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Original Article

Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective Study

Tu, Bo1; Lakoh, Sulaiman2; Xu, Biao1; Lado, Marta3,4; Cole, Reginald3; Chu, Fang1; Hastings-Spaine, Susan3; Jalloh, Mohamed Bole3; Zheng, Junjie1,∗; Chen, Weiwei1,∗; Sevalie, Stephen2,3,∗

Editor(s): Wang, Haijuan

Author Information
Infectious Diseases & Immunity: April 2022 - Volume 2 - Issue 2 - p 83-92
doi: 10.1097/ID9.0000000000000037
  • Open

Abstract

Introduction

The World Health Organization (WHO) declared that the coronavirus disease 2019 (COVID-19) reached a worldwide pandemic on March 11, 2020.[1] The pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the genus Betacoronavirus and subgenus Sarbecovirus (lineage B).[2] COVID-19 is a highly infectious respiratory disease, which is transmitted through droplets, respiratory secretions, and direct contact in humans.[3,4] Even worse, the virus could be isolated from the blood and fecal swabs, revealing its other transmittal means.[5] Fever and cough are the common symptoms at the early stages of onset.[6] With the aggressive disease progression, acute respiratory distress syndrome, respiratory failure, and multiple organ failure are frequently observed, leading to death.[7] The reported death rate of severe and critical COVID-19 is up to 15% to 18%.[8]

Until now, there is no recommended antiviral treatment approved for COVID-19 in Sierra Leone, and supportive care and protection of vital organ function are performed for the patients.[9,10] The low dose of systemic corticosteroids and antivirals and atomization inhalation of interferon are encouraged in clinical management for patients in critical conditions.[11] Several drugs have been reported in COVID-19 treatment, including chloroquine, remdesivir, favipiravir, lopinavir/ritonavir, convalescent plasma, and mesenchymal stem cell therapy.[12,13] However, these drugs could not be applied for routine treatment of COVID-19 based on the current clinical findings.[13]

Sierra Leone, an African country, was heavily affected by the Ebola virus during the 2014 to 2016 outbreak. With the assistance of the Chinese People's Liberation Army, the Tropical Infectious Diseases Prevention and Control Center (IDPC), was constructed at the 34th Military Hospital and handed over to the Sierra Leone military. Since the opening of the center in July 2018, the center is jointly staffed by local experts and members of the Chinese Military Medical Expert Group in the prevention and treatment of infectious diseases based on China-Sierra Leone collaboration. IDPC is designated as an essential COVID-19 testing and treatment unit for mainly severe cases in Sierra Leone since the COVID-19 outbreak. In this retrospective study, we investigated the risk factors for severity and death among COVID-19 cases treated at IDPC of the 34th Military Hospital in Sierra Leone. In addition, we discussed the clinical efficacy of dexamethasone treatment.

Methods

Ethics approval

This study was approved by the Ethics Committee of Sierra Leone (No. 20200712-SLESRC-003) and also has been carried out in accordance with the World Medical Association Declaration of Helsinki. Informed consent was obtained from all patients/ participants or their legal representatives.

Study population

A total of 180 COVID-19 patients were recruited from the Tropical Infectious Diseases Prevention and Control Center of the 34th Military Hospital in Sierra Leone in collaboration with the Chinese Military Medical Expert Group between March 31, 2020 and August 11, 2020. The clinical and laboratory information was retrospectively collected to assess the risk factors and treatment strategies for severe COVID-19. Demographic information, travel history, clinical symptoms and signs, laboratory detection results, chest examination findings, therapeutics, and clinical outcomes were collected from each case file.

The eligible patients were confirmed to be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on nasopharyngeal swabs, and met the diagnostic criteria of COVID-19 issued by the WHO.[14] The severity of COVID-19 was estimated according to the Guidelines issued by the National Health Committee of China[15] and WHO.[14] Patients with severe and critically ill are classified in the severe group, while patients that presented asymptomatic, mild, and moderate disease were grouped in the non-severe group. In addition, due to the limited medical conditions, the sudden symptoms were confirmed based on the patients’ clinical presentation and doctors’ experiments.

Nucleic acid testing

The laboratory diagnosis of SARS-CoV-2 was achieved using a real-time reverse transcription-polymerase chain reaction (RT-PCR). In brief, total RNA samples were obtained from the nasopharyngeal swabs using an automated extraction instrument (KingFisher Flex, ThernoFisher Scientific, MA, USA) or Trizol reagent (Sigma-Aldrich, St. Louis, MO, USA) by manual extraction. Then, PCR reaction was performed by a one-step real-time PCR kit (VR-11-120) for the detection of SARS-CoV-2 ORF1ab/N (Shanghai Huirui Biotechnology, Shanghai, China). The amplification was carried out in the RT-PCR detection system (CFX96 Bio-Rad, CA, USA) according to the instructions in the manufacturer's manual.

