key: cord-0693016-03l7p54q authors: Bennett, Sadie; Tafuro, Jaco; Mayer, Joseph; Darlington, Dan; Wai Wong, Chun; Muntean, Elena‐Andra; Wong, Nicholas; Mallen, Christian; Shing Kwok, Chun title: Clinical features and outcomes of adults with COVID‐19: A systematic review and pooled analysis of the literature date: 2020-09-23 journal: Int J Clin Pract DOI: 10.1111/ijcp.13725 sha: 6959369dfe643a8c22f6f2d689689ebba5aa9783 doc_id: 693016 cord_uid: 03l7p54q BACKGROUND: The 2019 coronavirus disease (COVID‐19) has become a global pandemic and the published literature describing the virus has grown exponentially. METHODS: We conducted a systematic review of the literature to identify the symptoms, comorbidities present, radiological features and outcomes for adults testing positive for COVID‐19 admitted to hospital. The results across multiple studies were numerically pooled to yield total estimated. RESULTS: A total of 45 studies were included in this review with 14,358 adult participants (average age 51 years, male 51%). The pooled findings suggest that the most common symptom among patients was fever (81.2%) followed by cough (62.9%), fatigue (38.0%) and anorexia/loss of appetite (33.7%). The comorbidities that were most prevalent among patients with the virus were hypertension (19.1%), cardiovascular disease (17.9%), endocrine disorder (9.3%) and diabetes (9.2%). Abnormal chest X‐ray findings were present in 27.7% of patients and ground‐glass opacity was demonstrated on chest CT in 63.0% of patients. The most frequent adverse outcomes were acute respiratory distress syndrome (27.4%), acute cardiac injury (16.2%) and acute kidney injury (12.6%). Death occurred in 8.2% of patients and 16.3% required intensive care admission and 11.7% had mechanical ventilation. Bacterial or secondary infections affected 8.5% of patients and 6.9% developed shock. CONCLUSIONS: COVID‐19 most commonly presents with fever, cough, fatigue and anorexia among patients with existing hypertension and cardiovascular disease. It is important as serious adverse outcomes can develop such as acute respiratory distress syndrome, acute cardiac injury, acute kidney injury and death. First identified in December 2019 as a cause of pneumonia in Wuhan China, the coronavirus disease 2019 (COVID- 19) has become a global pandemic [1] . As of June 2020 there are over 9 million cases worldwide and it is responsible for nearly 470,000 deaths [2] . As this is a new disease, literature which scientists, clinicians and politicians could rely on to determine how best to control the spread of the virus and manage infected patients was limited and largely based on experience drawn from managing or other respiratory virus pandemics. In the efforts to quickly understand this virus there has been an exponential growth of literature on COVID-19 over a relatively short time span [3, 4, 5, 6, 7] . At the same time, there have been numerous reports from experts within their respective clinical disciplines providing opinions based on the interpretation of the limited published literature [8, 9] The few reviews published have limitations including not being systematic in nature [10] , including a small number of studies [11] or including studies with low patient number including case reports and small patient case series [12] . In view of the urgent need to understand the literature and inform practice, we aimed to determine systematically the evidence from studies of more than 100 adult patients that reported clinical features and outcomes of those affected by COVID-19. As this virus affects patients from all settings such as community and hospitals, we pooled the findings of the individual studies to gain an estimate of how it affects the population as a whole. We conducted a systematic review of the literature to identify the symptoms, comorbidities present, radiological features and outcomes for adults testing positive for COVID-19 admitted to hospital. We included studies that evaluated adults with a laboratory confirmed diagnosis of COVID-19. The studies also had to report information on one or more of the following: clinical features of patients, comorbidities of patients, radiological findings for patients and outcomes for patients. In addition, we required that the sample size of the studies be greater than 100 patients so that less common symptoms would be captured and there would be sufficient sample size for This article is protected by copyright. All rights reserved calculating adverse event rates. There was no restriction based on language of study and Google Translate was used to convert studies from Chinese journals to English. We searched MEDLINE and EMBASE using OVID on 26 April 2020. We used the following broad search terms in our search strategy: ("COVID-19" OR "2019-nCoV" OR "SARS-COV-2" OR "Wuhan coronavirus" OR "novel coronavirus" OR "new coronavirus") AND ("clinical features" OR "presentation" OR "symptoms" OR "clinical course" OR "clinical characteristics" OR "outcomes" OR "complications" OR "ventilation" OR "intubation" OR "recovery" OR "death" OR "mortality" OR "survival"). We limited the search results to studies published in 2019 or 2020. Due to the initially large number of studies the search terms returned, we screened study titles and abstracts in independent pairs (SB & JM, JT & CSK and DD & CWW) to assess the potential for each study to meet the inclusion criteria. Full articles of potentially relevant studies were retrieved and reviewed for inclusion. Studies where there were discrepancies regarding inclusion were reviewed in detail and decisions about inclusion were made by consensus. Data was extracted by SB and JT and checked by CSK. The data was collected on study design, country, year when it took place, number of participants, mean/median age of participants, % male, patient inclusion criteria, symptoms, comorbidities, radiological findings, follow up and adverse outcomes. We further collected data on admission criteria, criteria for starting oxygen and renal disease (acute kidney injury, end-stage renal failure and dialysis). Risk of bias was performed based on the Ottawa-Newcastle scale [13] with studies being assessed out of a maximum of 7 stars over 3 different domains: selection, comparability and outcome. Data was extracted and