Clinical manifestation, laboratory and radiology finding, treatment and outcomes of COVID-19: A systematic review and meta-analysis
Nahid Dehghan Nayeri1, Javad Nadali2, Anahita Divani1, Mohammad Hasan Basirinezhad3, Mohsen Meidani4
1 School of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran, Iran
2 School of Nursing and Midwifery, Shahroud University of Medical Sciences, Shahroud, Iran
3 Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Infectious Diseases and Tropical Medicine, Imam-Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
|Date of Submission||12-Aug-2020|
|Date of Decision||04-Oct-2020|
|Date of Acceptance||19-Jan-2021|
|Date of Web Publication||30-Jun-2021|
[email protected] Mohsen Meidani
Department of Infectious Diseases and Tropical Medicine, Imam-Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran
Source of Support: None, Conflict of Interest: None
Background: Since December 2019, coronavirus (COVID-19) spread throughout the world. The high rate of infection and its unknown nature led specialists to report the condition of patients. The aim of this study is to systematically review of symptoms, laboratory and radiologic findings, treatment, and outcomes of patients with COVID-19. Materials and Methods: Databases such as PubMed, Embase, Scopus, Web of Science, Google Scholar, and Cochrane were searched. Finally, 46 articles were appropriate for the aim of the study. After quality evaluation, the necessary data were extracted and meta-analysis was performed. Results: 4858 articles were retrieved until March 30, 2020. After screening, the full-text of 46 articles was assessed. Of the reported cases, 31.7% had no comorbidities, 21.4% had high blood pressure, 70.6% had fever, and lymphopenia was reported in 55.2% of patients. For 16% bilateral patchy shadowing in radiography and for 51% ground-glass opacity was reported. Outcomes were remarkable for recover to death. Conclusion: COVID-19 leads to healthcare problems for countries. Nonspecific symptoms have made it difficult for differential diagnoses without computed tomography-scan or corona Test, but they are not available in many countries. Therefore, this systematic review can help health care staff to make decisions based on symptoms, treatments, and outcomes..
Keywords: COVID-19, coronavirus, meta-analysis, SARS-CoV-2
|How to cite this article:|
Nayeri ND, Nadali J, Divani A, Basirinezhad MH, Meidani M. Clinical manifestation, laboratory and radiology finding, treatment and outcomes of COVID-19: A systematic review and meta-analysis. J Res Med Sci 2021;26:41
|How to cite this URL:|
Nayeri ND, Nadali J, Divani A, Basirinezhad MH, Meidani M. Clinical manifestation, laboratory and radiology finding, treatment and outcomes of COVID-19: A systematic review and meta-analysis. J Res Med Sci [serial online] 2021 [cited 2021 Nov 27];26:41. Available from: https://www.jmsjournal.net/text.asp?2021/26/1/41/320517
| Introduction|| |
Recently, a family of viruses with developed and special genome called human coronaviruses has been responsible for a large number of respiratory system diseases. Currently, these viruses are known as one of the main causes of severe respiratory diseases such as bronchitis and bronchiolitis and pneumonia in children, young people, and adults. Six types of coronaviruses have already been identified. Over the past two decades, many people have died from these viruses, ranging from 10% severe acute respiratory syndrome-related coronavirus (SARS-CoV) to 37% Middle East respiratory syndrome-related coronavirus (MERS-CoV). Furthermore, these viruses are known as nosocomial infection agents and impose exorbitant costs to health systems.
Despite the world's familiarity with these types of viruses, in December 2019, a series of cases of pneumonia with unknown etiology emerged in Wuhan, China, which the early symptoms were greatly similar to viral pneumonia. However, a closer examination and analysis of lower lung samples revealed that a type of coronavirus (nCOV) is the cause of the symptoms. This virus is named new coronavirus 2019 or COVID-19 by the WHO. This time, the issue was quite different from previous times. The concern was not related to the mortality rate (MR) from the virus, rather it was about the high rate of its transmission. Furthermore, it was not known how to deal with this disease because of a lack of knowledge.
Despite the lower MR of this virus in comparison with its families, it is worrying due to its high prevalence and contagion so that the number of deaths and infections is very remarkable. Among 1,039,158 people have been infected with this virus in the world until April 4, 2020, 55,163 participants of them died.
Coronaviruses exhibit high resistance in the environment. This feature has made it difficult to control and prevent the disease. Furthermore, the rapid spread and transmission of this virus have caused worldwide concern. Until now more than 200 countries reported to have been infected by this virus and many patients have died. On the other hand, according to the Centers for Disease Control and Prevention report, the incubation period of 2019-nCov is 2–14 days and has recently mentioned this period can also be very momentous in the virus transmission.
