Clinical manifestation and disease progression in COVID-19 infection : Journal of the Chinese Medical Association

Secondary Logo

Journal Logo

Review Articles

Clinical manifestation and disease progression in COVID-19 infection

Tsai, Ping-Hsinga; Lai, Wei-Yia; Lin, Yi-Yinga; Luo, Yung-Hungb,c; Lin, Yi-Tsungc,d; Chen, Hsiao-Kangc,e; Chen, Yuh-Minb,c; Lai, Yi-Chunc,e; Kuo, Li-Chiaoc,e; Chen, Shew-Danc,e; Chang, Kao-Junga,c; Liu, Cheng-Hsuana,c; Chang, Shih-Chiehc,e,*; Wang, Fu-Derc,d,*; Yang, Yi-Pinga,c,f,*

Author Information
Journal of the Chinese Medical Association 84(1):p 3-8, January 2021. | DOI: 10.1097/JCMA.0000000000000463
  • Open


Coronavirus disease 2019 (COVID-19) is mainly an infectious disease of the respiratory system transmitted through air droplets, and pulmonary symptoms constitute main presentations of this disease. However, COVID-19 demonstrates a clinically diverse manifestation ranging from asymptomatic presentation to critically illness with severe pneumonia, acute respiratory distress syndrome, respiratory failure, or multiple organ failure. Accumulating evidences demonstrated that COVID-19 has extrapulmonary involvement, including neurological, smelling sensation, cardiovascular, digestive, hepatobiliary, renal, endocrinologic, dermatologic system, and others. Over a third of COVID-19 patients manifest a wide range of neurological symptoms involving the central/peripheral nervous system. Underlying cardiovascular comorbidities were associated with detrimental outcomes, meanwhile the occurrence of cardiovascular complications correlate to poor survival. Gastrointestinal symptoms frequently occur and have been associated with a longer period of illness. Impaired hepatic functions were associated with the severity of the disease. Higher rate of acute kidney injury was reported in critically ill patients with COVID-19. Endocrinologic presentations of COVID-19 include exacerbating hyperglycemia, euglycemic ketosis, and diabetic ketoacidosis. The most common cutaneous manifestation was acro-cutaneous (pernio or chilblain-like) lesions, and other skin lesions consist of maculopapular rash, vesicular lesions, livedoid/necrotic lesions, exanthematous rashes, and petechiae. This review article summarized the general clinical signs and symptoms, radiologic features, and disease manifestation with progression in patients with COVID-19.


Coronaviruses with RNA club-shaped spikes on the viral surface are one of the largest among RNA viruses.1 The structure of coronaviruses consists of enveloped surface, a nucleocapsid, and single-stranded RNA genome. In the 1930s, the first coronaviruses were discovered when infectious bronchitis virus caused an acute respiratory tract infection.2 In the 1940s, mouse hepatitis virus and transmissible gastroenteritis virus were identified as the first coronaviruses in mammals. The first human coronaviruses were identified in the 1960s.3 Two human coronaviruses, coronavirus 229E and OC43, cause upper respiratory tract infections, nasal symptoms, cough, and pharyngitis. According to previous reports, human coronavirus usually results in a low mortality rate and rarely causes critical illness.4,5 Nonetheless, the severe acute respiratory syndrome coronavirus (SARS-CoV) may cause more severe symptoms which are not usually caused by known coronavirus. In 2003, SARS-CoV caused pulmonary infection, and the mortality rate reached approximately 10%.4 Therefore, the World Health Organization (WHO) reported that SARS-CoV might cause severe acute infectious disease in the world. In 2012, another severe coronavirus infection was discovered in the Middle East. The discovery process was similar to SARS. A patient had severe unexplained pneumonia and was later found to be caused by a new type of coronavirus. The novel virus, Middle East respiratory syndrome coronavirus (MERS-CoV), was first found in a patient from Saudi Arabia with severe unexplained pneumonia.4 The MERS-CoV outbreak in 2012-2015 affected 25 countries (mostly Saudi Arabia and South Korea) with 2506 cases and 862 deaths (34% fatality rate).5 In December 2019, a new type of pneumonia with unknown cause occurred in Wuhan, China and started to spread rapidly. The Chinese government identified an extreme pathogenic coronavirus on January 9, 2020 when WHO named such novel SARS-CoV. People also called this disease of SARS-CoV-2 as COVID-19 or Wuhan pneumonia.6 The number of cases increased significantly in January 2020, and the global statistics as of August 4 had 18 166 298 confirmed cases, and the death toll had reached 690 953 all of which exceeded the SARS record of that year. Although COVID-19 was initially limited to China, it has rapidly spread to >180 countries because of its highly contagious pathogen. This pandemic infection is continuously spreading across the world with exponentially increasing death toll. It is important to clarify and understand the clinical manifestation and disease progression in COVID-19 pandemic infection.


