Antibody and T cell responses to COVID-19 vaccination in patients receiving anticancer therapies.

BACKGROUND: Patients with cancer were excluded from phase 3 COVID-19 vaccine trials, and the immunogenicity and side effect profiles of these vaccines in this population is not well understood. Patients with cancer can be immunocompromised from chemotherapy, corticosteroids, or the cancer itself, which may affect cellular and/or humoral responses to vaccination. PD-1 is expressed on T effector cells, T follicular helper cells and B cells, leading us to hypothesize that anti-PD-1 immunotherapies may augment antibody or T cell generation after vaccination. METHODS: Antibodies to the SARS-CoV-2 receptor binding domain (RBD) and spike protein were assessed in patients with cancer (n=118) and healthy donors (HD, n=22) after 1, 2 or 3 mRNA vaccine doses. CD4+ and CD8+ T cell reactivity to wild-type (WT) or B.1.617.2 (delta) spike peptides was measured by intracellular cytokine staining. RESULTS: Oncology patients without prior COVID-19 infections receiving immunotherapy (n=36), chemotherapy (n=15), chemoimmunotherapy (n=6), endocrine or targeted therapies (n=6) and those not on active treatment (n=26) had similar RBD and Spike IgG antibody titers to HDs after two vaccinations. Contrary to our hypothesis, PD-1 blockade did not augment antibody titers or T cell responses. Patients receiving B-cell directed therapies (n=14) including anti-CD20 antibodies and multiple myeloma therapies had decreased antibody titers, and 9/14 of these patients were seronegative for RBD antibodies. No differences were observed in WT spike-reactive CD4+ and CD8+ T cell generation between treatment groups. 11/13 evaluable patients seronegative for RBD had a detectable WT spike-reactive CD4+ T cell response. T cells cross-reactive against the B.1.617.2 variant spike peptides were detected in 31/59 participants. Two patients with prior immune checkpoint inhibitor-related adrenal insufficiency had symptomatic hypoadrenalism after vaccination. CONCLUSIONS: COVID-19 vaccinations are safe and immunogenic in patients with solid tumors, who developed similar antibody and T cell responses compared with HDs. Patients on B-cell directed therapies may fail to generate RBD antibodies after vaccination and should be considered for prophylactic antibody treatments. Many seronegative patients do develop a T cell response, which may have an anti-viral effect. Patients with pre-existing adrenal insufficiency may need to take stress dose steroids during vaccination to avoid adrenal crisis.

Impact of COVID-19 vaccination on the use of PD-1 inhibitor in treating patients with cancer: a real-world study.

Anti-COVID-19 vaccination may have functional implications for immune checkpoint inhibitor treatment in patients with cancer. This study was undertaken to determine whether the safety or efficacy of anti-PD-1 therapy is reduced in patients with cancer during COVID-19 vaccination. A large multicenter observational study was conducted in 83 Chinese hospitals between January 28, 2021 and September 30, 2021. A total of 3552 patients were screened and 2048 eligible patients with cancer receiving PD-1 inhibitor treatment were recruited. All enrolled patients had received camrelizumab treatment alone or in conjunction with other cancer therapies. Among these, 1518 (74.1%) patients received the BBIBP-CorV vaccine and were defined as the vaccinated subgroup. The remaining 530 (25.9%) patients did not receive anti-COVID-19 vaccination and were defined as the non-vaccinated subgroup. For all participants, Response Evaluation Criteria in Solid Tumor and Common Terminology Criteria for Adverse Events criteria were used to evaluate the efficacy and safety of camrelizumab treatment, respectively. Propensity score match analysis with the optimal pair matching was used to compare these criteria between the vaccinated and non-vaccinated subgroups. A total of 2048 eligible patients with cancer were included (median age 59 years, 27.6% female). Most patients (98.8%) had metastatic cancer of the lung, liver or intestinal tract. Aside from the PD-1 inhibitor treatment, 55.9% of patients received additional cancer therapies. 1518 (74.1%) patients received the BBIBP-CorV vaccine with only mild side effects reported. The remaining patients did not receive COVID-19 vaccination and had a statistically greater percentage of comorbidities. After matching for age, gender, cancer stage/types, comorbidity and performance status, 1060 patients (530 pairs) were selected for propensity score match analysis. This analysis showed no significant differences in overall response rate (25.3% vs 28.9%, p=0.213) and disease control rate (64.6% vs 67.0%, p=0.437) between vaccinated and non-vaccinated subgroups. Immune-related adverse events (irAEs) were reported in both subgroups after camrelizumab treatment. Among vaccinated patients who experienced irAEs, the median interval between the first dose of camrelizumab treatment and the first vaccine shot was ≤16 days. Compared with the non-vaccinated subgroup, irAEs in vaccinated patients were more frequently reported as mild (grade 1 or 2 irAEs; 33.8% vs 19.8%, p<0.001) and these patients were less likely to discontinue the PD-1 inhibitor treatment (4.2% vs 20.4%, p<0.001). Severe irAEs (grade 3 irAE or higher) related to camrelizumab treatment were reported, however no significant differences in the frequency of such events were observed between the vaccinated and non-vaccinated subgroups. The COVID-19 vaccine, BBIBP-CorV, did not increase severe anti-PD-1-related adverse events nor did it reduce the clinical efficacy of camrelizumab in patients with cancer. Thus, we conclude that patients with cancer need not suspend anti-PD-1 treatment during COVID-19 vaccination.

