Abstract
Introduction:
The world has faced the pandemic of COVID-19 in March 2020 and still it continues to affect in 2021. There is a great variation about the course of the disease and its features. Hence, in the present systemic review, we intend to determine the pooled estimations in the clinical features and prognosis along with the subgroups based on the severity of the disease in various regions of the world.
Materials and Methods:
Online data were collected from the search engines of EBSCO, PubMed, Google Scholar, and Scopus. The searched terms were COVID 19, CORONA, SARS-CoV-2, clinical features, Wuhan, etc. The study articles were collected that from January 2020 to February 2021. Based on the PRISMA guidelines, a meta-analysis was performed.
Results:
A total of 5067 articles were selected, of which 176 were finalized for the study. There were a total of 11 countries that were included, with a total of 2½ lakh participants. Mean age was 47.5 years. Around 22.5% had comorbidities. The mortality was 5.5%. We observed a strong association between the medical condition of the patient and the severity of the infection. In severe cases, the most common symptoms were respiratory and gastrointestinal. The mortality was registered in those with pneumonia and end-organ failure.
Conclusion:
It can be concluded from this meta-analysis that in a fourth of the positive patients, the disease was severe. In nearly 6% of the COVID-19 patients, mortality was seen. Patients with comorbidities and the severe form of the disease should be closely monitored.
KEYWORDS: Clinical features, COVID-19, meta-analysis, outcomes, systemic review
INTRODUCTION
The world went into a state of standstill after the declaration of the pandemic COVID-19.[1] There has been no specific therapy and treatment for the COVID-19 disease. Only recently, the vaccine has been given in some countries.[2] However, till date, there has been no specific data on the clinical course and the prognosis of the disease.[3,4,5,6,7,8] In all the available studies, there were only reports of the cases observed that were admitted into the hospital or in the centers of the specific region care centers.[1,2,3,4,5,6,7,8,9]
It is clear from the present studies that there is a great variation in the sociodemographic, clinical course, and the prognosis.[9,10] A thorough understanding of these features is a necessity for proper treatment planning and establishing a strategy for facing future pandemics. Hence, in the present systemic review, we evaluate and compare the sociodemographic, clinical course, and the prognosis across regions.
MATERIALS AND METHODS
We conducted the search for the data from online sources such as “EMBASE,” “PubMed,” “Scopus,” and other sources. The study was conducted by two reviewers independently. The PRISMA guidelines were followed.[11] The articles were collected from January 2020 to February 2021. The search words are COVID, COVID19, SARS, CoV2, and PANDEMIC. The animal studies, population data, epidemiology, reviews were excluded. The heterogeneity of the analysis was studied using Cochran Q-statistic and I2 statistic with P < 0.05 for Q-statistic, I2 ≥50% as significant. Total participants, sociodemographic, study type, clinical features, and comorbidities were noted for all the studies. Based on the WHO criteria, meta-regression was performed for the factors that may impact the severity.[12,13,14] A statistical analysis was done keeping P < 0.05.
RESULTS
In the present study, 5067 articles were selected. One hundred and seventy-six studies were finalized after the deletion of the duplicates, preprints, and special categories like pregnant and pediatric cases. Studies from ten countries were included. The flowchart of the selection of articles is given in Figure 1. The clinical characteristics and other features are shown in Table 1. The mean age noted is 47.5 years. Almost equal distribution of gender was seen. Polymerase chain reaction was done for the diagnosis of the COVID-19 in almost all the cases, along with computed tomography scan and antigen tests. The incubation period was between 5 and 7 days. No significant difference was seen between the studies for the incubation period. Majority in the initial studies reported traveling history that may be a mode of transmission. There was a significant difference between the hospitalizations between the nations (P = 0.002). The fever was common in all studies; however, there seldom were reports of cold. Shortness of breath was reported in severe cases in half the patients. Gastrointestinal disturbance was seen in majority of the studies with the diarrhea as common complaint. Other significant symptoms were pain in abdomen. Chills, dizziness common in severe cases.
Figure 1.
Flowchart describing the selection of the articles
Table 1.