In recent decades, two previous coronavirus outbreaks have been reported, and the clinical manifestations of SARS-CoV-2, in comparison with SARS-CoV and MERS-CoV, are summarized in the Table 1.7–9 Pulmonary infectious diseases, such as SARS and MERS, present a major threat to public health.10 In late December 2019, several new SARS-like pneumonia cases were reported in a Chinese city of Wuhan. A new coronavirus SARS-CoV-2 was rapidly identified as the etiologic pathogen leading to the outbreaks of COVID-19.10 This novel coronavirus infection demonstrated human-to-human transmission of SARS-CoV-2 among healthcare practitioners in a Wuhan hospital.11,12 The global spread and lethality of SARS-CoV-2 lead to primary challenges for the worldwide healthcare system. SARS-CoV-2 is highly contagious, and the incubation period of COVID-19 has been reported around 1 to 14 days (interquartile range [IQR], 2-7 days).11,13–15

Table 1 - Characteristic comparison of SARS-CoV, SARS-CoV-2, and MERS-CoV
Start time December 2019 November 2002 June 2012
Initial area Wuhan, China Guangdong, China Jedda, Saudi Arabia
Confirmed patients 214 894 8096 2494
Mean age (range) 47-56 (0.5-92) 39.9 (1-91) 56
Male 58%-75% 44% 76.70%
HCWs 2%-29% 23.10% 9.80%
 Fever 83%-98% 99%-100% 98%
 Dry cough 59%-78% 29%-75% 47%
 Dyspnea 19%-55% 40%-42% 72%
 Diarrhea 2%-10% 20%-25% ...
 Sore throat 5%-17% 13%-25% ...
 Ventilator support 2%-12% 14%-20% 80%
 ARDS 3%-29% 20%-30% Case reports
 Mortality 690 953 (3.8%) 744 (10%) 858 (37%)
ARDS = adult respiratory distress syndrome; HCWs = healthcare workers; MERS-CoV = Middle East respiratory syndrome coronavirus; SARS-CoV = severe acute respiratory syndrome coronavirus.

The common symptoms of SARS-CoV-2 infection are fever (83%-98%), cough (50%-82%), fatigue (25%-44%), shortness of breath (19%-55%), and muscle soreness (11%-44%).14,15 Some patients may suffer from sputum production, rhinorrhea, chest tightness, sore throat, nausea, vomiting, diarrhea, headache, ageusia, and anosmia a few days before the occurrence of fever, suggesting that fever is critical but not the only initial symptom of infection.14 Some patients only had a mild fever, mild fatigue, or even no symptoms.13,15–17