Analysis of the humoral and cellular immune response after a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors with or without chemotherapy: an update after 6 months of follow-up.

BACKGROUND: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine. PATIENTS AND METHODS: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/106 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. RESULTS: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/106 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively). CONCLUSIONS: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors.

PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response.

A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1ß, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cell-mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.

Intratumoral OH2, an oncolytic herpes simplex virus 2, in patients with advanced solid tumors: a multicenter, phase I/II clinical trial.

BACKGROUND: OH2 is a genetically engineered oncolytic herpes simplex virus type 2 designed to selectively amplify in tumor cells and express granulocyte-macrophage colony-stimulating factor to enhance antitumor immune responses. We investigated the safety, tolerability and antitumor activity of OH2 as single agent or in combination with HX008, an anti-programmed cell death protein 1 antibody, in patients with advanced solid tumors. METHODS: In this multicenter, phase I/II trial, we enrolled patients with standard treatment-refractory advanced solid tumors who have injectable lesions. In phase I, patients received intratumoral injection of OH2 at escalating doses (106, 107 and 108CCID50/mL) as single agent or with fixed-dose HX008. The recommended doses were then expanded in phase II. Primary endpoints were safety and tolerability defined by the maximum-tolerated dose and dose-limiting toxicities (DLTs) in phase I, and antitumor activity assessed per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) and immune-RECIST in phase II. RESULTS: Between April 17, 2019 and September 22, 2020, 54 patients with metastatic cancers were enrolled. Forty patients were treated with single agent OH2, and 14 with OH2 plus HX008. No DLTs were reported with single agent OH2 in phase I. Four patients, having metastatic mismatch repair-proficient rectal cancer or metastatic esophageal cancer, achieved immune-partial response, with two from the single agent cohort and two from the combination cohort. The duration of response were 11.25+ and 14.03+ months for the two responders treated with single agent OH2, and 1.38+ and 2.56+ months for the two responders in the combination cohort. The most common treatment-related adverse event (TRAE) with single agent OH2 was fever (n=18, 45.0%). All TRAEs were of grade 1-2, except one case of grade 3 fever in the 108CCID50/mL group. No treatment-related serious AEs occurred. Single agent OH2 induced alterations in the tumor microenvironment, with clear increases in CD3+ and CD8+ cell density and programmed death-ligand 1 expression in the patients' post-treatment biopsies relative to baseline. CONCLUSIONS: Intratumoral injection of OH2 was well-tolerated, and demonstrated durable antitumor activity in patients with metastatic esophageal and rectal cancer. Further clinical development of OH2 as single agent or with immune checkpoint inhibitors in selected tumor types is warranted.

