603
ORIGINAL SCIENTIFIC ARTICLE
Pathological lung changes in COVID-19 deceased patients
University Clinic of 
Pulmonary and Allergic 
Diseases Golnik, Golnik, 
Slovenia
Correspondence/
Korespondenca:
Mile Kovačević, e: mile.
kovacevic@klinika-golnik.si
Key words:
COVID-19; lungs; 
pathology; autopsy
Ključne besede:
covid-19; pljuča; patologija; 
obdukcija
Received: 27. 4. 2020
Accepted: 25. 6. 2020
eng slo element
en article-lang
10.6016/ZdravVestn.3097 doi
27.4.2020 date-received
25.6.2020 date-accepted
Microbiology and immunology Mikrobiologija in imunologija discipline
Original scientific article Izvirni znanstveni članek article-type
Pathological lung changes in COVID-19 de-
ceased patients
Patološke spremembe v pljučih pri umrlih bolni-
kih s covidom-19
article-title
Pathological lung changes in COVID-19 de-
ceased patients
Patološke spremembe v pljučih pri umrlih bolni-
kih s covidom-19
alt-title
COVID-19, lungs, pathology, autopsy covid-19, pljuča, patologija, obdukcija kwd-group
The authors declare that there are no conflicts 
of interest present.
Avtorji so izjavili, da ne obstajajo nobeni 
konkurenčni interesi.
conflict
year volume first month last month first page last page
2020 89 11 12 603 613
name surname aff email
Mile Kovačević 1 mile.kovacevic@klinika-golnik.
si
name surname aff
Gregor Vlačić 1
Izidor Kern 1
eng slo aff-id
University Clinic of Pulmonary 
and Allergic Diseases Golnik, 
Golnik, Slovenia
Univerzitetna klinika za pljučne 
bolezni in alergijo Golnik, Golnik, 
Slovenija
1
Pathological lung changes in COVID-19 
deceased patients
Patološke spremembe v pljučih pri umrlih bolnikih s covidom-19
Gregor Vlačić, Mile Kovačević, Izidor Kern
Abstract
Background: COVID-19 disease causes diffuse alveolar damage associated with a high mortality 
rate. The aim of the analysis of deceased patients with SARS-CoV-2 virus infection is to assess 
histopathological changes in the lungs as the key target organ in this infection.
Methods: We performed partial autopsies on patients with COVID-19 treated at the Universi-
ty Hospital of Respiratory and Allergic Diseases Golnik. We assessed various histopathological 
changes in the lungs of deceased patients with COVID-19 disease. We performed immunohisto-
chemical stainings to prove the presence of SARS-CoV-2 virus in lung samples.
Results: The main histopathological finding was diffuse alveolar damage with hyaline mem-
brane formation, interstitial and alveolar oedema and fibrinous exudation in the alveoli. Intersti-
tial inflammatory infiltration was mild to moderate. In some patients, alveolar damage was part-
ly organized, but without the presence of fibrosis. We found cytopathic changes of the alveolar 
epithelium consistent with viral infection in all patients. We found the presence of virus in lung 
samples of all patients.
Conclusion: COVID-19 disease affects the lungs, causing diffuse alveolar damage, which can lead 
to death. Autopsy still plays an important role in modern medicine, giving a contribution to the 
understanding of new diseases.
Izvleček
Izhodišče: Bolezen covid-19 povzroča difuzno alveolno okvaro, povezano z visoko stopnjo umrl-
jivosti. Namen analize umrlih bolnikov, okuženih z virusom SARS-CoV-2, je oceniti histopatološke 
spremembe v pljučih kot glavnem tarčnem organu pri tej okužbi.
Metode: Opravili smo delne obdukcije bolnikov s covidom-19, ki so se zdravili na Univerzitetni 
kliniki za pljučne bolezni in alergijo Golnik. Ocenjevali smo izraženost različnih histopatoloških 
sprememb v pljučih umrlih. Z imunohistokemično metodo smo dokazovali prisotnost virusa 
SARS-CoV-2 v vzorcih pljuč.