About 80% of SARS-CoV-2 infections in ambulatory patients manifest as a mild respiratory illness and could usually be managed by outpatient care. About 15% of patients need inpatient care for moderate to severe pneumonia.18 Among the hospitalized patients, the median time from initial symptoms to the occurrence of dyspnea is five days (IQR, 1-10 days), and the median time to be hospitalized is 5 days (IQR, 4-8 days).13 Disease course may show rapid progression to multiple organ failure and even death in severely ill patients.11,13 Patients (3%-29%) may require admission to an intensive care unit (ICU) for the management of complications, including hypoxemic respiratory failure or hypotension. Overall mortality rate appears to be approximately 3.8%11,13,14,16,19 (Table). Some patients with dyspnea and hypoxemia could quickly progress into acute respiratory distress syndrome (ARDS), septic shock, blood clotting dysfunction, and even multiple organ failure in 1 week.16,20 The median time to ARDS is 8 days (IQR, 6-12 days). The high incidence of multiple organ failure is one of the features of COVID-19.15 Most of the critically ill patients are related to comorbidities, including cardiovascular disease, hypertension, diabetes, and renal disease. Moreover, the mortality rates are relatively high in COVID-19 patients with these comorbidities.21 The severity of COVID-19 patients is also related to age, and the death toll was concentrated among those aged ≥40. Studies have shown that morbidity rate is lower in children and infants than in adults.22,23

Infected patients may have lymphopenia which is the most common laboratory manifestation, normal or lower white blood cell counts, or thrombocytopenia, with elevated C-reactive protein level.11,13,14,16 Fever, lymphopenia, or leukopenia with the symptoms of upper respiratory tract is highly suspected to be the manifestations of patients with COVID-19, which is supported by the traveling history to the endemic area or close exposure history. The asymptomatic individuals in incubation period are critical sources of infection, which results in difficulties in the epidemic prevention and disease control.24,25

Currently, respiratory droplets are believed to be the primary route of transmission; however, transmission via the ocular surface should also be carefully prevented because the conjunctival epithelium is vulnerable to the infectious droplets and body fluid.26 The fecal-oral route is suspected due to the identification of SARS-CoV-2 nucleic acids in the stool specimens from COVID-19 patients with pneumonia and abdominal symptoms.27 Additionally, vertical transmission between mothers and infants has been reported as a potential transmission route according to the finding of a 30-hour-old newborn tested positive for SARS-CoV-2 infection. Despite tremendous efforts on investigating this pathogen, the contagious period of SARS-CoV-2 still varies in different reports.19 Furthermore, the incidental hosts of SARS-CoV-2 are not yet clear to researcher. The unconfirmed incidental hosts may lead to repeated zoonotic transmission and the potentially underestimated contagious period also constitutes a significant challenge to the epidemic prevention. Additionally, the human-to-human transmission of SARS-CoV-2 occurs mainly in communities and between family members, suggesting that this pathogen could rapidly spread before the occurrence of symptoms. Another report showed that patients who have recovered from COVID-19 after two consecutive real-time reverse transcriptase-polymerase chain reaction tests turned out to demonstrate positive results a few days later.28 Therefore, infected patients could be contagious before the onset of symptoms and after treatment of COVID-19. Besides, the optimal strategy for hospital discharge and cessation of quarantine remains to be elucidated in order to achieve superior disease control.


Chest X-ray (CXR) and computed tomography (CT) scan are necessary radiological examinations for early identification of COVID-19.29 The radiological features of COVID-19 pneumonia are similar to influenza, SARS-CoV, and MERS-CoV pneumonia.30–34 CXR of patients with COVID-19 pneumonia may reveal unilateral, bilateral, peripheral, and patchy opacities. In the early stage of COVID-19 pneumonia, CXR may not be able to detect abnormal findings, because CXR is not sensitive for ground-glass opacity (GGO).35

Severe COVID-19 cases may show the bilateral multiple consolidative lesion in the CXR radiograph. Besides, CT-scan radiograph can provide more information to assist the COVID-19 diagnosis. According to the experience on CT scan, COVID-19 patients exhibit bilateral pulmonary GGOs and consolidative lesions in the lung parenchyma. In addition, CT scan detects the feature of multiple pulmonary nodules, pleural effusion, lymphadenopathy, and absence of pulmonary cavitary lesion. Clinical doctors can efficiently catch pneumonia from early stage of COVID-19 patient according to CT scans.15 Hence, CT scan provides a rapid evaluation of progression and severity of COVID-19. However, COVID-19 pneumonia and other pulmonary infectious diseases are sometimes difficult to distinguish from CT findings. Moreover, the early stage of COVID-19 patients might present no significant difference in the pulmonary image. Even nucleic acid detection sometimes show a false negative result due to the low virus abundance or inefficient sampling. As a result, the combination of nucleic acid detection assay and CT imaging is useful for the precise identification of COVID-19.36–40


