Immune Checkpoint Inhibitor-Induced Myocarditis vs. COVID-19 Vaccine-Induced Myocarditis-Same or Different?

Immune checkpoint inhibitor (ICI) and coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis possibly share common mechanisms secondary to overactivation of the immune system. We aimed to compare the presenting characteristics of ICIs and COVID-19 vaccine-induced myocarditis. We performed a retrospective analysis of characteristics of patients diagnosed with either ICIs or COVID-19 vaccine-induced myocarditis and compared the results to a control group of patients diagnosed with acute viral myocarditis. Eighteen patients diagnosed with ICIs (ICI group) or COVID-19 vaccine (COVID-19 vaccine group)-induced myocarditis, and 20 patients with acute viral myocarditis (Viral group) were included. The ICI group presented mainly with dyspnea vs. chest pain and fever among the COVID-19 vaccine and Viral groups. Peak median high sensitivity Troponin I was markedly lower in the ICI group (median 619 vs. 15,527 and 7388 ng/L, p = 0.004). While the median left ventricular (LV) ejection fraction was 60% among all groups, the ICI group had a lower absolute mean LV global longitudinal strain (13%) and left atrial conduit strain (17%), compared to the COVID-19 vaccine (17% and 30%) and Viral groups (18% and 37%), p = 0.016 and p = 0.001, respectively. Despite a probable similar mechanism, ICI-induced myocarditis's presenting characteristics differed from COVID-19 vaccine-induced myocarditis.

Value of new advanced hematological parameters in early prediction of severity of COVID-19.

INTRODUCTION: COVID-19 usually presents with upper respiratory tract infection in varying severity which can lead to sepsis. Early prediction of sepsis may reduce mortality by timely interventions. The intended purpose of this study was to determine whether the advanced parameters like the extended inflammation parameters (EIPs) can predict prognosis and early progression to sepsis as a sequel of COVID-19 infection and can be used as a screening profile. Also, to evaluate the Intensive Care Infection Score (ICIS) and the COVID-19 prognostic score and validate the scores for our population. METHODS: Prospective observational study of 50 reverse transcription- polymerase chain reaction (RT-PCR) proven admitted COVID-19 patients. The data assessed included complete blood counts (CBC) with EIP measurements, from Day 1 of admission to Day 10. The following groups were studied: noncritical (NC) and critical illness (CI) in COVID-19 positive cases, COVID negative sepsis and nonsepsis cases, and healthy volunteers for reference range. RESULTS: The parameters that showed statistically significant higher mean in CI group compared to the NC group are reactive lymphocyte number and percentage (RE-LYMPH#, RE-LYMPH%), antibody synthesizing lymphocyte number and percentage (AS-LYMPH#, AS-LYMPH%), Reactive monocyte count and percentage (RE-MONO#, RE-MONO%/M), ICIS, COVID-19 prognostic score (p-value <0.05). The AUC confirmed the diagnostic accuracy of all these parameters. From the multivariate logistic regression, the significant risk factor was RE-LYMPH# with cut-off >0.10 (p value: 0.011). CONCLUSION: The new EIP parameters, RE-MONO#, RE-MONO%/M, ICIS score and COVID-19 prognostic score are useful for early prediction of critical illness. AS-LYMPH is the most useful predictor of critical illness on multivariate analysis. RE-MONO# and RE-MONO%/M parameter are useful in distinguishing critical and noncritical non-COVID and COVID-19 patients.

Brief Research Report: Anti-SARS-CoV-2 Immunity in Long Lasting Responders to Cancer Immunotherapy Through mRNA-Based COVID-19 Vaccination.