Rezultati: V pljučih so izstopali znaki akutne alveolne okvare s tvorbo hialinih membran, inter-
sticijskim in alveolnim edemom ter fibrinsko eksudacijo v alveolih. Spremljajoča vnetna reakcija 
je bila blago do zmerno izražena. Pri nekaterih bolnikih je bila alveolna okvara že v fazi organi-
zacije, vendar brez prisotne fibroze. Pri vseh bolnikih smo našli citopatsko spremenjen alveolni 
epitel kot znak virusne okužbe celic. V vzorcih pljuč vseh bolnikov smo dokazali prisotnost virusa.
Zaključek: Bolezen covid-19 prizadene pljuča in povzroči difuzno alveolno okvaro, zaradi katere 
bolniki lahko umrejo. Obdukcija se je izkazala za pomembno tudi v svetu zaradi raziskovanja 
nove bolezni.
Slovenian
Medical
Journal
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1 Introduction
The COVID-19 disease pandem-
ic, which started in December 2019 in 
China and spread around the world in a 
few months, presents a major challenge 
for healthcare systems globally.
Following the declaration of the 
COVID-19 disease epidemic in Slovenia, 
the University Clinic of Respiratory and 
Allergic Diseases Golnik (UCG) start-
ed diagnosing and treating COVID-19 
patients.
COVID-19 disease affects the re-
spiratory tract and leads to respiratory 
distress with a high mortality rate in a 
small number of patients. Most stud-
ies published during the pandemic deal 
with the microbiology, epidemiology, 
clinical presentation and treatment of 
the disease. Pathology publications are 
scarce, making this disease still insuf-
ficiently explored from a pathological 
point of view. The biggest question re-
mains whether patients with COVID-19 
disease die from or with the disease (1).
Although the Slovenian guidelines 
for dealing with the COVID-19 epidem-
ic do not recommend carrying out au-
topsies on patients who have died from 
COVID-19, we believed that due to the 
fairly unknown pathogenetic mecha-
nisms and morphological characteris-
tics of the disease, a thorough analysis 
of autopsy samples was needed (2). All 
available publications to date analyzed 
single cases or small series of patients 
(3,4). The first reports of histological 
Cite as/Citirajte kot: Vlačić G, Kovačević M, Kern I. Pathological lung changes in COVID-19 deceased 
patients. Zdrav Vestn. 2020;89(11–12):603–13.
DOI: https://doi.org/10.6016/ZdravVestn.3097
Copyright (c) 2020 Slovenian Medical Journal. This work is licensed under a
Creative Commons Attribution-NonCommercial 4.0 International License.
changes in the lungs of deceased patients 
with COVID-19 disease were based on 
core-needle biopsies of the lung per-
formed post mortem (4). The most ex-
tensive study to date analyzed autopsy 
samples of 21 patients who died with 
COVID-19 (5). Even less data is avail-
able about lung pathological changes in 
living patients with confirmed SARS-
CoV-2 infection. In fact, the very first 
data on histopathological changes in 
the lungs of SARS-CoV-2-positive pa-
tients were from lung resections due to 
tumours, with SARS-CoV-2 infection 
confirmed afterwards (6). In the ma-
jority of cases, the leading pathological 
change is diffuse alveolar damage, in 
different phases of development, with 
subsequent cytopathic changes of the al-
veolar epithelium directly attributed to 
viral infection. Some authors describe 
frequent findings of pulmonary throm-
boembolism in patients who died from 
COVID-19 disease (7,8). Endothelial 
viral infection of lung blood vessels is 
also considered a possible pathogenetic 
mechanism of COVID-19 disease (5,9).
To analyze the histopathological 
characteristics of COVID-19 disease in 
the lungs, we examined autopsy lung 
samples taken from patients who died 
with confirmed SARS-CoV-2 infec-
tion. Autopsies, sampling, sample pro-
cessing and analysis were performed 
in the UCG Cytology and Pathology 
Laboratory.
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ORIGINAL SCIENTIFIC ARTICLE
Pathological lung changes in COVID-19 deceased patients
2 Materials and methods
Partial autopsies were performed on 
patients who died in UCG in the two 
months after the COVID-19 disease ep-
idemic was declared in the Republic of 
Slovenia. SARS-CoV-2 infection was 
confirmed with real-time polymerase 
chain reaction and reverse transcrip-
tion performed on nasopharyngeal 
swabs taken from subsequently hospi-
talized living patients. Autopsies were 
performed according to the legal reg-
ulations of the Republic of Slovenia. 