Although many COVID-19 patients suffered from respiratory symptoms, SARS-CoV-2 can also lead to several extrapulmonary manifestations, including thromboembolic complications, cardiac injury and arrhythmia, acute coronary syndromes, acute renal injury, gastrointestinal (GI) symptoms, liver function impairment, hyperglycemia and diabetic ketosis, neurologic deficits, and dermatologic complications.41 We summarized the extrapulmonary organ-specific manifestation and pathophysiology for patients with COVID-19 to facilitate the understanding and monitoring of various manifestations in COVID-19 patients.

4.1. Neurologic manifestations

Neurologic presentations in COVID-19 patients are shown in the Fig. 1. Neurologic symptoms were reported in 36% of the patients with severe COVID-19.42 The mild neurological symptoms in COVID-19 patients include headache, dizziness, anorexia, anosmia, myalgia/fatigue, and ageusia.11,13,14 More-severe manifestations consist of acute stroke,43,44 confusion or impaired consciousness,42,45 acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome),46,47 meningoencephalitis, acute necrotizing encephalopathy including the brainstem and basal ganglia.48,49

Fig. 1:
Extrapulmonary involvements in patients with coronavirus disease 2019 (COVID-19).

4.2. Thromboembolic manifestations

The thromboembolic manifestations of COVID-19 are shown in the Fig. 1. Thromboembolic complications were reported in up to 30% of patients from ICUs.50,51 Emerging evidence revealed the occurrence of thrombosis in intravenous catheters and extracorporeal circuits, acute myocardial infarction, acute limb ischemia, and cerebral vascular events, in patients with severe disease.43,52–55 High rates of thromboembolic events were reported in severely ill patients with COVID-19 (17%-22%) who had received prophylactic anticoagulant therapies.54,56–58 The rates of pulmonary emboli were reported to be notably higher in ICU patients with COVID-19 than those without (20.6% vs 6.1%, respectively).59 Moreover, several studies demonstrated high rates of thromboembolic complications in critically ill patients with COVID-19 who were routinely screened for the thrombotic disease, ranging from 69% to 85%, despite prophylactic anticoagulant therapies.41

4.3. Cardiovascular manifestations

Clinical manifestations of COVID-19 pertaining to the cardiovascular system are shown in the Figure. COVID-19 can lead to direct and indirect cardiovascular injury, including acute coronary syndrome, myocardial injury, cardiomyopathy, cardiac arrhythmias, cor pulmonale, cardiogenic shock, and thromboembolic complications.60,61 Around 20% to 30% of inpatients with COVID-19 were reported to have myocardial injury,62 and higher degree of troponin elevations was associated with more severe complications and worse outcomes.62,63 Biventricular cardiomyopathy occurred in approximately 7% to 33% of critically ill patients.64,65 Hospitalized patients (17%-44%) with COVID-19 were reported to have cardiac arrhythmias, including atrial fibrillation, ventricular arrhythmias, and heart block.13 Prolonged QTc was found in 6% of COVID-19 patients in a multicenter study. In an Italian cohort, the rate of out-of-hospital cardiac arrest increased by around 60% during COVID-19 pandemic compared with the similar period in 2019.

