6%) |
| Fatigue (worn out/lacking energy or zest) | 816 (39.4%) | 443 (22.4%) | 423 (21.2%) | 277 (14.5%) |
| Feeling more anxious/worrying | 371 (17.9%) | 213 (10.8%) | 177 (8.9%) | 150 (7.9%) |
| Breathlessness | 219 (10.6%) | 96 (4.9%) | 78 (3.9%) | 93 (4.9%) |
| Problems with memory, concentration or decision making | 176 (8.5%) | 293 (14.8%) | 623 (31.2%) | 165 (8.6%) |
| Chest pain | 174 (8.4%) | 85 (4.3%) | 85 (4.3%) | 98 (5.1%) |
| Palpitations | 171 (8.3%) | 92 (4.7%) | 173 (8.7%) | 163 (8.5%) |
| Myalgia (muscles aches) | 72 (3.5%) | 34 (1.7%) | 42 (2.1%) | 46 (2.4%) |
| Anosmia (no sense of smell) | 14 (0.7%) | 6 (0.3%) | 4 (0.2%) | 4 (0.2%) |
| No sense of taste | 24 (1.2%) | 7 (0.4%) | 21 (1.1%) | 20 (1.0%) |
| Intensity of fatigue | ||||
| Mean (SD) | 4.0 (2.3) | 3.4 (2.1) | 3.3 (2.1) | 3.1 (2.1) |
| None | 295 (14.3%) | 338 (17.1%) | 319 (16.0%) | 331 (17.3%) |
| Mild Fatigue (less than 5) | 585 (28.3%) | 752 (38.1%) | 853 (42.7%) | 892 (46.6%) |
| Moderate Fatigue (5) | 416 (20.1%) | 503 (25.5%) | 326 (16.3%) | 232 (12.1%) |
| Severe Fatigue (more than 5) | 519 (25.1%) | 185 (9.4%) | 209 (10.5%) | 205 (10.7%) |
| New onset of disease since discharge | ||||
| Onset of any 1 disease | 223 (10.8%) | 90 (4.6%) | 65 (3.3%) | 43 (2.2%) |
| Pulmonary embolism (PE, ‘Clot in lung’) | 127 (6.1%) | 35 (1.8%) | 7 (0.4%) | 4 (0.2%) |
| Kidney problems | 45 (2.2%) | 21 (1.1%) | 18 (0.9%) | 7 (0.4%) |
| New onset hypertension | 22 (1.1%) | 15 (0.8%) | 19 (1.0%) | 15 (0.9%) |
| New onset diabetes | 17 (0.8%) | 7 (0.4%) | 6 (0.3%) | 3 (0.2%) |
| Heart Failure | 10 (0.5%) | 9 (0.5%) | 5 (0.3%) | 8 (0.4%) |
| Stroke or mini stroke/TIA | 9 (0.4%) | 3 (0.2%) | 8 (0.4%) | 6 (0.3%) |
| Atrial Fibrillation | 7 (0.3%) | 7 (0.4%) | 7 (0.4%) | 2 (0.1%) |
| Heart attack | 5 (0.2%) | 4 (0.2%) | 6 (0.3%) | 6 (0.3%) |
| Deep vein thrombosis (DVT, ‘Clot in leg’) | 3 (0.1%) | 0 | 3 (0.2%) | 4 (0.2%) |
| Other | 28 (1.4%) | 14 (0.7%) | 15 (0.8%) | 14 (0.7%) |
Figure 2
Trends in mortality, MACE, and at least 1 persistent Long COVID symptom over the follow-up period.
Figure 3
Trends in EQ-5D dimensions over the follow-up period.
