Eosinophil-rich linear IgA bullous dermatosis induced by mRNA COVID-19 booster vaccine.

We present a case of eosinophil-rich linear IgA bullous disease (LABD) following the administration of a messenger RNA COVID-19 booster vaccine. A 66-year-old man presented to the emergency department with a 3-week history of a pruritic blistering rash characterized by fluid-filled bullae and multiple annular and polycyclic plaques. He was initially diagnosed with bullous pemphigoid based on a biopsy showing a subepidermal blister with numerous eosinophils. However, direct immunofluorescence studies showed linear IgA and IgM deposition along the basement membrane zone with no immunoreactivity for C3 or IgG. Additionally, indirect immunofluorescence was positive for IgA basement membrane zone antibody. The patient was subsequently diagnosed with LABD and initiated on dapsone therapy with resolution of his lesions at 3-month follow-up. This case illustrates the growing number of autoimmune blistering adverse cutaneous reactions from vaccination. Dermatopathologists should be aware that features of autoimmune blistering diseases can overlap and may not be distinguishable based on these histopathological findings alone. Confirmation with direct immunofluorescence and/or serological studies may be necessary for accurate diagnosis.

Factors Associated With Severe COVID-19 Among Vaccinated Adults Treated in US Veterans Affairs Hospitals.

Importance: With a large proportion of the US adult population vaccinated against SARS-CoV-2, it is important to identify who remains at risk of severe infection despite vaccination. Objective: To characterize risk factors for severe COVID-19 disease in a vaccinated population. Design, Setting, and Participants: This nationwide, retrospective cohort study included US veterans who received a SARS-CoV-2 vaccination series and later developed laboratory-confirmed SARS-CoV-2 infection and were treated at US Department of Veterans Affairs (VA) hospitals. Data were collected from December 15, 2020, through February 28, 2022. Exposures: Demographic characteristics, comorbidities, immunocompromised status, and vaccination-related variables. Main Outcomes and Measures: Development of severe vs nonsevere SARS-CoV-2 infection. Severe disease was defined as hospitalization within 14 days of a positive SARS-CoV-2 diagnostic test and either blood oxygen level of less than 94%, receipt of supplemental oxygen or dexamethasone, mechanical ventilation, or death within 28 days. Association between severe disease and exposures was estimated using logistic regression models. Results: Among 110 760 patients with infections following vaccination (97 614 [88.1%] men, mean [SD] age at vaccination, 60.8 [15.3] years; 26 953 [24.3%] Black, 11 259 [10.2%] Hispanic, and 71 665 [64.7%] White), 10 612 (9.6%) had severe COVID-19. The strongest association with risk of severe disease after vaccination was age, which increased among patients aged 50 years or older with an adjusted odds ratio (aOR) of 1.42 (CI, 1.40-1.44) per 5-year increase in age, such that patients aged 80 years or older had an aOR of 16.58 (CI, 13.49-20.37) relative to patients aged 45 to 50 years. Immunocompromising conditions, including receipt of different classes of immunosuppressive medications (eg, leukocyte inhibitor: aOR, 2.80; 95% CI, 2.39-3.28) or cytotoxic chemotherapy (aOR, 2.71; CI, 2.27-3.24) prior to breakthrough infection, or leukemias or lymphomas (aOR, 1.87; CI, 1.61-2.17) and chronic conditions associated with end-organ disease, such as heart failure (aOR, 1.74; CI, 1.61-1.88), dementia (aOR, 2.01; CI, 1.83-2.20), and chronic kidney disease (aOR, 1.59; CI, 1.49-1.69), were also associated with increased risk. Receipt of an additional (ie, booster) dose of vaccine was associated with reduced odds of severe disease (aOR, 0.50; CI, 0.44-0.57). Conclusions and Relevance: In this nationwide, retrospective cohort of predominantly male US Veterans, we identified risk factors associated with severe disease despite vaccination. Findings could be used to inform outreach efforts for booster vaccinations and to inform clinical decision-making about patients most likely to benefit from preexposure prophylaxis and antiviral therapy.

Learning through a Pandemic: The Current State of Knowledge on COVID-19 and Cancer.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has left patients with current or past history of cancer facing disparate consequences at every stage of the cancer trajectory. This comprehensive review offers a landscape analysis of the current state of the literature on COVID-19 and cancer, including the immune response to COVID-19, risk factors for severe disease, and impact of anticancer therapies. We also review the latest data on treatment of COVID-19 and vaccination safety and efficacy in patients with cancer, as well as the impact of the pandemic on cancer care, including the urgent need for rapid evidence generation and real-world study designs. SIGNIFICANCE: Patients with cancer have faced severe consequences at every stage of the cancer journey due to the COVID-19 pandemic. This comprehensive review offers a landscape analysis of the current state of the field regarding COVID-19 and cancer. We cover the immune response, risk factors for severe disease, and implications for vaccination in patients with cancer, as well as the impact of the COVID-19 pandemic on cancer care delivery. Overall, this review provides an in-depth summary of the key issues facing patients with cancer during this unprecedented health crisis.

Association of COVID-19 Vaccination With SARS-CoV-2 Infection in Patients With Cancer: A US Nationwide Veterans Affairs Study.