4.4. Renal manifestations

Clinical features pertaining to the kidney damage are shown in the Figure. The incidence of acute kidney injury (AKI) in hospitalized patients ranged from 0.5% to 37% with a median onset time of 7 to 14 days during admission.16,66–69 Higher rate of AKI, ranging from 78% to 90%, was reported in critically ill patients in New York City; an 31% of ICU patients with COVID-19 required renal replacement therapy.69–73 Up to 87% of critically ill patients had proteinuria in study.71 Higher mortality rate of COVID-19 was also reported in patients with end-stage renal disease and kidney transplant recipients compared with those without.74–76

4.5. GI manifestations

GI symptoms occur in some patients with COVID-19 (Figure). GI symptoms in COVID-19 patients have been associated with a longer duration of illness, with the incidence of 12% to 61%.77–80 The reported GI manifestations include anorexia (21%-35%), nausea/vomiting (7%-26%), diarrhea (9%-34%), and abdominal pain (3%).79,80 The occurrence of GI symptoms has been associated with a 70% increased risk of identification of COVID-19 in a research,81 and GI bleeding was rare in patients with prolonged mechanical ventilation or thrombocytopenia.81

4.6. Hepatobiliary manifestations

Clinical presentations of COVID-19 regarding the hepatobiliary system are shown in the Figure. In a systemic review, the prevalence of liver function impairment is around 19% (95% CI, 9%-32%) and associated with the severity of disease.79 Patients usually have elevated transaminases which are less than five times the upper limit of normal and severe acute hepatitis is rarely reported.82,83 Critically ill patients (14%-53%) with COVID-19 was reported to have hepatocellular injury.16,65–67,84 Some studies reported that elevated bilirubin was associated with the severity of disease and deterioration to critical illness.85,86

4.7. Endocrinologic manifestations

Endocrinologic presentations in COVID-19 patients are shown in the Figure. The abnormalities of glycemic metabolism in hospitalized patients with COVID-19 include exacerbating hyperglycemia, euglycemic ketosis, and diabetic ketoacidosis.16,18,87 A study in China reported that 6.4% of hospitalized patients had ketosis without the presence of fever or diarrhea.88

4.8. Dermatologic manifestations

Dermatologic manifestations of COVID-19 are shown in the Figure. A single-center study reported that 20% of hospitalized patients presented with dermatologic symptoms, including erythematous rash, urticaria, and chickenpox-like vesicles, and around 44% of dermatological findings occurred at disease onset.89 The most common cutaneous manifestation was acro-cutaneous (pernio or chilblain-like) lesions in a systemic review, and other skin lesions consist of maculopapular rash, vesicular lesions, livedoid/necrotic lesions, exanthematous rashes, and petechiae in patients with COVID-19.90–93

In conclusion, this review introduces the current status of knowledge on the global pandemic and clinical features of COVID-19. Given that SARS-CoV-2 is the third introduction of a deadly coronavirus into human society, after SARS-CoV in 2003 and MERS-CoV in 2012, respectively, various clinical manifestations of these three viruses were compared. Whereas SARS-CoV-2 is featured by relatively lower lethality compared with SARS-CoV and MERS-CoV, it has demonstrated significantly broader range of clinical presentation and apparent higher contagiousness. The COVID-19 outbreak started from China and then spread to other countries all over the world. Currently, the persistent pandemic still locates in Europe and North America. We also summarized the image findings for COVID-19.

Beside the deadly pulmonary complications of SARS-CoV-2, extrapulmonary spread, including neurological, smelling sensation, cardiovascular, digestive, hepatobiliary, renal, endocrinologic, and dermatologic system, are increasingly being appreciated. SARS-CoV-2 has undoubtedly catched the world’s attention at the beginning of 2020 by posing a significant challenge toward the public health system. Still, despite the rapid development of countermeasures looming on the horizon, further investigation and development of drugs and vaccines are in urgent need, as according to our current knowledge of coronaviruses, where and when the next outbreak would take place is unpredictable. Therefore, only by equipping ourselves with adequate understanding and diverse treatment modalities can we devise appropriate strategies against the constantly changing nature of novel coronaviruses.


This study was funded by Ministry of Science and Technology (106-3114-B-010-002, 107-2633-B-009-003, and 109-2320-B-075-008), Taipei Veterans General Hospital (V107E-002-2 and V108D46-004-MY2-1), and Yen Tjing Ling Medical Foundation (CI-109-26).


1. Woo PC, Huang Y, Lau SK, Yuen KY. Coronavirus genomics and bioinformatics analysis. Viruses. 2010; 2:1804–20
2. Estola T. Coronaviruses, a new group of animal RNA viruses. Avian Dis. 1970; 14:330–6
3. Kahn JS, McIntosh K. History and recent advances in coronavirus discovery. Pediatr Infect Dis J. 2005; 24(11 Suppl):S223–7
4. Tu YF, Chien CS, Yarmishyn AA, Lin YY, Luo YH, Lin YT, et al. A review of SARS-CoV-2 and the ongoing clinical trials. Int J Mol Sci. 2020; 21:2657
5. Liang Y, Wang ML, Chien CS, Yarmishyn AA, Yang YP, Lai WY, et al. Highlight of immune pathogenic response and hematopathologic effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 Infection. Front Immunol. 2020; 11:1022
6. Luo YH, Chiu HY, Weng CS, Chen YM. Overview of coronavirus disease 2019: treatment updates and advances. J Chin Med Assoc. 2020; 83:805–8
7. Lew TW, Kwek TK, Tai D, Earnest A, Loo S, Singh K, et al. Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA. 2003; 290:374–80
8. Graham RL, Donaldson EF, Baric RS. A decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol. 2013; 11:836–48
9. Kam KQ, Yung CF, Cui L, Tzer Pin Lin R, Mak TM, Maiwald M, et al. A well infant with coronavirus disease 2019 with high viral load. Clin Infect Dis. 2020; 71:847–9
10. Han Q, Lin Q, Jin S, You L. Coronavirus 2019-nCoV: a brief perspective from the front line. J Infect. 2020; 80:373–7
11. 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
12. Wang R, Zhang X, Irwin DM, Shen Y. Emergence of SARS-like coronavirus poses new challenge in China. J Infect. 2020; 80:350–71
13. 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
14. 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
15. Huang B, Ling R, Cheng Y, Wen J, Dai Y, Huang W, et al. Characteristics of the coronavirus disease 2019 and related therapeutic options. Mol Ther Methods Clin Dev. 2020; 18:367–75
16. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al.; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; 382:1708–20
17. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020; 395:514–23
18. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323:1239–42
19. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020; 395:470–3
20. Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G, Sourvinos G, Tsiodras S. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol. 2020; 79:104212
21. Li SY, Tang YS, Chan YJ, Tarng DC. Impact of the COVID-19 pandemic on the management of patients with end-stage renal disease. J Chin Med Assoc. 2020; 83:628–33
22. Jeng MJ. Coronavirus disease 2019 in children: current status. J Chin Med Assoc. 2020; 83:527–33
23. Cruz AT, Zeichner SL. COVID-19 in children: initial characterization of the pediatric disease. Pediatrics. 2020; 145:e20200834
24. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020; 382:1199–207
25. Tseng JY, Lai HY. Protecting against COVID-19 aerosol infection during intubation. J Chin Med Assoc. 2020; 83:582
26. Lu CW, Liu XF, Jia ZF. 2019-nCoV transmission through the ocular surface must not be ignored. Lancet. 2020; 395:e39
27. Zhang H, Kang Z, Gong H, Xu D, Wang J, Li Z, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. bioRxiv. 2020Doi:
28. Lan L, Xu D, Ye G, Xia C, Wang S, Li Y, et al. Positive RT-PCR test results in patients recovered from COVID-19. JAMA. 2020; 323:1502–3
29. Chen SG, Chen JY, Yang YP, Chien CS, Wang ML, Lin LT. Use of radiographic features in COVID-19 diagnosis: challenges and perspectives. J Chin Med Assoc. 2020; 83:644–7
30. Malainou C, Herold S. [Influenza]. Internist (Berl). 2019; 60:1127–35
31. de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016; 14:523–34
32. Hui DSC, Zumla A. Severe acute respiratory syndrome: historical, epidemiologic, and clinical features. Infect Dis Clin North Am. 2019; 33:869–89
33. Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev. 2015; 28:465–522
34. Chan JF, Li KS, To KK, Cheng VC, Chen H, Yuen KY. Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic? J Infect. 2012; 65:477–89
