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      An update on SARS-CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies

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          Abstract

          Coronavirus Disease 2019 (COVID-19), emerged in early December 2019 in China and became a pandemic situation worldwide by its rapid spread to nearly 190 countries. Bats are considered as the reservoir host, and the search of a probable intermediate host is still going on. The severe form of the infection is associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with inflammation in response to SARS-CoV-2 infection is considered as the leading cause of mortality in COVID-19 patients. COVID-19 patients have thus higher levels of many proinflammatory cytokines and chemokines. The blood lab profile of the COVID-19 patients exhibits lymphopenia, leukopenia, thrombocytopenia, and RNAaemia, along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortality, unlike other zoonotic coronaviruses such as SARS-CoV and MERS-CoV, and there is, to date, no evidence of intrauterine transmission to neonates. Rapid diagnostics have been developed, and significant efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapy, internationally, health care authorities are recommending the adoption of effective community mitigation measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-CoV-2/COVID-19 clinical pathology, pathogenesis, and immunopathology, along with recent research developments.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

              Fei Zhou, Ting Yu, Ronghui Du … (2020)
              Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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                Author and article information

                Contributors
                Kuldeep Dhama
                Alfonso J. Rodriguez-Morales
                Journal
                Journal ID (nlm-ta): Travel Med Infect Dis
                Journal ID (iso-abbrev): Travel Med Infect Dis
                Title: Travel Medicine and Infectious Disease
                Publisher: Elsevier Ltd.
                ISSN (Print): 1477-8939
                ISSN (Electronic): 1873-0442
                Publication date PMC-release: 30 May 2020
                Publication date (Electronic): 30 May 2020
                Electronic Location Identifier: 101755
                Affiliations
                [a ]Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, 243 122, Bareilly, Uttar Pradesh, India
                [b ]Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, 190025, Srinagar, Jammu and Kashmir, India
                [c ]Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, UP Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwavidyalay Evum Go-Anusandhan Sansthan (DUVASU), Mathura, 281001, India
                [d ]Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India
                [e ]Department of Microbiology, Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Nepal
                [f ]Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
                [g ]Semillero de Zoonosis, Grupo de Investigación BIOECOS, Fundación Universitaria Autónoma de las Américas, Sede Pereira, Pereira, Risaralda, Colombia
                [h ]Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnologica de Pereira, Pereira, Colombia
                [i ]Grupo de Investigacion Biomedicina, Faculty of Medicine, Fundacion Universitaria Autonoma de las Americas, Pereira, Risaralda, Colombia
                Author notes
                [∗ ]Corresponding author. Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnologica de Pereira, Pereira, Colombia. arodriguezm@ 123456utp.edu.co
                [∗∗ ]Corresponding author. Division of Pathology, ICAR –Indian Veterinary Research Institute, Izatnagar, Bareilly, India. kdhama@ 123456rediffmail.com
                Article
                Publisher ID: S1477-8939(20)30234-9 Publisher ID: 101755
                DOI: 10.1016/j.tmaid.2020.101755
                PMC ID: 7260597
                PubMed ID: 32479816
                SO-VID: d89ba0fa-22ac-4099-810b-28b6ed02e807
                Copyright © © 2020 Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 22 March 2020
                Date revision received : 13 May 2020
                Date accepted : 26 May 2020
                Categories
                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: sars-cov-2,covid-19,clinical pathology,pathogenesis,immunopathology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: sars-cov-2, covid-19, clinical pathology, pathogenesis, immunopathology

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