Due to the mentioned features of this virus, this worldwide outbreak calls for faster and wisely control by countries. For more effective control and prevention, recognizing the sign and symptoms of the patients in different periods of illness and isolating them plays an important role. However, a variety of symptoms have been mentioned so far, some only just have been added such as Anosmia, hyposmia, and ageusia., Furthermore, symptoms of fever, dry cough, and fatigue in the early stages without the typical symptoms of acute respiratory disease, and later pneumonia-like symptoms, gastrointestinal symptoms such as diarrhea with virus excretion (up to several weeks) and in some cases, central nervous system involvement such as multiple sclerosis has been reported. Although some of the clinical manifestations of SARS, MERS, and COVID appears to be similar, distinct symptoms have also been reported in some patients, so faster differential diagnosis is required for treatment.,,,
Laboratory findings of patients infected by COVID-19 showed lymphopenia and leukopenia. Furthermore, findings of chest computed tomography (CT) scan showed bilateral abnormalities in lung lobes, which are very similar to symptoms of influenza and other respiratory viruses. This pattern made it more difficult to early differential diagnosis., Other laboratory findings showed increased prothrombin time, increased D-dimer, increased liver enzymes, and increased cardiac enzymes in some cases. Pro calcitonin level was reported mostly normal, although these reports were contradictory in different studies.,,
Although viral diseases usually have an overestimated MR in the early stages, issues are different this time. MRs are rising rapidly as a result of severe contagion, world outbreak, and lack of differential diagnosis and lack of appropriate and specific treatment.
However, many countries are facing lack of facilities such as laboratory testing and sampling, hence priority is given only to subjects with very severe symptoms while recognizing symptoms and their incidence and frequency can have an effective role in the subsequent control of the disease. Since various symptoms have been mentioned in the studies, a systematic review is required to provide a conclusion for health and policymakers.
Likewise, there is no specific treatment for the disease so far, and various countries are trying different drugs and sometimes combinations therapy., The efficacy of these drugs has not been systematically investigated by using patient-centered outcomes such as MR, discharge of hospital, and remission. Therefore, this study was conducted with the aim of recognizing the specific symptoms of COVID-19 as well as its treatments and outcomes as a systematic review with meta-analysis.
| Methods|| |
Data sources and search strategy
Based on the PRISMA guide (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), we used an evidence-based model for framing a PICO question model (PICO: Participants, Intervention, Comparison, and Outcomes). The questions posed was the following: What are the symptoms of patients with patients with COVID-19? What are laboratory and radiologic findings in patients with COVID-19? What are the treatments for COVID-19? What are the outcomes of patients with COVID-19? (P) Participants: Patients with COVID-19.(I) Intervention: Treatments performed in patients with COVID-19.© Comparison: Not applicable. (O) Outcomes: Hospitalization, recovery, death.
Since the primary purpose of this study was to conclude of the articles that listed the symptoms or treatments of COVID-19, all valid databases were searched. A broad search was attempted and the search restrictions were moved to include the maximum number of articles in the study without missing any valuable and related article. Then, duplicate entering studies from various databases were removed. After that, all of the titles were read and unrelated articles were deleted.
We search databases- PubMed, Embase, Scopus, Google Scholar, web of sciences, and Cochrane with keywords included coronavirus, COVID 19, symptoms, signs, treatments, outcomes. No time limits were set for searches. However, since the emergence of the disease was in January 2020; the first articles were found on this time; and no studies had been done before. Therefore, all studies before that time were excluded after evaluating the titles. [Diagram 1] shows the flow of assessing studies. Selection criteria and data extraction. Due to the emergence of the disease and to obtain the maximum possible knowledge, there was no restriction on the type of articles in the searching level. However, all the descriptive and analytical studies as well as the observationally reported interventional studies were included in the study. The search keywords and how each site was searched along with the number of articles are listed in [Table 1]. All studies were included until March 30, 2020.
All articles were assessed based on authors, place of study, sample number, study design, patient characteristics, and symptoms. Furthermore, laboratory findings and treatments used for patients were evaluated completely. Studies lacking the essential components required by the current study objective were excluded from the systematic review; such as being a case report; not mention the definitive diagnosis of COVID-19 with either laboratory tests or definitive symptoms. Furthermore, some articles were removed because they have not assessed symptoms entirely or only, they mentioned one or two nonspecific symptoms.
Finally, all of 46 remaining articles were reviewed by two reviewers (J. N, A, D) independently and screened studies to identify all potentially eligible studies using the JBI Quality Assessment Tool, whose ratings are included in the [Supplementary Table 1].
