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Background: Assessing the composition of immune responses to SARS‐CoV‐2 vaccines is critical for our understanding of protective immunity, especially for immune compromised patients. The Pfizer (BNT162b2) vaccination showed >90% efficacy in protecting individuals from infection. However, these studies did not examine responses in immunocompromised kidney transplant patients (KT). Subsequent reports in KT have shown severe deficiencies in Spike‐specific immunoglobin G (IgG) responses prompting booster vaccinations, but a broader understanding of T‐cell immunity to vaccinating is lacking. Methods: We examined SARS‐CoV‐2 Spike IgG and CD4+/CD8+ Spike‐specific T‐cell responses in 61 KT patients maintained on different immunosuppressive protocols (ISP) (Tac + mycophenolate mofetil + prednisone) versus (belatacept + MMF + prednisone) and compared to 41 healthy controls. We also examined cytomegalovirus‐cytotoxic T‐cell responses (CMV‐Tc) in both groups to assess T‐cell memory. Results: Our data confirmed poor Spike IgG responses in vaccinated KT patients with both ISP (21% demonstrating Spike IgG 1M post‐second dose of BNT162b2 vs. 93% in controls). However, 35% of Spike IgG (‐) patients demonstrated CD4+ and/or CD8+ T‐cell responses. All but one CMV‐IgG+ patient demonstrated good CMV‐Tc responses. No differences in T‐cell immunity by ISP were seen. Conclusion: Immunocompromised KT recipients showed severe defects in humoral and T‐cell immune response after vaccination. No differences in immune responses to SARS‐CoV‐2 Spike peptides were observed in KT patients by ISP post‐vaccination. The detection of Spike‐specific T‐cell immunity in the absence of Spike IgG suggests that vaccination in immunocompromised KT patients may provide partial immunity, although not preventing infection, T‐cell immunity may limit its severity. [ABSTRACT FROM AUTHOR]

Background Preliminary data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is approved by the Food and Drug Administration for treatment of cytokine storm associated with chimeric antigen receptor T-cell therapy. Here we examined compassionate use of tocilizumab in patients with SARS-CoV-2 pneumonia. Methods We report on a single-center study of tocilizumab in hospitalized patients with SARS-CoV-2 pneumonia. All patients had confirmed SARS-CoV-2 pneumonia and oxygen saturations <90% on oxygen support with most intubated. We examined clinical and laboratory parameters including oxygen and vasopressor requirements, cytokine profiles, and C-reactive protein (CRP) levels pre- and post-tocilizumab treatment. Results Twenty-seven SARS-CoV-2 pneumonia patients received one 400 mg dose of tocilizumab. Interleukin (IL)-6 was the predominant cytokine detected at tocilizumab treatment. Significant reductions in temperature and CRP were seen post-tocilizumab. However, 4 patients did not show rapid CRP declines, of whom 3 had poorer outcomes. Oxygen and vasopressor requirements diminished over the first week post-tocilizumab. Twenty-two patients required mechanical ventilation; at last follow-up, 16 were extubated. Adverse events and serious adverse events were minimal, but 2 deaths (7.4%) occurred that were felt unrelated to tocilizumab. Conclusions Compared to published reports on the morbidity and mortality associated with SARS-CoV-2, tocilizumab appears to offer benefits in reducing inflammation, oxygen requirements, vasopressor support, and mortality. The rationale for tocilizumab treatment is supported by detection of IL-6 in pathogenic levels in all patients. Additional doses of tocilizumab may be needed for those showing slow declines in CRP. Proof of efficacy awaits randomized, placebo-controlled clinical trials. [ABSTRACT FROM AUTHOR]