Autopsies were performed at least 24 
hours after the patient’s death. The entire 
right lung was removed together with 
left heart ventricle and right liver lobe 
samples. Secondary sampling was per-
formed after 48 hours of fixation in 10% 
neutral buffered formalin. Five samples 
were systematically taken from every 
lobe of the right lung. The tissue sam-
ples were embedded in paraffin after 72 
hours of fixation. Histological samples 
were routinely stained with haematoxy-
lin-eosin (HE) and examined on a light 
microscope. 
Within the histological examination, 
we assessed the presence of interstitial 
and alveolar oedema, interstitial inflam-
matory infiltrate, intra-alveolar fibrin-
ous and inflammatory exudate, hyaline 
membranes, reactive changes of the al-
veolar epithelium, organizing inflamma-
tion and airway inflammation. Most of 
the morphological changes were assessed 
semiquantitatively with a 4-tier scale 
(- absence of changes; + mild/focal; ++ 
moderate; +++ severe). Inflammatory 
infiltration with neutrophils and lym-
phocytes was assessed qualitatively.
Special attention was given to chang-
es of the alveolar epithelium, as they are 
a potential sign of the presence of the vi-
rus in the cells. This is the so-called cy-
topathic effect, which includes enlarge-
ment of cells and nuclei, foamy and/or 
coarsely vacuolized cytoplasm, multiple 
nuclei, ground glass nuclei and coarse 
chromatin. Other observed histopatho-
logical changes were noted separately.
Additional immunohistochemistry 
was performed on the automated stainer 
Benchmark XT (Roche, USA). Subtyping 
of immune cells in mononuclear cell in-
filtrates was performed using the follow-
ing antibodies: CD20 (lymphocytes B), 
CD3 (lymphocytes T), CD4 (T helper 
cells), CD8 (T killer cells) and CD163 
(macrophages). We used anti-surfactant 
protein A antibody to mark the alveolar 
epithelium. We assessed the virus’s pres-
ence in different cells using rabbit an-
tibody SARS-CoV-2 (2019-nCoV) an-
ti-nuclear virus protein (clone 019, titer 
1:500, Sino Biological, China). Dot-like 
and diffuse positive cytoplasmic staining 
were considered positive.
The study was approved by the 
Committee for Medical Ethics of the 
Republic of Slovenia on 7 May 2020 (de-
cision no. 0120-201/2020/7).
3 Results
3.1 Patients
Seven patients (two female, five male) 
were included in the study. All patients 
were treated at UCG for confirmed 
SARS-CoV-2 infection, died during 
hospitalization and were taken to our 
lab for autopsy. The average age was 81.7 
years (range 68 – 91). Average hospital-
ization time was 16 days (range 3 – 28). 
All patients had multiple chronic diseas-
es. Cardiovascular disease was the most 
frequent, being present in six patients. 
Two patients had diabetes mellitus type 
2, one of whom was insulin-dependent. 
Three patients had dementia, one para-
noid schizophrenia, one parkinsonism 
and one epilepsy. Two patients had ac-
tive malignant diseases. Two patients 
had chronic lung disease (asthma and 
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chronic obstructive lung disease). Two 
patients were previously treated for acute 
conditions (biliary pancreatitis with sep-
sis, and sepsis of unknown origin, re-
spectively). One patient was clinically 
diagnosed with aspiration pneumonia as 
a complication of COVID-19 treatment. 
Clinical data are shown in Table 1.
3.2 Histopathological changes in 
the lungs
We found interstitial oedema in six 
patients (Figure 1); only one patient did 
not have any signs of interstitial oedema. 
All patients had congestion of lung blood 
vessels and alveolar oedema. Interstitial 
inflammatory infiltration was found in 
all patients. We graded it as mild to mod-
erate, and in all patients, it consisted of 
lymphocytes. Distribution of lympho-
cytes T and B was equal. There was an 
equal proportion of T helper and killer 
cells. An increased number of interstitial 
and alveolar macrophages was observed 
in all patients. Severe, moderate and mild 
Table 1: Patient data.
