Cold case: COVID-19-triggered type 1 cryoglobulinemia (preprint)

A 42-year-old male was referred to the internal medicine department because of renal failure and persistent malaise after a recent SARS-CoV-2 infection. Blood results showed anemia and severe renal insufficiency (hemoglobin of 6.4 mmol/l and a creatinine of 194 umol/l). Additional tests revealed a type I cryoglobulinemia with a cryoprecipitate composed of biclonal IgM (kappa and lambda). Further investigations on the cryoprecipitate revealed that the immunoglobulins were directed against SARS-CoV-2 antigens. In the meanwhile, our patient noticed improvement of his symptoms accompanied by resolution of laboratory abnormalities. Three months later, the cryoglobulin could no longer be detected. Type 1 cryoglobulinemia is usually associated with lymphoproliferative disorders and is characterized by various symptoms caused by cryoprecipitates occluding small blood vessels. This is, to our knowledge, the first case of type I cryoglobulinemia with proven precipitation of SARS-CoV-19 antibodies. COVID-19 induced cryoglobulinemia appears to have a mild disease course and to be self-limiting upon viral clearance.

[Epstein-Barr virus-associated lymphoproliferative disorders after BNT162b2 mRNA COVID-19 vaccination].

Epstein-Barr virus-associated lymphoproliferative disorders (EBV-LPD) is a rare disease characterized by persistent or recurrent inflammation accompanied by EBV infection of T or NK cells that is not self-limiting, and it is fatal, if untreated. After receiving the first dose of the BNT162b2 mRNA COVID-19 vaccine, a 79-year-old male presented to the hospital with a 2-week history of fever. Laboratory results indicated pancytopenia, elevated liver transaminase levels, hyperferritinemia, and hypofibrinogenemia. Computed tomography revealed hepatosplenomegaly, but lymphadenopathy was not observed. A bone marrow biopsy, a random skin biopsy, and a liver biopsy revealed no malignancy, but an infectious evaluation revealed EBV viremia (5.19 Log IU/ml). Flow cytometry and RT-PCR revealed that the EBV genome was localized in NK cells, suggesting the diagnosis of EBV-NK-LPD. We administered prednisolone, intravenous immunoglobulin, and etoposide, but the EBV-DNA load failed to decrease, and he died 2 months later. Recently, case reports of COVID-19 vaccination-related hemophagocytic lymphohistiocytosis have been published. Although the mechanisms and risk factors for EBV-LPD after BNT162b2 mRNA COVID-19 vaccination remain unknown, it is important to note the possibility of reactivation of EBV after COVID-19 vaccination to initiate early and targeted therapy.

Lack of effectiveness of Bebtelovimab Monoclonal Antibody Among High-Risk Patients with SARS-Cov-2 Omicron During BA.2, BA.2.12.1 and BA.5 Subvariants Dominated Era (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants are expected to be resistant to Bebtelovimab (BEB) monoclonal antibody (MAb) and the real-world experience regarding its effectiveness is scarce. This retrospective cohort study reports a data analysis in Banner Healthcare System (a large not-for-profit organization) between 4/5/2022 and 8/1/2022 and included 19,778 Coronavirus disease-19 (COVID-19) positive (by PCR or direct antigen testing) patients who were selected from Cerner-Electronic Health Record after the exclusions criteria were met. The study index date for cohort was determined as the date of BEB MAb administration or the date of the first positive COVID-19 testing. The cohort consist of COVID-19 infected patients who received BEB MAb (N=1,091) compared to propensity score (PS) matched control (N=1,091). The primary outcome was the incidence of 30-day all-cause hospitalization and/or mortality. All statistical analyses were conducted on the paired (matched) dataset. For the primary outcome, the event counts and percentages were reported. Ninety-five percent Clopper-Pearson confidence intervals for percentages were computed. The study cohorts were 1:1 propensity matched without replacement across 26 covariates using an optimal matching algorithm that minimizes the sum of absolute pairwise distance across the matched sample after fitting and using logistic regression as the distance function. The pairs were matched exactly on patient vaccination status, BMI group, age group and diabetes status. Compared to the PS matched control group (2.6%; 95% confidence interval [CI]: 1.7%, 3.7%), BEB MAb use (2.2%; 95% CI: 1.4%, 3.3%) did not significantly reduce the incidence of the primary outcome (p=0.67). In the subgroup analysis, we observed similar no-difference trends regarding the primary outcomes for the propensity rematched BEB MAb treated and untreated groups, stratified by patient vaccination status, age (<65 years or [≥]65), and immunocompromised status (patients with HIV/AIDS or solid organ transplants or malignancy including lymphoproliferative disorder). The number needed to treat (1/0.026-0.022) with BEB MAb was 250 to avoid one hospitalization and/or death over 30 days. The BEB MAb use lacked efficacy in patients with SARS-CoV-2 Omicron subvariants (mainly BA.2, BA.2.12.1, and BA.5) in the Banner Healthcare System in the Southwestern United States.