Hematologic analysis

The hematologic analysis was performed for all the patients on admission using automated analyzer devices like TEK5020 and TEK6030 (Tecom Science Corporation, Jiangxi, China). The detected hematologic indexes included white blood cell (WBC) with counts of lymphocytes, monocyte, neutrophils, hemoglobin (HGB), platelet count (PLT). The biochemical indices included serum albumin (ALB), total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), blood glucose, blood urea nitrogen (BUN), creatinine (CRE), uric acid (UA), and lactate dehydrogenase (LDH). D-dimer was assessed using quantitative detection kits (Hightop Biotech Co., Ltd. Qingdao, China), while C-reactive protein (CRP) and procalcitonin (PCT) were detected by quantitative detection kits using immunofluorescence chromatographic method (Sichuan Xincheng Biological Co., Ltd. Chengdu, China).

Statistical analysis

All the calculations were achieved using SPSS version 18.0 software (SPSS Inc., Chicago, IL, USA). The distributions of continuous data were estimated using Kolmogorov-Smirnov test. Normally distributed continuous variables were presented as means ± standard deviation and non-normally distributed continuous variables as medians (interquartile ranges; IQR). Categorical variables were summarized as numbers (percentages). Continuous variables were compared by the Student's t test or the Mann-Whitney U test, and categorical variables by the chisquare test or Fisher exact test. Multivariate logistic regression model performed by “Forward: LR” method was employed to identify the risk factors for disease severity and death of COVID-19 patients, and the variables with P values less than 0.01 would be entered into the analysis. All the tests were two-tailed, and P values less than 0.05 indicated the results’ statistical significance.

Results

Baseline characteristics of the study subjects

A total of 180 COVID-19 patients were retrospectively included in our study. Based on disease severity, 104 patients (57.78%) were divided into the non-severe group, while 76 patients (42.22%) were divided into the severe group. On discharge, 34 patients died (7 patients in the non-severe group, 27 patients in the severe group), and the death rate was 18.89%.

The average age of the enrolled patients was 52 ± 16years. There were 42 (23.33%) females and 138 (76.67%) males. The epidemiological link of 78 cases (43.33%) was identified in a confirmed community transmission area. The most common comorbidities were hypertension (57, 31.67%), and combined hypertension and diabetes (18, 10.00%). In addition, there were 2 (1.11%) pregnant women in our study. On admission, 22 cases (12.22%) were asymptomatic; 54 cases (30.00%) were diagnosed with the mild disease; and 28 cases (15.56%) exhibited moderate disease. Severe and critical diseases were confirmed in 41 (22.78%) and 35 (19.44%) cases, respectively. The median hospital stay time was 13 days. The detailed information was recorded in Table 1.

Table 1 - The baseline and demographic of the study subjects
Survival

Features Total Survivors (n = 146) Non-survivors (n = 34) P values
Mean age (years, means ± SD) 52 ± 16 50 ± 16 62 ± 14 <0.001
Gender [male, n (%)] 138 (76.67) 111 (76.03) 27 (79.41) 0.674
History of epidemiology [yes, n (%)] 78 (43.33) 75 (51.37) 3 (8.82) <0.001
Co-morbidity [n (%)]
 Hypertension 57 (31.67) 46 (31.51) 11 (32.35) 0.924
 Diabetes 7 (3.89) 6 (4.11) 1 (2.94) 0.502
 Hypertension+diabetes 18 (10.00) 13 (8.9) 5 (14.71) 0.310
 AIDS 8 (4.44) 4 (2.74) 4 (11.76) 0.021
 Pregnancy 2 (1.11) 2 (1.37) 0 (0) 1.000
 Others 4 (2.22) 3 (2.05) 1 (2.94) 0.752
Clinical types [n (%)] <0.001
 Asymptomatic 22 (12.22) 22 (15.07) 0 (0)
 Mild 54 (30.00) 52 (35.62) 2 (5.88)
 Moderate 28 (15.56) 23 (15.75) 5 (14.71)
 Severe 41 (22.78) 32 (21.92) 9 (26.47)
 Critical 35 (19.44) 17 (11.64) 18 (52.94)
Length of hospital stay [days, median (IQR)] 13 (9) 14 (7) 2 (5) <0.001
SD: standard deviation; AIDS: Acquired immunodeficiency syndrome; IQR: interquartile range.

The most common symptoms were fever (56.67%), cough (50.00%), dyspnea (39.44%), fatigue (37.22%), headache (11.67%), altered level of consciousness (10.56%), anorexia (10.56%), etc. According to chest examination, 7 (3.89%) cases had unilateral pneumonia; 79 cases (43.89%) had bilateral pneumonia; 27 (15.00%) cases showed multiple patch-like shadows (early stage); 45 (25.00%) cases showed ground-glass opacity in both lungs (intermediate stage); and 7 (3.89%) cases exhibited lung consolidation (late stage) [Table 2].

