key: cord-0691850-uz6usokd
authors: Wang, Yixuan; Wang, Yuyi; Chen, Yan; Qin, Qingsong
title: Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID‐19) implicate special control measures
date: 2020-03-29
journal: J Med Virol
DOI: 10.1002/jmv.25748
sha: a8934871dfe7ff600199821efc833fa3995e2329
doc_id: 691850
cord_uid: uz6usokd

By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID‐19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID‐19 has spread to 46 countries internationally. Total fatality rate of COVID‐19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID‐19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number (R(0)) of COVID‐19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID‐19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID‐19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID‐19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID‐19 and enhance our control measures in the future.

and Figure 1 , COVID-19 has caused 82 623 confirmed cases and 2858 deaths globally. The total case-fatality rate is 3.46% as shown in Table 1 . Because COVID-19 started from Wuhan, the capital city of Hubei province with a large population of nearly 14 million people, 58.3% cases are in Wuhan. A total of 1932 health workers have been infected in Wuhan alone, 9 which overwhelmed the local health system and resulted in the highest case-fatality rate (4.42%). Excluding Hubei province, the rest of China has 13 045 cases, 109 fatalities (0.84%). Outside of China, COVID-19 has spread to 46 countries and has caused 3664 infections and 67 fatalities (1.83%). Overall, the case-fatality rate of COVID-19 so far is much lower than either SARS (9.6%) or MERS (34.5%). 10 Here, we summarized common and discrete features of SARS-CoV-2 in comparison to its two predecessors (SARS-CoV and MERS-CoV) in genetics, epidemiology, clinical features, and further discussed challenges for diagnosis and special control measures for COVID-19.

Full-length genome sequences of SARS-CoV-2 were obtained from early infected individuals related to a wild animal market in Wuhan by different research groups through next-generation sequencing. 1, 2, 11 Full genomic length of this novel coronavirus ranges from 29 891 to 29 903 nucleotides (nt). 2 1, 2, 11 The close phylogenetic relationship to RaTG13 suggests bats are probably natural hosts for SARS-CoV-2. 2 Human SARS-CoV-2 have a unique RRAR motif in the spike protein which is not found in coronaviruses isolated from pangolins, suggesting SARS-CoV-2 may not come directly from pangolins. 12 An evolutionary study 13 based on 86 genomic sequences from GISAID (https://www.gisaid.org/) showed three deletions were found in isolates from Japan, USA, and Australia, 93 mutations found over the entire genomes. Of note, eight mutations were found in the spike surface glycoprotein, especially three mutations (D 354 , Y 364 , and F 367 ) located in the spike surface glycoprotein receptor-binding domain (RBD), which suggested SARS-CoV-2 may rapidly evolve to evade immune response and adapt to other hosts in the future. SARS-CoV-2 share 79% nt sequence identity to SARS-CoV and around 50% to MERS-CoV. 2 However, the seven conserved replicase domains in ORF1ab (used for CoV species classification) of SARS-CoV-2 are 94.6% identical to SARS-CoV, implying the two belong to same species. 1, 2 The receptor-binding protein spike (S) gene of SARS-CoV-2 is highly divergent to all previously described SARSr-CoVs with less than 75% nt sequence identity to except a 93.1% nt identity to RaTG13. Homology modeling revealed SARS-CoV-2 had a similar RBD structure to that of SARS-CoV. 11 Further study showed SARS-CoV-2 uses the same cell entry receptor, ACE2, as SARS-CoV, not CD26 as MERS-CoV. 2 Structural analysis by cryo-electron microscopy revealed SARS-CoVs protein binds ACE2 with 10 to 20 folds higher affinity than SARS-CoV, 14 which suggests that SARS-CoV-2 may be more infectious to human than SARS-CoV.

Transmission of infectious diseases must rely on three conditions: sources of infection, routes of transmission, and susceptible hosts. 21 With enforced implementation of isolation strategies, R 0 was expected to decline in coming days. The mean incubation period was around 6.4 days (ranges from 0 to 24 days). 19, 22 Similar to SARS and MERS, nosocomial transmission was a severe problem to COVID-19, and even worse. A recent retrospective study 9 indicated that a total of 1716 health workers were infected, accounting for 3.84% of total cases. Nosocomial infections extremely burdened the health system and hindered early infected individuals from getting immediate medical supports, therefore resulting in high case-fatality rate in Wuhan as shown in Table 1 Vertical transmission was sporadically reported in some media

but not yet proved. Chen et al 28 Hospital. 28 It is reasonable to assume that a newborn could be infected, either in utero or perinatally, and, thus, newborns should be placed in isolation to avoid exposure to any source of infection.