35. Zu ZY, Jiang MD, Xu PP, Chen W, Ni QQ, Lu GM, et al. Coronavirus disease 2019 (COVID-19): a perspective from China. Radiology. 2020; 296:E15–25
36. Al-Tawfiq JA, Memish ZA. Diagnosis of SARS-CoV-2 infection based on CT scan vs RT-PCR: reflecting on experience from MERS-CoV. J Hosp Infect. 2020; 105:154–5
37. Wang P, Anderson N, Pan Y, Poon L, Charlton C, Zelyas N, et al. The SARS-CoV-2 outbreak: diagnosis, infection prevention, and public perception. Clin Chem. 2020Doi: 10.1093/clinchem/hvaa080
38. Wang Y, Kang H, Liu X, Tong Z. Combination of RT-qPCR testing and clinical features for diagnosis of COVID-19 facilitates management of SARS-CoV-2 outbreak. J Med Virol. 2020; 92:538–9
39. Li T. Diagnosis and clinical management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2.0). Emerg Microbes Infect. 2020; 9:582–5
40. Huang Y, Cheng W, Zhao N, Qu H, Tian J. CT screening for early diagnosis of SARS-CoV-2 infection. Lancet Infect Dis. 2020; 20:1010–1
41. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020; 26:1017–32
42. 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
43. Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med. 2020; 382:e60
44. Yaghi S, Ishida K, Torres J, Mac Grory B, Raz E, Humbert K, et al. SARS-CoV-2 and stroke in a New York Healthcare System. Stroke. 2020; 51:2002–11
45. Pilotto A, Odolini S, Masciocchi S, Comelli A, Volonghi I, Gazzina S, et al. Steroid-responsive encephalitis in coronavirus disease 2019. Ann Neurol. 2020Doi: 10.1002/ana.25783
46. Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol. 2020; 19:383–4
47. Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, et al. Guillain-Barré syndrome associated with SARS-CoV-2. N Engl J Med. 2020; 382:2574–6
48. Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020; 94:55–8
49. Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: imaging features. Radiology. 2020; 296:E119–20
50. Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020; 18:1421–4
51. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020; 191:145–7
52. Bangalore S, Sharma A, Slotwiner A, Yatskar L, Harari R, Shah B, et al. ST-segment elevation in patients with Covid-19—a case series. N Engl J Med. 2020; 382:2478–80
53. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020; 382:2268–70
54. Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al.; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020; 46:1089–98
55. Perini P, Nabulsi B, Massoni CB, Azzarone M, Freyrie A. Acute limb ischaemia in two young, non-atherosclerotic patients with COVID-19. Lancet. 2020; 395:1546
56. Llitjos JF, Leclerc M, Chochois C, Monsallier JM, Ramakers M, Auvray M, et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost. 2020; 18:1743–6
57. Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, et al.; Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020; 191:9–14
58. Tavazzi G, Civardi L, Caneva L, Mongodi S, Mojoli F. Thrombotic events in SARS-CoV-2 patients: an urgent call for ultrasound screening. Intensive Care Med. 2020; 46:1121–3
59. Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, et al.; Lille ICU Haemostasis COVID-19 Group. Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence. Circulation. 2020; 142:184–6
60. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020; 75:2352–71
61. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. COVID-19 and cardiovascular disease. Circulation. 2020; 141:1648–55
62. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020; 5:811–8
63. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020; 5:802–10
64. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020; 46:846–8
65. 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
66. 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
67. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020; 180:934–43
68. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020; 97:829–38