Table 2 - The clinical characteristics of the study subjects
Survival

Features Total Survivors (n = 146) Non-survivors (n = 34) P values
Fever 102 (56.67) 82 (56.16) 20 (58.82) 0.512
Cough 90 (50) 77 (52.74) 13 (38.24) 0.214
Sore throat 4 (2.22) 4 (2.74) 0 (0) 1.000
Dyspnea 71 (39.44) 51 (34.93) 20 (58.82) 0.004
Fatigue 67 (37.22) 52 (35.62) 15 (44.12) 0.234
Myalgia 17 (9.44) 14 (9.59) 3 (8.82) 0.970
Nasal stuffiness 7 (3.89) 7 (4.79) 0 (0) 0.418
Running nose 3 (1.67) 3 (2.05) 0 (0) 1.000
Sneezing 2 (1.11) 2 (1.37) 0 (0) 1.000
Smell disturbances 6 (3.33) 6 (4.11) 0 (0) 0.502
Taste disturbances 2 (1.11) 2 (1.37) 0 (0) 1.000
Headache 21 (11.67) 18 (12.33) 3 (8.82) 0.639
Diarrhea 3 (1.67) 2 (1.37) 1 (2.94) 0.485
Anorexia 19 (10.56) 15 (10.27) 4 (11.76) 0.712
Alteration in the level of consciousness 19 (10.56) 4 (2.74) 15 (44.12) <0.001
Chest pain 8 (4.44) 8 (5.48) 0 (0) 0.350
Sputum 6 (3.33) 6 (4.11) 0 (0) 0.502
Chest examination 0.284
 Normal 94 (52.22) 76 (52.05) 18 (52.94)
 Unilateral pneumonia 7 (3.89) 5 (3.42) 2 (5.88)
 Bilateral pneumonia
  Early stage 27 (15.00) 21 (14.38) 6 (17.65)
  Middle stage 45 (25.00) 40 (27.40) 5 (14.71)
  Late stage 7 (3.89) 4 (2.74) 3 (8.82)
Azithromycin 105 (58.33) 89 (60.96) 16 (47.06) 0.139
Ceftriaxone 100 (55.56) 72 (49.32) 28 (82.35) <0.001
Hydroxychloroquine 37 (20.56) 31 (21.23) 6 (17.65) 0.641
Dexamethasone 62 (34.44) 44 (30.14) 18 (52.94) 0.012
Enoxaparin 39 (21.67) 30 (20.55) 9 (26.47) 0.450
PCM 49 (27.22) 44 (30.14) 5 (14.71) 0.069
Vit C 116 (64.44) 108 (73.97) 8 (23.53) <0.001
Multivitamins 116 (64.44) 108 (73.97) 8 (23.53) <0.001
Data are presented as number (%).PCM: Paracetamol; Vit C: Vitamin C.

During hospitalization, 105 (58.33%) patients received azithromycin (500 mg/day); 100 (55.56%) patients were treated with ceftriaxone (2 g/day); 37 (20.56%) received hydroxychloroquine (1000 mg/day); 62 (34.44%) patients received dexamethasone (20 mg/day in decreasing dose); 39 (21.67%) cases were treated with enoxaparin (40 mg/day); 49 (27.22%) patients received paracetamol; 116 (64.44%) patients received vitamin C; and 116 (64.44%) were treated with multivitamins (immunoboost) [Table 2].

The major reasons for deaths of COVID-19 patients were severe pneumonia (44.12%), septic shock (23.53%), stroke (14.71%), brain herniation (5.88%) (due to the lack of brain computed tomography, brain herniation was diagnosed according to the patients’ clinical presentation and doctors’ experiments), renal failure (5.88%), and diabetic ketosis or hyperosmotic decompensation (5.88%) [Figure 1A].

F1
Figure 1:
The prognostic data of patients with COVID-19. (A) Causes of death among the patients confirmed with COVID-19. (B) The clinical types and outcomes of the included patients. COVID-19: Coronavirus disease 2019.

On admission, all the patients received routine laboratory examinations. Their median temperature was 36.50°C, SpO2 was 96.00% (IQR, 8.00%), systolic blood pressure (SBP) was 133.99 ± 24.70mmHg, diastolic blood pressure (DBP) was 82.52 ± 15.84mmHg, heart rate (HR) was 92.27 ± 17.51beats/min, and respiratory rate (RR) was 24.00 (IQR, 8.00) breaths/min. The routine laboratory parameters are shown in Table 3.

