key: cord-1025195-umqowine authors: Tahvildari, Azin; Arbabi, Mahta; Farsi, Yeganeh; Jamshidi, Parnian; Hasanzadeh, Saba; Calcagno, Tess Moore; Nasiri, Mohammad Javad; Mirsaeidi, Mehdi title: Clinical features, Diagnosis, and Treatment of COVID-19: A systematic review of case reports and case series date: 2020-04-03 journal: nan DOI: 10.1101/2020.03.28.20046151 sha: ad357dd76eea58e5a29727e554d3ff431cbade5d doc_id: 1025195 cord_uid: umqowine Objectives: The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of patients presenting with COVID-19. Methods: We conducted a structured search using PubMed/Medline, Embase, Web of Science and the Cochrane Library to collect both case reports and case series on COVID-19 published up to February 30, 2020. Results: Thirty-four articles were included analyzing a total of 99 patients with a mean age of 46.2 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 83% of patients from 76.4% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies which reported C-reactive protein (CRP) measurements (44%), a large majority of patients displayed an elevated CRP (73%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (33%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (71.0%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor). Conclusions: Development of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for presence and severity of disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary. 1 Introduction 29 Late in December 2019 and early in January 2020, reports of a very progressive pneumonia-like 30 respiratory syndrome, starting in Wuhan, China, induced global health concerns [1] . Soon after 31 the onset of disease, it was found that the pathogen was a new member of the coronaviridae 32 family, named SARS-COV-2 which is now called 2019-n-CoV [2] . The respiratory syndrome 33 caused by 2019-n-CoV is called COVID-19. COVID-19 is characterized by low-grade fever, 34 cough, dyspnea, lymphopenia, and ground-glass opacities on chest CT scan [3, 4] . COVID-19 is 35 a highly contagious disease, probably an aerosol born one, with human to human transmission 36 capacity which has implicated many countries all around the world [5] . In this review article, we 37 systematically surveyed case reports and case series from many countries in the world to give a 38 picture of the epidemiology, clinical presentations, laboratory changes, imaging findings, 39 diagnostic criteria, treatments, outcomes, prognostic factors, and risk factors of COVID- 19. 40 . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03. 28.20046151 doi: medRxiv preprint As illustrated in Figure 1 , our systematic search resulted in an initial number of 1102 of 71 potentially relevant articles, of which 346 were excluded by title and abstract evaluation. 72 Applying the inclusion/exclusion criteria to the full-text documents, 34 articles were eligible for 73 inclusion in the systematic review. 23 [7] . Asymptomatic transfer leads to lower prevalence estimates and higher 99 transmission rates in the community. Until universal screening and vaccination become 100 . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03. 28.20046151 doi: medRxiv preprint available, it is necessary to trace close contacts of those testing positive for COVID-19 and 101 quarantining contacts to prevent asymptomatic transmission. 102 According to the articles we included, 2019-nCoV can only be transferred from person to 103 person [8] . Chen et al suggested that they had no evidence of vertical transmission from mother to 104 child [9] . Any person infected with 2019-nCoV can develop a clinical course of However, it is reported to cause the most severe symptoms such as respiratory failure in older 106 men with comorbidities [10] . Children, teenagers, and younger people mostly showed a mild 107 presentation of the disease [11] . 108 Based on our reviewed articles, hypertension, diabetes, cardiovascular disease, and pulmonary 109 disease were the most common morbidities among COVID-19 patients. This point was also 110 mentioned in Alraddadi et al. study about MERS-CoV patients [12] . They showed that 111 individuals with comorbidities like diabetes, smoking, and cardiovascular disease were 112 associated with a more severe clinical course [12] . According to Yang et al., chronic diseases can 113 debilitate the immune system and make proinflammatory conditions, leading to more severe 114 infection and subsequently higher mortality rates [13] . 115 According to the included studies, the most common clinical manifestations were fever, cough, 116 dyspnea, and myalgia or fatigue. Less common clinical manifestations included nausea or 117 vomiting, dizziness, rhinorrhea, and chills. Liu et al reported that infants had mild clinical 118 manifestations and a better prognosis. Furthermore, some asymptomatic cases were seen among 119 children. 120 The most common abnormal laboratory changes were lymphopenia, high concentrations of C-121 reactive protein, and elevated levels of aspartate aminotransferase; however, we do not know the 122 exact pathogenesis and the reason for these alterations. Laboratory abnormalities may indicate 123 the severity of disease and developing complications. According to Huang et al., most patients 124 with secondary infection had a procalcitonin level greater than 0.5 ng/Ml and ICU patients had 125 higher levels of prothrombin time and D-dimer [14] . Also, Liu et al. mentioned using 126 hypoalbuminemia, lymphopenia, high concentrations of CRP, and elevated LDH to predict 127 severity of acute lung injury [3] . Higher levels of angiotensin II are also proposed to be related to 128 acute lung injury [3] . Meanwhile, non-survivors are suggested to have higher D-dimer and FDP 129 levels, longer PT and aPTT, and lower fibrinogen and antithrombin levels [15] . 