Abbreviations: F – female, M – male, HF – heart failure, AF – atrial fibrillation, AH – arterial 
hypertension, COPD – chronic obstructive pulmonary disease, DM – diabetes mellitus, CVI – 
cerebrovascular insult, HLP - hyperlipidaemia
Patient Days of 
hospitalization
Age Sex Comorbidities
1 3 91 F HF, AF, AH
2 22 81 M Dementia, immobility, aspiration pneumonia
3 21 80 M St post biliary pancreatitis and sepsis, AF, HF, 
parkinsonism, COPD
4 8 90 F HF, DM, dementia, asthma, st. post CVI
5 28 68 M Small cell lung carcinoma (cT3N3M1b), AH, DM, 
schizophrenia, sepsis
6 12 74 M Dementia, HLP, epilepsy, AH, immobility
7 19 88 M Prostate cancer, AH, HLP, fibrothorax
hyaline membrane formation and fibrin-
ous exudate in the alveoli were found in 
four, one and one patient, respectively 
(Figures 1 and 2). We did not find hya-
line membrane formation and fibrinous 
exudate in the alveoli in the lungs of one 
Figure 2: Hyaline membranes (marked with arrows) (HE, 20x).
Figure 1: Interstitial oedema (marked with asterisks) and hyaline 
membranes (marked with arrows) (HE, 4x).
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ORIGINAL SCIENTIFIC ARTICLE
Pathological lung changes in COVID-19 deceased patients
hyaline membrane formation and fibrin-
ous exudate in the alveoli were found in 
four, one and one patient, respectively 
(Figures 1 and 2). We did not find hya-
line membrane formation and fibrinous 
exudate in the alveoli in the lungs of one 
Figure 2: Hyaline membranes (marked with arrows) (HE, 20x).
Figure 1: Interstitial oedema (marked with asterisks) and hyaline 
membranes (marked with arrows) (HE, 4x).
patient with small cell carcinoma. 
Reactive changes of the alveolar epi-
thelium with marked cytopathic changes 
were found in six patients (Figures 3 and 
4). The alveolar epithelium was mostly 
exfoliated, with a marked proliferation 
of type 2 pneumocytes. Severe, moder-
ate and mild alveolar exudative inflam-
mation was present in one, three and 
three patients, respectively. Qualitatively, 
the exudate consisted mostly of neutro-
phils in the severe inflammation case, 
mixed cellularity in moderate and lym-
phocytes-macrophages combination in 
mild cases. Moderate signs of organizing 
inflammation (interstitial and alveolar fi-
broplasia) were present in three patients. 
Severe, moderate and mild airway in-
flammation was present in one, four and 
two patients, respectively. Qualitatively, 
we observed the presence of neutrophils 
in patients with severe and moderate air-
way inflammation. Lymphocytes were 
present in one patient with moderate 
airway inflammation. Both patients with 
mild airway inflammation had lympho-
cytic inflammatory infiltrate. Squamous 
metaplasia was present in all patients, 
with predominant peribronchial distri-
bution (Figure 5). We observed foreign 
material with associated foreign body 
granulomatous reaction in the small air-
ways of three patients, which was con-
sidered a reliable sign of aspiration pneu-
monia. We found thromboemboli in the 
small branches of the pulmonary artery 
in three patients. One patient had signs 
of intra-alveolar haemorrhage, with 
erythrocyte extravasation and abundant 
siderophages in the alveoli. All semi-
quantitative histology assessment results 
are shown in Table 2.
Using immunohistochemistry, we 
confirmed the presence of SARS-CoV-2 
in the lungs of all patients. A positive re-
action was mostly observed in the alve-
olar epithelium, macrophages and endo-
thelium of small blood vessels (Figure 6).
Figure 3: Severe reactive changes (marked with arrows) of alveolar 
epithelial cells (HE, 40x).
Figure 4: Severe cytopathic changes (marked with asterisks) of alveolar 
epithelial cells (HE, 40x).
Figure 5: Squamous cell metaplasia in the alveoli (marked with arrows) 
(HE, 4x).
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4 Discussion
The main pathological change ob-
served in the lungs of autopsied pa-
tients who died of viral SARS-Cov-2 
infection was the presence of hyaline 
membranes and fibrinous exudate in 
the alveoli, the hallmarks of acute lung 
injury. All deceased patients treated at 
UCG for COVID-19 disease were el-
derly and had multiple comorbidities. 
Viral infection was confirmed in the 
alveolar epithelium and macrophages. 