Case report: Cellular therapy for hydroa vacciniforme-like lymphoproliferative disorder in pediatric common variable immunodeficiency with chronic active Epstein-Barr virus infection.

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a cutaneous form of chronic active Epstein-Barrvirus (EBV) infection, which can develop into the extremely rare systemic lymphoma. Patients with Inborn errors of immunity (IEI), such as common variable immunodeficiency (CVID), are at higher risk of developing a severe course of infections especially viral and malignancies than the general population. The aim of the study was to present complex diagnostic and therapeutic management of HV-LPD. The clinical diagnosis was confirmed at the histological and molecular level with next generation sequencing. HV-LPD was diagnosed in a patient with CVID and chronic active Epstein-Barr virus (CAEBV) infection. The patient was refractory to CHOP chemotherapy and immunosuppressive treatment in combination with antiviral drugs (prednisone, bortezomib, gancyclovir). The third-party donor EBV-specific cytotoxic T cells (EBV-CTL, tabelecleucel) were used, which stabilised the disease course. Finally, matched unrelated donor hematopoietic cell transplantation (MUD-HCT) was performed followed by another cycle of EBV-CTL.

Post-SARS-CoV-2 Atypical Inflammatory Syndrome in a Toddler with X-Linked Inhibitor of Apoptosis Deficiency After Stem Cell Transplant.

A 10-month-old boy was diagnosed with X-linked lymphoproliferative syndrome type 2 due to X-linked inhibitor of apoptosis deficiency after presenting with failure to thrive and refractory inflammatory bowel disease. He underwent a matched unrelated donor stem cell transplant with reduced intensity conditioning at 16 months. At 27 months, he presented with an atypical inflammatory syndrome in the setting of recent COVID-19 infection, Epstein-Barr viremia, and low chimerism (7.3%). He recovered after treatment with intravenous immunoglobulin and steroids.

Effects of B-Cell Lymphoma on the Immune System and Immune Recovery after Treatment: The Paradigm of Targeted Therapy.

B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune system a critical target for new therapies. In the current therapeutic scenario enriched by chemo-free regimens, it is important to establish the effect of various drugs on the disease, as well as on the restoration of immune functions. In fact, treatment of B-cell lymphoma with passive immunotherapy that targets tumor cells or targets the tumor microenvironment, together with adoptive immunotherapy, is becoming more frequent. The aim of this review is to report relevant data on the evolution of the immune system during and after treatment with targeted therapy of B-cell lymphomas.

B-cell cytopenia and time to last B-cell-depleting therapy predict response to SARS-COV-2 vaccines in patients with lymphoproliferative disorders.

