Discussion
The notable findings of this case series are as follows: (i) Tissue
acquisition through ultrasound-guided postmortem biopsies was
acceptable, particularly for the liver and the heart. A sufficient
amount of lung tissue was obtained in five out of the seven patients.
(ii) The universal radiological finding was the presence of GGO,
particularly in the lower lung lobes. The pathologic counterpart of
these images was the organizing phase of ARDS. All but one patient had
hyaline membranes in their alveoli. (iii) This is the first study to
report splenic postmortem biopsy results in COVID-19 patients. The
common finding was necrosis and neutrophil infiltration in the red pulp.
Several studies and case reports have been published to understand
histopathological changes and acquire possible ultrastructural clues
underlying the widespread damage inflicted by SARS-CoV-2. As the lungs
are the main target of the virus, pulmonary imaging and histopathology
have attracted much attention. Three rough stages have been defined for
COVID-19 [15]. The earliest phase is SARS-CoV-2 infection,
characterized by fever, dyspnea, and other flu-like symptoms. The second
stage involves viral pneumonia, which causes pulmonary inflammation and
coagulopathy. Some cases progress to ARDS in this stage. The third and
last stage is characterized by the relieving of symptoms and pulmonary
fibrosis. These stages are not necessarily consecutive and can coexist
in the same patient.
Pulmonary findings are histopathologically classified into three
patterns [16-18]. The most common and earliest pattern is diffuse
alveolar damage (DAD), which shows varying degrees of organization,
desquamation, type-2 pneumocyte hyperplasia, and viral cytopathic
changes. The second pattern (vascular) involves intra-alveolar fibrin
deposition and/or microvascular thrombi. Fibrotic patterns include
fibrotic DAD and/or interstitial fibrosis. A meta-analysis [19]
evaluating autopsy studies revealed that pulmonary histopathologic
examinations showed an epithelial pattern of injury in 85% of the
included patients. When present, mononuclear cells were the predominant
cell type infiltrating the lung interstitium. A vascular pattern was
present in 59% of the patients, and a fibrotic DAD pattern was observed
in 22% of the patients. Among the patients, 60% had more than one
pattern concurrently. Our findings were generally in agreement with
previous autopsy studies. The most common pulmonary injury pattern among
our patients was epithelial DAD. It was present in four out of the five
patients (80%), isolated in two patients, and alongside a vascular DAD
pattern in the other two patients. Interstitial inflammation was noted
in three patients (50%) and was mononuclear in all cases. One patient
had a concomitant fibrotic and vascular pattern.
Only a few studies to date have reported postmortem biopsy findings in
COVID-19 decedents [12-14]. In these studies, 18 COVID-19 decedents
were examined through postmortem biopsies. One study [13] evaluated
only lung tissue, and two [12, 14] studies also examined liver and
heart tissues, in addition to lung tissue. Beigmohammadi et al. [12]
performed postmortem biopsies with ultrasound guidance, whereas Tian et
al. [21] performed blind biopsies based on reference points.
Flickweert et al. [13] used ultrasound or CT guidance to perform
postmortem biopsies. In these studies, the authors obtained sufficient
lung tissue for histopathological examination. Conversely, sufficient
lung tissue was not obtained from the two patients in the present study.
Similar to our study, Flikweert et al. and Tian et al. [13, 14] also
included chest radiological findings in their reports. Regarding
pulmonary histopathologic findings, diffuse alveolar damage was the
predominant finding in all three studies.
Myocardial injury is prevalent in COVID-19 patients hospitalized in the
ICU [20-22]. In autopsy studies, no specific pathological finding
associated with COVID-19 was found in more than half of the patients.
Most of the cardiac histopathological findings could be explained by the
underlying cardiac disease of the patients, such as coronary artery
disease and heart failure [23, 24]. In the other half, mild
interstitial mononuclear cellular infiltration, lymphocytic myocarditis,
and myocardial edema were reported [19, 25, 26]. One remarkable
aspect was that pericardial effusion was rare. Postmortem biopsy studies
have reported nonspecific histopathological findings that are mostly
compatible with the underlying cardiac disease of the patients [12,
14]. In contrast to autopsy and postmortem biopsy studies, pericardial
effusion was frequent in our series. Four out of the six patients
(66.6%) had varying degrees of pericardial effusion. However, no
specific COVID-19-associated cardiac histopathologic findings were
observed in any of the examined specimens. The observed changes were in
accordance with the underlying cardiac diseases of the decedents.
Autopsy studies performed on patients who died of COVID-19 showed mild
steatosis, patchy hepatic necrosis, and mild sinusoidal dilation in the
vast majority of patients [23, 27]. In their postmortem series,
Beigmohammadi et al. [12] reported sinusoidal dilation,
microvesicular and macrovesicular steatosis, and mild portal
inflammation. Tian et al. [14] reported sinusoidal dilation and
patchy hepatocyte necrosis. Our results showed patchy hepatocyte
necrosis, mononuclear and/or neutrophil infiltration, and macrovesicular
steatosis in the liver biopsy samples.
Autopsy studies have shown lymphocyte reduction and focal necrosis,
infarction, and hemorrhage in the spleen [19, 28]. None of the
available postmortem studies have obtained splenic biopsies [12,
14]. In our series, splenic tissue was available in three patients.
Splenic tissue was not present in the four biopsy samples. All patients
had focal necrosis and neutrophil infiltration in the red pulp.
Histopathologic changes in the liver, lung, heart, and spleen in the
postmortem biopsy samples were generally similar to those obtained
through autopsy. The tissue acquisition rates were quite high: 100% for
liver, 88.8% for lung, and 88.8% for heart. Thus, we believe that
postmortem biopsies can provide comparably good histopathological
results compared with autopsy studies. Furthermore, in postmortem
studies, pulmonary histopathologic findings were concordant with
radiological images.
This study has several limitations. First, although our sample was not
smaller than that of other postmortem biopsy studies, examining more
cases can yield more generalizable results. Second, we did not use
immunohistochemical staining. Nevertheless, H&E staining was largely
sufficient for the purposes of the study. Third, we did not examine the
presence of SARS-CoV-2 in the biopsied tissues. These data, along with
the ACE2 expression level, can shed more light on the pathophysiological
changes seen in COVID-19. Lastly, as organ involvement could be patchy
and as there was no chance of seeing the organs macroscopically, as in
autopsy, postmortem biopsy studies have inherently more limited tissue
availability than autopsy studies. This might have affected our results
to some extent.
In conclusion, this study performed a postmortem biopsy series on
COVID-19 decedents by sampling lung, heart, liver, and spleen tissues.
This work is the first postmortem biopsy study to examine splenic core
needle biopsies. An adequate amount of tissue for histopathologic
examination was obtained in most biopsies. When adequate tissue was
sampled, the results were generally consistent with previous autopsy
studies. The pulmonary radiological findings were correlated with the
lung histopathologic examination results. A study design comparing
postmortem biopsies with autopsy findings in the same patients can
certainly determine the role of postmortem biopsies in COVID-19
decedents.
Acknowledgments: N/A
Conflict of Interest: The authors declare no conflicts of
interest.
Financial Disclosure: The authors declare that this study did
not receive financial support.