Table 3 - The laboratory parameters of the study subjects at admission
Survival

Parameters Total Survivors (n = 146) Non-survivors (n = 34) P values
Routine examinations
 Temperature (°C) 36.50 (0.40) 36.50 (0.40) 36.45 (0.60) 0.498
 SpO2 (%) 96.00 (8.00) 96.00 (7.00) 88.50 (13.25) <0.001
 SBP (mmHg) 133.99 ± 24.70 135.58 ± 23.53 127.18 ± 28.58 0.285
 DBP (mmHg) 82.52 ± 15.84 84.01 ± 14.38 76.15 ± 20.02 0.085
 HR (beats/min) 92.27 ± 17.51 89.24 ± 16.23 105.29 ± 17.06 <0.001
 RR (breaths/min) 24.00 (8.00) 22.00 (6.00) 27.00 (6.00) <0.001
Blood routine examinations
 WBC (×109/L) 7.80 (6.00) 7.10 (5.60) 13.35 (8.75) <0.001
 Lymphocytes (×109/L) 1.80 (1.22) 1.90 (1.30) 1.60 (0.645) 0.002
 Monocyte (×109/L) 0.42 (0.40) 0.40 (0.30) 0.92 (0.75) <0.001
 Neutrophils (×109/L) 4.60 (6.15) 4.30 (5.00) 9.80 (9.625) <0.001
 HGB (g/L) 142.00 (34.50) 142.00 (33.00) 118.50 (73.50) 0.058
 PLT (× 109/L) 174.00 (132.00) 170.00 (131.00) 193.50 (141.00) 0.592
 ALB (g/L) 42.28 ± 7.86 42.81 ± 7.69 38.93 ± 8.26 0.031
 ALT (U/L) 34.05 (33.125) 33.60 (30.25) 35.25 (53.05) 0.333
 AST (U/L) 29.80 (14.80) 29.60 (12.90) 40.20 (27.75) 0.016
 TB (μmol/L) 14.25 (7.375) 13.70 (6.825) 16.85 (12.125) 0.023
 Blood glucose (mmol/l) 6.30 (2.625) 6.20 (2.05) 9.20 (6.80) 0.009
 BUN (mmol/l) 4.80 (4.90) 4.40 (3.35) 15.25 (19.50) <0.001
 CRE (ml/min) 100.00 (40.00) 97.00 (30.00) 150.50 (180.25) <0.001
 UA (μmol/L) 366.20 (177.40) 360.70 (155.80) 498.60 (344.58) 0.005
 LDH (U/L) 341.25 ± 220.86 323.01 ± 218.48 447.63 ± 212.86 0.071
 CRP (mg/L) 43.38 (103.70) 38.62 (82.28) 134.05 (119.16) <0.001
 D-dimer (mg/L) 2.13 (6.52) 1.49 (5.29) 11.88 (10.50) <0.001
Continuous variables in normal distribution are shown as means ± standard deviations, while the continuous variables in abnormal distributions are expressed by median with IQR (interquartile range).SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HR: Heart rate; RR: Respiratory rate; WBC: White blood cell; HGB: Hemoglobin; PLT: Platelet count; ALB: Blood albumin; TP: Total protein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TB: Total bilirubin; BUN: Blood urea nitrogen; CRE: Creatinine clearance; UA: Uric acid; LDH: Lactic dehydrogenase; CRP: C-reaction protein.

The comparisons of baseline and laboratory parameters between survivors and non-survivors

Compared to the survivors, the non-survivors were more likely to exhibit older ages (P < 0.001) and have no history of foreign travel (P < 0.001). Moreover, most of the non-survivors had either critical (52.94%) or severe illness (26.47%) at presentation, only 2 (5.88%) were confirmed with mild illness, and no asymptomatic cases were observed in the non-survivor group at presentation. The occurrences of dyspnea and altered level of consciousness were significantly higher among non-survivors than in survivors (P = 0.004 and P < 0.001). The treatment strategies showed a slight difference between survivors and non-survivors. Ceftriaxone and dexamethasone treatments were more frequently administered to non-survivors, while Vitamin C and multivitamins (immunoboost) treatments were rarely used in non-survivors (P < 0.05 for all). The survivors had prolonged hospital stay time [14 (IQR, 7) days vs. 2 (IQR, 5) days] [Table 1 and Table 2].

The non-survivors showed significantly low levels of SpO2, high levels of HR, and RR (P < 0.05 for all). Routine blood examinations demonstrated that compared to survivors, the non-survivors were more likely to exhibit high levels of WBC, monocyte, neutrophils, AST, TB, glucose, BUN, CRE, UA, CRP, and D-dimer, as well as low lymphocytes and ALB levels (P < 0.05 for all) [Table 3].

The comparison of clinical manifestations between severe and non-severe groups

As shown in Figure 1B, the death rates were significantly higher in severe and critical groups. We compared the baseline characteristics between severe and non-severe groups. Analysis results demonstrated that the cases in the severe group exhibited older age (P < 0.001), and had no history of an epidemiology link in a setting with community transmission (P < 0.001). Moreover, the severe group was more likely to have the combined hypertension and diabetes (P = 0.001), fever (P = 0.001), cough (P < 0.001), dyspnea (P < 0.001), fatigue (P < 0.001), alteration in the level of consciousness (P = 0.003), and sputum (P = 0.013). In addition, 82.89% of cases in the severe group showed pneumonia, which was significantly higher than that of the non-severe group (P < 0.001). Azithromycin, ceftriaxone, hydroxychloroquine, dexamethasone, and prophylactic dose of enoxaparin were frequently used for the treatment of severe illness (P < 0.05 for all). The death rate was significantly higher in the severe group than in the non-severe group (35.53% vs. 6.73%) (P < 0.001). Furthermore, septic shock and septic shock were the primary reasons for death among severe cases, while stroke and brain herniation represented the leading reasons for deaths in the non-severe group [Table 4].