[A Case Report of Checkpoint Inhibitor Pneumonitis Caused by PD-1
Antibody-Safety and Effectiveness of Pirfenidone].

BACKGROUND: Immune checkpoint inhibitor associated pneumonia (CIP) is a serious side effect of immune checkpoint inhibitors. There is a consensus on the treatment of acute phase of CIP, but the treatment of pulmonary interstitial fibrosis after the acute phase is still a clinical problem to be solved. METHODS: The diagnosis and treatment of a non-small cell lung cancer (NSCLC) patient with immune checkpoint inhibitor associated pneumonia in the Stereotactic Radiotherapy Department of Qingdao Central Hospital were retrospectively analyzed, and literatures were reviewed. RESULTS: A 70-year-old male patient was diagnosed with Poorly differentiated squamous cell carcinoma of left lung with mediastinal lymph node metastasis T3N3M0 stage IIIc, EGFR/ALK/ROS1/RAF negative, PD-L1 (22c3) immunohistochemistry negative. After the progression of first-line chemotherapy, the patient was diagnosed as immune checkpoint inhibitor associated pneumonia grade 3 during second-line monotherapy with Nivolumab. After initial high-dose glucocorticoid pulse therapy, the lung computed tomography (CT) imaging and clinical symptoms of the patients were partially relieved, and then pirfenidone (300 mg tid) was given orally for more than 11 months. During the treatment of pirfenidone, the CT imaging and clinical symptoms of the patients were significantly improved, and there were no other adverse reactions except grade 1 nausea. During this period, chemotherapy and Anlotinib was given concurrently with pirfenidone and showed good safety profile. CONCLUSIONS: This case report is the first report of pirfenidone in the treatment of CIP, which provides a new idea for the clinical practice and research of CIP treatment.

Combination treatments with hydroxychloroquine and azithromycin are compatible with the therapeutic induction of anticancer immune responses.

Amid controversial reports that COVID-19 can be treated with a combination of the antimalarial drug hydroxychloroquine (HCQ) and the antibiotic azithromycin (AZI), a clinical trial (ONCOCOVID, NCT04341207) was launched at Gustave Roussy Cancer Campus to investigate the utility of this combination therapy in cancer patients. In this preclinical study, we investigated whether the combination of HCQ+AZI would be compatible with the therapeutic induction of anticancer immune responses. For this, we used doses of HCQ and AZI that affect whole-body physiology (as indicated by a partial blockade in cardiac and hepatic autophagic flux for HCQ and a reduction in body weight for AZI), showing that their combined administration did not interfere with tumor growth control induced by the immunogenic cell death inducer oxaliplatin. Moreover, the HCQ+AZI combination did not affect the capacity of a curative regimen (cisplatin + crizotinib + PD-1 blockade) to eradicate established orthotopic lung cancers in mice. In conclusion, it appears that HCQ+AZI does not interfere with the therapeutic induction of therapeutic anticancer immune responses.

A false alarm of COVID-19 pneumonia in lung cancer with anti-PD-1 related pneumonitis: a case report and review of the literature.

BACKGROUND: Pneumonitis belongs to the fatal toxicities of anti-PD-1/PD-L1 treatments. Its diagnosis is based on immunotherapeutic histories, clinical symptoms, and the computed tomography (CT) imaging. The radiological features were typically ground-glass opacities, similar to CT presentation of 2019 Novel Coronavirus (COVID-19) pneumonia. Thus, clinicians are cautious in differential diagnosis especially in COVID-19 epidemic areas. CASE PRESENTATION: Herein, we report a 67-year-old Han Chinese male patient presenting with dyspnea and normal body temperature on the 15th day of close contact with his son, who returned from Wuhan. He was diagnosed as advanced non-small cell lung cancer and developed pneumonitis post Sintilimab injection during COIVD-19 pandemic period. The chest CT indicated peripherally subpleural lattice opacities at the inferior right lung lobe and bilateral thoracic effusion. The swab samples were taken twice within 72 hours and real-time reverse-transcription polymerase-chain-reaction (RT-PCR) results were COVID-19 negative. The patient was thereafter treated with prednisolone and antibiotics for over 2 weeks. The suspicious lesion has almost absorbed according to CT imaging, consistent with prominently falling CRP level. The anti-PD-1 related pneumonitis mixed with bacterial infection was clinically diagnosed based on the laboratory and radiological evidences and good response to the prednisolone and antibiotics. CONCLUSION: The anti-PD-1 related pneumonitis and COVID-19 pneumonia possess similar clinical presentations and CT imaging features. Therefore, differential diagnosis depends on the epidemiological and immunotherapy histories, RT-PCR tests. The response to glucocorticoid is still controversial but helpful for the diagnosis.

