Covid-19: UK deaths are higher than previously reported, new data suggestBMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1330 (Published 01 April 2020) Cite this as: BMJ 2020;369:m1330
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Re: Covid-19: UK deaths are higher than previously reported, new data suggest Pathologenesis behind death of Covid 19 cases not only ARDS but coagulopathy, thrombosis and DIC . Low molecular weight heparin will be helpful showing signs of severe pneumonia
In the world, Corona virus cases jumped up till 14 th May 2020 from December 2019 is 45,25,490 with death 3,03,371 (6.7%) and 31.5 death per one million people of infected.Almost 212 countries worldwide and most affected countries are USA,( death rate 262) followed by Spain (544),Itali (519), UK (495), France (428) China( 03 )per million population when in India total cases of positive by RT PCR is 82,000death 2650 ( 02 ) per one million people and in West Bengal province of India total infected is 2300 with death 207 cases as per ministry of health government of India records on covid 19. The question to me is why such a huge percentage of death from this dangerous virus ( no more should be considered simple like influenza virus) inspite of lockdown, social distancing ventilation guided treatment protocol for mild moderate and severe pneumonia from covid 19?
Mortality from covid 19 is higher in groups at higher risks of thromboembolism including hypertension, types 2DM, obesity, coronary artery disease ,cardiomyopathy, pre existing renal pathology as co morbid condition known to all. It has been also seen world wide that the risk of thromboembolism ( both venous and arterial) are more likely to occur when patients are admitted at ICU or in PEP ventilation, ànd in aged over 60 yrs( approximately 63% of death in India from covid 19).
What did the autopsy studies revealed of these death, though very limited autopsy were performed with covid 19 death as the virus is HG 3 category virus. Brane Hanely (1) eral published in journal of clinical pathology of BMJ group showed histopathology of lungs on HE stain oedema, Type Ii pneumocytes hyperplasia,large pneumocytes with ground glass viral inclusions bodies focal inflammation, multinucleated giant cells,when no hyaline membrane ( a histopathological features of ARDS) diffuse alveolar damage. The pulmonary vessels showed hyaline necrosis with thrombus formation and capillary congestion.inflamatory infiltrate composed of alveolar macrophages in alveolar lumen and lymphocytes in interstitium. Zhe Xu et Al (2) in journal Lancet reported also one 50 year old man died on day 14 of covid 19 after being treated with lopinovir+retinovir+moxiflixain and high nasal cannula oxygen therapy and niddle autopsy of lungs liver and heart tissue showed diffuse alveolar damage with cellular fibrimyxiod exudate,dissquamation of pneumocytes and hyaline membrane formation (sign of ARDS) , interstitial mononuclear inflammatory infiltrate dominated by lymphocytes ( CD8) multi nucleated syncitial giant cells, atypical pneumocytes and microvascular thrombosis in pulmonary vessels (2).Sufang Tian et Al (3) did post mortem needle core autopsy of four patients who died of severe covid 19 pneumonia and patients age range were 59-81 years and time of death 15-52 days were in ventilation. Histology of their finding in lungs were again diffuse injury to alveolar epithelial cells, hyaline membrane formation, hyperplasia of type II pneumocytes , diffuse alveolar damage and consolidation by fibroblasts proliferation with extra cellular fibrin forming clusters.All these tour cases had vascular congestion with intravascular thrombus suggesting an acute phase components reaction and fibrinoid necrosis of blood vessels.The autopsy finding of heart was that endocardia and myocardia didn't contain inflammatory cellular infiltrate, although focally myocardium appeared irregular in shape with darkened cytoplasm and fibrinoid necrosis of blood vessels in myocardia.There were various degrees of focal oedema interstitial fibrosis and myocardial hypertrophy which suggests patients had underlying hypertension associated with hypertrophy or past ischemic injury. A large series of 38 cases of autopsy of lung by Luca carsana etall (5) showed from death cases of covid 19 in northern Itali on H&E stain showed also diffuse alveolar damage, capillary congratulations, necrosis, necrosis of pneumocytes, hyaline membrane, interstitial oedema,type II pneumocytes hyperplasia, platelet fibrin rich thrombus(5) .Electron microscopy showed viral particles within cytoplasmic vaccoule of pneumocytes.
So from above post mortem studies, besides ARDS like pictures in terminal event , platelet fibrin rich thrombosis of pulmonary vessels, myocardial vessels, hyaline necrosis of blood vessels of both lungs and of myocardium are prominent picture along with endothelial dysfunction according to this author.The severe cases of pneumonia from covid 19 also shows increased D Dimer value (4) prognostically bad , increased c reactive protein, increased pro calcitonin and increased FDP value
All these suggest to me that pathogenesis behind so many death in ventilation or at ICU of covid 19 patients are not ARDS itself but some kinds of coagulopathy or DIC occurred before death in severe pneumonia cases
Though lymphopenia, inflammatory cytokine stroms ( raised IL6,raised TNF are for cytokine stroms)are typical abnormalities described in almost all literature in highly pathogenic Covid 19 infection with disease severity ,only one rapid response in BMJ (4) suggest , based on post mortem finding use of low molecular weight heparin (LMWH) to be included in the treatment modules of covid 19, particularly those who have high D Dimer high FDP value in serum though TT,APTT,PT,INR may not show any significant difference.use of heparin therapy with constant monitoring for bleeding manifestation should be instituted in patients showing clinical signs of turning towards severe pneumonia,along with antiviral therapy with remdesvir (within 7 days onset of symptoms at scheduled disease)
If the pathology behind the death of severe pneumonia in covid 19 patients is DIC ( according to Autopsy finding the pneumocytes are not killed or destroyed by the virus nor by cytotoxic T cells, rather proliferation occur with much viral replication and virus load) there will be DIC , vascular congestion, thrombosis there will be AMI stroke ) then treatment at ICU with ventilation become useless unless if thromboembolism is not resolved first with LMWH infusion
1) Brain Hanley, Sebastian B Lucas,Esther youd,Benjamin swift,Michael Asbron "Autopsy in suspected covid 19 cases " JCP 73,(5):2020 http://dx.doi.org.10.1136/jclinpath-2020-20652
2) Xu Z,Shi L,Wang y eral "Pathological finding of covid 19 associated with acute respiratory distress syndrome " The Lancet respiratory medicine 8 (4):420-22 :2020
3) Sudan Tian, young xiong,Shu yuan xiao,Liu H et all "Study of 2019 novel Corona virus disease ( covid 19) through post mortem core biopsy" Modern pathology (Nature.com ) 14 th April 2020 http://doi.org/10.1038/s 41379-020-0536-
4) William Atenio ,Nadu Okonkwo "should prognostic models for covid 19 not also incorporate markers of thrombosis" Rapid Response published BMJ on 14th April 2020 to article"Prediction model for diagnosis and prognosis of covid 19 infection: systematic Review and clinical analysis" The BMJ 2020:369:m1328 published on 7th April 2020 https://doi.org/10.1136/bmj.m1328
5)Luca carsana, Aurelo sanzogoni ,Ahmed Nast, Roberta Rossi etall"pulmonary post mortem finding in a large series of covid 19 cases from northern Itali" MedRxiv https://doi.org/1101/2020.04.19.20054262
Competing interests: No competing interests