130 . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03. 28.20046151 doi: medRxiv preprint CT scan as a diagnostic tool can be used to evaluate severity of pulmonary involvement and 131 monitor clinical progression. CT scan has good sensitivity and can be used to establish COVID-132 19 diagnosis in patients who are highly suspicious based on epidemiologic history and clinical 133 manifestations, but have negative PCR-based test results [16, 17] . It is important to highlight that 134 the CT scan can be normal during initial days, and a normal CT scan in a suspected case would 135 never definitely rule out the diagnosis of COVID-19 [18] . Moreover, the CT scan is dynamic in 136 patients with COVID-19 and changes rapidly [19] [20] [21] . The earliest abnormal finding in the CT 137 scan is the appearance of ground-glass opacities in peripheral and sub-pleural areas [22] . As the 138 disease progresses, the GGO's will expand and distribute more, most commonly to the right 139 lower lung lobes. Later findings include consolidations, paving patterns, thickening of lobar 140 fissures and adjacent pleura. Pleural effusion, hilar lymphadenopathies, and mediastinal 141 lymphadenopathies are not common findings and have only been reported scarcely [23] . Lung 142 pathology can progress to a "white lung" with low functional capacity or heal with some fibrotic 143 remnants [24] . Dynamic changes in the lungs seen on CT imaging will continue even after the 144 patient's discharge [22] . complications were acute cardiac injury, acute kidney injury, secondary infection, and shock that 151 lead to multiple organ failure [26, 27] . ICU patients in comparison to non-ICU patients were also 152 more likely to have complications [28] . The mortality rate was higher in critically ill patients as 153 well as in older patients with comorbidities and ARDS. Yang et al reported that the median 154 duration from ICU admission to death was 7 days [25] . The window between the presentation to 155 the time of ICU admission and/or development of ARDS is an optimal time for medical 156 intervention. 157 There are many challenges in COVID-19 therapeutic strategies. There is currently no cure for 158 COVID-19. However, pharmacologic and non-pharmacologic symptom management and 159 supportive care measures should be given to all patients with symptomatic COVID-19. Other 160 various therapeutic strategies have been trialed in patients with COVID-19 with the goal of 161 . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.28.20046151 doi: medRxiv preprint slowing disease progression. There is a paucity of data surrounding the efficacy of treatments. Of 162 the case controls and case series we included, antiviral agents including HIV protease inhibitors 163 (lopinavir and ritonavir) as well as anti-influenza compounds (oseltamivir and arbidol) were used 164 as treatment regimens. Unfortunately, we didn't have enough information about the efficacy of 165 each regimen; however, according to some studies, anti-HIV based medications could have 166 benefits in more rapid improvement of clinical manifestations and decrease in viral load [19, 20, 167 29] . 168 In conclusion, we discussed the clinical symptoms, laboratory abnormalities, common 169 comorbidities, imaging modalities, and potential therapeutic options in COVID-19. We indicated 170 that the most common symptoms were fever, cough, and dyspnea, but some young infected cases 171 had no signs or symptoms. ARDS was the most common reported complication and was 172 associated with poor prognosis. In the wake of the COVID-19 pandemic, countries are 173 scrambling to produce enough RT-PCR diagnostic tests. Diagnostic information from other 174 surrogate markers would be valuable if markers proved to be sensitive and specific. Namely, we 175 learned that laboratory data like CRP may not only be related to the severity of disease, but it 176 may be predictive of disease outcomes. Further studies are needed to relate quantified elevations 177 in CRP to disease severity. Due to the high sensitivity of CT scan, it is considered as a good 178 diagnostic tool. However, it should be kept in mind that a normal CT scan will never rule out the 179 diagnosis of COVID-19 in a highly suspicious case based on history and clinical findings. Lastly, 180 there are different therapeutic strategies for COVID-19 patients, but we don't have enough data 181 for their efficacy. Additional investigations including randomized controlled trials will be 182 necessary to further our understanding in the treatment of COVID- 19 is the The copyright holder for this preprint . Ying-Chu Liu [45] . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . Rothe, C., et al. . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03. 28.20046151 doi: medRxiv preprint A novel coronavirus from patients with pneumonia in China Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. 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