Importance: Patients with cancer are at increased risk for severe COVID-19, but it is unknown whether SARS-CoV-2 vaccination is effective for them. Objective: To determine the association between SARS-CoV-2 vaccination and SARS-CoV-2 infections among a population of Veterans Affairs (VA) patients with cancer. Design, Setting, and Participants: Retrospective, multicenter, nationwide cohort study of SARS-CoV-2 vaccination and infection among patients in the VA health care system from December 15, 2020, to May 4, 2021. All adults with solid tumors or hematologic cancer who received systemic cancer-directed therapy from August 15, 2010, to May 4, 2021, and were alive and without a documented SARS-CoV-2 positive result as of December 15, 2020, were eligible for inclusion. Each day between December 15, 2020, and May 4, 2021, newly vaccinated patients were matched 1:1 with unvaccinated or not yet vaccinated controls based on age, race and ethnicity, VA facility, rurality of home address, cancer type, and treatment type/timing. Exposures: Receipt of a SARS-CoV-2 vaccine. Main Outcomes and Measures: The primary outcome was documented SARS-CoV-2 infection. A proxy for vaccine effectiveness was defined as 1 minus the risk ratio of SARS-CoV-2 infection for vaccinated individuals compared with unvaccinated controls. Results: A total of 184 485 patients met eligibility criteria, and 113 796 were vaccinated. Of these, 29 152 vaccinated patients (median [IQR] age, 74.1 [70.2-79.3] years; 95% were men; 71% were non-Hispanic White individuals) were matched 1:1 to unvaccinated or not yet vaccinated controls. As of a median 47 days of follow-up, 436 SARS-CoV-2 infections were detected in the matched cohort (161 infections in vaccinated patients vs 275 in unvaccinated patients). There were 17 COVID-19-related deaths in the vaccinated group vs 27 COVID-19-related deaths in the unvaccinated group. Overall vaccine effectiveness in the matched cohort was 58% (95% CI, 39% to 72%) starting 14 days after the second dose. Patients who received chemotherapy within 3 months prior to the first vaccination dose were estimated to have a vaccine effectiveness of 57% (95% CI, -23% to 90%) starting 14 days after the second dose vs 76% (95% CI, 50% to 91%) for those receiving endocrine therapy and 85% (95% CI, 29% to 100%) for those who had not received systemic therapy for at least 6 months prior. Conclusions and Relevance: In this cohort study, COVID-19 vaccination was associated with lower SARS-CoV-2 infection rates in patients with cancer. Some immunosuppressed subgroups may remain at early risk for COVID-19 despite vaccination, and consideration should be given to additional risk reduction strategies, such as serologic testing for vaccine response and a third vaccine dose to optimize outcomes.

Epidemiology, clinical characteristics, household transmission, and lethality of severe acute respiratory syndrome coronavirus-2 infection among healthcare workers in Ontario, Canada.

INTRODUCTION: Protecting healthcare workers (HCWs) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a priority to maintain a safe and functioning healthcare system. Our objective was to describe and compare the epidemiology, clinical characteristics, and lethality of SARS-CoV-2 infections among HCWs compared to non-HCWs. METHODS: Using reportable disease data at Public Health Ontario, we conducted a population-based cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with SARS-CoV-2 infections as of 30 September 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing based on residential address. We evaluated the risk of death using a multivariable logistic regression model adjusting for age, sex, comorbidities, symptoms, and long-term care home exposure. RESULTS: There were 7,050 (12.5%) HCW SARS-CoV-2 infections in Ontario, Canada, of whom 24.9% were nurses, 2.3% were physicians, and the remaining 72.8% other specialties, including personal support workers. Overall HCWs had an infection rate of 1,276 per 100,000 compared to non-HCWs of 346 per 100,000 (3.7 times higher). This difference decreased from a 7 times higher rate in April to no difference in September 2020. Twenty-six percent of HCWs had a household member with SARS-CoV-2 infection; 6.8% were probable acquisitions, 12.3% secondary transmissions, and 6.9% unknown direction of transmission. Death among HCWs was 0.2% compared to 6.1% of non-HCWs. The risk of death in HCWs remained significantly lower than non-HCWs after adjustment (adjusted odds ratio 0.09; 95%CI 0.05-0.17). CONCLUSION: HCWs represent a disproportionate number of diagnosed SARS-CoV-2 infections in Ontario, however this discrepancy is at least partially explained by limitations in testing earlier in the pandemic for non-HCWs. We observed a low risk of death in HCWs which could not be completely explained by other factors.

Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIGNIFICANCE: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.This article is highlighted in the In This Issue feature, p. 1426.

Changes in Cancer Management due to COVID-19 Illness in Patients with Cancer in Northern California.

PURPOSE: The response to the COVID-19 pandemic has affected the management of patients with cancer. In this pooled retrospective analysis, we describe changes in management patterns for patients with cancer diagnosed with COVID-19 in two academic institutions in the San Francisco Bay Area. MATERIALS AND METHODS: Adult and pediatric patients diagnosed with COVID-19 with a current or historical diagnosis of malignancy were identified from the electronic medical record at the University of California, San Francisco, and Stanford University. The proportion of patients undergoing active cancer management whose care was affected was quantified and analyzed for significant differences with regard to management type, treatment intent, and the time of COVID-19 diagnosis. The duration and characteristics of such changes were compared across subgroups. RESULTS: A total of 131 patients were included, of whom 55 were undergoing active cancer management. Of these, 35 of 55 (64%) had significant changes in management that consisted primarily of delays. An additional three patients not undergoing active cancer management experienced a delay in management after being diagnosed with COVID-19. The decision to change management was correlated with the time of COVID-19 diagnosis, with more delays identified in patients treated with palliative intent earlier in the course of the pandemic (March/April 2020) compared with later (May/June 2020) (OR, 4.2; 95% CI, 1.03 to 17.3; P = .0497). This difference was not seen among patients treated with curative intent during the same timeframe. CONCLUSION: We found significant changes in the management of cancer patients with COVID-19 treated with curative and palliative intent that evolved over time. Future studies are needed to determine the impact of changes in management and treatment on cancer outcomes for patients with cancer and COVID-19.