In this stage, data extracted from all articles were entered into STATA Version 16.0 software (StataCorp LLC Production, College Station, Texas, USA) software for meta-analysis and providing general conclusions about the symptoms and treatments. It should be noted that the heterogeneity of the studies was evaluated according to different symptoms, laboratory findings and treatments, and most of the criteria were heterogeneous in the studies. The Q and tests were used to investigate heterogeneity. Since the articles are heterogeneous, the random model has been used by the maximum likelihood estimation method. To describe each of the signs and symptoms, the ratio and confidence interval (CI) of 95% have been reported.
| Results|| |
In this systematic review, 46 articles remained after the final evaluation.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, The majority of articles were case series (73.3%), 25.7% were descriptive retrospective and <1% were descriptive prospective or epidemiological reports. Although most of the articles were originated in China, other articles–about 5%-were from countries such as Japan, the USA, Australia, France, and Taiwan. Besides, 44.5% of articles were published in March 2020. The characteristics of the studies have presented in [Table 2].
|Table 2: Baseline characteristics of all the studies included in the meta-analysis|
Click here to view
The total number of patients reported in these articles was 5570. Slightly more than half of the patients were male (52.74%); and the mean age of the patients was 53.2 (CI: 50.17–56.33) year. The incubation period was reported between 0 and 24 days. Half of the patients reported contact with Chinese people, 15.56% had contact with patients, and 5.94% were exposed to the Huanan seafood market. Moreover, only 1.79% mentioned that they haven't had any contact.
It should be noted that only some articles have dealt with coexisting disorders or clinical characteristics. For example, 16 articles cited coexisting disorders, in which 38% (n = 2969) subjects were present, of which 31.7% had no coexisting disorders. About 21.4% of patients had hypertension (CI = 0.18–0.27); 10.8% had endocrine disorder especially diabetes mellitus (CI = 0.009–0.13); 8.1% had cardiovascular disease (CI = 0.08–0.13); 3.8% had chronic obstructive pulmonary disease or other respiratory diseases (CI = 0.03–0.05); 4.7% had cerebrovascular disease (CI = 0.04–0.07);12.6% had a history of previous surgery (CI = 0.02–0.10); and 6.3% had digestive system disease.
The highest clinical characteristic (about 96% of the total number of patients surveyed) assessed was coughs. They reported that 60.5% of subjects (CI = 0.53–0.63) had dry coughs. However, expectoration and Sputum production was reported in 23.3% (CI = 0.18–0.31). As well as, about 15.8% reported chest pain (n = 225/1419). In this section, the sensitivity of the symptoms was not considered and only the prevalence of symptoms in patients was examined.
The second clinical characteristic (about 94%, equivalent to 5234 people) studied was the temperature which 70.6% of them fever was reported. However, only 5% of subjects had fever >39°. The forest plot of fever is shown in [Figure 1].
Moreover, 21.1% had a fever <37.5°. Feeling ill, malaise or severe fatigue and weakness had 35.7% prevalence. Shortness of breath/dyspnea existed only in 22.2%. Poor appetite and anorexia were prevalent in about one fourth of patients (23.6%), although, this symptom was examined in only 24% of subjects. Also, 18.5% reported myalgia and 11.1% had headache. Sore throat or pharyngalgia was about 12.2%.
Other signs and symptoms were rigor/chill (12%); diarrhoea/loose bowel movement (9.5%); rhinorrhoea/nasal congestion or sneezing/snotty nose (6.9%); nausea/vomiting (7.5%); dizziness (10.1%). Confusion/loss of consciousness was another important symptom that only assessed 7.7% of patients and 11.65% reported it. Other symptoms reported were tonsils well (2.09%); hmoptysis (1.8%); and hypogeusia/hyposmia (5.1%).
Other signs and symptoms were examined in few patients or they had a lower prevalence including conjunctivitis, abdominal pain, back pain, ataxia, and wheeze. The results of the sensitivity analysis are shown in [Supplementary Table 2].
One of the most important laboratory findings in COVID-19 is SpO2. However, only one study has reported this measure with 82 samples that 32.9% had Spo2 between 85% and 94% and 10.1% had Spo2 <85. No one had normal Spo2.
WBC counts were among the most important laboratory criteria; studies reported 58.7% of samples had normal range (3.5–9.5 count, ×109/L) and 24% <3.5 and 10.2% more than 9.5. For half of the samples were reported lymphocytes counts in the normal range (1.1–3.2 count, ×109/L) and 55.2% below normal and only 13.7% above normal. Half of the patients had normal platelet counts, 21.9% had less than normal; and 5.5% (38/681) had platelet more than >350.
