Autopsy Histopathologic Cardiac Findings in 2 Adolescents Following the Second COVID-19 Vaccine Dose/In Reply

The authors correctly stated that the Centers for Disease Control and Prevention (CDC) performed testing for SARS-CoV-2 and found no evidence of SARS-CoV-2 infection in autopsy tissues from the decedents. Molecular analysis included polymerase chain reaction (PCR) assays on nucleic acid extracted from FFPE heart tissue, including SARS-CoV-2 and enterovirus reverse transcriptase PCR (RT-PCR) assays2,3 and conventional PCR for parvovirus B19. Clostridium septicum produces multiple toxins that cause necrosis of striated muscle cells9,11 and inhibit influx of neutrophils to infected tissues;indeed, paucity of neutrophilic infiltrates in tissues infected with C septicum is considered a hallmark of this disease.9,12 Clostridium septicum is not considered normal flora of the human intestinal tract,13,14 but rather an opportunistic invader of immunologically compromised hosts, particularly persons with colonic adenocarcinoma, leukemia, diabetes, bowel ischemia, or cyclic, congenital, or acquired neutropenia.7,8 Spontaneous infections have been described for a few pediatric patients with no recognized risk factor and for whom microscopic breaches in the mucosa of the large intestine were considered the likely portal of entry.8,15 No representative samples of the small or large intestine were provided to the IDPB for evaluation;however, histologic evidence of bacterial invasion of the external surfaces of the adrenals, kidneys, liver, and spleen support an intraabdominal source of infection. The findings and conclusions in this letter are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. doi: 10.5858/arpa.2022-0084-LE In Reply.-We thank the Centers for Disease Control and Prevention's (CDC's) Infectious Diseases Pathology Branch laboratory for performing these tests and for sharing the full extent of its workup.

Intersecting Paths of Emerging and Reemerging Infectious Diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shares common clinicopathologic features with other severe pulmonary illnesses. Hantavirus pulmonary syndrome was diagnosed in 2 patients in Arizona, USA, suspected of dying from infection with SARS-CoV-2. Differential diagnoses and possible co-infections should be considered for cases of respiratory distress during the SARS-CoV-2 pandemic.

Evidence of Severe Acute Respiratory Syndrome Coronavirus 2 Replication and Tropism in the Lungs, Airways, and Vascular Endothelium of Patients With Fatal Coronavirus Disease 2019: An Autopsy Case Series.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case patients (age range, 1 month to 84 years; 21 COVID-19 confirmed, 43 suspected COVID-19) by SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR). For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in situ hybridization (ISH), subgenomic RNA RT-PCR, and whole-genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case patients (21 COVID-19 confirmed, 11 suspected). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes, and macrophages of lungs; epithelial cells of airways; and endothelial cells and vessel walls of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. The D614G variant was detected in 9 RT-PCR-positive case patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes.