IP Archives of Cytology and Histopathology Research

Print ISSN: 2581-5725

Online ISSN: 2456-9267

CODEN : IACHCL

IP Archives of Cytology and Histopathology Research (ACHR) open access, peer-reviewed quarterly journal publishing since 2016 and is published under the Khyati Education and Research Foundation (KERF), is registered as a non-profit society (under the society registration act, 1860), Government of India with the vision of various accredited vocational courses in healthcare, education, paramedical, yoga, publication, teaching and research activity, with the aim of faster and better dissemination more...


  • Article highlights
  • Article tables
  • Article images

Article statistics

Viewed: 50

PDF Downloaded: 25

Faizal, Kapoor, and Nambiar: A systematic review of autopsy findings in COVID 19: The road ahead


Introduction

As the novel coronavirus now known as the Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) originated in Wuhan district of china and later spread to the entire world, it triggered a pandemic of Coronavirus disease 2019 (COVID 19) and has resulted in more than 3,00,000 deaths worldwide as on 16th May 2020.

The family of coronavirus is known to cause many zoonotic disease outbreaks including the Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome Eastern (SARS) in the past.1

All the outbreaks originated from bats and infected secondary animal hosts like the dromedary camel (MERS) and the civet cat (SARS) before being transmitted to humans.2

The novelty of the SARS-CoV-2 virus combined with the higher infectivity than SARS-CoV and global hysteria has left a huge void in the understanding of the pathology of the disease with many medical governing bodies advising against autopsies in confirmed COVID 19 deaths.3, 4 The scarce post-mortem examination data needs to be examined to understand the course of the disease and determine future course of treatment protocols to improve patient outcomes.

Objective

This review aims to provide an overview of various autopsy findings in patients with COVID-19.

Materials and Methods

Data bases and search strategy

Our method protocol follows the recommendations established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and is outlined in (Figure 1).5 A literature search was conducted using PubMed / Medline, Scopus, Embase and Google search engines. The search terms used were: “Autopsy in COVID-19”, “Post mortem in COVID-19”, “Autopsy in SARS-CoV-2” and “Post mortem in SARS-CoV-2.” The search was limited to articles published in 2020 and due to the large number of search results in grey literature, keyword search was limited only to the titles in the Google scholar search engine whereas no such restriction was placed on the other databases.

The literature search was concluded by May 16, 2020, and two independent researchers evaluated the search results.

Study selection

After removal of duplicate search entries, the initial search results were first screened by language, title and abstract. The full texts of relevant articles were examined for inclusion and exclusion criteria.

Inclusion criteria

  1. Studies published till 16th May 2020.

  2. English language.

  3. Mentioning histopathology of any organ in partial or complete autopsies in confirmed cases of COVID 19.

Exclusion criteria

  1. Studies published in other languages.

  2. Studies not based on autopsy.

  3. Studies mentioning only gross examination and no histopathological examination of the autopsy specimens.

Studies on non-human subjects

The selected studies were assessed for quality using the National Institutes of Health Quality Assessment Tool for Case Series Studies by two independent observers (Figure 2).6

Data collection process

After assessment and selection of the study, Information on the type of publication, country, year and date of publication, the number of reported cases, age, sex, comorbidities, clinical features, laboratory findings, and findings at autopsy were filled independently by two investigators.

A third researcher checked the article list and data extrapolation to ensure that relevant studies were included and that no duplicate data was entered erroneously.

Data anaysis

This data was analysed and recorded by two independent researchers. In case of discrepancy, the third researcher was consulted and consensus achieved. Data was analysed using Medcalc version 19.0.7 and descriptive statistics were used to compare findings.Meta-analysis to corelate age and ethnicity with pathological features could not be carried out due to limited data.

Figure 1

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram outlining the study selection process.

*3 studies were in Chinese language, 3 studies not based on autopsy and 1 study on non-human subjects

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/562599a6-76f0-4c22-a837-363d1d52b1d8image1.png

Figure 2

Quality ratings of included studies according to NIH Quality Assessment Tool for Case Series Studies

Q1. Was the study question or objective clearly stated?

Q2. Was the study population clearly and fully described, including a case definition?