Patients with B-non-Hodgkin lymphoma (NHL) are at increased risk of morbidity and mortality from SARS-CoV-2. We investigated the relationship between B cell cytopenia and the SARS-CoV-2 vaccine response in B-NHL patients. We measured anti-RBD antibodies and the lymphocyte immunophenotype in 19 controls, 22 lymphoma patients on observation (cohort 1) and 55 lymphoma patients receiving their vaccines post B-cell depleting therapy (cohort 2). Half of the lymphoma patients in both cohorts achieved seropositivity compared to 100% of controls. In cohort 2, only 5% achieved an antibody response in the first year post B-cell depleting treatment, vs 88% treated >2 years prior. Also, 28% of patients with <50 B cells/µl achieved a serologic response vs 86% of patients with B-cell >50 B cells/µl. B-cell cytopenia is profound within the first year of exposure to B-cell depleting treatment, therefore an additional dose of vaccine within that timeframe is unlikely to raise antibody levels.

The role of Bruton's tyrosine kinase in the immune system and disease.

Bruton's tyrosine kinase (BTK) is a TEC kinase with a multifaceted role in B-cell biology and function, highlighted by its position as a critical component of the B-cell receptor signalling pathway. Due to its role as a therapeutic target in several haematological malignancies including chronic lymphocytic leukaemia, BTK has been gaining tremendous momentum in recent years. Within the immune system, BTK plays a part in numerous pathways and cells beyond B cells (i.e. T cells, macrophages). Not surprisingly, BTK has been elucidated to be a driving factor not only in lymphoproliferative disorders but also in autoimmune diseases and response to infection. To extort this role, BTK inhibitors such as ibrutinib have been developed to target BTK in other diseases. However, due to rising levels of resistance, the urgency to develop new inhibitors with alternative modes of targeting BTK is high. To meet this demand, an expanding list of BTK inhibitors is currently being trialled. In this review, we synopsize recent discoveries regarding BTK and its role within different immune cells and pathways. Additionally, we discuss the broad significance and relevance of BTK for various diseases ranging from haematology and rheumatology to the COVID-19 pandemic. Overall, BTK signalling and its targetable nature have emerged as immensely important for a wide range of clinical applications. The development of novel, more specific and less toxic BTK inhibitors could be revolutionary for a significant number of diseases with yet unmet treatment needs.

A Case Report of Posttransplant Lymphoproliferative Disorder After AstraZeneca Coronavirus Disease 2019 Vaccine in a Heart Transplant Recipient.

We report a case of a heart transplant recipient who presented with a rapidly growing Epstein-Barr virus (EBV)-positive, diffuse large B-cell lymphoma 7 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Because of the atypical radiologic presentation, the initial tentative diagnosis was a mediastinal abscess. This observation indicates a potential risk of EBV reactivation after coronavirus disease 2019 (COVID-19) vaccination, which might lead to or aggravate the presentation of posttransplant lymphoproliferative disorder in transplantation patients. Transplant surgeons should be aware of the potential immunomodulatory effects of the COVID-19 vaccination.

T-cell immune response after mRNA SARS-CoV-2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies.

Patients affected by lymphoid malignancies (LM) are frequently immune-compromised, suffering increased mortality from COVID-19. This prospective study evaluated serological and T-cell responses after complete mRNA vaccination in 263 patients affected by chronic lymphocytic leukaemia, B- and T-cell lymphomas and multiple myeloma. Results were compared with those of 167 healthy subjects matched for age and sex. Overall, patient seroconversion rate was 64·6%: serological response was lower in those receiving anti-cancer treatments in the 12 months before vaccination: 55% vs 81·9% (P < 0·001). Anti-CD20 antibody plus chemotherapy treatment was associated with the lowest seroconversion rate: 17·6% vs. 71·2% (P < 0·001). In the multivariate analysis conducted in the subgroup of patients on active treatment, independent predictors for seroconversion were: anti-CD20 treatment (P < 0·001), aggressive B-cell lymphoma diagnosis (P = 0·002), and immunoglobulin M levels <40 mg/dl (P = 0·030). The T-cell response was evaluated in 99 patients and detected in 85 of them (86%). Of note, 74% of seronegative patients had a T-cell response, but both cellular and humoral responses were absent in 13·1% of cases. Our findings raise some concerns about the protection that patients with LM, particularly those receiving anti-CD20 antibodies, may gain from vaccination. These patients should strictly maintain all the protective measures.

