Search result
A total of 333 relevant publications on PubMed and other databases were identified. 68 were removed because of duplication, and 224 were removed based on above-mentioned inclusion/exclusion criteria. 23 publications did not report clinical signs, and four were excluded due to overlapped cases[8, 9, 15, 16]. Finally, 14 articles were included for analysis[10, 11, 13, 17–27]. Figure 1 is the study selection flowchart. Data from all eligible studies were obtained from published manuscripts.
Synthesis of results
A systematic review showed that 610 patients (42.8%) with COVID-19 pneumonia were female. Fever (89.2%) and cough (67.2%) were the most common symptoms, followed by fatigue (43.6%), phlegm (28.6%), and shortness/difficulty of breathing (21.7%). The less common symptoms were dizziness (0.9%), hemoptysis (0.8%), abdominal pain (0.8%), and conjunctiva congestion/conjunctivitis (0.7%). 1,377 cases were divided into groups of severe (1,110) and non-severe COVID-19 pneumonia (267). Stratified chi-square test showed that there was no significant difference in gender between the two groups (p > 0.05), and the median age of severe patients was slightly older (details in Table 2). Dyspnea in patients of severe group was significantly more common than that in non-severe group (42.7% vs.16.3%, p < 0.0001). The incidence of fever and diarrhea were also significantly higher in severe group (p = 0.0374 and 0.0267 respectively). Although conjunctival congestion/conjunctivitis (p = 0.0176), hemoptysis (p = 0.0344), anorexia (p = 0.0008), dizziness (p = 0.0023) and abdominal pain (p = 0.0015) all appeared to be much more common in severe patients, as the dates of these symptoms were only reported in one or two literatures, the inter-group comparisons of these symptoms should be treated with caution. (See Tables 1 and 2)
Table 1
A summary of clinical presentations from COVID-19 pneumonia*
| Article 1 [10] N = 1099 | Article 2 [11] N = 138 | Article 3 [13] N = 140 | Article 4 [17] N = 13 | Article 5 [18] N = 15 | Case reports summary (9 articles [19–27]) N = 19 | Total N = 1424 |
Age,median (IQR or range) | 47.0 (35.0– 58.0) | 56 (42–68) | 57 (25–87) | 34 (34–48) | 43 (8–66) | 31 (1–49) | - |
Gender, n (%) | 459 (41.8) | 63 (45.7) | 69/140 (49.3) | 3 (23.1) | 6 (40.0) | 10 (52.6) | 610 (42.8) |
Fever, n (%) | 966 (87.9) | 136 (98.6) | 110/120 (91.7) | 12 (92.3) | 14 (93.3) | 15 (78.9) | 1253 (89.2) |
Cough,n (%) | 744 (67.7) | 82 (59.4) | 90/120 (75.0) | 6 (46.2%) | 11 (73.3) | 11 (57.9) | 944 (67.2) |
Sore throat,n (%) | 153 (13.9) | 24 (17.4) | - | - | 7 (46.7) | 3 (15.8) | 187 (14.7) |
Sputum,n (%) | 367 (33.4) | 37 (26.8) | - | 2 (15.4) | - | 1 (5.3) | 407 (32.1) |
Fatigue,n (%) | 419 (38.1) | 96 (69.6) | 90/120 (75.0) | - | 4 (26.7) | 3 (15.8) | 612 (44.0) |
Dyspnea,n (%) | 204 (18.6) | 43 (31.2) | 44/120 (36.7) | 8 (61.5) | 1 (6.7) | 5 (26.3) | 305 (21.7) |
Nausea/vomiting,n (%) | 55 (5.0) | 14 (10.1) | 24/139 (17.3) | - | 1 (6.7) | 2 (10.5) | 96 (6.8) |
