Introduction
Since December 2019, severe acute respiratory syndrome-coronavirus-2
(SARS-CoV-2) has been threatening the world. Despite the initial fears
of this pandemic, an increasing number of autopsy cases have been
reported, and pathophysiology of Coronavirus infectious disease 2019
(COVID-19) is getting better understood. Pathology of 662 patients in 58
studies from June 4, 2020 to September 30, 2020, was reviewed, and most
frequently-described pulmonary findings were diffuse alveolar damage
(DAD), followed by thromboembolisms, and non-specific shock injury in
multiple organs1. Indeed, DAD, corresponding to the
acute respiratory distress syndrome (ARDS) in the clinical status, is a
major cause of death. Thus, therapeutic efforts have been made to save
global lives.
Remdesivir is an RNA polymerase inhibitor, which has antiviral
activities against RNA viruses2. The drug can
incorporate into nascent viral RNA, and inhibit the RNA-dependent RNA
polymerase, which results in premature termination of viral replication.
Clinical course of COVID-19 is biphasic, consisting an early viral
proliferating phase and a subsequent inflammatory
phase3. Thus, remdesivir is effective with the first
5-day administration4. But later, depending on the
severity of the patient’s conditions, the optimal medication would
differ.
Anti-inflammatory therapy is required, if the clinical condition
worsened with overexuberant host immune response. After the anti-viral
treatment, some patients may deteriorate, in approximately 7 days. Then,
anti-inflammatory therapy starts to prevent unfavorable immune response,
such as cytokine storm or ARDS. Here, glucocorticoids, such as
dexamethasone, modulates inflammation-mediated lung injury and thereby
is expected to reduce progression of respiratory
failure5. Efficacy of dexamethasone was reported for
hospitalized patients with respiratory support, either invasive
mechanical ventilation or oxygen alone6. There is also
growing interest in the use of tocilizumab, a monoclonal antibody
against interleukin-6 receptor (IL-6R). Although its efficacy is not yet
concluded7, its additional use to corticosteroids has
been reported beneficial8-10. Nonetheless,
pathophysiological evidence is needed to prove therapeutic effects of
these drugs.
Hear, we present an autopsy case of COVID-19 with treatment of
remdesivir, dexamethasone, and tocilizumab. During the
4th wave in Japan (April, 2021), biphasic anti-viral
and anti-inflammatory treatment was applied with approval to overcome
this disease. Unlike the previous autopsy reports conducted early in the
pandemic, pathology reflecting the host unfavorable response, such as
DAD and fibrosis was not so prominent in this case, likely suggesting
the therapeutic effects. However, severe pulmonary hemorrhage seemed
fatal, of which reason could not be concluded.