Table 4 - The comparisons of baseline clinical characteristics between severe and non-severe patients
Clinical types

Features Non-severe (n = 104) Severe (n = 76) P values
Baseline and demographic
 Mean age (years, mean ± SD) 46 ± 16 60 ± 14 <0.001
 Gender [n (%)] 0.924
  Female 24 (23.08) 18 (23.68)
  Male 80 (76.92) 58 (76.32)
 History of epidemiology [n (%)] <0.001
  No 41 (39.42) 61 (80.26)
  Yes 63 (60.58) 15 (19.74)
 Co-morbidity [n (%)]
  Hypertension 27 (25.96) 30 (39.47) 0.054
  Diabetes 4 (3.85) 3 (3.95) 1.000
  Hypertension+diabetes 4 (3.85) 14 (18.42) 0.001
  AIDS 2 (1.92) 6 (7.89) 0.120
  Pregnancy 2 (1.92) 0 (0) 0.509
  Others 2 (1.92) 2 (2.63) 1.000
On admission [n (%)]
 Fever 49 (47.12) 53 (69.74) 0.001
 Cough 37 (35.58) 53 (69.74) <0.001
 Sore throat 2 (1.92) 2 (2.63) 1.000
 Dyspnea 10 (9.62) 61 (80.26) <0.001
 Fatigue 24 (23.08) 43 (56.58) <0.001
 Myalgia 9 (8.65) 8 (10.53) 0.629
 Nasal stuffiness 7 (6.73) 0 (0) 0.055
 Running nose 3 (2.88) 0 (0) 0.366
 Sneezing 2 (1.92) 0 (0) 0.509
 Smell disturbances 5 (4.81) 1 (1.32) 0.385
 Taste disturbances 2 (1.92) 0 (0) 0.509
 Headache 16 (15.38) 5 (6.58) 0.079
 Diarrhea 2 (1.92) 1 (1.32) 1.000
 Anorexia 7 (6.73) 12 (15.79) 0.043
 Alteration in the level of consciousness 5 (4.81) 14 (18.42) 0.003
 Chest pain 4 (3.85) 4 (5.26) 0.958
 Sputum 0 (0) 6 (7.89) 0.013
Chest examination <0.001
 Normal 81 (77.88) 13 (17.11)
 Unilateral pneumonia 6 (5.77) 1 (1.32)
 Bilateral pneumonia
  Early stage 15 (14.42) 12 (15.79)
  Middle stage 2 (1.92) 43 (56.58)
  Late stage 0 (0) 7 (9.21)
Treatments [n (%)]
 Azithromycin 43 (41.35) 62 (81.58) <0.001
 Ceftriaxone 30 (28.85) 70 (92.11) <0.001
 Hydroxychloroquine 12 (11.54) 25 (32.89) <0.001
 Dexamethasone 7 (6.73) 56 (73.68) <0.001
 Enoxaparin 9 (8.65) 30 (39.47) <0.001
 PCM 30 (28.85) 19 (25) 0.567
 Vit C 70 (67.31) 46 (60.53) 0.348
 Multivitamins 70 (67.31) 46 (60.53) 0.348
On discharge
 Length of hospital stay [days, median (IQR)] 14 (6) 13 (14) 0.460
 Outcomes [n (%)] <0.001
  Discharged 97 (93.27) 49 (64.47)
  Died 7 (6.73) 27 (35.53)
 Reasons for death [n (%)] <0.001
  Septic shock 0 (0) 8 (10.53)
  Severe pneumonia 0 (0) 15 (19.74)
  Brain herniation 2 (1.92) 0 (0)
  Stroke 4 (3.85) 1 (1.32)
  Renal failure 0 (0) 2 (2.63)
  Diabetic ketosis 1 (0.96) 1 (1.32)
SD: standard deviations; AIDS: Acquired immunodeficiency syndrome; PCM: Paracetamol; IQR: interquartile range.

The patients with severe COVID-19 exhibited significantly low SpO2 and high levels of HR and RR (P < 0.05 for all). Severe COVID-19 patients frequently had high levels of WBC, monocyte, neutrophils, PLT, ALT, AST, blood glucose, CRE, UA, LDH, CRP, and D-dimer, and low levels of lymphocytes, HGB, and ALB (P < 0.05 for all) [Table 5].

Table 5 - The comparison of laboratory parameters between severe and non-severe patients at admission
Clinical types

Parameters Non-severe (n = 104) Severe (n = 76) P values
Routine examinations
 Temperature (°C) 36.50 (0.50) 36.40 (0.40) 0.041
 SpO2 (%) 98.00 (3.00) 88.00 (10.00) <0.001
 SBP (mmHg) 132.07 ± 20.02 136.63 ± 29.89 0.222
 DBP (mmHg) 84.44 ± 14.2 79.89 ± 17.59 0.057
 HR (beats/min) 86.12 ± 14.13 100.7 ± 18.26 <0.001
 RR (breaths/min) 20.50 (4.00) 28.00 (4.00) <0.001
Blood routine examinations
 WBC (×109/L) 6.20 (3.45) 11.50 (5.20) <0.001
 Lymphocytes (×109/L) 2.15 (1.00) 1.50 (1.03) 0.001
 Monocyte (×109/L) 0.30 (0.28) 0.60 (0.55) <0.001
 Neutrophils (×109/L) 3.15 (2.50) 8.80 (4.65) <0.001
 HGB (g/L) 145 (27) 129 (41) 0.007
 PLT (× 109/L) 155 (116) 209 (159) <0.001
 ALB (g/L) 44.18 ± 7.55 39.52 ± 7.52 <0.001
 ALT (U/L) 31.50 (24.00) 41.20 (54.13) <0.001
 AST (U/L) 27.00 (13.13) 35.90 (18.55) <0.001
 TB (μmol/L) 14.20 (6.80) 14.25 (7.70) 0.241
 Blood glucose (mmol/L) 5.90 (1.10) 7.80 (6.40) <0.001
 BUN (mmol/L) 3.90 (2.30) 7.00 (6.475) <0.001
 CRE (ml/min) 95.50 (26.00) 117.00 (69.00) <0.001
 UA (μmol/L) 342.90 (131.40) 413.90 (189.175) <0.001
 LDH (U/L) 240.26 ± 132.28 452.58 ± 245.71 <0.001
 CRP (mg/L) 10.00 (57.74) 87.85 (113.95) <0.001
 D-dimer (mg/L) 0.35 (1.82) 6.78 (12.05) <0.001
Continuous variables are shown as mean ± standard deviations or median (interquartile range) depending on whether they are normally distributed.SpO2: oxygen saturation; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HR: Heart rate; RR: Respiratory rate; WBC: White blood cell; HGB: Hemoglobin; PLT: Platelet count; ALB: Blood albumin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TB: Total bilirubin; BUN: Blood urea nitrogen; CRE: Creatinine clearance; UA: Uric acid; LDH: Lactic dehydrogenase; CRP: C-reaction protein.

Risk factors for prognosis of COVID-19 patients

Multivariate logistic regression model was performed to identify the risk factors for deaths in COVID-19 patients. Alteration in the level of consciousness [odds ratio (OR) = 56.574, 95% confidence interval (CI) 5.645–566.940, P = 0.001), high neutrophils (OR = 1.341 95%CI 1.109–1.621, P = 0.002), and high CRP (OR = 1.014, 95%CI 1.003–1.025, P = 0.016) were independently correlated with death caused by COVID-19 [Table 6].

Table 6 - Multivariate analysis for the clinical outcomes of the patients confirmed with COVID-19
Variables B S.E. Wals OR 95%CI P values
Alteration in the level of consciousness 4.036 1.176 11.778 56.574 5.645–566.940 0.001
Neutrophils 0.293 0.097 9.200 1.341 1.109–1.621 0.002
BUN 0.009 0.011 0.744 1.010 0.988–1.031 0.389
CRP 0.014 0.006 5.857 1.014 1.003–1.025 0.016
BUN: Blood urea nitrogen; CRP: C-reaction protein; S.E.: Standard error; OR: Odds ratio; CI: Confidence interval.

Dexamethasone treatment for COVID-19

During hospitalization, we found that dexamethasone could significantly improve the clinical outcomes of COVID-19. As shown in Figure 2A, the daily administration dose of dexamethasone was significantly lower in survivors than that in non-survivors (P < 0.001). Moreover, the daily dose of dexamethasone did not show significant differences between non-severe and severe groups (P > 0.05) [Figure 2B]. Among the patients with severe stage, dexamethasone treatment could reduce the death rate 30.36% (17/56) vs. 50.00% (10/20), but the results were insignificant (P > 0.05) [Figure 2C].

F2
Figure 2:
Dexamethasone treatment for COVID-19 patients. (A) The comparison of Dexamethasone daily dose between the survivors and non-survivors. ∗∗∗P < 0.001; ns: not significant. (B) The comparison of Dexamethasone application between the non-severe group and severe group. ns: not significant. (C) The influences of Dexamethasone treatment on clinical outcomes of the patients confirmed with COVID-19 based on their clinical types. Yes: Dexamethasone treatment; no: without Dexamethasone treatment. COVID-19: Coronavirus disease 2019.

Discussion

COVID-19 is a severe respiratory infection, without effective treatments. Although various studies have reported the clinical presentation of COVID-19 in different regions,[16–19] little is known about the spread of COVID-19 in Sierra Leone, due to the disease heterogeneity. This study summarized the clinical characteristics, medications, and clinical outcomes of 180 COVID-19 patients in the 34th Military Hospital in Sierra Leone.

Among the included patients, fever and cough were the main clinical symptoms. The death rate was 18.89%; severe pneumonia and septic shock represented the leading causes of death. Multivariate analysis found that consciousness status, and the levels of CRP and neutrophils were independently associated with death of COVID-19. A meta-analysis of 1,994 hospitalized patients with COVID-19 analyzed from 10 articles showed the death rate of COVID-19 was 5%.[20] As IDPC was selected as a referral center for moderate risk factors, nearly half of the included patients were developed to severe and critical conditions that contributed to the high mortality. According to reports, the mortality rate of COVID-19 cases requiring intensive care was as high as 40%.[21] Timely treatment at early stages might be an effective way to improve the prognosis of COVID-19.

