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Our first paper on COVID has just been submitted – the pre-print is already available online and free for distribution (the “biorxiv” link below): Alexander Lehmann, Greg A Kirchenbaum, Ting Zhang, Pedro A Reche, Paul V Lehmann. Deconvoluting the T cell response to SARS-CoV-2: specificity versus chance- and cognate cross-reactivity. 2020. Submitted to Frontiers in Immunology. bioRxiv: https://biorxiv.org/cgi/content/short/2020.11.29.402677v1 The main messages are: By using IFN-g ELISPOT (that detects effector memory cells) one can distinguish between SARS-CoV-2 infected vs non-infected humans. Based on the literature, other flowcytometry-based techniques like AID, multimers, CFSE dilution provide false positive results in non-infected individuals allegedly due to detecting central memory cells that cross-react with seasonal coronaviruses causing common cold (or, just by not being sensitive enough to provide clean data when the frequencies are rather low) Several protein antigens on SARS-CoV-2 are immunogenic and need to be monitored to detect all infected individuals (good luck multimers looking at one/few peptide(s) only.) We show here that T cell affinity measurements (serial dilution of peptide pools)are also important for a clear SARS-CoV2 infected/non-infected distinction. Such can be easily done with ELISPOT due to (a) efficient cell utilization, and (b) high throughput capability with little labor involved. Irrelevant mega peptide pools as specificity controls: as more and more scientists start to understand that T cell immune monitoring cannot rely on few peptides (multimers), more and more (including most in SARS-CoV-2 T cell diagnostic) use mega peptide pools. However, it has not been so far established that this is a valid approach – we did it here！