Sociodemographic and clinical features among the studies
| Variables | Articles | Sample | Observation | 95% clearance |
|---|---|---|---|---|
| Age/sex | ||||
| Average age | 89 | 8909 | 46.70 | 42.80-53.06 |
| Men (%) | 167 | 171,659 | 51.90 | 50.40-53.20 |
| Women (%) | 165 | 171,024 | 48.950 | 47.5-50.41 |
| Presentations | ||||
| Onset | 25 | 3507 | 5.51 | 4.60-6.40 |
| Incubation period (days) | 7.1 | 744 | 5.30 | 4.50-5.98 |
| Others (%) | ||||
| Fever | 155 | 15,921 | 78.81 | 76.21-81.2 |
| Chills | 27 | 4432 | 15.70 | 12.30-19.7 |
| Fatigue | 98 | 13,680 | 32.20 | 28.2-36.50 |
| Myalgia | 79 | 10,722 | 21.30 | 18.2-24.80 |
| Malaise | 38 | 2522 | 37.90 | 29.4-47.00 |
| Cough | 116 | 12,770 | 53.90 | 50.1-57.60 |
| Expectoration | 62 | 8745 | 24.20 | 21.1-27.17 |
| Respiration (%) | ||||
| SOB | 82 | 11,104 | 17.990 | 14.7-21.80 |
| Pain in chest | 36 | 3511 | 8.9100 | 5.92-12.91 |
| Rhinorrhea | 42 | 6171 | 6.50 | 5.6-8.60 |
| GI | ||||
| Nausea | 47 | 7483 | 4.70 | 3.8-5.80 |
| Pain per abdomen | 24 | 3351 | 3.950 | 2.93-5.920 |
| Motions | 93 | 12,148 | 8.950 | 6.98-10.95 |
| Anorexia | 31 | 3611 | 13.98 | 10.4-18.4 |
| Nausea | 37 | 5598 | 6.97 | 5.3-9.12 |
| Neurological | ||||
| Light headedness | 22 | 2351 | 8.94 | 6.91-11.9 |
| Headaches | 75 | 12,383 | 8.97 | 7.83-10.9 |
| Other diseases | ||||
| Respiratory | 32 | 785,692 | 4.0 | 2.3-6.95 |
| Cancer | 47 | 8732 | 3.312 | 1.60-4.2 |
| Diabetes | 74 | 84,262 | 10.2 | 7.4-13.9 |
| Kidney | 31 | 81,472 | 6.8 | 1.2-6.1 |
| Hypertension | 75 | 9921 | 19.4 | 17.3-21.6 |
| Liver | 33 | 79,522 | 3.3 | 1.7-6.3 |
| Cardiac | 51 | 82,212 | 5.9 | 2.9-12.6 |
| Clinical course and outcomes | ||||
| Heart injury | 11 | 1485 | 9.40 | 3.5-12.8 |
| Kidney injury | 15 | 77,666 | 3.60 | 2.2-12.1 |
| Death | 86 | 52,802 | 5.60 | 3.2-6.5 |
| Liver injury | 11 | 77,352 | 7.90 | 1.6-11.7 |
| Shocks | 11 | 2981 | 4.30 | 3.3-6.9 |
| ICU | 39 | 80,489 | 10.95 | 1.6-27.6 |
| Ventilator | 36 | 6155 | 7.10 | 3.5-10.0 |
SOB: Shortness of breath, ICU: Intensive care unit, GI: Gastrointestinal
The pooled data show ~11% admissions in intensive care unit (ICU) and nearly 6.8% requiring ventilators. Approximately one-fourth of the patients had severe disease [Figure 2a and b]. Among those with the severe disease, the aged male people were significantly more (P < 0.0001). A significant association was seen between diabetes, hypertension, malignancy, renal diseases, organ failure, and the severity [Figure 2c]. The mortality was ~ 6%, and there was a difference significantly seen among the countries, P < 0.0001 [Figure 2d].
Figure 2.
(a) Distribution of Admitted to intensive care unit in various countries. (b) Distribution of requirement of ventilators among countries. (c) Distribution of severity among countries. (d) Distribution of mortality among countries
When laboratory investigations were assessed, the serum creatinine, lactate dehydrogenase, C-reactive protein, white blood cell, neutrophil count, alanine aminotransferase, aspartate aminotransferase, and procalcitonin were consistently high in the severe than moderate patients. However, the lymphocytes were lower. Similarly, they were higher in mortality cases also.