As well, ten articles measured Creatine kinase-about 2000 patients-and reported that 10% have been above creatine kinase normal range (171 U/L). In 15 articles which evaluated 2276 patients reported that D-dimer of 26.5% of patients has been >500 mg/l., but an article reported D-dimer in a normal range when they measured 51 people.
Criteria such as erythrocyte sedimentation rate (ESR), Fibrinogen, creatine kinase MB, PT, PTT, BUN, Na, K, and Chloride were reported in a small number of articles, the abnormal rate of which was not noteworthy. Other laboratory findings are shown in [Table 3]. The forest plot of C-reactive protein has displayed in [Figure 2].
|Table 3: Laboratory findings and abnormalities in patients with coronavirus disease 2019|
Click here to view
Because one of the organs involved in the COVID-19 disease is the lungs, chest radiography and CT-Scan can show the involvement of this tissue. Therefore, some studies have addressed this issue in addition to laboratory findings and symptoms. However, various studies showed different features. Three studies reported bilateral patchy shadowing in 16% (193/1202) in radiology and 18 studies showed Ground glass opacity (GGO) on 51.6% (1579/3055) patients in the CT-scan. The forest plot of GGO is presented in [Figure 3]. Other radiologic features are shown in [Table 4].
|Figure 3: Forest plot of ground-glass opacity in computed tomography scan|
Click here to view
COVID-19 is an emergent disease and no specific treatment has been well-known for it, therefore different drugs were used in combination. Oxygen therapy is the first and popular treatment as mentioned Spo2 is decreased in the patients. Antiviral such as oseltamivir, lopinavir/ritonavir (Kaletra), darunavir/cobicistat, and Arbidol were used. Other medications used for COVID-19 are shown in [Table 5].
Although medical staff have tried to provide the best available treatment for patients with COVID-19 severe complications that happened in some of the patients, and has even led to mortality. Some of the most important complications mentioned in the articles are: 22.9% acute respiratory injury/acute respiratory distress syndrome (448/1995); 11.2% septic shock (93/826); 35.1% electrolyte disorder (109/310); 13.6% Disseminated intravascular coagulation (63/461); 10.3% liver disorder (133/1288), and 14.4% ventilator-associated pneumonia (31/215).
Different outcomes have been recorded after getting the disease in the studies including discharge 23% (549/2381); hospitalization 76.9% (1767/2297); recovery 24.1% (493/2042); death 12.4% (311/2502).
| Discussion|| |
This study investigated systematically physical symptoms and signs, as well as laboratory and radiological findings and treatment in published studies on patients with COVID-19. Despite the new emergence and lack of confirmed knowledge of the symptoms of the disease and the ways of treatment, many studies have been done on patients with COVID-19 during their physical examination and treatment. In addition to their therapeutic duties, specialists from different countries have provided detailed reports on the patients' condition and their outcomes, as evidenced by the publication of several thousand articles in this field. Despite a lot of articles in this regard, it was tried to observe all of the principles and procedures of systematic review with high quality; so that the studies were evaluated carefully in terms of quality and relevance with the intention of the studies that remained for the final review be valid and invaluable. Hence, 46 articles remained in the final stage. These articles were all reviewed for quality and they were worthy to study.
Slightly more than half of the patients were male. However, studies were heterogeneous (CI = 0.49–0.54; P < 0.001). Given that men have social attendance and COVID-19 is contagious, this can be a possible sensible explanation. Contact with Chinese people was the most reason of transmission, which was expected due to the initial emergence of the disease in China and the most of published papers were from this country.
In this study, most of the studies confirmed the presence of comorbidities in patients with COVID-19. The comorbidities were confirmed not only in COVID-19 but also in previous influenza viral infections such as MERS and H1N1.,
The most common symptoms reported were dry cough and fever. These symptoms and the extent of involvement contain important messages. The fact that fever has been reported in two-thirds of patients, and only one-tenth of patients had a fever above 39°C, raises doubts about the use of temperature to separate and quarantine of patients.
