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Thirty-five patients with COVID-19 were discharged from 13 hospitals from January 22, 2020 to May 6, 2022. Three cases were excluded. Among them, one case declined to attend the follow-up, one case could not be reached during the follow-up, and one case died 2 months after discharge due to cardiovascular, renal failure, electrolyte disturbance, and so forth. The patient was an 81-year-old man with a 60-year history of PTB, 20 years of hypertension, and 50 years of smoking. The patient was a critical COVID-19 case on admission.
In this study, 32 cases were enrolled in the analysis. The median (P25, P75) age was 51.5 (44.5, 62.5) years, and 23 (71.9%) were men. Apart from PTB, more than half [19 (59.4%)] had at least one comorbidity, mainly including hypertension [4 (12.5%)], fatty liver [3 (9.4%)], diabetes [2 (6.3%)], and coronary heart disease [2 (6.3%)]. The most common symptoms were fever [14 (43.8%)], cough [13 (40.6%)], followed by fatigue [8 (25.0%)], sore throat [4 (12.5%)], and asthma [4 (12.5%)]. Additionally, 22 (68.8%) survivors showed abnormal changes in their lung lesions on admission. Demographics and clinical characteristics are shown in Table 1.
Characteristics Total
(n = 32)Non-severe
(n = 22)Severe
(n = 3)Asymptomatic
(n = 7)Age, years [M (P25, P75)] 51.5 (44.5, 62.5) 50.5 (43.2, 59.5) 72 (47.0, 72.0) 52.0 (39.0, 57.0) Gender, n (%) Male 23 (71.9) 15 (68.2) 3 (100.0) 5 (71.4) Female 9 (28.1) 7 (31.8) 0 (0) 2 (28.6) History of close contact with
confirmed COVID-19, n (%)20 (62.5) 15 (68.2) 2 (66.7) 3 (42.9) Comorbidities, n (%) Any 19 (59.4) 12 (54.5) 2 (66.7) 5 (71.4) Hypertension 4 (12.5) 1 (4.5) 2 (66.7) 1 (14.3) Diabetes 2 (6.3) 0 (0) 1 (33.3) 1 (14.3) Coronary heart disease 2 (6.3) 2 (9.0) 0 (0) 0 (0) Fatty liver 3 (9.4) 3 (13.6) 0 (0) 0 (0) Other 12 (37.5) 7 (31.8) 2 (66.7) 3 (42.9) Classification of PTB Active 1 (3.1) 1 (4.5) 0 (0) 0 (0) Non-active 31 (96.9) 21 (95.5) 3 (100.0) 7 (100.0) Symptoms in hospital, n (%) Fever 14 (43.8) 12 (54.5) 2 (66.7) 0 (0) Cough 13 (40.6) 10 (45.5) 3 (75.0) 0 (0) Expectoration 3 (9.4) 1 (4.5) 2 (66.7) 0 (0) Fatigue 8 (25.0) 5 (22.7) 3 (75.0) 0 (0) Anorexia 2 (6.3) 1 (4.5) 1 (33.3) 0 (0) Sore throat 4 (12.5) 4 (18.2) 0 (0) 0 (0) Nasal congestion 2 (6.3) 1 (4.5) 0 (0) 0 (0) Rhinorrhea 1 (3.1) 0 (0) 1 (33.3) 0 (0) Asthma 4 (12.5) 2 (9.0) 2 (66.7) 0 (0) Diarrhea 3 (9.4) 2 (9.0) 1 (33.3) 0 (0) CT findings, n (%) No abnormal lesions 10 (31.3) 3 (13.6) 0 (0) 7 (100.0) Unilateral lung injury 8 (25.0) 8 (36.4) 0 (0) 0 (0) Bilateral lung injury 14 (43.87) 11 (50.0) 3 (100.0) 0 (0) Treatment, n (%) Antiviral 24 (75.0) 17 (77.3) 3 (100.0) 4 (57.1) Antibiotic 11 (34.4) 8 (36.4) 3 (100.0) 0 (0) Glucocorticoids 3 (9.4) 1 (4.5) 2 (66.7) 0 (0) TCM 26 (81.3) 18 (81.8) 2 (66.7) 6 (85.7) Symptomatic treatment 19 (59.4) 13 (59.1) 2 (66.7) 4 (57.1) Outcomes, days [M (P25, P75)] Length of first viral shedding 10.0 (7.3, 13.0) 9.5 (6.7, 13.7) 15.0 (13.0, 15.0) 8.0 (2.0, 11.0) Length of hospital stay 14.5 (10.0, 21.0) 12.0 (9.7, 21.5) 20.0 (18.0, 20.0) 14.0 (11.0, 15.0) Table 1. Characteristics of 32 COVID-19 with PTB patients
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All patients received traditional Chinese medicine (TCM) or/and western medicine (WM). TCM mainly included Qingfei Paidu Decoction (QFPDD) [15 (46.9%)], Lianhua Qingwen Granule [8 (25.0%)], and Yinlian Qingwen oral liquid [6 (18.8%)]. WM mainly included antiviral treatment (Alpha interferon-α, Ribavirin, Arbidol, Oseltamivir, etc.), antibiotics (Moxifloxacin, Ofloxacin, etc.), and supportive treatments, such as oxygen therapy. Moreover, one patient was diagnosed with active PTB after COVID-19. The patient received anti-PTB treatments in addition to the treatment for COVID-19 (Table 1). No serious adverse events were observed in the patients during hospitalization. The median duration of the first viral shedding and hospitalization was 10.0 (7.3, 13.0) and 14.5 (10.0, 21.0) days, respectively. The detailed course of the 32 cases is shown in Figure 1.
