Betacoronavirus Infection Research Articles

COVID-19 (SARS-COV-2) structural features, pathophysiology and current drug therapy

The 2019 coronavirus pandemic disease has spread globally. SARS-CoV-2 species in the first and second time waves and new species of Omicron show symptoms in the third wave of COVID-19 worldwide. The first patients were found in Wuhan, China. Due to COVID-19, the main highly infected countries are the U.S. China, European countries, and also India. The SARS-CoV-2 species are betacoronavirus infections that spread from person to person and another object. The COVID-19 SARS species (RNA virus) is majorly infected in the lungs. Some vaccines and some drugs are provided worldwide, but these vaccines are not proper treatment for COVID-19. These vaccines boost immunity and provide relief from the symptoms of COVID-19, but they are not a proper treatment. Antimalarial drugs, antiviral drugs, monoclonal antibodies, and antibiotics are used in the current treatment to stop mechanisms like fusion entry and replication. Identification of COVID-19 through symptoms and properly identified by RT-PCR Prevention and treatment of COVID-19 disease is a promising new research area for pharma companies to develop novel therapeutic agents' inhibition for COVID-19 pathological targets.

Antiviral effect of lysosomotropic disaccharide trehalose on porcine hemagglutinating encephalomyelitis virus, a highly neurotropic betacoronavirus

Many members of the genus Betacoronavirus are neurotropic viruses that frequently cause serious harm to humans or animals, including highly neurotropic porcine hemagglutinating encephalomyelitis virus (PHEV). Nevertheless, very few approved treatments exist to combat these viruses. Lysosomotropic trehalose, a widely used, nontoxic, natural disaccharide that can traverse the blood-brain barrier, has been proposed as a potential antiviral agent for use in prevention or treatment of betacoronavirus-associated infections. The purpose of this study was to determine if trehalose could inhibit PHEV infection of cells of a mouse central nervous system-derived neuroblastoma cell line in vitro or brain cells in vivo. Our results demonstrated that treatment of PHEV-infected mouse neuroblastoma cells and mice with trehalose reduced viral replication and that these trehalose antiviral effects were dependent on expression of lysosomal protein progranulin. Collectively, these results indicated that trehalose holds promise as a new antiviral agent for use in controlling neurotropic betacoronavirus infections.

Baseline laboratory parameters for preliminary diagnosis of COVID-19 among children: a cross-sectional study.

ABSTRACTBACKGROUND:Clinical judgment of initial baseline laboratory tests plays an important role in triage and preliminary diagnosis among coronavirus disease 2019 (COVID-19) patients.OBJECTIVES:To determine the differences in laboratory parameters between COVID-19 and COVID-like patients, and between COVID-19 and healthy children. Additionally, to ascertain whether healthy children or patients with COVID-like symptoms would form a better control group.DESIGN AND SETTING:Cross-sectional study at the Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia.METHODS:A retrospective study was conducted on 42 pediatric patients of both sexes with COVID-19. Hematological parameters (white blood cell count, absolute lymphocyte count and platelet count) and biochemical parameters (natremia, kalemia, chloremia, aspartate aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase [LDH] and C-reactive protein [CRP]) were collected. The first control group was formed by 80 healthy children and the second control group was formed by 55 pediatric patients with COVID-like symptoms.RESULTS:Leukocytosis, lymphopenia, thrombocytosis, elevated systemic inflammatory index and neutrophil-lymphocyte ratio, hyponatremia, hypochloremia and elevated levels of AST, ALT, LDH and CRP were present in COVID patients, in comparison with healthy controls, while in comparison with COVID-like controls only lymphopenia was determined.CONCLUSIONS:The presence of leukocytosis, lymphopenia, thrombocytosis, elevated systemic inflammatory index and neutrophil-lymphocyte ratio, hyponatremia, hypochloremia and elevated levels of AST, ALT, LDH and CRP may help healthcare providers in early identification of COVID-19 patients. Healthy controls were superior to COVID-like controls since they provided better insight into the laboratory characteristics of children with novel betacoronavirus (SARS-CoV-2) infection.