presented in Tables. Statistical pooling according to methods by Kwok et al [14] . Pooled results were presented in Figures for patient symptoms, comorbidities, radiological findings and outcomes along with the number of studies and number of patients that were pooled. A total of 45 studies [3, 4, 5, 6, 7, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54] were included in this review ( Figure 1 ). The findings from chest X-ray and CT scans are reported for each study in Supplementary Table 6 . The pooled results suggest that 27.7% of patients had abnormal chest X-rays, 79.9% had bilateral changes on chest X-ray or CT scans and 63.0% had ground-glass opacities on imaging ( Figure 5 ). This article is protected by copyright. All rights reserved The outcomes for patients with COVID-19 are presented in Table 2 . Studies had follow-up of up to 31 days and the pooled results for outcomes are shown in Figure 6 . The most common adverse outcome was acute respiratory distress syndrome (27.4%), acute cardiac injury (16.2%) and acute kidney injury (12.6%). Death occurred in 8.2% of patients and 16.3% required intensive care admission while 11.7% had mechanical ventilation. Bacterial or secondary infections affected 8.5% of patients and 6.9% developed shock. Our study has several key findings. First, the majority of the literature is currently A major challenge of the current study was to ensure that the population that was pooled did not count patients from the same hospital. Many of the included studies in this review took place in Wuhan hospitals the epicentre of the virus outbreak. We therefore had to be careful and analyse which individual hospitals contributed to the reported findings. We took the approach of including the studies with the greatest number of patients because this would most likely include the most recent data in the pooled analysis. We observed significant heterogeneity in the follow up period for the included studies which ranged from only in-hospital events to at least 34 days post discharge. While we expect that mortality risk would be greatest at time of hospitalization for the acute illness, there is still risk of mortality when discharged from hospital especially when patients are discharged for self-isolation or they are discharged before complete symptom resolution. A key consideration which we are unable to capture is the discharge criteria at each hospital as this may affect mortality rates in the community after hospitalization. This is further complicated by hospital policies that may have changed depending on the timing of the epidemic when the study took place. Mortality and outcomes for patients with COVID-19 depend on duration of follow up and the time point of the epidemic when the study occurred. As the pandemic continues to progress, the challenge has and will remain in detecting COVID-19 cases and identifying local outbreaks as early as possible to prevent spread and secondary outbreaks. The common symptoms of patients who present to hospital as seen in this review include fever, cough, fatigue and anorexia or loss of appetite. However, we have shown that there are many other symptoms such as anosmia/loss of taste, weakness and facial/ear pain that appear in patients affected by the virus. More understanding is needed as to the timeline of symptomatology and disease progression with COVID-19 is not known. We expect that some patients present early to hospital while other wait for further symptoms to develop or increase in severity of symptoms before coming to hospital. As treatments are being developed and used in practice such as dexamethasone (RECOVERY trial) [59] informing the public and clinicians of the range of symptoms of COVID-19 is important so that patients with the virus can be identified quickly and they can undergo treatment before it progresses or spreads uncontrollably within local communities. This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. 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Acute liver injury 34/102. Shock 10/102. Acute infection 17/102 Alkalosis 19/76. Acute kidney injury 29/274. Disseminated intravascular coagulation 21/274. Hyperkalaemia 62/274. Shock 46/ 274, acute liver injury 13/274, gastrointestinal bleeding 1/274. Deng 2020a None. Death 109/225. Acute respiratory distress syndrome 108/225, acute cardiac injury 66/225, acute kidney injury 20/225, shock 123/225, disseminated intravascular coagulation 7/225, Deng 2020b 20 days. Intensive care admission 26/112. Mechanical ventilation 28/112. Extracorporeal membrane oxygenation 3/112. Death hospital 23/476. Death 38/476. Secondary bacterial infection 35/410. Guan 2020a None All rights reserved Guan 2020b None. Death 50/1590. Intensive care admission 90/1590. Invasive ventilation 50/1590. significant difference in hospital stay amongst patients with digestive only symptoms vs digestive and respiratory symptoms Acute respiratory distress syndrome 210/549. Cardiac injury 119/549. Liver dysfunction 106/549. Acute kidney injury 95/549. Bacteraemia infection 38/549 Seizure-like symptoms 2/304. Brain insults or metabolic imbalances 84/304. Death 10/304. Septic shock 5/304. in hospital 120/135. Death 1/135. Acute respiratory distress syndrome 21/135. Acute cardiac injury 10/135. Acute kidney injury 5/135. Secondary infection 7/135. Shock 1/135. Wang 2020a 5 days Remained in hospital 215/339. Death 76/339. Acute respiratory distress syndrome 71/339. Acute cardiac injury 70/339. Cardiac insufficiency 58/339. Acute kidney injury 27/339. Liver enzyme abnormalities 86/339. Bacterial infection 143/339 Acute respiratory shock distress syndrome 6/125. Secondary infection 6/125. Wang 2020g 4 days. Remained in hospital 85/138. Death 6/138. Intensive care admission 36/138. Mechanical ventilation 6/138. Acute respiratory distress syndrome 12/138. Acute cardiac injury 10/138. Shock 12/138. Arrhythmia 23/138. Xu 2020 4 days Discharged 42/221. Remained in hospital 167/221. Death 12/221. Acute respiratory distress syndrome 48/221. Acute cardiac injury 16/221. Acute kidney injury 10/221 Acute respiratory distress syndrome 49/191. Respiratory failure 103/191. Acute cardiac injury 33/191. Heart failure 44/191. Acute kidney injury 28/191 None This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved