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.