Many of the other symptoms are not specific to COVID-19, and they are similar to other virus infections in this family and other viruses that make it difficult to differentiate. However, it is recommended that protective measures be taken even in suspicious cases and the symptoms be considered corona to prevent further spread. Symptoms such as feeling ill, malaise or severe fatigue or weakness, and dyspnea are also seen in other flu and pneumonia.,, Sore throat or pharyngalgia and rhinorrhea, Nasal congestion, sneezing and snotty nose, as well as rigor/chill are also nonspecific symptoms and have been reported with other influenza and common cold.,,
Myalgia and headache have also been reported in other pneumonia with other origin. Furthermore, symptoms such as dizziness and confusion/loss of consciousness have been reported before the emergence of COVID-19.,, Poor appetite, anorexia, nausea/vomiting, and diarrhea/loose bowel movement are also common symptoms of other viral infections and pneumonia.,,
Laboratory findings suggest that arterial blood saturation is significantly reduced. This finding has also been observed in other pneumonia due to lung tissue damage. Both lymphopenia and lymphocytosis were found in patients. Meanwhile, half of the patient had lymphopenia, while slightly more than one-tenth had Lymphocytosis. This discrepancy can go back to the time of measurement. As the disease progresses, the risk of lymphopenia increases. Some studies confirmed that lymphopenia is a frequent finding in hospitalized patients with community-acquired pneumonia (CAP), affecting approximately 50% of the patients and it is associated with a deregulated immune response, increased severity, and mortality. Some authors suggested that is lymphocytosis evidence of active inflammation in pneumonia.
Although other studies have shown that monocyte was positively correlated with ESR and negatively with body temperature, in the current studies, this correlation has not been evaluated.
The study revealed the platelet counts of one-fifth of evaluated people were lower than normal; it has been noted in other studies so that a study indicated that an increase in mean platelet measurements during admission can predict the prognoses of patients with pneumonia and related to poor outcomes. However, in the current study, only 5.5% had more platelet.
Creatine kinase was also reported to be high in 10% of those measured. This is consistent with other infections that lead to pneumonia. D-dimer was measured in only one article; however, more than a quarter of patients had a high rate of that. However, a study has shown in CAP patients, a D-dimer >2 μg/mL was risk factor associated with in-hospital mortality.
Radiological findings included chest X-ray (CXR) and CT scan of patients in current studies have shown lung tissue involvement. Chest CT scan can be performed after the detection of abnormalities in CXR. Combination of radiological findings with clinical manifestations can lead to better clinical judgment. In current studies, some have shown bilateral patchy shadowing or GGO in CT scans of the lungs. In a multicentre study, this feature has also been confirmed. It showed a mixed and diverse pattern with both lung parenchyma and the Interstitial involved. Another modality is chest CT-scan. It can be ordered in suspected cases with typical symptoms at the first step, or it can be performed after the detection of any abnormalities in CXR.
Therapies in the studies indicated that specialists have used various combination therapies in addition to oxygen therapy. They were usually a combination of antiviral, antibiotic, and miscellaneous treatments. Nevertheless, more specific treatments have been given for other pneumonia or viral infections because of more comprehensive knowledge and broader research.,
| Conclusions|| |
Up to the present, the studies of COVID-19 usually have been observational, and experts have reported them along with their medical prescriptions. Nevertheless, research is ongoing and new signs and symptoms of the disease are being identified. However, the results of the current study could be useful because it showed the most popular symptoms and the validity of them for identifying and isolating patients. Because some symptoms, such as fever, occur in only two-thirds of people, they are not a good measure of isolation and more measures should be done. Although CT scan is a valid test for detecting the typical pattern of COVID-19 pneumonia, in the early stages of the disease is not recommended since in this period CT scan of lungs may be completely normal. Furthermore, in other forms of COVID-19 which affect organs other than the respiratory system, CT scan is not a valuable diagnostic test.
Further studies in European countries, the United States, and Asia are needed to identify new dimensions of the disease; therefore, systematic reviews can be done regularly.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| Supplementary Tables|| |
| References|| |
Geller C, Varbanov M, Duval RE. Human coronaviruses: Insights into environmental resistance and its influence on the development of new antiseptic strategies. Viruses 2012;4:3044-68.
Tang Q, Song Y, Shi M, Cheng Y, Zhang W, Xia XQ. Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition. Sci Rep 2015;5:17155. doi: 10.1038/srep17155; https://www.nature.com/articles/srep17155
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al
. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
Kobayashi T, Jung SM, Linton NM, Kinoshita R, Hayashi K, Miyama T, et al
. Communicating the risk of death from novel coronavirus disease (COVID-19). In: Multidisciplinary. J Clin Med 2020;9:580. doi: 10.3390/jcm9020580; https://www.mdpi.com/2077-0383/9/2/580
Peters A, Vetter P, Guitart C, Lotfinejad N, Pittet D. Understanding the emerging coronavirus: What it means for health security and infection prevention. J Hosp Infect 2020;104:440-8.
Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R, et al
. Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: Experts' consensus statement. World J Pediatr 2020;16:223-31.
Bagheri SHR, Asghari AM, Farhadi M, Shamshiri AR, Kabir A, Kamrava SK, et al
. Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak. Med J Islam Repub Iran 2020;34:62. doi: 10.34171/mjiri.34.62. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500422/
. [Last accessed on 2020 Apr 12].