Diarrhea,n (%) | 41 (3.7) | 14 (10.1) | 18/139 (12.9) | 1 (7.7) | 5 (33.3) | 3 (15.8) | 82 (5.8) |
Muscle/joint pain,n (%) | 163 (14.8) | 48 (34.8) | - | 3 (23.1) | 2 (13.3) | 4 (21.1) | 220 (17.1) |
Chilly,n (%) | 125 (11.4) | - | - | - | - | 3 (15.8) | 128 (11.4) |
Headache,n (%) | 150 (13.6) | 9 (6.5) | - | 3 (23.1) | 3 (20.0) | 1 (5.3) | 166 (12.9) |
Nasal discomfort (congestion, overflow, runny),n (%) | 53 (4.8) | - | - | 1 (7.7) | 5 (33.3) | 6 (31.6) | 64 (5.6) |
Conjunctival congestion/conjunctivitis,n (%) | 9 (0.8) | - | - | - | - | 1 (5.3) | 10 (0.9) |
Hemoptysis,n (%) | 10 (0.9) | - | - | - | - | 1 (5.3) | 11 (1.0) |
Apocleisis,n (%) | - | 55 (39.9) | 17/139 (12.2) | - | - | - | 72 (26.0) |
Dizzy,n (%) | - | 13 (9.4) | - | - | - | - | 13 (9.4) |
Abdominal pain,n (%) | - | 3 (2.2) | 8/139 (5.8) | - | - | - | 11 (4.0) |
*If certain clinical sign/symptoms was not reported, case “0” was used for analysis. Article 3 clearly stated that not all the data from 140 patients were collected (e.g., the fever data was collected from only 120 patients). Therefore the actual documented cases were used for calculation. |
Table 2
The comparison of clinical features from severe vs. non-severe COVID-19 pneumonia*
| Article 1 [10] | Article 2 [11] | Article 3 [13] | Total | P value |
| Non-severe (N = 926) | Severe (N = 173) | Non-severe (N = 102) | Severe (N = 36) | Non-severe (N = 82) | Severe (N = 58) | Non-severe (N = 1110) | Severe (N = 267) |
Age,median (IQR or range) | 45.0 (34.0– 57.0) | 52.0 (40.0– 65.0) | 51 (37–62) | 66 (57–78) | 51.5 (26–78) | 64 (25–87) | - | - | - |
Gender,n (%) | 386 (41.7) | 73 (42.2) | 49 (48.0) | 14 (38.9) | 44/82 (53.7) | 25/58 (43.1) | 479/1110 (43.2) | 112/267(41.9) | 0.4588 |
Fever,n (%) | 808 (87.3) | 158 (91.3) | 100 (98.0) | 36 (100) | 59/67 (88.1) | 51/53 (96.2) | 967/1095 (88.3) | 245/262 (93.5) | 0.0374 |
Cough,n (%) | 622 (67.2) | 122 (70.5) | 61 (59.8) | 21 (58.3) | 45/67 (67.2) | 45/53 (84.9) | 728/1095(66.5) | 188/262 (71.8) | 0.1418 |
Sore throat,n (%) | 130 (14.0) | 23 (13.3) | 12 (11.8) | 12 (33.3) | | | 142/1028 (13.8) | 35/209 (16.7 | 0.3136 |
Sputum,n (%) | 306 (33.0) | 61 (35.3) | 29 (28.4) | 8 (22.2) | | | 335/1028 (32.6) | 69/209 (33.0) | 0.7974 |
Fatigue,n (%) | 350 (37.8) | 69 (39.9) | 67 (65.7) | 29 (80.6) | 51/67 (76.1) | 39/53 (73.6) | 468/1095 (42.7) | 137/262(52.3) | 0.3552 |
Dyspnea,n (%) | 139 (15.0) | 65 (37.6) | 20 (19.6) | 23 (63.9) | 20/67 (29.9) | 24/53 (45.3) | 179 /1095(16.3) | 112/262 (42.7) | < 0.0001 |
Nausea/vomiting,n (%) | 43 (4.6) | 12 (6.9) | 10 (9.8) | 4 (11.1) | 19/82 (23.2) | 5/57 (8.8) | 72/1110 (6.5) | 21/266 (7.9) | 0.7600 |
Diarrhea,n (%) | 31 (3.3) | 10 (5.8) | 8 (7.8) | 6 (16.7) | 9/82 (11.0) | 9/57 (15.8) | 48/1110 (4.3) | 25/266 (9.4) | 0.0267 |
Muscle/joint pain,n (%) | 133 (14.4) | 30 (17.3) | 36 (35.3) | 12 (33.3) | - | - | 169/1028 (16.4) | 42/209 (20.1) | 0.4404 |
Chilly,n (%) | 99 (10.7) | 26 (15.0) | - | - | - | - | 99/926 (10.7) | 26/173 (15.0) | 0.0992 |