Generally, the immunity of COVID-19 patients with severe and critical illness were significantly dysregulated, which was characterized by lack of antigen-presenting cells, varying number, function of T cells, and the activation of negative immune regulation.[22,23] Our laboratory findings were consistent with this view. The non-survivors and severe cases exhibited significantly higher levels of white cells, neutrophils, and low levels of lymphocytes and monocyte, revealing the aggressive inflammatory conditions and poor immune response. Therefore, for cases confirmed with COVID-19, especially cases under critical conditions, host immune surveillance was very necessary.

Clinical-stage is an important factor for the survival of COVID-19 patients. Our study found that the death rates of asymptomatic, mild, moderate, severe, and critical cases were 0, 3.70%, 17.86%, 21.95%, and 51.43%, respectively. The mortality rate of severe and critical patients was much higher than in non-severe cases. Respiratory failure and septic shock were the major causes of death in severe cases.

Until now, there are no recommended antiviral drugs for the clinical treatment of COVID-19.[24,25] In the current analysis, we found that dexamethasone treatment could reduce the fatality rate of severe COVID-19 cases, but the results were insignificant. A preliminary report including hospitalized patients with COVID-19 showed that dexamethasone treatment could reduce the mortality among the patients who received oxygen, but the efficacy was not obvious among those with respiratory support.[26] Dexamethasone might improve the respiratory infection syndromes secondary to COVID-19, thus prolonging ventilator-free days.[27] Well-designed randomized controlled trials with a large sample size are required to explore the long-term therapeutic efficacy of dexamethasone among African patients with SARS-CoV-2.

The death rate of the severe cases included in this study was 35.53%. That is because the source of the cases in this study was from IDPC, a critical care institution designated by the Sierra Leone government, which admitted more than half of the severe cases in Sierra Leone. The COVID-19 epidemic in Sierra Leone is not accounted for so serious. According to the WHO website as of October 29, 2021, the number of COVID-19 confirmed cases in Sierra Leone is 6397, with 121 deaths (mortality rate 1.89%), which ranked 181 out of 233 countries and regions in the world.[28] As a country severely affected by the Ebola epidemic from 2014 to 2015, Sierra Leone has greatly improved its investment in public health, and the awareness of people on infectious disease prevention and control is improved. So at the beginning of the COVID-19 epidemic, the National COVID-19 Emergency Reaction Center was founded quickly. With the assistance of countries around the world, Sierra Leone has been fully prepared in terms of personnel, technology and medical supplies, and the surveillance for suspicious cases was enhanced as well. When the first case was confirmed, he was quickly admitted to the IDPC ward. Subsequently, the severe cases were actively rescued, and the mild cases were effectively isolated. There is no intensive care unit with good facilities, but mortality is not so high in Sierra Lenon, which is partly due to the Chinese aid experts in our research group working together with local colleagues to actively rescue patients. This approach is a positive example for the prevention and control of COVID-19 and other novel outbreaks in underdeveloped countries, as well as a positive contribution to the global fight against COVID-19.

Limitations

There were several limitations in the current study. First, due to the limited detection conditions, some laboratory factors, such as LDH and CRP, were not estimated initially but were added later, which affected the statistical results to a certain extent. Second, some of these patients’ test results and clinical details were incomplete, which reduced the statistical power of multivariate analysis. Nonetheless, the study has provided insight into the clinical characteristics and risk factors of severe COVID-19 disease and its mortality in a typical African setting.

Conclusion

In conclusion, the mortality rate of severe COVID-19 patients is as high as 35.53% in our study which was administrated in 34th Military Hospital in Sierra Leone between March 31, 2020 and August 11, 2020. Older age, hypertension and diabetes, fever, alteration in the level of consciousness, and high levels of inflammatory markers are closely related to the severity of COVID-19. Moreover, the alteration in the level of consciousness and high levels of neutrophils and CRP may increase the death risk in patients with COVID-19. Dexamethasone treatment may improve the survival of severe COVID-19 patients, but the clinical effect requires further verification.

Funding

This work was supported by the National Grand Program on Key Infectious Disease (No. 2018ZX10103002-001-007) and the Biosafety Special Program (No. 19SWAQ 13).

Author Contributions

Bo Tu, Biao Xu, and Weiwei Chen designed, drafted the manuscript. Marta Lado, Reginald Cole, Fang Chu, Susan Hastings-Spaine, and Mohamed Boie Jalloh contributed to the acquisition and analysis of the data. Junjie Zheng, Sulaiman Lakoh, and Stephen Sevalie conceived the manuscript and substantively revised it. All authors revised and approved the final manuscript.

Conflicts of Interest

None.