A Dual Role of Complement Activation in the Development of Fulminant Hepatic Failure Induced by Murine-Beta-Coronavirus Infection

With the epidemic of betacoronavirus increasing frequently, it poses a great threat to human public health. Therefore, the research on the pathogenic mechanism of betacoronavirus is becoming greatly important. Murine hepatitis virus strain-3 (MHV-3) is a strain of betacoronavirus which cause tissue damage especially fulminant hepatic failure (FHF) in mice, and is commonly used to establish models of acute liver injury. Recently, MHV-3-infected mice have also been introduced to a mouse model of COVID-19 that does not require a Biosafety Level 3 (BSL-3) facility. FHF induced by MHV-3 is a type of severe liver damage imbalanced by regenerative hepatocellular activity, which is related to numerous factors. The complement system plays an important role in host defense and inflammation and is involved in first-line immunity and/or pathogenesis of severe organ disorders. In this study, we investigated the role of aberrant complement activation in MHV-3 infection-induced FHF by strategies that use C3-deficient mice and intervene in the complement system. Our results showed that mice deficient in C3 had more severe liver damage, a higher viral load in the liver and higher serum concentrations of inflammatory cytokines than wild-type controls. Treatment of C57BL/6 mice with C3aR antagonist or anti-C5aR antibody reduced liver damage, viral load, and serum IFN-γ concentration compared with the control group. These findings indicated that complement system acts as a double-edged sword during acute MHV-3 infection. However, its dysregulated activation leads to sustained inflammatory responses and induces extensive liver damage. Collectively, by investigating the role of complement activation in MHV-3 infection, we can further understand the pathogenic mechanism of betacoronavirus, and appropriate regulation of immune responses by fine-tuning complement activation may be an intervention for the treatment of diseases induced by betacoronavirus infection.

Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator.

Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the infection of HCoV-OC43 in distinct cells in a dose- and time- dependent manner. Additionally, the results showed that montelukast induced release of HCoV-OC43 genomic RNA by disrupting the integrity of the viral lipid membrane, and irreversibly inhibited viral infection. Considering the similarity among HCoV-OC43, MERS-CoV, and SARS-CoV-2, it suggests that montelukast may be a potential candidate for the treatment of human beta-coronavirus infection.

Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection

Coronaviruses constitute a global threat to the human population; therefore, effective pan-coronavirus antiviral drugs are required to tackle future re-emerging virus outbreaks. Protein kinase CK2 has been suggested as a promising therapeutic target in COVID-19 owing to the in vitro antiviral activity observed after both pharmacologic and genetic inhibition of the enzyme. Here, we explored the putative antiviral effect of the anti-CK2 peptide CIGB-325 on bovine coronavirus (BCoV) infection using different in vitro viral infected cell-based assays. The impact of the peptide on viral mRNA and protein levels was determined by qRT-PCR and Western blot, respectively. Finally, pull-down experiments followed by Western blot and/or mass spectrometry analysis were performed to identify CIGB-325-interacting proteins. We found that CIGB-325 inhibited both the cytopathic effect and the number of plaque-forming units. Accordingly, intracellular viral protein levels were clearly reduced after treatment of BCoV-infected cells, with CIGB-325 determined by immunocytochemistry. Pull-down assay data revealed the physical interaction of CIGB-325 with viral nucleocapsid (N) protein and a group of bona fide CK2 cellular substrates. Our findings evidence in vitro antiviral activity of CIGB-325 against bovine coronavirus as well as some molecular clues that might support such effect. Altogether, data provided here strengthen the rationale of inhibiting CK2 to treat betacoronavirus infections.

Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection

Training of the innate immune system with orally ingested bacterial extracts was demonstrated to have beneficial effects on infection clearance and disease outcome. The aim of our study was to identify cellular and molecular processes responsible for these immunological benefits. We used a murine coronavirus (MCoV) A59 mouse model treated with the immune activating bacterial extract Broncho-Vaxom (BV) OM-85. Tissue samples were analysed with qPCR, RNA sequencing, histology, and flow cytometry. After BV OM-85 treatment, interstitial macrophages accumulated in lung tissue leading to a faster response of type I interferon (IFN) signalling after MCoV infection resulting in overall lung tissue protection. Moreover, RNA sequencing showed that lung tissue from mice receiving BV OM-85 resembled an intermediate stage between healthy and viral infected lung tissue at day 4, indicating a faster return to normal tissue homoeostasis. The pharmacologic effect was mimicked by adoptively transferring naive lung macrophages into lungs from recipient mice before virus infection. The beneficial effect of BV OM-85 was abolished when inhibiting initial type I IFN signalling. Overall, our data suggest that BV OM-85 enhances lung macrophages allowing for a faster IFN response towards a viral challenge as part of the oral-induced innate immune system training.

Experimental-clinical analysis of some aspects of the Coronaviruses emergence in piggery during 1987–2020

The paper presents an analysis of own clinical and experimental data on the participation of ducks in the possible emergence of swine alpha-coronavirus — a virus of endemic diarrhea (PED-CoV), as well as of the porcine beta-coronavirus threats (hemagglutinating encephalomyelitis virus, PHE-CoV) in the COVID pandemia context. The coronavirus of duck enteritis (DE-CoV) was studied in the nineties of the twentieth century: biodiversity of its morphology includes the morphological variants identical to the morphology of PED-CoV and PHE-CoV. Moreover, hemagglutinins of all these viruses have a bilateral affinity among them on the level 24–42%. Obtained data suggest the real risk of ducks’ participation in the emergence of at least alpha-coronavirus infections in pigs. There are also threats of the emergence of porcine beta-coronavirus infection under the influence of COVID-19 in industrial pig herds

Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of angiotensin-converting enzyme 2 (ACE2) expression. Remarkably, H522 infection requires the E484D S variant; viruses expressing wild-type S are not infectious. Anti-S monoclonal antibodies differentially neutralize SARS-CoV-2 E484D S in H522 cells as compared to ACE2-expressing cells. Sera from vaccinated individuals block this alternative entry mechanism, whereas convalescent sera are less effective. Although the H522 receptor remains unknown, depletion of surface heparan sulfates block H522 infection. Temporally resolved transcriptomic and proteomic profiling reveal alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type I interferon signaling. These findings establish an alternative SARS-CoV-2 host cell receptor for the E484D SARS-CoV-2 variant, which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis.

Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice.

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.

Association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19 including clinical course, morbidity and mortality outcomes? A systematic review

ObjectiveTo systemically review and critically appraise published studies of the association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19, including clinical course,...

Epidemiological Study of Betacoronaviruses in Captive Malayan Pangolins.

The coronavirus disease 2019 (COVID-19) outbreak has significantly affected international public health safety. It has been reported that the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, could originate from bats and utilize the Malayan pangolin (Manis javanica) as an intermediate host. To gain further insights into the coronaviruses carried by pangolins, we investigated the occurrence of Betacoronavirus (β-CoV) infections in captive Malayan pangolins in the Guangdong province of China. We detected three β-CoV-positive M. javanica individuals with a positive rate of 6.98% and also detected β-CoV in two dead pangolins sampled in August 2019. The CoV carried by pangolins is a new β-CoV, which is genetically related to SARS-CoV-2. Furthermore, the expression of angiotensin-converting enzyme 2 (ACE2) was detected in eight organs of pangolins, with the highest ACE2 mRNA levels in the kidney, suggesting that these organs could be at a risk of β-CoV infection. These results enable us to better understand the status of β-CoV carried by Malayan pangolins, while providing a theoretical basis for better pangolin protection and viral control.

Consequences of coronavirus infections for primitive and mature hematopoietic cells: new insights and why it matters.