Q3. Were the cases consecutive?

Q4. Were the subjects comparable?

Q5. Was the intervention clearly described?

Q6. Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants?

Q7. Was the length of follow-up adequate?

Q8. Were the statistical methods well-described?

Q9. Were the results well-described?

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/562599a6-76f0-4c22-a837-363d1d52b1d8image2.png

Guidelines for performing autopsy on confirmed/suspected covid 19 cases

Various regulatory health bodies like The Royal College of Pathologists (RCPath, UK), the Centre for Disease Control (CDC, USA) and the Ministry of Health and Family Welfare (MoHFW, India) have released guidance on post-mortem examination for mortuary workers in suspected/ confirmed COVID 9 cases.4

Adequate training and strict adherence to institutional SOPs in accordance with the guidelines should ensure minimal exposure of the mortuary staff.

Results

Findings from a total of 15 studies describing 139 autopsies in confirmed cases of COVID 19 by RT PCR were analysed. Additionally, histopathological findings were reported from the lung specimens of 2 patients who underwent lobectomy for lung carcinoma but were found to be positive for COVID 19 subsequently. Since these were technically not autopsies, the findings were not included in our data but have been discussed separately.7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22

The average age of all the deceased individuals was 62.5 years with an age range of 17 to 96 years. More than 75% of deaths were in males. Ethnicity was specified in only 8 cases amongst which 6 were African American and 2 were Hispanic.9, 18, 21

All the fatal cases had a history of one or more previous underlying disorders including diabetes mellitus, hypertension, obesity, CKD, COPD, malignancy, myotonic dystrophy, liver cirrhosis, hepatitis C with hypertension and obesity being the most common.

In the fatal cases studied, the predominant clinical feature was mentioned in 65 cases, which was cough (49%) followed by progressive dyspnoea (47%) and fever (43%). An initial presentation with Diarrhoea was reported in 2 cases. The youngest patient included in this study was a 17-year-old African American male who presented with headache, nausea and vomiting.21

Laboratory findings were available variably amongst the studies and elevated levels of LDH (96%), D-Dimer (100%) and Creatinine (81%) were seen in a majority of cases in which the reports were available.

Lymphocyte counts were available in 32 cases of which 29 showed lymphocytopenia. One autopsy series from Switzerland mentions lymphocytopenia as a prominent finding but individual patient data was not available. 20 Levels of Brain natriuretic peptide (4/4), serum ferritin (2/2) and CK MB (2/2) were elevated in all the recorded cases.

The demographic and laboratory data has been summarized in Table 1.

Autopsy findings were recorded from the lungs in 113 cases followed by heart (50), kidney (41), liver (23), spleen (12), Lymph nodes (9). bone marrow (5), brain (2) and skin (2). The findings have been summarised in Table 2.

Of the 113 cases in which pathological findings of the lung were recorded, the histological picture consisted of multiple features in every case. However, to facilitate enumeration of the most prominent changes, the features were individually recorded from the various studies.

The most common findings were features consistent with varying stages of Diffuse Alveolar Damage (DAD) including hyaline membrane formation, vascular congestion, pneumocyte injury with focal sloughing and intraalveolar haemorrhages.

57 of the 113 cases showed features of microthrombi formation in the pulmonary vessels with 39 cases showing presence of increased CD61 positive megakaryocytes in the alveolar capillaries.

Complement mediated Necrotising capillary injury was reported in the lungs of both cases studied by Magro et al. 10

Amongst the 50 recorded findings from the heart, Cardiomegaly on gross examination and/or myocyte hypertrophy histologically were noted in 39 cases. Four studies recorded focal individual myocyte injury in a total of 11 cases. Senile amyloidosis was seen in 6 cases. Myocarditis was noted in 3 cases amongst which the heart tissue from the 17-year-old showed features of fulminant eosinophilic myocarditis.21

Histological findings from the Kidney were recorded in 42 cases of which 41 showed features of acute tubular injury with loss of brush border, vacuolar degeneration and occasional necrosis. Segmental fibrin thrombi and features of Disseminated intravascular coagulation were seen in 4 and 3 cases respectively. Electron microscopy was done in 23 cases of which 21 demonstrated spherical virus particles in the proximal tubular epithelium.