Efficacy and Safety of the CVnCoV SARS-CoV-2 mRNA Vaccine Candidate: Results from Herald, a Phase 2b/3, Randomised, Observer-Blinded, Placebo-Controlled Clinical Trial in Ten Countries in Europe and Latin America (preprint)

Background: Additional safe and effective vaccines are needed to control the COVID-19 pandemic.Methods: HERALD is an ongoing phase 2b/3 randomised, observer-blinded, placebo-controlled clinical trial in ten countries in Europe and Latin America. SARS-CoV-2 naïve adults were randomised 1:1 to receive two doses of CVnCoV mRNA vaccine candidate or placebo 28 days apart. Primary efficacy analysis included symptomatic COVID-19 more than 14 days after second dose. Solicited adverse events (AEs) were assessed in phase 2b participants and unsolicited AEs in all participants. The study is registered at ClinicalTrials.gov (NCT04652102).Findings: Between 11 December 2020 and 12 April 2021, 39 680 participants were randomised and 39 529 received CVnCoV (19 783) or placebo (19 746). Overall VE was 48·2% (95% CI: 31·0–61·4; 83/12 851 vs. 145/12 221 in CVnCoV and placebo recipients, respectively). Overall VE against moderate-to-severe COVID-19 was 70·7% (95% CI: 42·5–86·1; 12/12 851 vs. 37/12 211, respectively). In participants aged 18–60 years VE was 52·5% (95% CI: 36·2–64·8; 71/11 532 vs. 136/11 031, respectively). Too few cases occurred in participants aged ≥61 years (CVnCoV: 12, placebo: 9) precluding VE evaluation. Wild type SARS-CoV-2 was detected in 7/204 (3%) sequenced cases, with 14 variants being responsible for the other cases. Solicited adverse events, mostly systemic, were more common in CVnCoV recipients; 542/2002 CVnCoV recipients and 61/1980 placebo recipients reported grade 3 events. Unsolicited serious AEs were reported for 82/19 746 CVnCoV recipients and 66/19 746 placebo recipients; 8 and 2 SAEs, respectively were considered related to vaccination. Fatal SAEs were reported for 8 and 6 CVnCoV and placebo recipients.Interpretation: CVnCoV is efficacious in the prevention of COVID-19 of any severity and has an acceptable safety profile.Trial Registration: Study number: ClinicalTrials.gov Identifier: NCT04652102. Funding: This trial was funded by the German Federal Ministry of Education and Research (grant01KI20703), and CureVac AG.Declaration of Interest: MB declares institutional funding from CureVac during the conduct of this study, from Janssen Vaccines, molecular partners, and Merck outside of the submitted work, and consulting fees from Janssen Vaccines. EJLDB, and MFMR, TO and XSL declare institutional funding from CureVac during the conduct of this study. LE, and LG declare institutional funding from CureVac during the conduct of this study and outside of the submitted work. CFL declares institutional funding from CureVac during the conduct of this study, and outside of the submitted work, and is a member of WHO Covid-19 Vaccine Effectiveness Working Group and WHO Product Development for Vaccines Advisory Committee (PDVAC). CL declares institutional funding from CureVac during the conduct of this study, and is a member of the of German Society of Infection board. ILR declares institutional funding from CureVac during the conduct of this study and from J &J, and OSE Immunotherapeutics outside of the submitted work. PGK declares institutional funding from CureVac during the conduct of this study, and is a member of the scientific advisory board for the HERALD clinical trial. VVRH declares institutional funding from CureVac during the conduct of this study, and speakers fees from Gilead outside of the submitted work. HJ declares consultant fees from CureVac, is the Medical Responsible Person for the HERALD clinical trial, and is co-chair of DSMB for the HERALD clinical trial. AK and PM are employed by CureVac, and hold stock options. OSK declares consultant fees from CureVac during the conduct of this study, and is a member of the DSMB for a CVnCoV phase 1 trial. TV declares consultant fees from CureVac during the conduct of this study, and consultant fees from CureVac, AstraZeneca, Pfizer, Johnson&Johnson, and Moderna outside of the submitted work. LO is employed by CureVac, and holds stock options, and is the holder of a pending patent. The other authors declare no competing interests.Ethical Approval: The trial protocol and amendments have been approved by the appropriate independent ethics committee or institutional review board at each study centre

The Status and Prospects of Epstein-Barr Virus Prophylactic Vaccine Development.

Epstein-Barr virus (EBV) is a human herpesvirus that is common among the global population, causing an enormous disease burden. EBV can directly cause infectious mononucleosis and is also associated with various malignancies and autoimmune diseases. In order to prevent primary infection and subsequent chronic disease, efforts have been made to develop a prophylactic vaccine against EBV in recent years, but there is still no vaccine in clinical use. The outbreak of the COVID-19 pandemic and the global cooperation in vaccine development against SARS-CoV-2 provide insights for next-generation antiviral vaccine design and opportunities for developing an effective prophylactic EBV vaccine. With improvements in antigen selection, vaccine platforms, formulation and evaluation systems, novel vaccines against EBV are expected to elicit dual protection against infection of both B lymphocytes and epithelial cells. This would provide sustainable immunity against EBV-associated malignancies, finally enabling the control of worldwide EBV infection and management of EBV-associated diseases.

SARS-CoV-2 Antibody Seroprevalence and Associated Risk Factors in an Urban District in Cameroon (preprint)

Background: The extent of SARS-CoV-2 circulation in many African countries remains unclear, underscoring the need for antibody sero-surveys to accurately assess the cumulative attack rate. Methods: We conducted a community-based, cross-sectional sero-survey in Cité Verte, a densely-populated district of Yaoundé, Cameroon, from October 14 to November 26, 2020. Households were randomly selected from a set of all putative residential buildings in the district, and residents between five and 80 years of age were surveyed. The Abbott Panbio SARS-CoV-2 nucleocapsid IgM/IgG rapid antibody test was administered, along with a questionnaire on disease symptoms and health-seeking behavior. Final seroprevalence estimates were adjusted for test accuracy and re-weighted to the city’s age-sex distribution. Random-intercept logistic regression was used to identify risk factors for anti-SARS-CoV-2 IgG seropositivity. Findings: Of 255 households randomly selected, 180 (70·6%) agreed to participate, yielding a sample of 971 participants. The adjusted seroprevalence of SARS-CoV-2 IgG antibodies was 29·2% (95%CI 24·3–34·1). Out of the 302 IgG seropositive individuals, the majority (64·2% [58·7–69·4]) did not report any symptoms over the pandemic period, and most (91·1% [87·3–93·8]) did not consult medical care. Significantly greater odds of IgG seropositivity was found for men (OR: 1·61 [95%CI 1·2–2·2]), residents of households with six or more residents (OR: 1·6 [1·1–2·4]; reference: households with three to five residents) and individuals with a BMI above 30 kg/m² (OR: 1·84 [1·1–3·0]; reference: 18·5–24.9 kg/m²).  Interpretation: By November 2020, the cumulative attack rate of COVID-19 was high in this Cameroonian city, about 323 times greater than the 0.09% nationwide attack rate implied by PCR and antigen- confirmed case counts at the time. The predominantly asymptomatic nature of cases may explain the low COVID-19-related healthcare consultation. Despite the high seroprevalence, most of the population has not been infected with SARS-CoV-2, underlining the importance of continued measures to control viral spread and of quick vaccine deployment to protect the vulnerable. Funding: The UHC Program and Bilateral Health Project in Cameroon of the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH, the P4H Health Financing Network, and the Canton of Geneva. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study protocol obtained the ethical clearance (N°2020/09/1292/CE/CNERSH/SP) and the administrative authorization of the Ministry of Health of Cameroon (N°D30- 845/L/MINSANTE/SG/DROS).