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Among 32 patients discharged, not all patients met the interval of 24 months from discharge to follow-up based on the long enrollment period (from January 22, 2020 to May 6, 2022). As of August 26, 2022, 32 patients had completed 3-month follow-ups, while 26 and 19 had completed 12- and 24-month follow-ups, respectively. The proportion of COVID-19 survivors with at least one sequela symptom decreased significantly from 13 (40.6%) of 32 at 3 months to 8 (30.8%) of 26 at 12 months to 3 (15.8%) of 19 at 24 months, with fatigue and anxiety always being the most frequent. Among these, chromatosis disappeared after a 3-month follow-up; cough and amnesia recovered after a 12-month follow-up, but fatigue, anxiety, and trouble sleeping remained after 24 months. Additionally, one (3.1%) had two recurrences of PTB and no COVID-19 re-positive during the follow-up period. Notably, a similar downward trend in sequela was observed among 19 patients who completed three follow-up visits, as shown in Table 2 and Figures 2–3.
Figure 2. Proportion of clinical symptoms at admission and persistent symptoms at different appointments after discharge.
Characteristics 3-month (n = 32) 12-month (n = 26) 24-month (n = 19) Fatigue, n (%) 10 (31.3) 4 (15.4) 1 (5.3) Anxiety, n (%) 4 (12.5) 2 (7.7) 3 (15.8) Cough, n (%) 3 (9.4) 1 (3.8) 0 (0) Chromatosis, n (%) 1 (3.1) 0 (0) 0 (0) Amnesia, n (%) 1 (3.1) 1 (3.8) 0 (0) Difficulty falling asleep, n (%) 1 (3.1) 1 (3.8) 1 (5.3) Re-positive of COVID-19, n (%) 0 (0) 0 (0) 0 (0) Recurrence of PTB, n (%) 0 (0) 1 (3.8) 1 (5.3) Table 2-a. The proportion of persistent symptoms in COVID-19 with PTB cases at different appointment after discharge
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To the best of our knowledge, this is the first prospective, multicenter follow-up study among COVID-19 with PTB survivors. This study found that the proportion of sequelae, such as fatigue and cough, decreased with the extension of follow-up time and was as low as 15.8% at 24 months; however, anxiety had a higher proportion (15.8%) among survivors. We also observed no positive results in PCR retests, but one patient had two recurrences, that is, positive sputum culture for Mycobacterium TB.
Growing evidence has shown that COVID-19 survivors may experience long-term sequela and affect different organ systems and quality of life [4,15-19]. A systematic review reported that 80% of COVID-19 patients had long-term symptoms following acute infection [20]. A study from Italy observed that 40.5% of patients reported at least one symptom at a 12-month follow-up [21]. Literature published in China reported that the proportion of patients with at least one sequela symptom was 68% and 49% at 6 and 12 months, respectively [22]. Yang et al. reported that 19.8% of survivors had symptoms at 2 years after discharge [23]. However, the persistence of symptoms among COVID-19 with PTB cases after discharge was still unclear. The results showed that the proportion of patients with at least one sequela symptom was 40.6%, 30.8%, and 15.8% at 3, 12, and 24 months after discharge, which were lower than the above studies. Moreover, we also found that the proportion of one sequela symptom decreased over follow-up, while anxiety was the most common sequela symptom. The results conformed to other studies [5,21], suggesting that the long-term impact of COVID-19 could not be ignored, and more attention should be paid to psychological counseling and humanistic care.