In terms of susceptible populations, all groups were generally susceptible to COVID-19 regardless of age or sex. 9 Patients aged from 30 to 79 accounted for 86.6% of all cases. 9 The median age of the patients was 47 years. 30 Unlike SARS and MERS, patients diagnosed as COVID-19 have presented with high viral loads even when those have no fever or mild symptoms. 31 High titers of SARS-CoV-2 were detected in travelers who recently visited Wuhan and have no fever or mild symptoms in the United States 31 and Germany 32 and other places. 33 A study showed high viral loads were detected in upper respiratory specimens of patients with COVID-19, and viral shedding pattern of patients resembles that of patients with influenza. 33 This suggests SARS-CoV-2 may stay around for some time like influenza viruses.

The full spectrum of disease severity as shown in the guidelines for diagnosis and treatments for COVID-19 34 36 Less common symptoms included muscle ache, confusion, headache, sore throat, rhinorrhoea, chest pain, sputum production, 36 and nausea and vomiting. 35 Severe complications included ARDS, RNAaemia, acute cardiac injury, and multiple organ failure. 36 The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. 23 67 White blood cell count is generally not high. 76 

fell in the early course, it was associated with adverse clinical outcome. 88 

APTT, elevated D-dimer, and ALT. 39 1. Similar to SARS, common laboratory findings include leukopenia, 79, 80, 84, 89 elevated LDH, AST, thrombocytopenia, and lymphopenia. 79 2. Several cases: viral RNA in blood, urine, and stool but at much lower viral loads 80,90 compared to SARS. 3. Elevated liver enzymes, 91 which may be related to liver injury.

1. Depressed total lymphocytes, prolonged PT, elevated levels of LDH, 23 AST, ALT, 73 blood urea, and creatinine. 23 

and erythrocyte sedimentation rate and normal procalcitonin. 34 

and peripheral blood lymphocytes progressively decreased. 34 4. Critically ill patients: elevated inflammatory factors. 34 

Nonsurvivors: the neutrophil count, D-dimer, blood urea, and creatinine levels is very high. 23 Radiologic features 1. The predominant involvement of lung periphery and the lower zone. Absence of pleural effusion. 67 2. Ground-glass opacification and lobe thickening. 92 1. Bilateral hilar infiltration, unilateral or bilateral patchy densities or infiltrates, ground-glass opacities, and small pleural effusions. 67 

Lower lobes are affected with more rapid radiographic progression than SARS. 67 1. Bilateral distribution of patchy shadows and ground-glass opacity was a typical hallmark of CT scan for NCIP. 23 

a substantial proportion of patients on initial presentation. 73 Pleural effusion is rare. 34 Abbreviations: ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; ARDS, acute respiratory distress syndrome; AST, aspartate aminotransferase; CK, creatine kinase. CRP, C reactive protein; DIC, disseminated intravascular coagulation; LDH, lactate dehydrogenase; MERS-CoV, Middle East respiratory syndrome coronavirus; PT, prothrombin time; SARS-CoV, severe acute respiratory syndrome-coronavirus.

cross-contamination of samples, and inconsistence of sample collections and preparations.

RT-PCR methods generated false-positive or false-negative results, 42, 44 which caused troubles for isolating sources of infections and determining hospitalization days. According to current guidelines for diagnosis and treatments for COVID-19, if one is tested by RT-PCR negative for twice, he/she is considered the cured and should be discharged. However, some of cured and discharged patients later have been tested positive by RT-PCR. 45 Presumably, many factors mentioned above could lead to "false negative" in these cases. On the other hand, a proportion of patients with fever or pneumonia were wrongly isolated together with other confirmed patients with COVID-19 in general medical wards because RT-PCR could produce false-positive results due to sample contaminations or other reasons. These patients turned out to be infected by influenza or other pneumonia associated pathogens.

A recent large diagnostic study 42 57 In addition to the 

The authors declare that there are no conflict of interests.

QQ conceived, wrote, and revised the paper. YW, YW, and YC equally contribute to writing. All authors approved the final version of the manuscript before submission.

Qingsong Qin http://orcid.org/0000-0001-6315-5809

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