Compared to the published results of 
Chinese studies performed with post 
mortem core-needle biopsy of the lung 
(4), our study has the advantage of sys-
tematic sampling and examination of 
the entire lung, which excludes possible 
sampling errors. We focused on histo-
pathological changes in the lungs, which 
was the first goal of this analysis, albeit 
we took samples from other organs as 
well.
The cause of death in almost all of 
the patients who died from COVID-19 
in our analysis was diffuse alveolar dam-
age. We found hyaline membranes and 
fibrinous exudate in the alveolar spaces 
and some other signs of the exudative 
phase of diffuse alveolar damage, such 
as senescence and reactive changes of 
the alveolar epithelium, first described 
in early reports from Chinese authors 
(4,10). In the lung samples of some pa-
tients, we found signs of early organi-
zation of diffuse alveolar damage with 
mild thickening of the alveolar septa 
due to interstitial fibroplasia and foci 
of intra-alveolar fibroplasia. We did not 
find signs of advanced fibrosis in any of 
our cases. We observed foci of alveolar 
squamous metaplasia without cell atyp-
ia in all our cases which, combined with 
marked organization of inflammation, 
confirms the presence of the prolifer-
ative phase of diffuse alveolar damage, 
as demonstrated in other large series of 
patients (5,7). The extent of the inflam-
matory reaction in the lung parenchyma 
was surprisingly small, showing mild to 
moderate interstitial lymphatic infil-
tration composed of B and T lympho-
cytes, the proliferation of macrophages 
in the alveoli and interstitium and mild 
to moderate granulocytic exudate in the 
alveoli. Lymphatic infiltration is most 
probably caused by the viral infection 
itself (4,6). Some patients had bron-
chopneumonic exudative inflammatory 
Table 2: Histopathological changes in the lungs. The number of 
patients with appropriate assessment of intensity of the changes is 
noted.
No. 
changes
Mild 
changes 
(+)
Moderate 
changes 
(++)
Severe 
changes 
(+++)
Interstitial oedema 0 1 2 4
Interstitial inflammation 0 3 4 0
Alveolar inflammation 0 3 3 1
Airway inflammation 0 2 4 1
Hyaline membranes, 
fibrinous exudate
1 1 1 4
Reactive alveolar 
epithelium
1 1 3 2
Organizing inflammation 4 0 3 0
Figure 6: Immunohistochemical confirmation of SARS-CoV-2 virus 
presence in alveolar epithelial cells (marked with arrows) and 
macrophages (marked with asterisks)(40x).
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ORIGINAL SCIENTIFIC ARTICLE
Pathological lung changes in COVID-19 deceased patients
changes, which were limited to the air-
ways and surrounding lung parenchy-
ma and were most probably caused by 
aspiration or bacterial superinfection. 
Other authors also reported aspiration 
bronchopneumonia in a number of cas-
es (11). Almost half of the patients in the 
Swiss study died of bronchopneumonia 
caused by bacterial superinfection (5). 
Among other pathological changes ob-
served in our study, it is worth mention-
ing the congestion of blood vessels, alve-
olar oedema and, in one patient, marked 
alveolar haemorrhage. We found lung 
thromboembolism in three out of sev-
en cases. Blood clots were found in 
small-calibre lung arteries, possibly due 
to advanced coagulopathy seen in se-
vere COVID-19 disease (7). Two studies 
reported more frequent findings of lung 
thromboembolism. The German series 
reports lung thromboembolism in one 
third of patients, which is comparable 
to our results (7). Microthrombosis was 
found in all 12 patients, which is similar 
to the Swiss series (5). In the published 
study conducted by Austrian colleagues, 
which reported thrombosis of the pul-
monary arteries in all 11 patients, we 
found the presented photomicrographs 
of blood clots unconvincing, as the 
changes presented there most probably 
show post mortem clotting (8). They 
propose that in-life forming of blood 
clots is directly connected with the vi-
ral infection of endothelial cells, which 
present on their surface receptors for 
SARS-CoV-2 (9). The histopathological 
changes found in the lungs of patients 
who died with COVID-19 disease are 
not pathognomonic for SARS-CoV-2 
viral infection. Equal changes were 
described in the lung samples of pa-
tients infected with other coronaviruses 
(SARS-CoV and MERS-CoV) and also 
with other viral infections. Ackermann 
et al. compared the histopathological 
changes in the lungs of patients who 
died of COVID-19 disease to those who 
died of influenza (H1N1). They found 
signs of diffuse alveolar damage and 
mild interstitial inflammatory infiltra-
tion in both, while endothelial changes 
and microthromboses were more fre-
quent in COVID-19 disease (12). All 
findings in the lungs of patients who 
died with COVID-19 reported to date, 
including in our analysis, represent an 
advanced, severe course of infection 
(Table 3). Among the first published 
cases of patients infected with SARS-
CoV-2 are two patients who had lung 
cancer surgery (6). Resected lung sam-
ples of both patients showed changes 
consistent with early acute lung injury, 
with alveolar oedema, fibrinous exu-
date, and mild inflammatory infiltrate, 
but without the formation of hyaline 
membranes. One of the patients in our 
analysis, who was previously diagnosed 
and treated for disseminated small cell 
lung carcinoma, also showed mild his-
topathological changes in the lung; thus, 
we concluded that he died of his prima-
ry malignant disease, with concomitant 
COVID-19 disease.