Headache,n (%) | 124 (13.4) | 26 (15.0) | 6 (5.9) | 3 (8.3) | - | - | 130/1028 (12.6) | 29/209(13.9) | 0.4836 |
Nasal discomfort (congestion, overflow, runny),n (%) | 47 (5.1) | 6 (3.5) | - | - | - | - | 47/926 (5.1) | 6/173 (3.5) | 0.3652 |
Conjunctival congestion/conjunctivitis,n (%) | 5 (0.5) | 4 (2.3) | - | - | - | - | 5/926 (0.5) | 4/173 (2.3) | 0.0176 |
Hemoptysis,n (%) | 6 (0.6) | 4 (2.3) | - | - | - | - | 6/926 (0.6) | 4/173 (2.3) | 0.0344 |
Apocleisis,n (%) | - | - | 31 (30.4) | 24 (66.7) | 9/82 (11.0) | 8/57 (14.0) | 40/184 (21.7) | 32/93 (34.4) | 0.0008 |
Dizzy,n (%) | - | - | 5 (4.9) | 8 (22.2) | - | - | 5/102 (4.9) | 8/36 (22.2) | 0.0023 |
Abdominal pain,n (%) | - | - | 0 (0) | 3 (8.3) | 2/82 (2.4) | 6/57 (10.5) | 2/184 (1.1) | 9/93 (9.7) | 0.0015 |
*Symptoms such as conjunctival congestion/conjunctivitis, hemoptysis, anorexia, dizziness, and abdominal pain, etc. were documented in only some of the studies. Therefore, only studies that reported were included in the final analysis of the relevant symptoms. |
Meta-analysis results
Three high-quality studies, all of which were from China and clearly classified COVID-19 pneumonia as severe and non-severe were used for subsequent meta-analysis. When used to study fever, these studies included in total 262 cases in the severe group (245 cases with fever, 93.51%) and 1,095 cases in the non-severe group (967 cases with fever, 88.31%), and were considered to be homogeneous as they fit the fixed effect model nicely (Chi2 = 0.88, P = 0.64, I2 = 0%). The pooled effect was 1.70 (95%CI, 1.01–2.87; Fig. 2A), indicating that the incidence of fever in the severe group was 1.70 times higher than that of non-severe group. On symptoms of dyspnea, there were 262 cases in the severe group (112 dyspnea, 42.75%) and 1095 cases in the non-severe group (179 dyspnea, 68.32%). Q-test and I2 statistic test showed that certain heterogeneity exists (Chi2 = 5.26, P = 0.07, I2 = 62%), therefore the random effect model was adopted. The individual OR effect showed inconsistently that Article 1 and Article 2 show the severe patients have a higher incidence of dyspnea and Article 3 shows there is no statistically significant difference, but combined OR effect was 3.53 (95%CI, 1.95–6.38; Fig. 2B), indicating that the incidence of dyspnea in the severe group was 3.53 times higher than that of non-severe group. On symptoms of diarrhea, we included 266 cases in the severe group (25 cases with diarrhea, 9.40%) and 1,110 cases in the non-severe group (48 cases with diarrhea, 4.32%). Model test showed homogeneity among these studies (Chi2 = 0.32, P = 0.85, I2 = 0%), and therefore the fixed effect model was used. The combined OR value was 1.80 (95%CI, 1.06–3.03; Fig. 2C), indicating the incidence of diarrhea in the severe group was 1.80 times higher than that of non-severe group. Importantly, the funnel plots of fever, dyspnea and diarrhea are all largely symmetrical, suggesting no significant publication deviation exists (Fig. 3).