Table 3
Factors associated with mortality using Generalized Estimating Equation (GEE) models.
| FACTORS | DEATH | RR* [95% CI] | |||||
|---|---|---|---|---|---|---|---|
| IN-HOSPITAL (N = 128) | 1 MONTH (N = 28) | 3 MONTH (N = 41) | 6 MONTH (N = 98) | 9–12 MONTH (N = 87) | OVERALL (N = 382) | ||
| MARGINAL ESTIMATES | |||||||
| Overall | 4.40(3.74,5.06) | 1.52(1.0,2.08) | 2.36(1.63,3.09) | 5.22(4.19,6.24) | 4.74(3.82,5.66) | 3.63 (3.28,3.98) | |
| Age, years | |||||||
| <50 | 0.62(0.35,0.9) | 0.22(0.09,0.35) | 0.34(0.16,0.52) | 0.83(0.47,1.19) | 0.74(0.42,1.07) | 0.56(0.33,0.79) | 1 |
| 51–60 | 1.14(0.6,1.68) | 0.4(0.16,0.65) | 0.63(0.29,0.96) | 1.52(0.82,2.23) | 1.36(0.74,1.98) | 1.02(0.57,1.47) | 1.83 (1.00,3.33) |
| 61–70 | 2.92(2.11,3.73) | 1.04(0.59,1.48) | 1.61(0.98,2.25) | 3.92(2.76,5.07) | 3.5(2.42,4.57) | 2.62(1.97,3.28) | 4.69 (2.89,7.61) |
| >70 | 13.89(11.8,15.98) | 4.94(3.16,6.72) | 7.67(5.36,9.98) | 18.61(15.1,22.12) | 16.61(12.88,20.34) | 12.46(11.19,13.72) | 22.30 (14.29,34.80) |
| Gender | |||||||
| Male | 4.86(4.05,5.67) | 1.69(1.06,2.33) | 2.63(1.8,3.46) | 5.85(4.59,7.11) | 4.55(3.5,5.61) | 4.04(3.54,4.55) | 1 |
| Female | 3.73(2.98,4.48) | 1.3(0.79,1.81) | 2.02(1.33,2.7) | 4.49(3.47,5.51) | 3.5(2.63,4.37) | 3.1(2.61,3.6) | 0.77 (0.63,0.94) |
| Ethnicity** | |||||||
| Caucasian | 2.13(–2.07,6.32) | 0.62(–0.66,1.89) | 0.95(–0.94,2.85) | 2.19(–2.14,6.51) | 1.92(–1.88,5.72) | 1.58(–1.54,4.7) | 1 |
| Hispanic | 18.76(13.33,24.19) | 5.44(3.07,7.81) | 8.42(5.17,11.66) | 19.29(13.61,24.98) | 16.93(12.09,21.78) | 13.95(10.51,17.4) | 8.82(1.21,64.32) |
| Black | 7.8(3.61,11.99) | 2.26(0.82,3.7) | 3.5(1.35,5.66) | 8.02(3.7,12.34) | 7.04(3.13,10.96) | 5.8(2.77,8.84) | 3.67(0.48,28.24) |
| Middle Eastern | 3.93(1.66,6.19) | 1.14(0.4,1.88) | 1.76(0.69,2.84) | 4.04(1.76,6.31) | 3.54(1.54,5.55) | 2.92(1.32,4.52) | 1.85(0.24,14.32) |
| Asian | 4.18(3.54,4.83) | 1.21(0.77,1.66) | 1.88(1.31,2.45) | 4.3(3.39,5.21) | 3.78(2.91,4.65) | 3.11(2.75,3.47) | 1.97(0.27,14.21) |
| Other | 4.25(2.51,5.99) | 1.23(0.53,1.94) | 1.91(0.91,2.9) | 4.37(2.57,6.18) | 3.84(2.23,5.45) | 3.16(1.91,4.41) | 2.00 (0.27,14.95) |
| Region** | |||||||
| Europe | 5.5(2.87,8.13) | 1.57(0.6,2.54) | 2.41(1.02,3.79) | 5.57(2.9,8.24) | 4.92(2.52,7.32) | 4.05(2.17,5.93) | 1 |