All patients who died with COVID-19 
disease had in-life infection with the 
SARS-CoV-2 virus, confirmed with a 
nasopharyngeal swab. We confirmed 
the viral SARS-CoV-2 infection with the 
immunohistochemical technique and 
marked cytopathic changes of the alve-
olar epithelium in all our patients. For 
immunohistochemical confirmation of 
SARS-CoV-2 infection, we used anti-
body against antigen on the nuclear pro-
tein of the virus, similarly as in two other 
studies, which together included three 
patients (14,15). Confirmation of the 
presence of the virus in formalin-fixed 
paraffin-embedded tissue is also possi-
ble with in situ hybridization techniques 
(16). Most publications used real-time 
polymerase chain reaction with reverse 
transcription to confirm viral infection 
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(4,5,7,15). Due to the rapid degradation 
of RNA post mortem, the above-men-
tioned method can be problematic in 
samples obtained during autopsy, al-
though it should be considered in the 
case of autopsy of patients who died of 
respiratory failure of unknown aetiology. 
This method could also be useful in in-
cidental findings of acute lung injury in 
tissue samples from living patients. The 
presence of the virus was also confirmed 
with electron microscopy, showing viral 
particles in cytoplasmic vesicles bound 
to the cell membrane and floating free in 
the alveolar spaces (5,9,17). Cytopathic 
changes of the alveolar epithelium ob-
served in histological samples of the 
lung included cell enlargement, foamy 
and coarsely granular cytoplasm, en-
larged nuclei, multiple nuclei, ground 
glass change of nuclei and coarse chro-
matin. Other authors described similar 
changes (17). We could expect to see the 
cytopathic changes of alveolar epitheli-
al cells listed above in different types of 
samples obtained from living patients 
with COVID-19 disease, i.e. in bron-
choalveolar lavage. Due to their simi-
larity to tumour cells, these could pose 
a diagnostic challenge for a pathologist. 
We are familiar with cytopathic changes 
in different viral infections of the lung 
(adenovirus, respiratory syncytial virus, 
influenza virus, parainfluenza virus, cy-
tomegalovirus, herpes simplex virus, 
measles virus). For some of them, we 
can identify relatively specific cytomor-
phological changes, while for the vast 
majority of them, there is a considerable 
overlap of changes and confirmation of 
the presence of the virus in the sample is 
mandatory. We found similar changes in 
the lung samples from our patients who 
died with COVID-19. There is an inter-
esting publication of changes found in 
bronchoalveolar lavage obtained from 
a patient put on extracorporeal mem-
brane oxygenation (18). A markedly 
increased level of activated plasma cells 
was observed between macrophages 
in lymphocytes, which was discordant 
with histopathological changes known 
to date.
In the time of the COVID-19 disease 
pandemic, autopsy has regained its fun-
damental purpose in exploring this new, 
previously unknown disease. According 
to recommendations published in the 
Republic of Slovenia for handling pa-
tients who have died from COVID-19 
disease, autopsy was not recommended. 
Post-mortem contagiousness of patients 
who died with COVID-19 disease is not 
known, although the virus is included 
in the high-risk group of viruses, similar 
to SARS-CoV, MERS-CoV, HIV, rabies 
Table 3: Review of published histopathological changes in the lungs in the literature available in English.