BTK inhibitors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Systematic Review (preprint)

ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes.Evidence ReviewWe searched PubMed, Embase, and Web of Science: Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.FindingsOne hundred twenty-five articles were identified, 6 of which met inclusion criteria. Sample size ranged from 6 to 126 patients. Patient populations included subjects hospitalized with COVID-19 (6/6) and admitted to the intensive care unit (5/6). Patient age ranged between 35 and 98 years. Four studies included patients already receiving BTKinibs for their lymphoproliferative disease, 1 for Waldenstrom’s macroglobulinemia and 3 for chronic lymphocytic leukemia (CLL). The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Differences in standard-of-care reflected the date of study and pre-existing conditions in the various patient cohorts. Full-dose acalabrutinib was evaluated in 2 studies, one study evaluated full-dose ibrutinib, and another study evaluated both ibrutinib and acalabrutinib. The remainder 2 studies described outcomes in CLL patients on multiple BTKinibs and other CLL-targeted treatments. Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs. Conclusions and RelevanceBTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration. However, randomized clinical trials are needed to validate the beneficial effects of BTKinibs for acute SARS-CoV-2 infection.

A pilot “Telephone-and-Test” (Modified Straight-to-Test) for ENT two-week wait referrals (preprint)

Objective: To assess the efficacy and outcome of a pilot model in triaging urgent suspected head and neck cancer referrals during the Covid-19 pandemic. Design Prospective observational cohort study Setting Regional Head and Neck Cancer hub, United Kingdom. Participants 84 patients who were referred via the 2 week wait pathway and streamed directly for imaging investigations after initial telephone consultation. Main outcome measures The malignancy detection rate using the telephone-and-test model Results 495 2-week wait referrals were received during the study period. 104 patients were discharged following their initial telephone consultation. 84 (17%) patients were streamed directly for imaging investigations following their telephone consultation. Malignancy was identified in 11.9% of patients which included squamous cell carcinoma, differentiated thyroid carcinoma and lymphoproliferative disease. 51% of patients had other benign pathologies such as benign salivary gland tumour, benign thyroid disease and physiological lymphadenopathy. Following their radiological investigation, 48.8% of patients were discharged without any need for further consultations. Conclusions The telephone-and-test approach is an effective and efficient model for triaging head and neck two-week wait referrals, which could be applicable outside the pandemic times.

Social Distancing, Mask Use and the Transmission of SARS-CoV-2: A Population-Based Case-Control Study (preprint)

Background: Ecologic studies support non-pharmacologic measures to protect against SARS-CoV-2, but few studies have evaluated their effects at the individual level in the community. We aimed to assess the magnitude of the associations of social distancing and mask use with laboratory-confirmed infection by SARS-CoV-2 in adults living in Porto Alegre, Brazil, a city with 1,483,771 inhabitants.Methods: We conducted a population-based case-control study from late April to June 2020. Cases came from a list of all cases mandatorily notified to municipal authorities; controls were antibody-negative participants of three representative household surveys conducted at the same time-period.Findings: In logistic regression analyses of 271 cases and 1396 controls adjusted for age, sex, race, educational attainment, income, household size and pandemic moment, those reporting moderate to greatest adherence to social distancing had between 59% (OR=0·41; 95%CI 0·24-0·70) and 75% (OR=0·25; 0·15-0·42) lower odds of becoming infected, compared to those reporting very little adherence. Lesser out-of-household exposure reduced odds between 52% (OR=0·48; 0·29-0·77) and 75% (OR=0·25; 0·18-0·36), compared to going out every day all day. In a subsample of controls with data on mask use and cases of equivalent pandemic moment (198 cases and 420 controls), mask use reduced odds of infection by 87% (OR=0·13; 0·04-0·36).Interpretation: Greater social distancing and always using masks while away from home provided major protection against SARS-CoV-2. These simple measures can be of great benefit during the upcoming phases of the pandemic.Funding: IATS/FAPERGS, UNIMED Porto Alegre, Instituto Cultural Floresta, Instituto Serrapilheira, Ministry of Health.Declaration of Interests: The authors have no conflicts of interest to declare.Ethics Approval Statement: The ethics committee of the Hospital de Clínicas de Porto Alegre approved our study (No. 31499420·5·0000·5327) and the Brazilian National Ethics Committee (No. 30415520·2·0000·5313) approved the accompanying seroprevalence surveys. All participants gave prior informed consent, in written form by the controls and verbally for cases.