| Asia Pacific | 3.81(2.75,4.87) | 1.09(0.62,1.55) | 1.67(0.98,2.36) | 3.86(2.72,4.99) | 3.41(2.35,4.46) | 2.81(2.1,3.51) | 0.69(0.41,1.18) |
| Latin America | 13.16(9.21,17.11) | 3.76(2.14,5.38) | 5.76(3.58,7.95) | 13.33(9.53,17.12) | 11.78(8.55,15.01) | 9.69(7.34,12.05) | 2.39(1.42,4.03) |
| Middle East | 4.01(1.69,6.33) | 1.15(0.4,1.89) | 1.76(0.68,2.83) | 4.07(1.78,6.35) | 3.59(1.56,5.62) | 2.96(1.34,4.57) | 0.73(0.36,1.5) |
| South East Asia | 4.33(3.62,5.05) | 1.24(0.78,1.7) | 1.9(1.33,2.46) | 4.39(3.4,5.37) | 3.88(2.94,4.82) | 3.19(2.78,3.61) | 0.79(0.49,1.28) |
| Sub Saharan Africa | 6.67(3.73,9.61) | 1.91(0.78,3.03) | 2.92(1.31,4.53) | 6.76(3.66,9.85) | 5.97(3.12,8.83) | 4.92(2.77,7.07) | 1.21(0.64,2.29) |
| Income group** | |||||||
| LIC | 9.24(0,18.48) | 2.58(–0.11,5.27) | 3.95(–0.17,8.06) | 9.2(0,18.4) | 8.36(0.04,16.68) | 6.76(0.08,13.44) | 1 |
| LMIC | 4.39(3.67,5.1) | 1.22(0.77,1.68) | 1.87(1.31,2.43) | 4.37(3.41,5.32) | 3.97(3.03,4.9) | 3.21(2.82,3.6) | 0.47(0.18,1.28) |
| UMIC | 7.64(5.66,9.62) | 2.13(1.24,3.02) | 3.26(2.08,4.45) | 7.61(5.79,9.43) | 6.91(5.28,8.55) | 5.59(4.5,6.69) | 0.83(0.3,2.27) |
| HIC | 4.36(2.97,5.74) | 1.22(0.67,1.76) | 1.86(1.06,2.66) | 4.34(2.93,5.74) | 3.94(2.6,5.29) | 3.19(2.27,4.11) | 0.47(0.17,1.32) |
| Smoking status | |||||||
| Never | 3.36(2.72,4.01) | 1.17(0.71,1.64) | 1.82(1.2,2.44) | 4.09(3.18,4.99) | 3.16(2.37,3.95) | 2.8(2.36,3.23) | 1 |
| Current smoker | 2.37(1.16,3.58) | 0.83(0.3,1.35) | 1.28(0.58,1.99) | 2.88(1.43,4.34) | 2.23(1.08,3.39) | 1.97(1.01,2.94) | 0.71(0.42,1.18) |
| Former smoker | 6.86(5.41,8.31) | 2.39(1.45,3.33) | 3.71(2.45,4.97) | 8.34(6.2,10.48) | 6.45(4.65,8.25) | 5.71(4.65,6.77) | 2.04(1.59,2.61) |
| Unknown | 5.55(4.11,6.98) | 1.93(1.13,2.73) | 3(1.88,4.11) | 6.74(4.78,8.7) | 5.22(3.75,6.69) | 4.61(3.58,5.65) | 1.65(1.24,2.19) |
| Pre-existing conditions | |||||||
| Hypertension | |||||||
| Yes | 5.56(4.68,6.44) | 1.92(1.2,2.64) | 2.98(2.04,3.91) | 6.54(5.15,7.93) | 5.19(3.96,6.42) | 4.58 (4.03,5.14) | 1.77 (1.43,2.19) |
| Coronary Artery Disease | |||||||
| Yes | 7.45(5.62,9.29) | 2.6(1.53,3.66) | 4.05(2.58,5.53) | 8.97(6.41,11.54) | 6.98(4.78,9.18) | 6.20 (4.80,7.60) | 1.88 (1.45,2.43) |
| Stroke*** | |||||||
| Yes | 8.15(5.02,11.29) | 2.19(1.07,3.31) | 3.37(1.78,4.96) | 7.95(4.86,11.04) | 7.36(4.44,10.28) | 5.89 (3.78,8.01) | 1.67 (1.15,2.42) |