Abbreviations: HM – hyaline membranes, OP – organizing pneumonia, DAD – Diffuse alveolar damage
Author Number 
of 
patients
Living 
patient/post 
mortem
Sampling 
method
Main findings
Tian S et al (4) 4 Post 
mortem
Core-needle 
biopsy
HM, pneumocyte type 2 hyperplasia, OP
Barton LM et al (11) 2 Post 
mortem
Autopsy DAD, bronchopneumonia, aspiration, chronic bronchitis, 
oedema
Tian S et al (6) 2 Living 
patient
Lobectomy Oedema, pneumocyte type 2 hyperplasia, interstitial 
inflammation, multinucleated giant cells
Xu Z et al (10) 1 Post 
mortem
Autopsy DAD, interstitial inflammation, reactive pneumocytes 
type 2, cytopathic effect, aspiration
Zeng Z et al (12) 1 Alive patient Lobectomy Exudative inflammation, multinucleated giant cells, 
pneumocyte type 2 hyperplasia, cytopathic effect
Lacy JM et al (20) 1 Post 
mortem
Autopsy HM, interstitial inflammation, pneumocyte type 2 
hyperplasia, alveolar haemorrhage
Wichmann D et al (7) 12 Post 
mortem
Autopsy DAD, pneumocyte type 2 hyperplasia, organization, 
bronchopneumonia
Lax S et al (8) 11 Post 
mortem
Autopsy DAD, pulmonary thromboembolism, oedema, 
pneumocyte type 2 hyperplasia
Menter T et al (5) 21 Post 
mortem
Autopsy DAD, bronchopneumonia, pulmonary thromboembolism, 
alveolar haemorrhage
Konopka KE et al (3) 1 Post 
mortem
Autopsy DAD, interstitial inflammation, pneumocyte type 2 
hyperplasia
Adachi T et al (14) 1 Post 
mortem
Autopsy DAD, organization, squamous cell metaplasia, 
pneumocyte type 2 hyperplasia
Yao et al (24) 3 Post 
mortem
Minimally 
invasive 
autopsy
HM, lung fibrosis, interstitial inflammation
Golnik 7 Post 
mortem
Partial autopsy HM, pneumocyte type 2 hyperplasia, interstitial 
oedema, squamous cell metaplasia, organization, 
bronchopneumonia
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ORIGINAL SCIENTIFIC ARTICLE
Pathological lung changes in COVID-19 deceased patients
glass change of nuclei and coarse chro-
matin. Other authors described similar 
changes (17). We could expect to see the 
cytopathic changes of alveolar epitheli-
al cells listed above in different types of 
samples obtained from living patients 
with COVID-19 disease, i.e. in bron-
choalveolar lavage. Due to their simi-
larity to tumour cells, these could pose 
a diagnostic challenge for a pathologist. 
We are familiar with cytopathic changes 
in different viral infections of the lung 
(adenovirus, respiratory syncytial virus, 
influenza virus, parainfluenza virus, cy-
tomegalovirus, herpes simplex virus, 
measles virus). For some of them, we 
can identify relatively specific cytomor-
phological changes, while for the vast 
majority of them, there is a considerable 
overlap of changes and confirmation of 
the presence of the virus in the sample is 
mandatory. We found similar changes in 
the lung samples from our patients who 
died with COVID-19. There is an inter-
esting publication of changes found in 
bronchoalveolar lavage obtained from 
a patient put on extracorporeal mem-
brane oxygenation (18). A markedly 
increased level of activated plasma cells 
was observed between macrophages 
in lymphocytes, which was discordant 
with histopathological changes known 
to date.
In the time of the COVID-19 disease 
pandemic, autopsy has regained its fun-
damental purpose in exploring this new, 
previously unknown disease. According 
to recommendations published in the 
Republic of Slovenia for handling pa-
tients who have died from COVID-19 
disease, autopsy was not recommended. 
Post-mortem contagiousness of patients 
who died with COVID-19 disease is not 
known, although the virus is included 
in the high-risk group of viruses, similar 
to SARS-CoV, MERS-CoV, HIV, rabies 
Table 3: Review of published histopathological changes in the lungs in the literature available in English.