Meta-regression depicted a significant association between disease severity and various factors. These factors are diabetes, abdominal pain, immunosuppression, and malignancy [Table 2]. In those with, mortality was reported a significant presence of comorbidities and higher age along with ARDS, renal failure, cardiomyopathies, and lung infections [Table 3].
Table 2.
Association of the COVID-19 and severity
| Factors | Coefficients | 95% clearance | Significance |
|---|---|---|---|
| Diabetes | 23.41 | 14.99-31.70 | <0.0001 |
| Neutrophil count (g/L) | 0.61 | 0.1-0.91 | 0.00080 |
| Albumin | −lbum | −lbumin1g/ | 0.00091 |
| Immunosuppressed | 53.90 | 31.3-76.40 | <0.0001 |
| CVD | 18.62 | 1.6-26.60 | 0.02 |
| HT | 4.11 | 2.1-8.11 | 0.01 |
| Nausea | 10.32 | 0.20-19.70 | 0.050 |
| Pain per abdomen | 24.71 | 17.4-31.91 | <0.0001 |
| Lymphocytes | −ymph | −ymphocyt | 0.040 |
| SOB | 5.40 | 4.1-6.71 | <0.0001 |
| CRP | 0.021 | 0.01-0.141 | 0.0070 |
| Malignancy | 23.41 | 9.9-36.90 | 0.00070 |
CVD: Cardiovascular disease, CRP: C-reactive protein, SOB: Shortness of breath, HT: Hypertension
Table 3.
Association of the COVID-19 and mortality
| Variables | Coefficients | 95% clearance | Significance |
|---|---|---|---|
| Age | 0.051 | 0.02-0.08 | 0.0005 |
| Men | 4.12 | 1.4-6.90 | 0.00010 |
| SOB | 2.80 | 1.0-4.61 | 0.0021 |
| HT | 6.97 | 3.3-10.7 | 0.0002 |
| DM | 7.21 | 1.4-173.99 | 0.006 |
| Chills | 5.80 | 2.8-8.91 | 0.00020 |
| Fatigue | 2.50 | 0.5-4.50 | 0.01 |
| Pyrexia | 2.90 | 0.2-5.70 | 0.04 |
| Cough | 2.10 | 0.2-4.11 | 0.03 |
| Kidney injury | 14.40 | 9.0-19.80 | <0.0001 |
| Pneumonia | 11.70 | 5.9-17.50 | <0.00010 |
| Malaise | 2.70 | 0.7-4.80 | 0.0097 |
| Diarrhea | 3.40 | 0.01-6.90 | 0.051 |
| Heart failure | 6.20 | 2.3-10.11 | 0.0021 |
| ARDS | 6.10 | 4.5-7.60 | <0.0001 |
| Shock | 23.30 | 13.7-32.90 | <0.0001 |
| Respiratory failure | 2.50 | 0.4-4.60 | 0.021 |
| TWBC (g/L) | 0.30 | 0.07-0.60 | 0.010 |
| ALT (U/L) | 0.060 | 0.01-0.100 | 0.010 |
| Total bilirubin (µmol/L) | 0.20 | 0.01-0.40 | 0.040 |
| Lymphocyte count (g/L) | −ymph | −ymphocyte | 0.0010 |
| AST (U/L) | 0.030 | 0.01-0.050 | 0.002 |
| Albumin (g/L) | −lbum | −lbumin (g | <0.0001 |
| LDH (U/L) | 0.010 | 0.00-0.002 | 0.007 |
| Procalcitonin (ng/mL) | 2.10 | 0.7-3.50 | 0.0041 |
| NC (g/L) | 0.50 | 0.3-0.80 | <0.0001 |
| Creatinine (μmol/L) | 0.030 | 0.01-0.050 | 0.0005 |
| CRP (mg/L) | 0.040 | 0.02-0.051 | <0.0001 |
| BUN (mmol/L) | 0.40 | 0.09-0.60 | 0.009 |
| CK (U/L) | −K (U/ | −K (U/L) 0/L)μ | 0.0032 |
| PT (s) | 0.40 | 0.01-0.80 | 0.041 |
| Antibiotic usage | 4.10 | 2.9-5.40 | <0.0001 |
| Corticosteroids usage | 4.30 | 2.6-6.11 | <0.0001 |
| IgG | 2.60 | 0.7-6.40 | 0.010 |
| ICU | 4.10 | 2.0-7.21 | ≤0.0001 |
HT: Hypertension, DM: Diabetes mellitus, CRP: C-reactive protein, SOB: Shortness of breath, ALT: Alanine aminotransferase, TWBC: Total white blood cell counts, AST: Aspartate aminotransferase, LDH: Lactic dehydrogenase, BUN: Blood urea nitrogen, PT: Prothrombin time, IgG: Immunoglobulin G, NC: Neutrophil count, ICU: Intensive care unit, CK: Creatine kinase
DISCUSSION
In the present meta-analysis a total of 176 articles were taken around the world that includes 10 countries. Maximum data is from the West. A total of nearly 2.5 lakh patients were included. It was observed that middle-aged men were at higher risk of contracting the disease. This distribution was similar in all the countries. The disease severity was seen in 22.5% of the cases, and similarly, mortality was seen in nearly 6% of the cases. The maximum severity and mortality of the patients was seen in Wuhan followed by European countries. In the severe cases also, men were slightly greater than women and of middle age.