Liver was studied in 23 cases in which steatosis and sinusoidal dilation were the most common findings.

Findings from the spleens in 12 cases revealed diminished white pulp with loss of marginal zone in 6 and features of splenitis in 6. In addition to diminished white pulp, 3 cases also showed red pulp expansion with lymphoplasmacytic infiltrate.

Bone marrow was studied in 5 cases and 3 showed left shift corelating with neutrophilic leucocytosis whereas 2 showed infiltrates of Hematolymphoid malignancy.

Skin biopsies were available from 2 patients and showed complemented mediated vasculopathy.

Punctate haemorrhages were noted in the subarachnoid and brainstem in one case each Electron microscopy was used to demonstrate the viral particles in the pneumocytes in the studies conducted at Italy and New York whereas the series from Washington demonstrated the viral particles in the lung trachea, kidney and large intestine. 11, 17, 19

Individual data was available from ultrastructural study of 23 kidney biopsies of which 21 showed the presence of viral particles.

Additionally PCR was used to determine the viral load in various tissues by Bradley et al. The highest concentrations were noted in lung, kidney, heart, liver, spleen, large intestines and lymph nodes. Viral RNA was not detected in the brain, bladder, esophagus or stomach.19

Table 1

Demographic and clinical data from 139 autopsies

Total autopsies

139

Gender (134)

Male

102

Female

33

Not specified

04

Age

Average age

68.1*

Youngest

17

Oldest

96

Comorbidities (137)

Hypertension

65

Obesity

43

Diabetes Mellitus/Prediabetes

30

Pre-existing heart disease

33

Malignancy

15

Pre-existing COPD

6

Clinical features

Fever

28

Cough

32

Dyspnea

31

Diarrhoea

2

Laboratory findings

Increased LDH

24/25

Increased D Dimer

38/38

Lymphopenia

29/32 †

Elevated creatinine

31/38 †

Elevated BUN

13/22

Elevated BNP

4/4

Elevated CK MB

2/2

Elevated ferritin

2/2

[i] *Data not available from cases in New York. Both cases mentioned as middle aged.17

[ii] *Data not available from cases in New York. Both cases mentioned as middle aged.$

Table 2

Autopsy findings from various organs

Organ

Findings

Number

LUNG (data available from 113 cases)

Diffuse Alveolar Damage (exudative, proliferative or both)

102

Thrombi in pulmonary vessels

57

Pulmonary embolism

13

Pulmonary edema (varying degrees)

48

Pneumonia

38

Tracheitis

16

Emphysema

13

Reactive pneumocytes, metaplasia and syncytial cells

61

Prominent lymphoid infiltrate

42

Necrotising capillary injury

2

Pulmonary hemorrhage

41

Amyloidosis of pulmonary vessels

3

Vasculitis

1

Increased CD 61 + Megakaryocytes in capillaries

39

Viral particles by EM

2*

HEART (n=50)

Cardiomegaly/ Hypertrophy

39

Senile amyloidosis

7

Individual myocyte injury

11

MI

2 †

Myocarditis

3

Pericarditis / epicarditis

3

No change

5

SPLEEN (n=12)

White pulp diminished with loss of marginal zone

6

Red pulp expansion with lymphoplasmacytic infiltrate

3

Splenitis

6

KIDNEY (n=42)

Acute tubular injury

41/42

Segmental fibrin thrombi

4

Virus particles by EM

21/23

DIC

3

Hypertensive nephropathy

15

Diabetic nephropathy

7

LIVER (n=23)

Sinusoidal dilatation

11

Regenerative nodules

1

Steatosis

20

Shock necrosis

9

Steatohepatitis/NASH

3

Mild lobular lymphocytic infiltrate

6

Bone marrow (n=5)

Reactive left shift

3

Infiltration by hematopoietic malignancy

2

Skin (n= 2)

Complement mediated vascular injury

2

Brain (n=2)

Punctate subarachnoid haemorrhages

1

Punctate brainstem haemorrhages

1

Other

Thrombi in Para testicular veins

1

Increased plasmablasts in lymph nodes

5/9

[i] *Studies from Italy and Washington also reported viral particles in pneumocytes but did not mention exact number of cases.