Management of immune checkpoint therapy for patients with cancer in the face of COVID-19.

The COVID-19 outbreak caused by SARS-CoV-2 challenges the medical system by interfering with routine therapies for many patients with chronic diseases. In patients with cancer receiving immune checkpoint inhibitors (ICIs), difficulties also arise from the incomplete understanding of the intricate interplay between their routine treatment and pathogenesis of the novel virus. By referring to previous ICI-based investigations, we speculate that ICIs themselves are not linked to high-infection risks of respiratory diseases or inflammation-related adverse effects in patients with cancer. Moreover, ICI treatment may even enhance coronavirus clearance in some patients with malignant tumor by boosting antiviral T-cell responsiveness. However, the 'explosive' inflammation during COVID-19 in some ICI-treated patients with cancer was illustrated as exuberant immunopathological damage or even death. In case of the COVID-19 immunopathogenesis fueled by ICIs, we propose a regular monitor of pathogenic T-cell subsets and their exhaustion marker expression (eg, Th17 and interleukin (IL)-6-producing Th1 subsets with surface programmed death 1 expression) to guide the usage of ICI. Here we aimed to address these considerations, based on available literature and experience from our practice, that may assist with the decision-making of ICI administration during the pandemic.

Impact of COVID-19 on patients with rheumatic complications of cancer immunotherapy: results of a registry survey.

Immune checkpoint inhibitors (ICI) block negative regulatory molecules, such as CTLA-4, PD-1 and PD-L1, in order to mount an antitumor response. T cells are important for antiviral defense, but it is not known whether patients with cancer treated with ICI are more or less vulnerable to viral infections such as COVID-19. Furthermore, immunosuppressive treatment of immune-related adverse events (irAE) may also impact infection risk. Rheumatic irAEs are often persistent, and can require long-term treatment with immunosuppressive agents. The aim of this study was to determine the incidence of COVID-19 infection and assess changes in ICI and immunosuppressive medication use among patients enrolled in a prospective rheumatic irAE registry during the height of the COVID-19 pandemic. On April 16 2020, following the 'surge' of COVID-19 infections in the New York Tri-State area, we sent a 23-question survey to 88 living patients enrolled in a single institutional registry of patients with rheumatic irAE. Questions addressed current cancer and rheumatic irAE status, ICI and immunosuppressant medication use, history of COVID-19 symptoms and/or diagnosed infection. A follow-up survey was sent out 6 weeks later. Sixty-five (74%) patients completed the survey. Mean age was 63 years, 59% were female, 70% had received anti-PD-(L)1 monotherapy and 80% had had an irAE affecting their joints. Six patients (10%) had definite or probable COVID-19, but all recovered uneventfully, including two still on ICI and on low-to-moderate dose prednisone. Of the 25 on ICI within the last 6 months, seven (28%) had their ICI held due to the pandemic. In patients on immunosuppression for irAE, none had changes made to those medications as a result of the pandemic. The incidence of COVID-19 was no higher in patients still on ICI. Ten percent of rheumatic irAE patients developed COVID-19 during the NY Tri-state 'surge' of March-April 2020. Oncologists held ICI in a quarter of the patients still on them, particularly women, those on anti-PD-(L)1 monotherapy, and those who had had a good cancer response. The incidence of COVID-19 was no higher on patients still on ICI. None of the patients on disease-modifying antirheumatic drugs or biological immunosuppressive medications developed COVID-19.

Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region. METHODS: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options. RESULTS: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones. CONCLUSION: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.

Association of immune checkpoint inhibitors with respiratory infections: A review.

Treatment with immune-checkpoint inhibitors (ICIs) has shown efficacy against a variety of cancer types. The use of anti PD-1, anti PD-L1, and anti CTLA-4 antibodies is rapidly expanding. The side effects of ICIs are very different from conventional cytocidal anticancer and molecular target drugs, and may extend to the digestive organs, respiratory organs, thyroid gland, pituitary gland, skin, and others. Although the details of these adverse events are becoming increasingly apparent, much is unknown regarding the effects and adverse events related to infections. This review focuses specifically on the impact of ICIs on respiratory infections. The impact of ICIs on pathogens varies depending on the significance of the role of T-cell immunity in the immune response to the specific pathogen, as well as the different modes of infection (i.e., acute or chronic), although the impact of ICIs on the clinical outcome of infections in humans has not yet been well studied. Enhanced clearance of many pathogens has been shown because immune checkpoint inhibition activates T cells. In contrast, reactivation of tuberculosis associated with ICI use has been reported, and therefore caution is warranted. In COVID-19 pneumonia, ICI administration may lead to exacerbation; however, it is also possible that ICI may be used for the treatment of COVID-19. It has also been shown that ICI has potential in the treatment of intractable filamentous fungal infections. Therefore, expanded clinical applications are expected.

COVID-19 in a patient with advanced Merkel cell carcinoma receiving immunotherapy.

Background: Little is known about the 2019 novel coronavirus disease (COVID-19) course and outcomes in patients receiving immunotherapy. Here we describe a metastatic Merkel cell carcinoma patient with a severe acute respiratory syndrome coronavirus 2 infection while receiving pembrolizumab. Case presentation: A 66-year-old man, with a metastatic Merkel cell carcinoma receiving pembrolizumab, presented with fever. Chest computed tomography (CT) showed pulmonary ground-glass opacities, suggesting viral or immuno-related etiology. On day 7, the patient was hospitalized due to dyspnea and worsening of the radiological findings. Real time polymerase chain reaction (RT-PCR) testing confirmed COVID-19. The patient developed acute respiratory distress syndrome and acute kidney injury. Hydroxychloroquine was administered for 5 days, but discontinued after supraventricular extrasystoles. Clinical improvement allowed the patient's discharge after 81 days of hospitalization. Conclusion: A careful evaluation of oncologic patients receiving immunotherapy during the COVID-19 pandemic is of utmost importance.

ICI Impact on COVID-19 Severity Modest at Best.

Several retrospective studies have examined whether patients with cancer who develop COVID-19 may be at risk of more severe viral disease if their therapy includes immune checkpoint inhibition. Although the data are not uniform, for now, halting or modifying cancer treatment decisions is unnecessary; meanwhile, vigilance with testing for COVID-19 in this population is recommended.

Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the "cytokine storm" may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.

Pneumonitis from immune checkpoint inhibitors and COVID-19: current concern in cancer treatment.

Pneumonitis is a rare but serious adverse event caused by cancer immunotherapy. The diagnosis between COVID-19-induced pneumonia and immunotherapy-induced pneumonitis may be challenging in the era of COVID-19 outbreak. Some clinical symptoms and radiological findings of pneumonitis can be attributed to the coronavirus infection as well as to an immune-related adverse event. Identifying the exact cause of a pneumonitis in patients on treatment with immunotherapy is crucial to promptly start the most appropriate treatment. The proper management of immune checkpoint inhibitors for the risk of pneumonia must take into account a series of parameters. Accurate attention should be payed to symptoms like cough, fever and dyspnea during immunotherapy.

Repurposing anticancer drugs for COVID-19-induced inflammation, immune dysfunction, and coagulopathy.

Three cardinal manifestations of neoplasia, namely inflammation, immune dysfunction, and coagulopathy are also seen in patients with severe SARS-CoV-2 infection, providing a biological rationale for testing selected anticancer drugs for their ability to control the symptoms and/or modify the course of COVID-19.