Virology, Epidemiology, Pathogenesis, and Control of COVID-19.
TL;DR: The present understanding of COVID-19 is detailed and the current state of development of measures are introduced in this review to provide a comprehensive summary to public health authorities and potential readers worldwide.
Abstract: The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Scientific advancements since the pandemic of severe acute respiratory syndrome (SARS) in 2002~2003 and Middle East respiratory syndrome (MERS) in 2012 have accelerated our understanding of the epidemiology and pathogenesis of SARS-CoV-2 and the development of therapeutics to treat viral infection. As no specific therapeutics and vaccines are available for disease control, the epidemic of COVID-19 is posing a great threat for global public health. To provide a comprehensive summary to public health authorities and potential readers worldwide, we detail the present understanding of COVID-19 and introduce the current state of development of measures in this review.
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TL;DR: Results, which reveal the early kinetics of Sars-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-Co V-2 neutralizing antibodies in people.
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.
733 citations
TL;DR: Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.
482 citations
Cites background from "Virology, Epidemiology, Pathogenesi..."
...may contribute to pathology in young patients with no obvious risk factors (100)....
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...(Figures 2,3,4), that contribute to tissue and organ damage, including acute respiratory distress syndrome (ARDS) (98-100)....
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TL;DR: Factors that might protect children include differences in innate and adaptive immunity, more frequent recurrent and concurrent infections, pre-existing immunity to coronaviruses, and differences in microbiota.
Abstract: In contrast to other respiratory viruses, children have less severe symptoms when infected with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we discuss proposed hypotheses for the age-related difference in severity of coronavirus disease 2019 (COVID-19).Factors proposed to explain the difference in severity of COVID-19 in children and adults include those that put adults at higher risk and those that protect children. The former include: (1) age-related increase in endothelial damage and changes in clotting function; (2) higher density, increased affinity and different distribution of angiotensin converting enzyme 2 receptors and transmembrane serine protease 2; (3) pre-existing coronavirus antibodies (including antibody-dependent enhancement) and T cells; (4) immunosenescence and inflammaging, including the effects of chronic cytomegalovirus infection; (5) a higher prevalence of comorbidities associated with severe COVID-19 and (6) lower levels of vitamin D. Factors that might protect children include: (1) differences in innate and adaptive immunity; (2) more frequent recurrent and concurrent infections; (3) pre-existing immunity to coronaviruses; (4) differences in microbiota; (5) higher levels of melatonin; (6) protective off-target effects of live vaccines and (7) lower intensity of exposure to SARS-CoV-2.
347 citations
TL;DR: A review will be a summa of the key features of novel coronavirus (nCoV), the virus causing disease 2019 and the present epidemic situation worldwide up to April 20, 2020.
338 citations
Cites background from "Virology, Epidemiology, Pathogenesi..."
...review articles summarizing the epidemiology, pathogenesis, clinical characteristics, and management of COVID-19 (Huang et al., 2020c; Jin et al., 2020; Lai et al., 2020a; Lupia et al., 2020; Moriyama et al., 2020; Rodríguez-Morales et al., 2020; Rothan and Byrareddy, 2020; Shereen et al., 2020; Song and Karako, 2020; Vellingiri et al., 2020)....
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TL;DR: Research findings on the physics of aerosol and droplet dispersion relevant to the hypothesized aerosol transmission of SARS-CoV-2 during the current pandemic are provided.
324 citations
Cites background from "Virology, Epidemiology, Pathogenesi..."
...Viral replication leads to local and systemic inflammatory responses, resulting in a cytokine storm that promotes variable and severe pathological responses (Chung et al., 2020) and multi-organ dysfunction (Jin et al., 2020)....
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...SARS-CoV-2 transmission is thought to be mostly by inhalation of droplets and contact contamination (Jin et al., 2020)....
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..., 2020) and multi-organ dysfunction (Jin et al., 2020)....
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References
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TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
"Virology, Epidemiology, Pathogenesi..." refers background in this paper
...Additionally, several studies have reported that lymphopenia is a common feature of COVID-19 [2,5], suggestive of a critical factor accounting for severity and mortality....
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...However, such a decisive conclusion was disputed because the earliest case had had no reported link connection to the mentioned market [5]....
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...The representative chest CT findings of non-ICU patients showed bilateral ground-glass opacity and subsegmental areas of consolidation [2,5]....
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...Blood test showed normal or reduced (25%) white blood cell count and lymphopenia (65%) [5]....
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...In the initial 41 patients [5], fever (98%), cough (76%), and myalgia or fatigue (44%) were the most common symptoms....
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TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
21,455 citations
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Abstract: Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV. Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.
16,857 citations
"Virology, Epidemiology, Pathogenesi..." refers background or methods in this paper
...However, there is 94.6% sequence identity between the seven conserved replicase domains in ORF1ab of SARS-CoV-2 and SARS-CoV [8], and less than 90% sequence identity between those of SARS-CoV-2 and other β-CoVs [2], implying that SARS-CoV-2 belongs to the lineage B (Sarbecovirus) of β-CoVs [12]....
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...Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor hijacked by SARS-CoV-2 for cell entry, similar to SARS-CoV [8,16]....
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...98% sequence identity, implying that not much variation has taken place [8,11]....
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...6% sequence identity between the seven conserved replicase domains in ORF1ab of SARS-CoV-2 and SARS-CoV [8], and less than 90% sequence identity between those of SARS-CoV-2 and other β-CoVs [2], implying that SARS-CoV-2 belongs to the lineage B (Sarbecovirus) of β-CoVs [12]....
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...It has been shown that patients with SARS-CoV-2 infection possess acute serological responses [8]....
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TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Abstract: Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). 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. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
16,635 citations
TL;DR: There is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019 and considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere.
Abstract: Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the...
13,101 citations
"Virology, Epidemiology, Pathogenesi..." refers background in this paper
...The initial outbreak (8 December 2020) only occurred in Wuhan and its surroundings inHubei Province before an imported case was first reported in Guangdong Province on January 19, 2020 [1,29]....
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...At the end of 2019, COVID-19 emerged in several local hospitals of Wuhan, Hubei Province, China (Figure 1)....
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...At the end of 2019, a cluster of pneumonia patients with an unidentified cause emerged in Wuhan, Hubei Province, China [1]....
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