Impact of COVID-19 Pandemic on Intervals and Outcomes of Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma (preprint)

Background: Transarterial chemoembolization (TACE) may not be repeated “on-demand” timely for hepatocellular carcinoma (HCC) patients in the era of the novel coronavirus disease (COVID-19). We aim to evaluate the impact of the COVID-19 pandemic on the intervals and outcomes of TACE in HCC patients. Methods: This retrospective study included HCC patients who underwent TACE from Jan 1, 2020 to March 31, 2020 (study group) and Jan 1, 2019 to Mar 31, 2019 (control group) at two institutions in China. The endpoints included the TACE interval and the overall response rate (ORR). Uni- and multivariate logistic analyses were performed to identify independent risk factors associated with a worse ORR. The cut-off point was determined to divide repeated TACE time into long- and short- intervals. Findings: 154 patients (71 in the study group, 83 in the control group) were enrolled. The median TACE interval in the study group was 82·0 days (IQR, 61–109), longer than 66·0 days (IQR, 51–94) in the control group (p=0·004). The ORR was 23·9% in the study group, while 39·8% in the control group (p=0·037). The cut-off value was 95 days. The group (OR, 2·402; 95% CI, 1·040–5·546; p=0·040), the long interval (OR, 2·573; 95% CI, 1·022–6·478; p=0·045), and the stage system (OR, 2·500; 95% CI, 1·797–3·480; p<0·001) were independent predictors. Interpretation: For HCC patients, the COVID-19 pandemic results in a longer re-TACE schedule, which may further lead to a lower ORR. Patients with a TACE interval of more than 95 days may have a worse prognosis. Funding: This study was supported by the National Key Research and Development Project of China (2018YFA0704100), the National Natural Science Foundation of China (Major Scientific Research Instrument Development Program 81827805, 81441054, 81520108015, 81671796, 81901847), Jiangsu Provincial Medical Youth Talent Program (ZDRCA2016078), the Key Research and Development Project of Jiangsu Province (BE2019750), the Natural Science Foundation of Jiangsu Province (BK20190177), Innovation Platform of Jiangsu Provincial Medical Center (YXZXA2016005), and the Suzhou Science and Technology Youth Plan (KJXW2018003).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was approved by the institutional ethics review boards in two participating institutions and the requirement for written informed consent was waived due to its retrospective nature.

Evaluation of COVID 19 infection in 279 cancer patients treated during a 90-day period in 2020 pandemic (preprint)

Background: The aim of this study was investigation of COVID-19 disease and its outcome in cancer patients who needed treatment, in a 90-day period. Methods: Cancer patient who required treatment, were evaluated for potential COVID-19 infection in a 90-day period, starting from beginning of this epidemic in Iran, January, to April 19, 2020. For treatment of solid tumor patients, if they did not have symptoms related to COVID-19, just chest X-ray was requested. If they showed COVID-19 related symptoms, High Resolution CT scan of lungs was requested. For hematology cancer patients, PCR test for COVID-19 infection was requested as well. Protection measures were considered for personnel of oncology wards. Results: In this study, 279 patients were followed up in this 90-day period. No COVID-19 infection was observed in 92 cases of breast cancer, 72 cases of colon cancer, 14 cases of gastric cancer and 12 cases of pancreaticobiliary cancer .However, in 11 cases of lung cancer, 5 cases brain tumors and 12 cases ovarian cancer; 3 case of COVID-19 were observed. In the hematology cancers group, which included 14 cases of Hodgkin Lymphoma, 23 cases of lymphoproliferative disorder, 12 cases of acute leukemia and 12 cases of multiple myeloma; three of COVID-19 were observed. Conclusion: Patients with cancer who need treatment can be treated by taking some measures. These measures include observing individual and collective protection principles in patients and health-care personnel, increasing patients awareness particularly about self-care behavior, performing a COVID-19 test, and taking a chest X ray, before the treatment starts