Cancer patients (CPs) have been identified as particularly vulnerable to SARS-CoV-2 infection, and therefore are a priority group for receiving COVID-19 vaccination. From the patients with advanced solid tumors, about 20% respond very efficiently to immunotherapy with anti-PD1/PD-L1 antibodies and achieve long lasting cancer responses. It is unclear whether an efficient cancer-specific immune response may also correlate with an efficient response upon COVID-19 vaccination. Here, we explored the antiviral immune response to the mRNA-based COVID-19 vaccine BNT162b2 in a group of 11 long-lasting cancer immunotherapy responders. We analysed the development of SARS-CoV-2-specific IgG serum antibodies, virus neutralizing capacities and T cell responses. Control groups included patients treated with adjuvant cancer immunotherapy (IMT, cohort B), CPs not treated with immunotherapy (no-IMT, cohort C) and healthy controls (cohort A). The median ELISA IgG titers significantly increased after the prime-boost COVID vaccine regimen in all cohorts (Cohort A: pre-vaccine = 900 (100-2700), 3 weeks (w) post-boost = 24300 (2700-72900); Cohort B: pre-vaccine = 300 (100-2700), 3 w post-boost = 8100 (300-72900); Cohort C: pre-vaccine = 500 (100-2700), 3 w post-boost = 24300 (300-72900)). However, at the 3 w post-prime time-point, only the healthy control group showed a statistically significant increase in antibody levels (Cohort A = 8100 (900-8100); Cohort B = 900 (300-8100); Cohort C = 900 (300-8100)) (P < 0.05). Strikingly, while all healthy controls generated high-level antibody responses after the complete prime-boost regimen (Cohort A = 15/15 (100%), not all CPs behaved alike [Cohort B= 12/14 (84'6%); Cohort C= 5/6 (83%)]. Their responses, including those of the long-lasting immunotherapy responders, were more variable (Cohort A: 3 w post-boost (median nAb titers = 95.32 (84.09-96.93), median Spike-specific IFN-γ response = 64 (24-150); Cohort B: 3 w post-boost (median nAb titers = 85.62 (8.22-97.19), median Spike-specific IFN-γ response (28 (1-372); Cohort C: 3 w post-boost (median nAb titers = 95.87 (11.8-97.3), median Spike-specific IFN-γ response = 67 (20-84)). Two long-lasting cancer responders did not respond properly to the prime-boost vaccination and did not generate S-specific IgGs, neutralizing antibodies or virus-specific T cells, although their cancer immune control persisted for years. Thus, although mRNA-based vaccines can induce both antibody and T cell responses in CPs, the immune response to COVID vaccination is independent of the capacity to develop an efficient anti-cancer immune response to anti PD-1/PD-L1 antibodies.

Intensive Care Infection Score (ICIS) is elevated in patients with moderate and severe COVID-19 in the early stages of disease.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus is still a very dangerous and life-threatening disease with an extremely heterogeneous course. Older patients and those with comorbidities are at increased risk of death from the disease but young patients can develop potentially lethal complications too. For those reasons, numerous recent studies focus on the analysis of markers associated with early assessment of COVID-19 prognosis. Previous publications provided evidence for the Intensive Care Infection Score (ICIS) as an easy to use tool to assess the risk for bacterial infection in ICU patients based on a combination of haematologic parameters. This study evaluated the performance of ICIS as a prognostic marker of stages of disease in COVID-19 patients. METHODS: A total of 205 COVID-19 patients admitted to the University Hospital Hradec Kralove, Czech Republic, with symptoms of respiratory tract infection and a positive RT-PCR test for SARS-CoV-2 virus were enrolled in this study. Forty-nine patients developed mild COVID-19 symptoms (no oxygen therapy needed), 156 patients developed moderate or severe symptoms (supplemental oxygen therapy or death). RESULTS: ICIS predicted the mild or moderate/severe course with the highest AUC (0.773). The cut-off value (ICIS = 3.5) was selected as the value with the highest Youden index (0.423). The cut-off value could predict a mild or moderate/severe course of the disease with the highest specificity (77.6%) and positive predictive value (90.2%) of all markers used in this study. Sensitivity was 64.7%. CONCLUSION: ICIS is a reliable, cheap, fast and simply interpretable score for the early identification of moderate/severe course of COVID-19 in an early stage of the disease. ICIS> 3 predicts a severe course of the disease with high specificity and positive predictive value.