In recent history there have been three outbreaks of betacoronavirus infections in humans, with the most recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; causing Coronavirus disease 2019 [COVID-19]) outbreak leading to over two million deaths, with a rapidly rising death toll. Much remains unknown about host cells and tissues affected by coronavirus infections, including the hematopoietic system. Here, we discuss the recent findings examining effects that coronavirus infection or exposure has on hematopoietic cells and the clinical implications for these effects. Recent studies have centered on SARS-CoV-2, demonstrating that hematopoietic stem and progenitor cells and mature immune cells may be susceptible to infection and are impacted functionally by exposure to SARS-CoV-2 Spike protein. These findings have important implications regarding hematologic complications arising from COVID-19 and other coronavirus-induced disease, which we discuss here. Infection with coronaviruses sometimes leads to hematologic complications in patients, and these hematologic complications are associated with poorer prognosis. These hematologic complications may be caused by coronavirus direct infection or impact on primitive hematopoietic cells or mature immune cells, by indirect effects on these cells, or by a combination thereof. It is important to understand how hematologic complications arise in order to seek new treatments to improve patient outcomes.

Repurposing existing drugs: identification of SARS-CoV-2 3C-like protease inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Since its emergence, the COVID-19 pandemic has not only distressed medical services but also caused economic upheavals, marking urgent the need for effective therapeutics. The experience of combating SARS-CoV and MERS-CoV has shown that inhibiting the 3-chymotrypsin-like protease (3CLpro) blocks the replication of the virus. Given the well-studied properties of FDA-approved drugs, identification of SARS-CoV-2 3CLpro inhibitors in an FDA-approved drug library would be of great therapeutic value. Here, we screened a library consisting of 774 FDA-approved drugs for potent SARS-CoV-2 3CLpro inhibitors, using an intramolecularly quenched fluorescence (IQF) peptide substrate. Ethacrynic acid, naproxen, allopurinol, butenafine hydrochloride, raloxifene hydrochloride, tranylcypromine hydrochloride, and saquinavir mesylate have been found to block the proteolytic activity of SARS-CoV-2 3CLpro. The inhibitory activity of these repurposing drugs against SARS-CoV-2 3CLpro highlights their therapeutic potential for treating COVID-19 and other Betacoronavirus infections.

Dynamic data-driven meta-analysis for prioritisation of host genes implicated in COVID-19

The increasing body of literature describing the role of host factors in COVID-19 pathogenesis demonstrates the need to combine diverse, multi-omic data to evaluate and substantiate the most robust evidence and inform development of therapies. Here we present a dynamic ranking of host genes implicated in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses). We conducted an extensive systematic review of experiments identifying potential host factors. Gene lists from diverse sources were integrated using Meta-Analysis by Information Content (MAIC). This previously described algorithm uses data-driven gene list weightings to produce a comprehensive ranked list of implicated host genes. From 32 datasets, the top ranked gene was PPIA, encoding cyclophilin A, a druggable target using cyclosporine. Other highly-ranked genes included proposed prognostic factors (CXCL10, CD4, CD3E) and investigational therapeutic targets (IL1A) for COVID-19. Gene rankings also inform the interpretation of COVID-19 GWAS results, implicating FYCO1 over other nearby genes in a disease-associated locus on chromosome 3. Researchers can search and review the gene rankings and the contribution of different experimental methods to gene rank at https://baillielab.net/maic/covid19. As new data are published we will regularly update the list of genes as a resource to inform and prioritise future studies.

Myocardial involvement in coronavirus disease 19.

BackgroundIn late 2019, a cohort of patients presenting with pneumonia of unclear etiology in Wuhan, China, heralded the outbreak of coronavirus disease 19 (COVID-19). Previous severe acute respiratory syndrome (SARS) beta-coronavirus infections have been associated with tachyarrhythmias and signs and symptoms of heart failure. The emergence of SARS coronavirus 2 (SARS-CoV-2), which causes COVID-19, has rapidly developed into a pandemic, and a large number of infected patients have been reported to have underlying cardiovascular disease.ObjectiveSince there are only scant published data regarding cardiovascular burden in the wake of viral epidemics, this study aimed to evaluate cardiac involvement in COVID-19.Material and methodsThis prospective cohort study included 40 adult inpatients at two centers in Germany. Adult patients diagnosed with COVID-19 in accordance with World Health Organization (WHO) interim guidance were included in the study, which focused on the potential cardiac involvement of SARS-CoV‑2. It was based on laboratory parameters as well as electro- and echocardiographic values to determine the impact of SARS-CoV‑2 virus on heart tissues.ResultsThe conducted investigations confirmed the relationship between the presence of acute cardiac injury and COVID-19.ConclusionMyocardial injury and impaired myocardial function due to COVID-19 are common; however, no correlation was established between cardiac laboratory or echocardiographic values and mortality. Cardiovascular monitoring upon COVID-19 infection is crucial to determine the burden of cardiac involvement.

Complicating Infections Associated with Common Endemic Human Respiratory Coronaviruses.

Coronaviruses OC43, 229E, NL63, and HKU1 are endemic human respiratory coronaviruses that typically cause mild to moderate upper respiratory infections, similar to the common cold. They also may cause simple and complicated lower respiratory infections, otitis media, asthma exacerbations, gastroenteritis, and a few systemic complications. These viruses are usually seasonal (with winter dominance) and affect nearly all age groups. The seasonal and annual variation in virus prevalence has implications for understanding the concept of acquired immunity and its persistence or diminution. Coronaviruses generally have outbreak potential in susceptible populations of any age, particularly in patients with comorbidities, who tend to have increased clinical disease. These 4 coronaviruses are often found in the context of what appears to be coinfection with other pathogens, but especially other viruses. If coronaviruses are not specifically tested for, the sole detection of a viral copathogen would suggest the pathogen is the causative agent, when a coronavirus may be culpable, or both. The detection of these viruses in circumstances where respiratory viruses are generally sought in clinical samples is, therefore, justified. These pathogens can be chronically shed from the respiratory tract, which is more likely to occur among immunocompromised and complicated patients. These viruses share the potential for genetic drift. The genome is among the largest of RNA viruses, and the capability of these viruses to further change is likely underestimated. Given the potential disease among humans, it is justified to search for effective antiviral chemotherapy for these viruses and to consider uses in niche situations should effective therapy be defined. Whereas SARS-CoV-2 may follow the epidemiological pattern of SARS-CoV and extinguish slowly over time, there is yet concern that SARS-CoV-2 may establish itself as an endemic human respiratory coronavirus similar to OC43, 2299E, NL63, and HKU1. Until sufficient data are acquired to better understand the potential of SARS-CoV-2, continued work on antiviral therapy and vaccination is imperative.

Suppression of SARS-CoV-2 infection in ex-vivo human lung tissues by targeting class III phosphoinositide 3-kinase.

The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged at the end of 2019 and caused the coronavirus disease 19 (COVID‐19) pandemic due to its high transmissibility and early immunosuppression. Previous studies on other betacoronaviruses suggested that betacoronavirus infection is associated with the host autophagy pathway. However, it is unclear whether any components of autophagy or virophagy can be therapeutic targets for COVID‐19 treatment. In this report, we examined the antiviral effect of four well‐characterized small molecule inhibitors that target the key cellular factors involved in key steps of the autophagy pathway. They include small molecules targeting the ULK1/Atg1 complex involved in the induction stage of autophagy (ULK1 inhibitor SBI0206965), the ATG14/Beclin1/VPS34 complex involved in the nucleation step of autophagy (class III PI3‐kinase inhibitor VPS34‐IN1), and a widely‐used autophagy inhibitor that persistently inhibits class I and temporary inhibits class III PI3‐kinase (3‐MA) and a clinically approved autophagy inhibitor that suppresses autophagy by inhibiting lysosomal acidification and prevents the formation of autophagolysosome (HCQ). Surprisingly, not all the tested autophagy inhibitors suppressed SARS‐CoV‐2 infection. We showed that inhibition of class III PI3‐kinase involved in the initiation step of both canonical and noncanonical autophagy potently suppressed SARS‐CoV‐2 at a nano‐molar level. In addition, this specific kinase inhibitor VPS34‐IN1, and its bioavailable analogue VVPS34‐IN1, potently inhibited SARS‐CoV‐2 infection in ex vivo human lung tissues. Taken together, class III PI3‐kinase may be a possible target for COVID‐19 therapeutic development.