Abbreviations: HM – hyaline membranes, OP – organizing pneumonia, DAD – Diffuse alveolar damage
Author Number 
of 
patients
Living 
patient/post 
mortem
Sampling 
method
Main findings
Tian S et al (4) 4 Post 
mortem
Core-needle 
biopsy
HM, pneumocyte type 2 hyperplasia, OP
Barton LM et al (11) 2 Post 
mortem
Autopsy DAD, bronchopneumonia, aspiration, chronic bronchitis, 
oedema
Tian S et al (6) 2 Living 
patient
Lobectomy Oedema, pneumocyte type 2 hyperplasia, interstitial 
inflammation, multinucleated giant cells
Xu Z et al (10) 1 Post 
mortem
Autopsy DAD, interstitial inflammation, reactive pneumocytes 
type 2, cytopathic effect, aspiration
Zeng Z et al (12) 1 Alive patient Lobectomy Exudative inflammation, multinucleated giant cells, 
pneumocyte type 2 hyperplasia, cytopathic effect
Lacy JM et al (20) 1 Post 
mortem
Autopsy HM, interstitial inflammation, pneumocyte type 2 
hyperplasia, alveolar haemorrhage
Wichmann D et al (7) 12 Post 
mortem
Autopsy DAD, pneumocyte type 2 hyperplasia, organization, 
bronchopneumonia
Lax S et al (8) 11 Post 
mortem
Autopsy DAD, pulmonary thromboembolism, oedema, 
pneumocyte type 2 hyperplasia
Menter T et al (5) 21 Post 
mortem
Autopsy DAD, bronchopneumonia, pulmonary thromboembolism, 
alveolar haemorrhage
Konopka KE et al (3) 1 Post 
mortem
Autopsy DAD, interstitial inflammation, pneumocyte type 2 
hyperplasia
Adachi T et al (14) 1 Post 
mortem
Autopsy DAD, organization, squamous cell metaplasia, 
pneumocyte type 2 hyperplasia
Yao et al (24) 3 Post 
mortem
Minimally 
invasive 
autopsy
HM, lung fibrosis, interstitial inflammation
Golnik 7 Post 
mortem
Partial autopsy HM, pneumocyte type 2 hyperplasia, interstitial 
oedema, squamous cell metaplasia, organization, 
bronchopneumonia
virus, and hepatitis B, C and D viruses 
(19). Because there were no published 
data on histopathological changes in the 
lung caused by the SARS-CoV-2 virus 
at the time the epidemic was declared, 
we decided to perform autopsies on pa-
tients who died of COVID-19 in UCG. 
To prevent excessive risk of infection of 
employees, we performed partial autop-
sy with in situ sampling of the lungs, 
liver and heart. We performed the au-
topsies according to the protocol based 
on international recommendations for 
performing autopsies of patients infect-
ed with SARS-CoV-2 (20-23). Only two 
persons were present at the autopsy, the 
pathologist and autopsy assistant, both 
using personal protective equipment. 
To avoid the formation of aerosol, we 
did not use water and an oscillatory 
saw. Subatmospheric air pressure and 
appropriate ventilation with more than 
15 cycles of air change per hour were 
provided.
During the COVID-19 epidemic, we 
faced a challenge in successfully pro-
tecting the staff in pathology laborato-
ries who manage fresh, non-fixed cy-
tological and histological samples from 
the airway of living patients. Since we 
did not have specific guidelines for that 
situation in the Republic of Slovenia, 
we successfully implemented interna-
tional guidelines, which included the 
use of personal protective equipment 
(FFP2 masks, goggles or glasses, nitrile 
gloves) when handling and processing 
non-fixed cytological samples, especial-
ly with centrifugation (24). By following 
the guidelines, we did not record any 
cases of infection among our laborato-
ry personnel. We adjusted our work in 
the autopsy room and the laboratory to 
the possibility of unrecognized SARS-
CoV-2 virus infection.
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MICROBIOLOGY AND IMMUNOLOGY
Zdrav Vestn | November – December 2020 | Volume 89 | https://doi.org/10.6016/ZdravVestn.3097
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5 Conclusion
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forming autopsies on patients who died 
from previously unknown diseases in 
modern times.
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ORIGINAL SCIENTIFIC ARTICLE
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