69. Hirsch JS, Ng JH, Ross DW, Sharma P, Shah HH, Barnett RL, et al.; Northwell COVID-19 Research Consortium; Northwell Nephrology COVID-19 Research Consortium. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020; 98:209–18
70. Petrilli CM, Jones SA, Yang J, Rajagopalan H, O’Donnell L, Chernyak Y, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020; 369:m1966
71. Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020; 395:1763–70
72. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al.; the Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020; 323:2052–9
73. Argenziano MG, Bruce SL, Slater CL, Tiao JR, Baldwin MR, Barr RG, et al. Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series. BMJ. 2020; 369:m1996
74. Pereira MR, Mohan S, Cohen DJ, Husain SA, Dube GK, Ratner LE, et al. COVID-19 in solid organ transplant recipients: initial report from the US epicenter. Am J Transplant. 2020; 20:1800–8
75. Valeri AM, Robbins-Juarez SY, Stevens JS, Ahn W, Rao MK, Radhakrishnan J, et al. Presentation and outcomes of patients with ESKD and COVID-19. J Am Soc Nephrol. 2020; 31:1409–15
76. Akalin E, Azzi Y, Bartash R, Seethamraju H, Parides M, Hemmige V, et al. Covid-19 and kidney transplantation. N Engl J Med. 2020; 382:2475–7
77. Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J, et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. Am J Gastroenterol. 2020; 115:766–73
78. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020; 382:1787–99
79. Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020; 5:667–78
80. Redd WD, Zhou JC, Hathorn KE, McCarty TR, Bazarbashi AN, Thompson CC, et al. Prevalence and characteristics of gastrointestinal symptoms in patients with severe acute respiratory syndrome coronavirus 2 infection in the United States: a multicenter cohort study. Gastroenterology. 2020; 159:765–767.e2
81. Nobel YR, Phipps M, Zucker J, Lebwohl B, Wang TC, Sobieszczyk ME, et al. Gastrointestinal symptoms and coronavirus disease 2019: a case-control study from the United States. Gastroenterology. 2020; 159:373–5.e2
82. Wander P, Epstein M, Bernstein D. COVID-19 presenting as acute hepatitis. Am J Gastroenterol. 2020; 115:941–2
83. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020; 5:428–30
84. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. Covid-19 in critically ill patients in the seattle region—case series. N Engl J Med. 2020; 382:2012–22
85. Feng Y, Ling Y, Bai T, Xie Y, Huang J, Li J, et al. COVID-19 with different severities: a multicenter study of clinical features. Am J Respir Crit Care Med. 2020; 201:1380–8
86. Liang W, Liang H, Ou L, Chen B, Chen A, Li C, et al.; China Medical Treatment Expert Group for COVID-19. Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. JAMA Intern Med. 2020; 180:1081–9
87. Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020; 323:1775–6
88. Li J, Wang X, Chen J, Zuo X, Zhang H, Deng A. COVID-19 infection may cause ketosis and ketoacidosis. Diabetes Obes Metab. 2020Doi: 10.1111/dom.14057
89. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. 2020; 34:e212–3
90. Jia JL, Kamceva M, Rao SA, Linos E. Cutaneous manifestations of COVID-19: a preliminary review. J Am Acad Dermatol. 2020; 83:687–90
91. Gianotti R, Veraldi S, Recalcati S, Cusini M, Ghislanzoni M, Boggio F, et al. Cutaneous clinico-pathological findings in three COVID-19-positive patients observed in the metropolitan area of Milan, Italy. Acta Derm Venereol. 2020; 100:adv00124
92. Joob B, Wiwanitkit V. COVID-19 can present with a rash and be mistaken for dengue. J Am Acad Dermatol. 2020; 82:e177
93. Diaz-Guimaraens B, Dominguez-Santas M, Suarez-Valle A, Pindado-Ortega C, Selda-Enriquez G, Bea-Ardebol S, et al. Petechial skin rash associated with severe acute respiratory syndrome coronavirus 2 infection. JAMA Dermatol. 2020; 156:820–2

Coronavirus; COVID-19; Severe acute respiratory syndrome coronavirus 2

Copyright © 2020, the Chinese Medical Association.