Impact of chemotherapy and immunotherapy on the composition and function of immune cells in COVID-19 convalescent with gynecological tumors.

Ongoing pandemic and potential resurgence of Coronavirus disease 2019 (COVID-19) has prompted urgent efforts to investigate the immunological memory of convalescent patients, especially in patients with active cancers. Here we performed single-cell RNA sequencing in peripheral blood samples of 3 healthy donors (HDs), 4 COVID-19 patients (Covs) and 4 COVID-19 patients with active gynecological tumor (TCs) pre- and post- anti-tumor treatment. All Covs patients had recovered from their acute infection. Interestingly, the molecular features of PBMCs in TCs are similar to that in Covs, suggesting that convalescent COVID-19 with gynecologic tumors do not have major immunological changes and may be protected against reinfection similar to COVID-19 patients without tumors. Moreover, the chemotherapy given to these patients mainly caused neutropenia, while having little effect on the proportion and functional phenotype of T and B cells, and T cell clonal expansion. Notably, anti-PD-L1 treatment massively increased cytotoxic scores of NK cells, and T cells, and facilitated clonal expansion of T cells in these patients. It is likely that T cells could protect patients from SARS-CoV-2 virus reinfection and anti-PD-L1 treatment can enhance the anti-viral activity of the T cells.

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review.

Immune checkpoint inhibitors are immune stimulatory drugs used to treat many types of cancer. These drugs are antibodies against inhibitory proteins, such as CTLA-4 and PD-1/PD-L1, that are expressed on immune cells. When bound, they allow for increased stimulation of T cells to fight tumor cells. However, immune checkpoint inhibitors have several immune-related adverse effects. Many cases have come to light recently of cardiotoxicity as a result of treatment with these drugs. Cardiotoxicity from immune checkpoint inhibitors is unique due to its rarity and high mortality rate. Patients with this toxicity may present with myocarditis, pericarditis, Takotsubo cardiomyopathy, conduction disorders, and others within just a few weeks of starting immune checkpoint inhibitors. We present here a review of the current research on immune checkpoint inhibitors, their associated cardiotoxicities, the timing of presentation of these conditions, lab tests and histology for each condition, and finally the treatment of patients with cardiotoxicity. We observe a positive skew in the onset of presentation, which is significant for the treating physician.

Immunotherapy may protect cancer patients from SARS-CoV-2 infection: a single-center retrospective analysis.

Coronavirus disease 2019 (COVID-19) global pandemic has created unique challenges to healthcare systems throughout the world. Ensuring subjects' safety is mandatory especially in oncology, in consideration of cancer patients' particular frailty. We examined the proportion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgM and/or IgG positive subjects in three different groups from Istituto Nazionale Tumori - IRCCS "Fondazione G. Pascale" in Naples (Campania region, Italy): cancer patients treated with Innovative Immunotherapy (Immune Checkpoint Inhibitors, ICIs), cancer patients undergoing standard Chemotherapies (CHTs) and healthcare providers. 9 out of 287 (3.1%) ICIs patients resulted positive, with a significant lower percentage in respect to CHTs patients (39 positive subjects out of 598, 6.5%) (p = 0.04). There was no statistically significant difference between ICIs cohort and healthcare providers, 48 out of 1050 resulting positive (4.6%). Performing a Propensity Score Matching based on gender and tumor stage, the effect of treatment on seropositivity was analyzed through a regression logistic model and the ICIs treatment resulted to be the only protective factor significantly (p = 0.03) associated with positivity (odds ratio-OR: 0.41; 95% confidence interval-CI 0.18-0.91). According to these preliminary data, ICIs would appear to be a protective factor against the onset of COVID-19 infection.