Molecular Methods in the Identification of Pulmonary Pathologic Traits of the SARS-CoV-2 Delta Variant at Autopsy

ABSTRACT

Background: The highly contagious Delta variant of COVID-19 accounts for more than 80% of SARS-CoV-2 cases in the fall of 2021. Our aim was to determine whether molecular methods for variant and lineage detection could be utilized at autopsy to examine pathologic findings of Delta variant as compared to non-Delta variant cases. Design: We evaluated the lungs from 20 decedents with death due to SARS-CoV-2 confirmed by antemortem nasopharyngeal RTPCR in July and August 2021 (Delta wave), as well as from 40 autopsy cases prior to February 2021 with death due to SARS-CoV- 2. The patient population included males and females, with an age range of 37-67 years in the Delta group, and 44-79 In the non- Delta group. The population demographic was considered at risk for death due to COVID-19, and only one decedent, with immunosuppression, was known to be vaccinated. Lung specimens were examined on H&E and with SARS-CoV-2 nucleocapsid immunostain (IHC). Results: The time from initial symptoms to death averaged 9 days within the Delta wave and 16 days in non-Delta cases. Steroids, anticoagulation, antibiotics, and monoclonal antibody infusion were frequently part of the clinical treatment of Delta wave cases. Notably, SARS-CoV-2 PCR of lung swabs at autopsy were positive in all but one case examined in the Delta variant group, and viral genome RNA sequencing from lung at autopsy confirmed Delta variant lineage. In both groups, gross features of the lungs included edema, while grossly identifiable thrombi were more commonly seen in non-Delta variant cases. Histologic examination revealed diffuse alveolar damage (DAD) in all cases, most commonly early stage DAD in Delta variant cases. SARS-CoV-2 IHC demonstrated patchy to strong positivity in the alveoli of the majority of Delta variant cases - a finding not frequently seen in non-Delta cases. Figure 1 - 15 Conclusions: Our study is the first to incorporate PCR and viral genome sequencing from the lung at autopsy to correlate the Delta variant wave with histopathologic findings - a technique that may be useful in identifying important pathologic features of future variants. While the finding of DAD remains the same across viral variants, the majority of Delta cases showed a significant presence of SARS-CoV-2 in the lung by IHC, with minimal inflammatory infiltrate and reduced thrombotic complication. Whether these findings are the result of a shorter time interval between disease onset and death, therapeutic intervention, or increased viral load remains to be determined.