References

[1]. World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19-11 March 2020. Available from: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19-11-march-2020. Accessed March 25, 2020.
[2]. Valencia DN. Brief review on COVID-19: the 2020 pandemic caused by SARS-CoV-2. Cureus 2020;12(3):e7386. doi:10.7759/cureus.7386.
[3]. Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382(13):1199–1207. doi: 10.1056/NEJMoa2001316.
[4]. Zheng J. SARS-CoV-2: an emerging coronavirus that causes a global threat. Int J Biol Sci 2020;16(10):1678–1685. doi: 10.7150/ijbs.45053.
[5]. Ludwig S, Zarbock A. Coronaviruses and SARS-CoV-2: a brief overview. Anesth Analg 2020;131(1):93–96. doi: 10.1213/ANE.0000000000004845.
[6]. Lai CC, Shih TP, Ko WC, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents 2020;55(3):105924. doi: 10.1016/j.ijantimicag.2020.105924.
[7]. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497–506. doi: 10.1016/S0140-6736 (20)30183-5.
[8]. Kumar A, Arora A, Sharma P, et al. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab Syndr 2020;14(4):535–545. doi: 10.1016/j.dsx.2020.04.044.
[9]. Cunningham AC, Goh HP, Koh D. Treatment of COVID-19: old tricks for new challenges. Crit Care 2020;24(1):91. doi: 10.1186/s13054-020-2818-6.
[10]. Song Y, Zhang M, Yin L, et al. COVID-19 treatment: close to a cure? A rapid review of pharmacotherapies for the novel coronavirus (SARS-CoV-2). Int J Antimicrob Agents 2020;56(2):106080. doi: 10.1016/j. ijantimicag.2020.106080.
[11]. Liu Y, Li J, Feng Y. Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China. Crit Care 2020;24(1):56. doi: 10.1186/s13054-020-2786-x.
[12]. Esposito S, Noviello S, Pagliano P. Update on treatment of COVID-19: ongoing studies between promising and disappointing results. Infez Med 2020;28(2):198–211.
[13]. Xu X, Ong YK, Wang Y. Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines. Mil Med Res 2020;7(1):22. doi: 10.1186/s40779-020-00251-x.
[14]. WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. 2019. Available from: https://apps.who.int/iris/bitstream/handle/10665/178529/WHO_MERS_Clinical_178515.178521_eng.pdf?sequence=178521&isAllowed=y. Accessed August 30, 2021.
[15]. Committee. CNH. Diagnosis and treatment of pneumonia caused by 2019-nCoV (version 7). 2020. Available from: http://www.nhc.gov.cn/yzygj/s7653p/202003/202046c209294a202007dfe202004cef202080dc 202007f205912eb201989.shtml. Accessed August 30, 2021.
[16]. Lian J, Jin X, Hao S, et al. Epidemiological, clinical, and virological characteristics of 465 hospitalized cases of coronavirus disease 2019 (COVID-19) from Zhejiang province in China. Influenza Other Resp 2020;14(5):564–574. doi: 10.1111/irv.12758.
[17]. Lo IL, Lio CF, Cheong HH, et al. Evaluation of SARS-CoV-2 RNA shedding in clinical specimens and clinical characteristics of 10 patients with COVID-19 in Macau. Int J Biol Sci 2020;16(10):1698–1707. doi: 10.7150/ijbs.45357.
[18]. Tabata S, Imai K, Kawano S, et al. Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis. Lancet Infect Dis 2020;20(9):1043–1050. doi: 10.1016/S1473-3099(20)30482-5.
[19]. Su YJ, Lai YC. Comparison of clinical characteristics of coronavirus disease (COVID-19) and severe acute respiratory syndrome (SARS) as experienced in Taiwan. Travel Med Infect Dis 2020;36:101625. doi: 10.1016/j.tmaid.2020.101625.
[20]. Li LQ, Huang T, Wang YQ, et al. COVID-19 patients’ clinical characteristics, discharge rate, and fatality rate of meta-analysis. J Med Virol 2020;92(6):577–583. doi: 10.1002/jmv.25757.
[21]. Wiersinga WJ, Rhodes A, Cheng AC, et al. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA 2020;324(8):782–793. doi: 10.1001/jama.2020.12839.
[22]. Wang F, Hou H, Luo Y, et al. The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI Insight 2020;5(10):e137799. doi:10.1172/jci.insight.137799.
[23]. Zhand S, Saghaeian Jazi M, Mohammadi S, et al. COVID-19: the immune responses and clinical therapy candidates. Int J Mol Sci 2020;21(15):5559. doi: 10.3390/ijms21155559.
[24]. Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak-an update on the status. Mil Med Res 2020;7(1):11. doi: 10.1186/s40779-020-00240-0.
[25]. Simsek Yavuz S, Unal S. Antiviral treatment of COVID-19. Turk J Med Sci 2020;50(SI-1):611–619. doi: 10.3906/sag-2004-145.
[26]. Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with covid-19-preliminary report. N Engl J Med 2020;384(8):693–704. doi: 10.1056/NEJMoa2021436.
[27]. Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA 2020;324(13):1307–1316. doi: 10.1001/jama.2020.17021.
[28]. World Health Organization. WHO Coronavirus (COVID-19) Dashboard. Available from: https://covid19.who.int/table. Accessed October 29, 2021.
Keywords:

COVID-19; Clinical type; Dexamethasone; Risk factor

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