key: cord-0829592-qxlbwf09
authors: Wilson, Tais M.; Paddock, Christopher D.; Reagan-Steiner, Sarah; Bhatnagar, Julu; Martines, Roosecelis B.; Wiens, Andrea L.; Madsen, Michael; Komatsu, Kenneth K.; Venkat, Heather; Zaki, Sherif R.
title: Intersecting Paths of Emerging and Reemerging Infectious Diseases
date: 2021-05-03
journal: Emerg Infect Dis
DOI: 10.3201/eid2705.204779
sha: 78a0ad7aa5a467b473be90d149b2f1f347ebf5c1
doc_id: 829592
cord_uid: qxlbwf09

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.

S evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), emerged in Wuhan, China, during December 2019 and spread rapidly to other parts of China and the world (1) . However, the clinical and pathologic features of COVID-19 are also found for other respiratory disease, such as hantavirus pulmonary syndrome (HPS). In 1993, a hantavirus (Sin Nombre virus) and its rodent reservoir (Peromyscus maniculatus deer mouse) were identified as the causative agent and vertebrate reservoir responsible for an outbreak of severe pulmonary illness, named HPS, in the Four Corners region in the southwestern United States (2) (3) (4) .

Soon after the emergence and recognition of COVID-19 in the United States in early 2020, the Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention initiated diagnostic testing of fixed tissue specimens from deceased persons who had suspected or confirmed SARS-CoV-2 infection (5,6). During May 2020, Infectious Diseases Pathology Branch received tissues from an 11-year-old child (patient 1) from Arizona, who died after a brief illness culminating in severe respiratory distress. Histopathological findings included diffuse alveolar damage with rare hyaline membranes, intraalveolar edema, leukocytosis with a left shift ( Figure, panel A) , interstitial pneumonitis and immunoblasts in the red pulp and periarteriolar sheaths of the spleen (Figure, panel B) . RNA extracted from formalin-fixed, paraffin-embedded trachea and lung tissues was positive for SARS-CoV-2 by conventional reverse transcription PCR (RT-PCR) and sequencing of positive amplicons. However, evaluation for SARS-CoV-2 by using an immunohistochemical (IHC) assay (5) showed negative results.

Subsequently, embalmed lung tissues were received from the child`s mother, a 25-year-old woman (patient 2) who died 2 days before the child after a brief illness characterized by progressive shortness of breath, cough, abdominal pain, fever, and hemoptysis. Histopathologic findings for the lungs of patient 2 resembled those identified for patient 1 (Figure, The clinicopathologic and IHC findings indicate that both patients died from HPS. Although SARS-CoV-2 RNA was detected by RT-PCR in patient 1, it was not the probable underlying cause of death. This scenario provides an essential reminder that previously recognized, nonendemic infectious diseases that clinically resemble COVID-19 continue to occur during the pandemic, in a manner similar to other clinicopathologic mimics described previously during other pandemic diseases (7).

Consideration of alternative diagnoses of diseases that precipitate acute respiratory distress syndrome and co-infections remains crucial for diagnosing and treating of critically ill patients, as well as accurately determining causes of death. For HPS, triage tools such as peripheral blood smear review and identifying 4 of 5 findings (thrombocytopenia, hemoconcentration, granulocytic left shift, absence of toxic changes, and >10% immunoblasts) can be used During a subsequent round of contact tracing, 14 additional SARS-CoV-2-positive cases were detected both in the community (n = 3) and Danang hospitals (n = 11). Vietnam then initiated large-scale contact tracing and quarantining. A total of 551 confirmed cases were reported from 15 cities and provinces across the country; 540 (98%) either were related to major hospitals in Danang or were in patients who had visited Danang during July 25-September 3. This cluster included 35 COVID-19 fatalities, most (32) hospital-acquired and associated with concurrent conditions or old age (2, 5) . Danang General Hospital, the epicenter of the outbreak, reported 246 cases among inpatients, caregivers, and healthcare workers. Strict prevention measures of contact tracing, quarantine, and isolation were again implemented nationally, and the outbreak was successfully contained. We describe the molecular epidemiology of this cluster.

We performed sequencing of 26 nasopharyngeal or throat swab specimens that were sent to the National Institute of Hygiene and Epidemiology (Hanoi, Vietnam) for diagnostics; all were positive for SARS-CoV-2 and had cycle threshold value <30 by real-time reverse transcription PCR (6-8). Of those specimens, 18 were collected from patients in hospitals and communities in Danang and the rest from outside Danang: Ha Nam (1), Quang Nam (1), Thanh Hoa (1), Hanoi (2), Lang Son (2), and Hai Duong (1). We uploaded sequences to the GISAID database (https://www.gisaid.org; accession nos. 759869-91 and 766029-31).

All 26 sequences belonged to lineage B.1.1 and clustered together in the global tree, with the exception of DN013 (Figure 1, panel A) 

A cluster of severe acute respiratory syndrome coronavirus 2 infections in Danang, Vietnam, began July 25, 2020, and resulted in 551 confirmed cases and 35 deaths as of February 2021. We analyzed 26 sequences from this cluster and identified a novel shared mutation in nonstructural protein 9, suggesting a single introduction into Vietnam.

China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China

Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease

Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness

Hantavirus pulmonary syndrome: pathogenesis of an emerging infectious disease

COVID-19 Pathology Working Group. Pathology and pathogenesis of SARS-CoV-2 associated with fatal coronavirus disease, United States