[ii] † 8 cases also showed signs of old myocardial infarction.

Discussion

Even though most guidelines advise against autopsy in known COVID 19 patients, many authors have called for increased autopsy studies to further the knowledge about the disease process and guide therapy.23

The mean age of patients who underwent autopsy in the studies reviewed by us was 62.5 and had one or more comorbidities with hypertension and obesity being the most common. This corelates with most of the demographic data available.24

Clinical studies have mentioned the most common manifestations of COVID 19 to include fever, dyspnoea, dry cough, headache, muscle pain, chest pain, diarrhoea, nausea and vomiting. A meta-analysis performed by Rodriguez Morales et al found fever, cough and dyspnea to be the most prevalent clinical manifestations with the frequency of fever being significantly higher in adults as compared to children. However, in the fatal cases included in our study, the most common clinical features were cough and dyspnoea. Amongst laboratory findings in clinical studies, indicators of acute inflammatory response like decreased albumin, high C-reactive protein, high lactate dehydrogenase, lymphopenia, and high erythrocyte sedimentation rate were most prevalent.25 In our study, the laboratory findings in the fatal cases included high incidence of elevated D- dimer, LDH and serum creatinine accompanied by lymphocytopenia. This suggests infection related septic coagulopathy and/or organ dysfunction. Therefore elevated D-dimer and serum creatinine may be uses as an adverse prognostic marker in confirmed cases of COVID 19.

65% of the autopsy cases in the study by Menter et al had the blood type A which corelated with a population study in China suggesting that individuals with the blood type A were more susceptible to the thromboembolic sequelae of the disease.26 Studies suggesting the effect of ABO alleles on the activity of Von Willebrand Factor(vWF) with the A1A1 subtype increasing vWF activity the most may explain this phenomenon.27

Earlier studies on the SARS coronavirus have suggested that the Viral S protein interacts with the A antigen to facilitate its entry into the cells which may be a shared characteristic with the SARS-CoV-2. 28

The primary pathology in all the studies was noted in the lung and broadly composed of two patterns. Diffuse alveolar damage was the only striking feature in the 4 post-mortem samples studies by Tian et al in China and the single case reports from China and Iran whereas the autopsies carried out in Brazil, Italy, New Orleans and Texas showed bilateral DAD with alveolar capillary thickening and fibrin thrombi with presence of atypical megakaryocytes in the capillary lumen. 2 cases studied by Magro et al showed predominant changes in the septal capillaries consistent with complement mediated destruction whereas alveolar damage was negligible.

The demonstration of deep vein thrombosis (58%) and massive pulmonary embolism (33.3%) in the autopsy series by Wichmann et al suggests that pulmonary embolism may be an overlooked clinical feature in cases of sudden death especially when CT chest is being avoided to minimize exposure of hospital staff.15

Amongst the pulmonary pathology of other coronavirus infections, varying degrees of exudative and proliferative phase of acute lung injury, along with vascular fibrin thrombi have been recorded in patients with SARS-CoV infection whereas the lungs of MERS patients only revealed DAD and no vascular thrombi. Therefore, some similarities exist in the pathogenesis and the mechanisms of tissue damage due to coronaviruses infections.29, 30, 31 However DAD seems to strike early in SARS CoV-2 with patients succumbing after a brief history of the disease showing alveolar damage on autopsy whereas in SARS infection, DAD developed after longer duration of hospital stay.32

The different patterns of pathological presentations in the lung of COVID 19 patients warrant an investigation into the role of host factors including ethnicity, underlying comorbidity and immunity or the effect of different virus strains present in different geographical areas.