| Heart failure*** | |||||||
| Yes | 9.71(6.6,12.82) | 2.66(1.37,3.95) | 4.1(2.27,5.93) | 9.66(6.38,12.94) | 8.93(5.81,12.06) | 7.11 (4.96,9.26) | 2.07 (1.50,2.85) |
| Renal disease*** | |||||||
| Yes | 9.51(7.25,11.78) | 2.56(1.52,3.6) | 3.94(2.56,5.33) | 9.35(6.94,11.76) | 8.71(6.32,11.11) | 6.92 (5.54,8.29) | 2.17 (1.73,2.73) |
| COPD/Asthma | |||||||
| Yes | 6.97(5.42,8.52) | 2.43(1.42,3.44) | 3.77(2.45,5.08) | 8.27(6.08,10.47) | 6.51(4.65,8.36) | 5.77 (4.62,6.92) | 1.79 (1.41,2.26) |
| Diabetes | |||||||
| Yes | 5.69(4.7,6.68) | 1.97(1.21,2.73) | 3.05(2.07,4.04) | 6.75(5.23,8.27) | 5.29(3.97,6.61) | 4.70 (4.03,5.38) | 1.55 (1.27,1.89) |
| Tuberculosis | |||||||
| Yes | 2.61(–1.12,6.35) | 0.9(–0.41,2.22) | 1.4(–0.67,3.47) | 3.1(–1.35,7.54) | 2.42(–1.05,5.89) | 2.16 (–0.92,5.23) | 0.59 (0.14,2.47) |
| HIV | |||||||
| Yes | 5.72(0.56,10.88) | 1.98(0.05,3.91) | 3.07(0.21,5.93) | 6.8(0.59,13.01) | 5.3(0.4,10.21) | 4.73 (0.49,8.96) | 1.31 (0.53,3.22) |
| Oxygen therapy | |||||||
| Yes | 10.79(8.25,13.34) | 3.82(2.29,5.34) | 5.97(3.92,8.02) | 13.1(9.79,16.41) | 10.36(7.48,13.25) | 8.92 (7.19,10.65) | 3.76 (2.92,4.84) |
| ICU admission | |||||||
| Yes | 12.91(9.89,15.94) | 3.78(2.15,5.42) | 5.8(3.7,7.91) | 13.38(10.02,16.74) | 12.35(9.12,15.57) | 9.76 (7.82,11.70) | 3.23 (2.57,4.06) |
| BMI categories*** | |||||||
| Normal 18–24 | 4.78(2.26,7.3) | 1.88(0.6,3.16) | 3.19(1.31,5.08) | 9.55(4.65,14.45) | 8.29(3.89,12.7) | 5.43(2.76,8.1) | 1 |
| Underweight <18 | 2.78(2.05,3.51) | 1.09(0.59,1.59) | 1.86(1.17,2.55) | 5.55(4.32,6.79) | 4.82(3.65,6) | 3.16(2.67,3.64) | 1.72(1.02,2.89) |
| Overweight 25–29 | 2.13(1.48,2.77) | 0.83(0.43,1.24) | 1.42(0.83,2.01) | 4.25(2.96,5.54) | 3.69(2.54,4.83) | 2.41(1.83,3) | 0.76(0.57,1.02) |
| Obese ≥30 | 2.22(1.11,3.34) | 0.87(0.36,1.38) | 1.48(0.64,2.33) | 4.44(2.35,6.53) | 3.86(1.95,5.76) | 2.52(1.39,3.65) | 0.8(0.49,1.31) |
[i] *RR for mortality over time for each covariate is calculated by keeping the site name as a fixed effect variable.
**For variables ethnicity, region, and income group, the analysis did not include site name because of correlation.
***For variables stroke, heart failure, CKD and BMI categories, the models with site as fixed effect did not converge, hence site was excluded from the model.