During human CMV infection, there is a preferential expansion of natural killer (NK) cells expressing the activating CD94-NKG2C receptor complex, implicating this receptor in the recognition of CMV-infected cells. We hypothesized that NK cells expanded in response to pathogens will be marked by expression of CD57, a carbohydrate antigen expressed on highly mature cells within the CD56

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T o date, hundreds of thousands of deaths have been attributed to coronavirus disease 2019 (COVID-19) 1. Millions of infections by SARS-CoV-2, the virus responsible for COVID-19, have been reported, although its full extent has yet to be determined owing to limited testing 2. Government interventions to slow viral spread have disrupted daily life and economic activity for billions of people. Strategies to ease restraints on human mobility and interaction without provoking a major resurgence of transmission and mortality will depend on accurate estimates of population levels of infection and immunity 3. Current testing for the virus largely depends on labor-intensive molecular techniques 4. Individuals with positive molecular tests represent only a small fraction of all infections, given limited deployment and the brief time window when real-time (RT)-PCR testing has the highest sensitivity 5-7. The proportion of undocumented cases in the original epidemic focus was estimated to be as high as 86% 8 , and asymptomatic infections are suspected to play a substantial role in transmission 9-14. Widely available, reliable antibody detection assays would enable more accurate estimates of SARS-CoV-2 prevalence and incidence. On February 4, 2020, the Secretary of the US Department of Health and Human Services issued an emergency use authorization (EUA) for the diagnosis of SARS-CoV-2 15 , allowing nucleic acid detection and immunoassay tests to be offered based on manufacturer-reported data without formal US Food and Drug Administration (FDA) clearance 16. In response, dozens of companies began to market laboratory-based immunoassays and point-of-care (POC) tests. Rigorous, comparative performance data are crucial to inform clinical care and public health responses.

BackgroundA subset of CD3negCD56negCD16+ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations.ResultsUsing CD7 as an additional NK cell marker, we found that CD3negCD56negCD16+ cells are a heterogeneous population comprised of CD7+ NK cells and CD7neg non-classical myeloid cells. CD7+CD56negCD16+ NK cells are significantly expanded in HIV-1 infection. CD7+CD56negCD16+ NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to CD7+CD56+CD16+ NK cells. CD7+CD56neg NK cells in healthy donors produced minimal IFNγ following K562 target cell or IL-12 plus IL-18 stimulation; however, they degranulated in response to K562 stimulation similar to CD7+CD56+ NK cells. HIV-1 infection resulted in reduced IFNγ secretion following K562 or cytokine stimulation by both NK cell subsets compared to healthy donors. Decreased granzyme B and perforin expression and increased expression of CD107a in the absence of stimulation, particularly in HIV-1-infected subjects, suggest that CD7+CD56negCD16+ NK cells may have recently engaged target cells. Furthermore, CD7+CD56negCD16+ NK cells have significantly increased expression of CD95, a marker of NK cell activation.ConclusionsTaken together, CD7+CD56negCD16+ NK cells are activated, mature NK cells that may have recently engaged target cells.

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