Within these infected patients, the comorbidities such as diabetes, hypertension, malignancy, renal diseases, and organ failure were seen more as the severity increased. Hence, these patients may be identified at the earliest diagnosis, and proper attention be given to them.
The pooled average time of onset to hospitalization was 6 days averaging between 5 and 7 days. A greater number of ventilator support and ICU admissions were seen in China than other regions. This is obvious with the strain first spreading in China. This also suggests us that the early identification will prevent the loss of life and prevent the burden on the health-care workers.
We observed that though an uncommon symptom, the pain in the abdomen was associated with the severe disease, and it was significant. Not only that these patients are to be watched cautiously also in the patients with lower counts of lymphocytes and levels of albumin have been associated with quick progress to severity. It can be proposed from our study that in the poor nutritional status, the disease severity and mortality were greater as seen in the levels of albumin. Furthermore, this view is supported by the greater number of patients with severity of disease in those with lower nutritional diet like in old-age homes where greater mortality was reported.[15] Hence in those patients who have lower immunity and nutrition they must be closely monitored for the progression of the disease. The health systems have to mobilize in these areas where facilities may be low.[16] Additional research has to be done in this area to know the exact association between these variables and the outcome.
There were few limitations in our study. We were unable to classify the age groups as there were data with no specific age group classification. It is expected to have unreported cases that are higher than registered. Furthermore, the estimate that we have presented in the study is from the clinical setup and hence might be overestimated.[17] In a recent study, the mortality was as high as 22%.[18] This was reported in the USA. Another limitation in the present review and meta-analysis was that higher than normal routine clinical presentations may have been reported as we considered the clinical reports as well. Hence, there might have been a bias toward an increased report of the mortality. We took care to include the studies with >50 patients. The various systems and protocol of the reporting of the death in case of the COVID-19 may have led to the variation among the nations. There may be reported death that may have been considered as the direct cause of the COVID-19. The deaths happening in these patients may have been missed. This could lead to a bias in the actual number of mortalities and risks associated with it.
Accordingly, a general definition has to be established to define COVID deaths. The general criteria to conclude as a death due to COVID have to be given. This is essential for the nations to establish management strategies in handling the pandemic for the health department. This may be different for the different countries. Some of the studies considered in our analysis were hospital based that may have reported critical and severe cases that may lead to increased mortality rates in their studies. This may not be generalized to the population as many are asymptomatic or mild.
Ultimately, with the rapid spread of the pandemic in various countries, there have been new studies with respect to the probability of the second and third waves. A much detailed analysis with the latest data and the consideration of all the types of cases has to be collected for a better understanding and strategic planning.
CONCLUSION
It can be concluded from this meta-analysis that in a fourth of the positive patients, the disease was severe. In nearly 6% of the COVID-19 patients, mortality was seen. Patients with comorbidities and the severe form of the disease should be closely monitored. These data from this study may be used to educate health workers and policymakers to better face any pandemic while still facing the current one. This may also help in identification of the risk groups.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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