The therapeutic implications of understanding the primary pathology in the lung is that by starting anti coagulation therapy early in the course of the disease, perfusion can be maintained thereby improving patient outcomes. A Chinese single-centre retrospective study of 449 consecutive patients classified as having severe COVID-19 indicates that prophylactic anticoagulation therapy might be associated with improved survival in patients with sepsis induced coagulopathy.33 Prophylactic low molecular weight heparin has been recommended by some authors in all patients admitted with suspected COVID 19 and has recently been included in the Ministry of Health and Family Welfare guidelines in the management of the disease.34, 35

The demonstration of complement mediated destruction of the septal capillaries and the presence of vascular deposition of C5b-9 which is a feature of many microthrombotic syndromes like Paroxysmal Nocturnal Hemoglobinuria and Hemolytic Uremic Syndrome points towards a possible role of anti-complement therapy like Eculizumab in such patients.36, 37 Similar findings in the skin biopsies suggest a systemic involvement rather than a local reaction.

Even though case reports have mentioned petechial rash and urticaria amongst the rarer manifestations of the disease, in a majority of them the severity of cutaneous lesions was unlikely to be or was not correlated with COVID-19 severity.38

Pathological changes in the heart were not characteristic as they may be sequelae of underlying comorbidities. However, scattered individual myocyte necrosis and myocarditis were noted in a few cases with one case showing extensive eosinophilic infiltrate. The elevated levels of BNP and CK MB noted in some patients accompanied by the demonstration of Viral RNA in the heart tissue support a study by Chen et al which suggests that pericytes may be infected by the virus and causes capillary endothelial cell dysfunction causing individual cell necrosis.39

Acute tubular injury was the most noted finding in the kidneys followed by changes suggestive of underlying diabetic or hypertensive disease. Few cases showing segmental fibrin thrombi suggest a thromboembolic component in the pathology in the kidney which also explains the rising serum creatinine levels in deteriorating cases.

The demonstration of coronavirus particles by electron microscopy in the various organs including Pneumocytes, Kidney, trachea, large intestine and spleen, a high viral RNA load detected by PCR in samples from Lung, pharyngeal tisue, kidney, heart, liver, spleen, large intestines and lymph nodes combined with the histological findings suggest direct invasion and cytopathic effect of the SARS Cov -2.15, 19

Studies have suggested the entry of the virus into the cell via ACE 2 and CD 147 receptors.40, 41 The presence of ACE 2 receptors in the lungs and kidneys and the expression of CD 147 in the proximal tubular epithelial cells and the frequent demonstration of viral particles in these tissues provide merit to this hypothesis. The role of Cyclosporine A which downregulates the expression of CD147 needs to be investigated.42, 43, 44

It should also be noted that patients with hypertension, cardiac diseases, obesity related sleep apnea are frequently placed on angiotensin converting enzyme inhibitors or angiotensin receptor blockers which causes up-regulation of the ACE 2 receptors. This may contribute to the increased susceptibility of these patients to the virus.

The presence of high viral RNA load in various tissues and the presence of viral particles in the blood and stool suggest a simultaneous multiorgan involvement and raises apprehension in the fields such as transplant surgery and transfusion medicine as a negative nasopharyngeal test may not completely rule out the disease.45, 46

Conclusion

The spectrum of pathological changes in the lung and other organs suggest a microvascular thrombotic pathology in addition to DAD. Pulmonary embolism may be an overlooked clinical feature and prophylactic dose of low molecular weight heparin is recommended in all patients with suspected COVID 19 admitted to the hospital. In addition, chest CT and serial D-dimer levels are recommended for early detection of Pulmonary thromboinflammatory process and prognostic stratification. The demonstration of complement mediated injury to various tissues also suggest a role of anti-complement therapy to improve patient outcomes. The role of cyclosporine A as an inhibitor of CD147 which is suggested as an entry mechanism for the virus needs to be examined.

The increased susceptibility of individuals with blood group A needs to be investigated further by obtaining the available records of all fatalities of COVID 19.

Detailed autopsy studies are required to evaluate the pathology of COVID 19 in various organs to understand the disease process better.

Conflict of Interest

The authors declare that there are no conflicts of interest in this paper.

Source of Funding

None.