Recalcati S. Cutaneous manifestations in COVID-19: A first perspective. J Eur Acad Dermatol Venereol 2020;34:e212-3.
Al-Tawfiq JA, Zumla A, Memish ZA. Travel implications of emerging coronaviruses: SARS and MERS-CoV. Travel Med Infect Dis 2014;12:422-8.
Tian S, Chang Z, Wang Y, Wu M, Zhang W, Zhou G, et al
. Clinical characteristics and reasons of different duration from onset to release from quarantine for patients with COVID-19 Outside Hubei province, China. medRxiv 2020. [Preprint]. doi: 10.1101/2020.03.21.20038778.
Tian S, Hu N, Lou J, Chen K, Kang X, Xiang Z, et al
. Characteristics of COVID-19 infection in Beijing. J Infect 2020;80:401-6.
Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, et al
. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J Med Virol 2020;92:797-806.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al
. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.
Hutton B, Catalá-Lépez F, Moher D. The PRISMA statement extension for systematic reviews incorporating network meta-analysis: PRISMA-NMA. Med Clin (Barc) 2016;147:262-6.
Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al
. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA 2020;323:1612-4.
Cao J, Hu X, Cheng W, Yu L, Tu WJ, Liu Q. Clinical features and short-term outcomes of 18 patients with corona virus disease 2019 in intensive care unit. Intensive Care Med 2020;46:851-3.
Cao W. Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei. medRxiv 2020. [Preprint]. doi: 10.1101/2020.02.23.20026963.
Chany C, Moscovici O, Lebon P, Rousset S. Association of coronavirus infection with neonatal necrotizing enterocolitis. Pediatrics 1982;69:209-14.
Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al
. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ 2020;368:m1091.
Duan Q, Guo G, Ren Y, Shang H, Du J, Li M, et al
. Treatment outcomes, influence factors of 116 hospitalized COVID-19 patients with longer/prolonged treatment course in Wuhan, China. Lancet 2020;116. [Preprint]. doi: 10.2139/ssrn.3550017.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al
. Clinical characteristics of 2019 novel coronavirus infection in China. N Engl J Med 2020;382:1708-20.
Hsih WH, Cheng MY, Ho MW, Chou CH, Lin PC, Chi CY, et al
. Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan. J Microbiol Immunol Infect 2020;53:459-66.
Hu Z, Song C, Xu C, Jin G, Chen Y, Xu X, et al
. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci 2020;63:706-11.
Huang Y, Tu M, Wang S, Chen S, Zhou W, Chen D, et al
. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis. Travel Med Infect Dis 2020;4:101606. [Epub 1477-8939]. doi: 10.1016/j.tmaid.2020.101606.
Huang Y, Zhou H, Yang R, Xu Y, Feng X, Gong P. Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China. medRxiv 2020. [Preprint]. doi: 10.1101/2020.02.27.20029009.
Inui S, Fujikawa A, Jitsu M, Kunishima N, Watanabe S, Suzuki Y, et al
. Chest CT findings in cases from the cruise ship “Diamond Princess” with coronavirus disease 2019 (COVID-19). Radiology 2020;22:e204002. doi: 10.1148/ryct.2020200110. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233452/
. [Last accessed on 2020 Apr 10].
Jian-Ya G. Clinical characteristics of 51 patients discharged from hospital with COVID-19 in Chongqing, China. medRxiv 2020. [Preprint]. doi: 10.1101/2020.02.20.20025536.
Jin X, Lian JS, Hu JH, Gao J, Zheng L, Zhang YM, et al
. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut 2020;69:1002-9.
Li K, Wu J, Wu F, Guo D, Chen L, Fang Z, et al
. The clinical and chest CT features associated with severe and critical COVID-19 pneumonia. Invest Radiol 2020;55:327-31.
Li X, Wang L, Yan S, Yang F, Xiang L, Zhu J, et al
. Clinical characteristics of 25 death cases with COVID-19: A retrospective review of medical records in a single medical center, Wuhan, China. Int J Infect Dis 2020;94:128-32.
Liang Y, Liang J, Zhou Q, Li X, Lin F, Deng Z, et al
. Prevalence and clinical features of 2019 novel coronavirus disease (COVID-19) in the Fever Clinic of a teaching hospital in Beijing: A single-center, retrospective study. medRxiv 2020. [Preprint]. doi: 10.1101/2020.02.25.20027763.
Lin Y, Ji C, Weng W, Xu P, Hu Y, Liang W, et al
. Epidemiological and Clinical Characteristics of 124 Elderly Outpatients with COVID-19 in Wuhan, China. medRxiv 2020. [Preprint]. doi: 10.1101/2020.03.09.20033118.
