Background
Identification of the Th17 T cell subset as important mediators of host defense and pathology, prompted us to determine their susceptibility to HIV infection.
Methods and Results
We found that a sizeable portion of Th17 cells express HIV co-receptor CCR5 and produce very low levels of CCR5 ligands MIP-1α and MIP-1β. Accordingly, CCR5+ Th17 cells were efficiently infected with CCR5-tropic HIV and were depleted during viral replication in vitro. Remarkably, HIV+ individuals under treatment showed significantly reduced Th17 cells compared to HIV− subjects, regardless of their viral loads or CD4 numbers, whereas treatment naïve subjects had normal levels. However, there was a preferential reduction in CCR5+ T cells that were also CCR6+, which is expressed on all Th17 cells, as compared to CCR6−CCR5+ cells, in both treated and untreated HIV+ subjects. This observation suggests preferential targeting of CCR6+CCR5+ Th17 cells by CCR5-tropic viruses in vivo. Th17 cell levels also inversely correlated with activated CD4+ T cells in HIV+ individuals under treatment.
Conclusion
Our findings suggest a complex perturbation of Th17 subsets during the course of HIV-disease potentially through both direct viral infection and virus indirect mechanisms such as immune activation.
Background
Reports suggest that some persons previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lack detectable IgG antibodies. We aimed to determine the proportion IgG seronegative and predictors for seronegativity among persons previously infected with SARS-CoV-2.
Methods
We analyzed serologic data collected from health care workers and first responders in New York City and the Detroit metropolitan area with history of a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) test result and who were tested for IgG antibodies to SARS-CoV-2 spike protein at least 2 weeks after symptom onset.
Results
Of 2,547 persons with previous confirmed SARS-CoV-2 infection, 160 (6.3%) were seronegative. Of 2,112 previously symptomatic persons, the proportion seronegative slightly increased from 14 to 90 days post symptom onset (p=0.06). The proportion seronegative ranged from 0% among 79 persons previously hospitalized to 11.0% among 308 persons with asymptomatic infections. In a multivariable model, persons taking immunosuppressive medications were more likely to be seronegative (31.9%, 95% confidence interval [CI] 10.7%-64.7%), while participants of non-Hispanic Black race/ethnicity (versus non-Hispanic White) (2.7%, 95% CI 1.5%-4.8%), with severe obesity (versus under/normal weight) (3.9%, 95% CI 1.7%-8.6%), or with more symptoms were less likely to be seronegative.
Conclusions
In our population with previous RT-PCR confirmed infection, approximately one in 16 persons lacked IgG antibodies. Absence of antibodies varied independently by illness severity, race/ethnicity, obesity, and immunosuppressive drug therapy. The proportion seronegative remained relatively stable among persons tested up to 90 days post symptom onset.
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