Clinical courses and outcomes of five patients with primary lung cancer surgically treated while affected by Severe acute respiratory syndrome coronavirus 2.

OBJECTIVESThere is currently a lack of clinical data on the novel beta-coronavirus infection [caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and concomitant primary lung cancer. Our goal was to report our experiences with 5 patients treated for lung cancer while infected with SARS-CoV-2.METHODSWe retrospectively evaluated 5 adult patients infected with SARS-CoV-2 who were admitted to our thoracic surgery unit between 29 January 2020 and 4 March 2020 for surgical treatment of a primary lung cancer. Clinical data and outcomes are reported.RESULTSAll patients were men with a mean age of 74.0 years (range 67–80). Four of the 5 patients (80%) reported chronic comorbidities. Surgery comprised minimally invasive lobectomy (2 patients) and segmentectomy (1 patient), lobectomy with en bloc chest wall resection (1 patient) and pneumonectomy (1 patient). Mean chest drain duration was 12.4 days (range 8–22); mean hospital stay was 33.8 days (range 21–60). SARS-CoV-2-related symptoms were fever (3 patients), persistent cough (3 patients), diarrhoea (2 patients) and syncope (2 patients); 1 patient reported no symptoms. Morbidity related to surgery was 60%; 30-day mortality was 40%. Two patients (1 with a right pneumonectomy, 74 years old; 1 with a lobectomy with chest wall resection and reconstruction, 70 years old), developed SARS-CoV-2-related lung failure leading to death 60 and 32 days after surgery, respectively.CONCLUSIONSLung cancer surgery may represent a high-risk factor for developing a severe case of coronavirus disease 2019, particularly in patients with advanced stages of lung cancer. Additional strategies are needed to reduce the risk of morbidity and mortality from SARS-CoV-2 infection during treatment for lung cancer.

Clinicopathologic Findings from Autopsy of the first autopsy done for Patient with COVID-19, Sylhet

The China Health Authority alerted the World Health Organization (WHO) on December 31 2019, to several cases of pneumonia of unknown aetiology in Wuhan City in Hubei Province in central China. Since December 8, 2019, these cases had been reported, worked at or lived around the local Huanan Seafood Market. Radiology finding may vary with patients age, disease progression, immunity status, comorbidity, and initial medical intervention. In a study describing 41 of the initial cases of 2019-nCoV infection, all 41 patients had pneumonia with abnormal findings on chest computed tomography (CT-scan). Abnormalities on chest CT-scan were also seen in another study of 6 cases, in which all of them showed multifocal patchy ground-glass opacities notably nearby the peripheral sections of the lungs. Complete autopsy studies were almost nonexistent in the initial phases of the outbreak; reasonably so, due to concerns related to infectivity, transmission rates, and biosafety. The few reports initially published were limited to postmortem biopsies in COVID-19–positive patients or from lobectomy specimens initially resected for lung adenocarcinoma, but patients were later found to be COVID-19–positive (7). Pathologic features of exudative and proliferative phases of diffuse alveolar damage (DAD) were noted in these initial reports and overlapping features with SARS were also noted. Later complete autopsies performed in United States further supported the presence of DAD. The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERSCoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy. The macroscopic features of COVID-19 are likely to be in the chest and may include pleurisy, pericarditis, lung consolidation and pulmonary oedema. Lung weight may be increased above normal. It should be noted a secondary infection may be superimposed on the viral infection that can lead to purulent inflammation more typical of bacterial infection. The pulmonary histologic characteristics of COVID-19 resembled those observed in diseases caused by other Betacoronavirus infections such as severe acute respiratory syndrome4 and Middle East respiratory syndrome. Histopathology of the lungs showed diffuse alveolar damage, consistent with early acute respiratory distress syndrome in 8 cases. Predominant findings were hyaline membranes, activated pneumocytes, microvascular thromboemboli, capillary congestion, and proteinenriched interstitial edema. As described by Wang and colleagues, a moderate degree of inflammatory infiltrates concurred with clinically described leukopenia in patients with COVID-19 and predominant infiltration of lymphocytes fit the picture of a viral pathogenesis.