Liu J, Ouyang L, Guo P, sheng Wu H, Fu P, liang Chen Y, et al
. Epidemiological, clinical characteristics and outcome of medical staff infected with COVID-19 in Wuhan, China: A retrospective case series analysis. medRxiv 2020. [Preprint]. doi: 10.1101/2020.03.09.20033118.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al
. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.
Lo IL, Lio CF, Cheong HH, Lei CI, Cheong TH, Zhong X, 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;16:1698-707.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al
. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-90.
Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, et al
. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clin Infect Dis 2020. doi: 10.1093/cid/ciaa270.
Qian GQ, Yang NB, Ding F, Ma AH, Wang ZY, Shen YF, et al
. Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series. QJM 2020;113:474-81.
Qin X, Qiu S, Yuan Y, Zong Y, Tuo Z, Li J, et al
. Clinical Characteristics and Treatment of Patients Infected with COVID-19 in Shishou, China. China 2020. [Preprint]. doi: 10.2139/ssrn.3541147.
Bernard Stoecklin S, Rolland P, Silue Y, Mailles A, Campese C, Simondon A, et al
. First cases of coronavirus disease 2019 (COVID-19) in France: Surveillance, investigations and control measures, January 2020. Euro Surveill 2020;25:2000094. doi: 10.2807/1560-7917.ES.2020.25.6.2000094.
Tabata S, Imai K, Kawano S, Ikeda M, Kodama T, Miyoshi K, et al
. Non-severe vs severe symptomatic COVID-19: 104 cases from the outbreak on the cruise Ship'Diamond Princess' in Japan. medRxiv 2020. [Preprint]. doi: 10.1101/2020.03.18.20038125.
Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. Clin Infect Dis 2020;71:769-77.
Wu J, Liu J, Zhao X, Liu C, Wang W, Wang D, et al
. Clinical characteristics of imported cases of COVID-19 in Jiangsu Province: A multicenter descriptive study. Clin Infect Dis 2020;71:706-12.
Wu J, Wu X, Zeng W, Guo D, Fang Z, Chen L, et al
. Chest CT findings in patients with corona virus disease 2019 and its relationship with clinical features. Invest Radiol 2020;10:257-61.
Xu T, Chen C, Zhu Z, Cui M, Chen C, Dai H, et al
. Clinical features and dynamics of viral load in imported and non-imported patients with COVID-19. Int J Infect Dis 2020;94:68-71.
Yang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, et al
. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): A multi-center study in Wenzhou city, Zhejiang, China. J Infect 2020;80:388-93.
Yao T, Gao Y, Cui Q, Shen J, Peng B, Chen Y, et al
. Clinical characteristics of 55 cases of deaths with COVID-19 pneumonia in Wuhan, China: Retrospective Case Series. Lancet 2020. [Preprint ]. doi: 10.2139/ssrn.3550019.
Zhang B, Zhou X, Qiu Y, Feng F, Feng J, Jia Y, et al
. Clinical characteristics of 82 death cases with COVID-19. PLoS ONE 2020;15:e0235458. doi: 10.1371/journal.pone.0235458.
Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al
. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy 2020;75:1730-41.
Zhao W, Yu S, Zha X, Wang N, Pang Q, Li T, et al
. Clinical characteristics and durations of hospitalized patients with COVID-19 in Beijing: A retrospective cohort study. medRxiv 2020. [Preprint]. doi: 10.1101/2020.03.13.20035436.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al
. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.
Zhou S, Wang Y, Zhu T, Xia L. CT features of coronavirus disease 2019 (COVID-19) pneumonia in 62 patients in Wuhan, China. AJR Am J Roentgenol 2020;214:1-8.
Brender N. Cases comparison: Outlook on H1N1 influenza pandemic and conclusions. In: Global Risk Governance in Health. Palgrave Macmillan, London: Springer; 2014. p. 166-95.
Garibaldi BT, Danoff SK. Symptom-based management of the idiopathic interstitial pneumonia. Respirology 2016;21:1357-65.
Seki M, Fuke R, Oikawa N, Hariu M, Watanabe Y. Association of influenza with severe pneumonia/empyema in the community, hospital, and healthcare-associated setting. Respir Med Case Rep 2016;19:1-4.
Nichols L. Pneumonia as a trigger for atrial fibrillation. J Rural Med 2017;12:146-8.
Wang XM, Hu S, Hu CH, Hu XY, Yu YX, Wang YF, et al
. Chest imaging of H7N9 subtype of human avian influenza. Radiol Infect Dis 2015;1:51-6.
van Werkhoven CH, Huijts SM, Postma DF, Oosterheert JJ, Bonten MJ. Predictors of bacteraemia in patients with suspected community-acquired pneumonia. PLoS One 2015;10;1-12. doi: 10.1371/journal.pone.0143817.
