Hantavirus Disease and COVID-19

Evaluation of the Hantavirus 5-Point Screen in 139 COVID-19 Patients

Allison K. Joyce, MSc; Tarrah T. Oliver; Aaron D. Kofman, MD; Donna L. Talker; Shahrokh Safaeian; Deniz Peker Barclift, MD; Adam J. Perricone, MD, PhD; Shawn M. D'Andrea, MD; Amy N. Whitesell, MPH; Del Yazzie, MPH; Jeannette Guarner, MD; Mozafar Saleki, MS; Glynnis B. Ingall, MD, PhD; Mary J. Choi, MD; Ramona Antone-Nez, MPH


Am J Clin Pathol. 2022;157(3):470-475. 

In This Article


Our findings suggest the criteria on the 5-point screen can be used to differentiate between HCPS and COVID-19 in regions endemic for HCPS. There were a number of differences in the 5-point screen results for these two cohorts. First, there were differences in the distribution of scores between the two groups, with 64% of individuals at TMC receiving a score of 1, compared with only 24% at Emory. In addition, Emory showed higher frequencies of left shift and immunoblasts and plasma cells more than 10% of lymphoid cells. The reasons for these differences are likely varied and may include the following. First, the participants enrolled at Emory and TMC were very different from one another in terms of demographics, medical history, clinical presentation, and outcome. Notably, at Emory, all patients went on to be admitted to the hospital for their COVID-19 illness, whereas a lesser number (75%) of TMC patients were admitted. Second, there were differences in who performed the 5-point screens. At TMC, the screens were performed by medical technicians and technologists with previous experience implementing the screens. At Emory, the screens were performed by pathologists. Third, although most individuals from both cohorts had respiratory symptoms at the time of sample collection, not all did. Thus, individuals may not have been at the same stage in their disease progression when the sample was collected for the screen. Perhaps different severity of COVID-19 disease affected the peripheral blood findings. Fourth, the medical chart reviews performed at Emory were more complete compared with TMC. The demographic, medical history, clinical presentation, and outcome variables were available for 97% to 100% of the Emory cohort but ranged from 67% to 100% for the TMC cohort. Finally, it is important to acknowledge the hantavirus 5-point screen contains some subjective criteria and is subject to interobserver variability. However, because the purpose of the screen is to distinguish individuals at high risk for HCPS (scores of 4–5) from those at intermediate (3) or low (1–2) risk, we contend these cutoffs allow for a difference in interpretation of the markers that ultimately do not change the results.

We found that irrespective of who performed the 5-point screen, the demographics of the population screened, or when in the COVID-19 disease course the sample was taken, individuals positive for COVID-19 received a low score on the screen. None of the 139 individuals in the project positive for COVID-19 demonstrated all five hallmarks of hantavirus infection, and only 3 (2%) individuals received a score of 4 on the screen. Although there were differences in the frequency of scores 1, 2, and 3 between the TMC and Emory populations Figure 1, these scores would all be considered non–high risk for HCPS. Thrombocytopenia was seen in 30% of the project participants but was mild, with thrombocytopenic individuals having a median platelet count of 107 × 109/L at TMC and 123 × 109/L at Emory. This is consistent with other studies in patients positive for COVID-19.[16–18] In contrast, thrombocytopenia seen in HCPS patients is typically more profound, with some platelet counts dipping to dangerously low levels of less than 30 × 109/L.[10] In addition, none of the individuals with thrombocytopenia who had a repeat platelet count done within 12 to 24 hours demonstrated the 20% or more drop that is characteristic of patients with HCPS. Therefore, while thrombocytopenia was seen in our cohort of 139 patients positive for COVID-19, it is generally milder than what is seen in patients with HCPS.

Given the overlap in signs and symptoms, it is difficult to distinguish early HCPS and COVID-19 disease. In May 2020, a mother and her 11-year-old son died after a brief severe respiratory illness in Arizona.[14] Initial testing of tissue collected from the child's trachea and lung were positive for SARS-CoV-2 by rRT-PCR. Testing of the mother's lung tissue was negative for SARS-CoV-2 by rRT-PCR but demonstrated clinicopathologic features suggestive of HCPS. Subsequent immunohistochemical evaluation of lung tissue from both the mother and the child confirmed hantavirus infection. This case underscores the importance of considering hantavirus disease in the differential diagnosis in patients presenting with respiratory illness who live in hantavirus endemic areas. In addition, clinicians in hantavirus endemic areas should consider performing the hantavirus 5-point screen even in patients positive for COVID-19 to identify potential instances of coinfection.