References

1 

Z Grimes C Bryce E M Sordillo Fatal Pulmonary Thromboembolism in SARS-CoV-2-InfectionCardiovasc Pathol202048107227107227

2 

J Guarner Three Emerging Coronaviruses in Two DecadesAm J Clin Pathol20091534420110.1093/ajcp/aqaa029

3 

S R Gong L L Bao The battle against SARS and MERS coronaviruses: Reservoirs and Animal ModelsAnimal Model Exp Med20181212533

4 

D Wrapp N Wang K S Corbett Cryo-EM structure of the 2019-nCoV spike in the prefusion conformationScience202036764831260310.1126/science.abb2507

5 

Government of India Ministry of Health & Family Welfare Directorate General of Health Services (EMR Division) COVID-19: Guidelines on dead body management dated 15 Mar 2020https://www.mohfw.gov.in/pdf/1584423700568_COVID19GuidelinesonDeadbodymanagement.pdf

6 

D Moher A Liberati J Tetzlaff Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statementPLoS Med200967270759910.1371/journal.pmed.1000097

7 

National Heart, Lung, and Blood Institute website. Study quality assessment tools. www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Accessed May 17, 2020

8 

S Tian Y Xiong H Liu Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsiesMod Pathol202033100714

9 

L M Barton E J Duval E Stroberg COVID-19 AutopsiesAm J Clin Pathol202015367253310.1093/ajcp/aqaa062

10 

S E Fox A Akmatbekov J L Harbert Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New OrleansmedRxiv202010.1101/2020.04.06.20050575

11 

C Magro JJ Mulvey D Berlin G Nuovo Sn Salvatore J Harp Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five casesTransl Res202022011310.1016/j.trsl.2020.04.007

12 

L Carsana A Sonzogni A Nasr RS Rossi A Pellegrinelli P Zerb Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive studyLancet Infect Dis2020201011354010.1016/S1473-3099(20)30434-5

13 

H Su M Yang C Wan Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in ChinaKidney Int20099812192710.1016/j.kint.2020.04.003

14 

Z Xu L Shi Y Wang Pathological findings of COVID-19 associated with acute respiratory distress syndromeLancet Respir Med202084420210.1016/S2213-2600(20)30076-X

15 

M Dolhnikoff A N Duarte-Neto R A De Almeida Monteiro Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19J Thromb Haemost2020

16 

D Wichmann J Sperhake M Lütgehetmann Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort StudyAnn Intern Med202010.7326/M20-2003

17 

P Karami M Naghavi A Feyzi MS Novin A Mobaien M Qorbanisani Mortality of a pregnant patient diagnosed with COVID-19: A case report with clinical, radiological, and histopathological findingsTravel Med Infect Dis20201110166510.1016/j.tmaid.2020.101665

18 

L M Buja D Wolf B Zhao Emerging Spectrum Of Cardiopulmonary Pathology Of The Coronavirus Disease 2019 (Covid-19): Report Of Three Autopsies From Houston, Texas And Review Of Autopsy Findings From Other United States CitiesCardiovasc Pathol20204810723310.1016/j.carpath.2020.107227

19 

B T Bradley H Maioli R Johnston Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case seriesLancet2020396102473203210.1016/S0140-6736(20)31305-2

20 

T Menter JD Haslbauer R Nienhold Sa Savic H Hopfer N Deigendesch Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunctionHistopathology202077219820210.1111/his.14134

21 

R Craver S Huber M Sandomirsky J Schieffelin L Finger Fatal Eosinophilic Myocarditis in a Healthy 17-Year-Old Male with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2c)Fetal Pediatr Pathol2020393263810.1080/15513815.2020.1761491

22 

S Tian W Hu L Niu Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung CancerJ Thorac Oncol2020155700410.1016/j.jtho.2020.02.010

23 

X Xu R F Barth L M Buja A call to action : the need for autopsies to determine the full extent of organ involvement associated with COVID-19 infectionsCHEST2020158143410.1016/j.chest.2020.03.060

24 

JM Jin P Bai W He F Wu XF Liu DM Han Gender Differences in Patients With COVID-19: Focus on Severity and MortalityPublic Health2020815210.3389/fpubh.2020.00152

25 

A J Rodriguez-Morales J A Cardona-Ospina E Gutiérrez-Ocampo Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysisTravel Med Infect Dis20203410162310.1016/j.tmaid.2020.101623

26 

J Zhao Y Yang H Huang D Li D Gu X Lu Relationship between the ABO Blood Group and the COVID-19 Susceptibility (pre-print, not peer-reviewed)medRxiv20201-1810.1101/2020.03.11.20031096

27 

V M Morelli M C De Visser N H Van Tilburg ABO blood group genotypes, plasma von Willebrand factor levels and loading of von Willebrand factor with A and B antigensThromb Haemost200797453441PMID

28 

P Guillon M Clement V Sebille Inhibition of the interaction between the SARS-CoV spike protein and its cellular receptor by anti-histo-blood group antibodiesGlycobiology20081810859310.1093/glycob/cwn093

29 

D M Hwang D W Chamberlain S M Poutanen Pulmonary pathology of severe acute respiratory syndrome in TorontoMod Pathol200518111010.1038/modpathol.3800247PMCID

30 

J Gu C Korteweg Pathology and pathogenesis of severe acute respiratory syndromeAm J Pathol2007170411364710.2353/ajpath.2007.061088

31 

J M Van Den Brand S L Smits B L Haagmans Pathogenesis of Middle East respiratory syndrome coronavirusJ Pathol201523521758410.1002/path.4458

32 

T J Franks P Y Chong P Chui Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from SingaporeHum Pathol2003348743810.1016/S0046-8177(03)00367-8

33 

N Tang H Bai X Chen D Li Z Sun Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathyJ Thromb Haemost20201851094910.1111/jth.14817

34 

M Oudkerk H R Büller D Kuijpers Diagnosis, Prevention, and Treatment of Thromboembolic Complications in COVID-19: Report of the National Institute for Public Health of the NetherlandsRadiology202010.1148/radiol.2020201629

35 

Government of India Ministry of Health & Family Welfare Directorate General of Health Services (EMR Division) Revised Guidelines on Clinical Management of COVID – 19Government of India Ministry of Health & Family Welfare Directorate General of Health Services (EMR Division) Revised Guidelines on Clinical Management of COVID - 19https://www.mohfw.gov.in/pdf/RevisedNationalClinicalManagementGuidelineforCOVID1931032020.pdf

36 

C L Harris R B Pouw D Kavanagh Developments in anti-complement therapy; from disease to clinical trialMol Immunol20181028911910.1016/j.molimm.2018.06.008

37 

S Meri Complement activation in diseases presenting with thrombotic microangiopathyEur J Intern Med201324649650210.1016/j.ejim.2013.05.009

38 

M Sachdeva R Gianotti M Shah Cutaneous manifestations of COVID-19: Report of three cases and a review of literatureJ Dermatol Sci2020203014930152

39 

L Chen X Li M Chen The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2Cardiovasc Res2020116671845077184507PMCID

40 

M Hoffmann H Kleine-Weber S Schroeder SARSCoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor2020http://www.sciencedirect.com/science/article/pii/S0092867420302294

41 

K Wang W Chen Y S Zhou SARS-CoV-2 invades host cells via a novel route: CD147-spike protein202010.1038/s41392-020-00426-x

42 

F Qi S Qian S Zhang Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronavirusesBiochem Biophys Res Commun202052611354010.1016/j.bbrc.2020.03.044

43 

X Zou K Chen J Zou Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infectionFront Med20201421859210.1007/s11684-020-0754-0PMCID

44 

V Yurchenko T Pushkarsky J H Li Regulation of CD147 cell surface expression: involvement of the proline residue in the CD147 transmembrane domainJ Biol Chem20052801717013910.1074/jbc.M412851200

45 

W Wang Y Xu R Gao Detection of SARS-CoV-2 in Different Types of Clinical SpecimensJAMA2020https://jamanetwork.com/journals/jama/fullarticle/2762997

46 

Y Xu X Li B Zhu Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral sheddingNat Med2020264502510.1038/s41591-020-0817-4



jats-html.xsl

© This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Article type

Review Article


Article page

145-152


Authors Details

Felice Faizal, Umesh Kapoor, Balachandra Nambiar


Article History

Received : 05-07-2021

Accepted : 20-08-2021

Available online : 16-09-2021


Article Metrics


View Article As

 


Downlaod Files

   








Wiki in hindi