Retested positive COVID-19 patients after discharge are the main cause of re-hospitalization and the potential cause of the outbreak. A narrative review demonstrated that the proportion of re-positive tests in discharged COVID-19 patients varied from 2.4% to 69.2% and persisted from 1 to 38 days after discharge [24]. A meta-analysis including 3,644 patients from 41 studies reported that the proportion of re-positive cases was 14% from China and 31% from Korea. Notably, 39% of subjects among re-positive cases had at least one comorbidity [25]. However, the proportion of positive retested among COVID-19 with PTB has not been reported. In this study, no re-positive cases during the 24-month follow-up and showed a favorable outcome. The exact causes and mechanisms of positive retests for SARS-CoV-2 RNA in COVID-19 with PTB cases remain unclear. Therefore, further studies should be conducted to confirm the findings.
The recurrence of TB continues to be a significant problem and remains a challenge for the global control of TB. A previous study reported that the rate of recurrence ranged from 4.9% to 47% [26]. Additionally, a study from South Africa demonstrated a 14% of recurrence rate with a 5-year follow-up [27], and a study from China observed 3.9% and 5.4% at 2- and 5-year follow-ups, respectively [28]. In this study, one (3.12%) case of a 73-year-old COVID-19 with PTB survivor had two recurrences after being cured at 12 and 24 months, respectively. Many factors, including gender, age, inadequate treatment, viral infections, and diabetes, were associated with PTB recurrence [29-32]. COVID-19 with PTB coinfection caused excessive inflammation in the lungs, and a highly inflammatory environment can accelerate the progression of TB [33]. A recent study showed that COVID-19 might lead to recurrence in PTB patients [34]. Meanwhile, glucocorticoids and immunosuppressants used to treat COVID-19 may also promote PTB recurrence by compromising T-cell immunity and weakening immune responses [35-36]. However, whether COVID-19 reactivates or exacerbates active PTB remains unclear and needs to be confirmed by further studies.
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There are several notable strengths in this study. To the best of our knowledge, this is the first study to investigate the clinical outcome, including the persistence of symptoms and recurrence among COVID-19 with PTB survivors at 24-month follow-up after discharge. Moreover, this study is a multicenter study. The results showed favorable clinical outcomes as the proportion of sequela decreased with the extension of the follow-up period, while anxiety had a higher proportion among the persistence of symptoms. Notably, this study further observed that no retested positive PCR while recurrence of PTB during follow-up. The findings should be confirmed through further studies. Despite the strengths of this study, there are also a number of limitations. First, this study is a small sample size study. Second, no parallel control group was analyzed in this study. Further studies with large samples and multicenter need to be conducted to confirm the findings.
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Characteristics 3-month (n = 19) 12-month (n = 19) 24-month (n = 19) Fatigue, n (%) 7 (36.8) 3 (15.8) 1 (5.3) Anxiety, n (%) 4 (21.1) 2 (10.5) 3 (15.8) Cough, n (%) 1 (5.3) 0 (0) 0 (0) Chromatosis, n (%) 0 (0) 0 (0) 0 (0) Amnesia, n (%) 0 (0) 0 (0) 0 (0) Difficulty falling asleep, n (%) 1 (5.3) 2 (10.5) 1 (5.3) Re-positive of COVID-19, n (%) 0 (0) 0 (0) 0 (0) Recurrence of PTB, n (%) 0 (0) 1 (5.3) 1 (5.3) Table 2-b. The proportion of persistent symptoms in 19 COVID-19 with PTB cases at different appointment after discharge
3- to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge: Results from a Prospective, Multicenter Study
doi: 10.3967/bes2022.126
- Received Date: 2022-09-22
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Key words:
- COVID-19 /
- Pulmonary tuberculosis /
- Long-term /
- Sequela /
- Recurrence /
- Re-positive
Abstract:
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
&These authors contributed equally to this work.
Citation: | WANG Jing Ya, ZONG Xing Yu, WU Gui Hui, QI Yuan Lin, LI Hui Zhen, JI Xin Yu, TONG Lin, ZHANG Lei, YANG Ming Bo, YANG Pu Ye, LI Ji Ke, XIAO Fu Rong, ZHANG Lin Song, HU Yun Hong, LIU Hong De, XU Shou Fang, SUN Sheng, WU Wei, MAO Ya, LI Min Qing, HOU Hao Hua, GONG Zhao Yuan, GUO Yang, JIAO Li Wen, QIN Jin, WANG Ding Yi, WANG Fang, GUAN Li, LIN Gang, MA Yan, WANG Yan Ping, SHI Nan Nan. 3- to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge: Results from a Prospective, Multicenter Study[J]. Biomedical and Environmental Sciences, 2022, 35(12): 1091-1099. doi: 10.3967/bes2022.126 |