Hanamsagar MH, Sherwani AM. Upper respiratory tract infection and evidence based medicine – A Review. Int J Physiol Nutrit Phys Educ 2019;4:1506-8.
Sharma L, Losier A, Tolbert T, Dela Cruz CS, Marion CR. Atypical pneumonia: Updates on legionella, chlamydophila, and mycoplasma pneumonia. Clin Chest Med 2017;38:45-58.
Martínez-González J, Robles-Arias C, Rodríguez-Cintrén W. Rapidly progressive and almost lethal pneumonia. P
R Health Sci J 2017;36:41-3.
Chaudhary M, Ayub SG, Mir MA, Protocol G. Comparative efficacy and safety analysis of CSE-1034: An open labeled phase III study in community acquired pneumonia. J Infect Public Health 2018;11:691-7.
Ferrer M, Travierso C, Cilloniz C, Gabarrus A, Ranzani OT, Polverino E, et al
. Severe community-acquired pneumonia: Characteristics and prognostic factors in ventilated and non-ventilated patients. PLoS One 2018;13:1-14.
Santos C, Oliveira RC, Serra P, Baptista JP, Sousa E, Casanova P, et al
. Pathophysiology of acute fibrinous and organizing pneumonia – Clinical and morphological spectra. Pathophysiology 2019;26:213-7.
Cilléniz C, Rodríguez-Hurtado D, Torres A. Characteristics and management of community-acquired pneumonia in the era of global aging. Med Sci (Basel) 2018;6:35.
Xiang R, Tang Q, Chen XQ, Li MY, Yang MX, Yun X, et al
. Effects of zinc combined with probiotics on antibiotic-associated diarrhea secondary to childhood pneumonia. J Trop Pediatr 2019;65:421-6.
Tse CF, Chan YYF, Poon KM, Lui CT. Clinical prediction rule to predict pneumonia in adult presented with acute febrile respiratory illness. Am J Emerg Med 2019;37:1433-8.
Bermejo-Martin JF, Cilloniz C, Mendez R, Almansa R, Gabarrus A, Ceccato A, et al
. Lymphopenic Community Acquired Pneumonia (L-CAP), an immunological phenotype associated with higher risk of mortality. EBioMedicine 2017;24:231-6.
Méndez R, Menéndez R, Amara-Elori I, Feced L, Piré A, Ramírez P, et al
. Lymphopenic community-acquired pneumonia is associated with a dysregulated immune response and increased severity and mortality. J Infect 2019;78:423-31.
Huang Y, Liu A, Liang L, Jiang J, Luo H, Deng W, et al
. Diagnostic value of blood parameters for community-acquired pneumonia. Int Immunopharmacol 2018;64:10-5.
Lee JH, Park M, Han S, Hwang JJ, Park SH, Park SY. An increase in mean platelet volume during admission can predict the prognoses of patients with pneumonia in the intensive care unit: A retrospective study. PLoS One 2018;13:e0208715. doi: 10.1371/journal.pone.0208715.
Tao RJ, Luo XL, Xu W, Mao B, Dai RX, Li CW, et al
. Viral infection in community acquired pneumonia patients with fever: A prospective observational study. J Thorac Dis 2018;10:4387-95.
Dai RX, Kong QH, Mao B, Xu W, Tao RJ, Wang XR, et al
. The mortality risk factor of community acquired pneumonia patients with chronic obstructive pulmonary disease: A retrospective cohort study. BMC Pulm Med 2018;18:12.
Shirani K, Sheikhbahaei E, Torkpour Z, Ghadiri Nejad M, Kamyab Moghadas B, Ghasemi M, et al
. A narrative review of COVID-19: The new pandemic disease. Iran J Med Sci 2020;45:233-49.
Wu J, Liu J, Zhao X, Liu C, Wang W, Wang D, et al
. Clinical characteristics of imported cases of coronavirus disease 2019 (COVID-19) in Jiangsu Province: A Multicenter Descriptive Study. Clin Infect Dis 2020;71:706-12.
Maqbool K, Sadiq S, Mir AW, Bashir N, Bashir N. Influenza A, H1N1 and H3N2 experience at a tertiary care ICU. Int J 2018;1:56.
Maruyama T, Fujisawa T, Suga S, Nakamura H, Nagao M, Taniguchi K, et al
. Outcomes and prognostic features of patients with influenza requiring hospitalization and receiving early antiviral therapy: A prospective multicenter cohort study. Chest 2016;149:526-34.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]