Table 1.

Key studies of the immune response to SARS-CoV-2 infection in SOT recipients

Immune response	Reference	Study design	Relevant immune assays	Population	Key findings	Limitations
Innate	[56]	Observational cohort study	IL-6 measurement with a commercial chemiluminescent immunoassay	49 kidney transplant recipients in France with COVID-19 44 PCR-confirmed 2 diagnosed by serology 3 clinical diagnoses	CRP and IL-6 levels (as well as other markers of inflammation and coagulopathy) strongly predictive of severe COVID-19 and death Nasopharyngeal SARS-CoV-2 viral loads were not associated with disease severity	Only kidney transplant recipients No non-transplant patients for comparison No other cytokine measurements
Humoral	[57••]	Cross-sectional seroprevalence study	3 commercial SARS-CoV-2 antibody assays 1 anti-nucleocapsid antibody assay 2 anti-RBD assay	855 kidney transplant patients in the UK 69 tested positive 38 with PCR-confirmed SARS-CoV-2 infection (82% had received alemtuzumab induction) PCR-positive patients served as their own controls (pre-pandemic sera) 85 immunocompetent healthcare workers with PCR-confirmed SARS-CoV-2 infection were also tested using 2 of the same antibody assays	10.4% overall seropositivity rate Widely differing performance characteristics of 3 antibody assays, including differences with the immunocompetent comparison group	Only kidney transplant recipients High rates of alemtuzumab induction therapy Only 1 of 3 assays detected IgM antibody No details of antibody titer data No assessment of neutralization
	[58]	Observational cohort study	Commercial anti-nucleocapsid antibody assay	10 SOT recipients (3 outpatients and 7 hospitalized) with PCR-confirmed COVID-19 in the USA	None 6 of 7 hospitalized patients had detectable antibodies 1 patient with severe illness (ARDS, shock) did not seroconvert Median time to seroconversion was 15 days	No non-transplant patients for comparison No details of antibody titer data No assessment of neutralization Limited follow-up and small sample size
	[51••]	Observational cohort study	Commercial anti-nucleocapsid and anti-spike antibody assay	40 kidney transplant recipients hospitalized with laboratory-confirmed COVID-19 in France 38 PCR-confirmed 2 diagnosed by serology	36 survivors seroconverted, whereas 4 non-survivors did not 13 had detectable IgM and/or IgG antibodies by day 14 All had seroconverted by days 15–28 Antibodies were maintained through day 59 No difference in antibody titers between severe and non-severe cases	Only kidney transplant recipients No non-transplant patients for comparison Authors did not report anti-nucleocapsid and anti-spike results separately No assessment of neutralization
	[59••]	Observational cohort study (follow-up to [51••])	Commercial anti-nucleocapsid and anti-spike antibody assay	29 kidney transplant recipients with laboratory-confirmed COVID-19 in France	21 of 29 (72%) had detectable IgG up to day 190	Only kidney transplant recipients No non-transplant patients for comparison Authors did not report anti-nucleocapsid and anti-spike results separately No assessment of neutralization
	[60••]	Observational cohort study	Commercial multiplex anti-nucleocapsid and anti-spike antibody assay	6 kidney transplant recipients hospitalized with COVID-19 5 PCR-confirmed 1 clinical diagnosis 5 kidney transplant recipients with suspected mild COVID-19 (outpatients that were PCR-negative) 2 hemodialysis patients with PCR-confirmed COVID-19 (1 hospitalized)	All 7 patients with PCR-confirmed COVID-19 seroconverted by days 21–42 7 had anti-nucleocapsid IgG 5 had anti-spike IgG 3 had anti-spike IgM In the 3 patients tested twice (2 transplant, 1 non-transplant), trend toward declining titers by day 60	Only kidney transplant recipients and small sample size Authors did not report titers from transplant and non-transplant patients separately No assessment of neutralization
Cellular	[60••]	Observational cohort study	IFN-gamma ELISpot using overlapping 15mer SARS-CoV-2 peptide pools (representing structural and non-structural proteins)	6 kidney transplant recipients hospitalized with COVID-19 5 PCR-confirmed 1 clinical diagnosis 5 kidney transplant recipients with suspected mild COVID-19 (outpatients that were PCR-negative) 2 hemodialysis patients with PCR-confirmed COVID-19 (1 hospitalized)	All 7 patients with PCR-confirmed COVID-19 displayed CD4+ and CD8+ T cells reactive to at least 6 of 9 peptides (anti-spike reactivity was dominant) All 5 transplant patients underwent reduction of immunosuppression at time of diagnosis 3 PCR-negative patients had no SARS-CoV-2 reactive T cells	Only kidney transplant recipients and small sample size No assessment of T cell subsets and phenotype
	[61••]	Observational cohort study	Commercial anti-nucleocapsid antibody assay Flow cytometry for B and T cell assays and intracellular cytokine staining for T cell assays	18 kidney transplant recipients hospitalized with PCR-confirmed COVID-19 Banked PBMCs (pre-pandemic) from 36 kidney transplant recipients served as negative controls 14 COVID-negative and 16 COVID-positive non-transplant controls	16 transplant patients underwent antibody testing, and 60% had detectable antibodies (mostly between day 10 and 30) Transplant patients with COVID-9 had Higher frequencies of B cell subsets (naïve, switched, activated) compared with uninfected controls No change in TFH, plasmablast, or circulating plasma cell frequencies Reductions in effector and memory CD4+ and CD8+ T cells No evidence of exhausted T cells, unlike non-transplant patients with COVID-19 No differences in B or T cell populations by disease severity	Only kidney transplant recipients No assessment of neutralizing antibodies No assessment of memory B cells No assessment of SARS-CoV-2–specific T cell reactivity