SARS-CoV-2 Seropositivity and Seroconversion in Patients Undergoing Active Cancer-Directed Therapy.

PURPOSE: Multiple studies have demonstrated the negative impact of cancer care delays during the COVID-19 pandemic, and transmission mitigation techniques are imperative for continued cancer care delivery. We aimed to gauge the effectiveness of these measures at the University of Pennsylvania. METHODS: We conducted a longitudinal study of SARS-CoV-2 antibody seropositivity and seroconversion in patients presenting to infusion centers for cancer-directed therapy between May 21, 2020, and October 8, 2020. Participants completed questionnaires and had up to five serial blood collections. RESULTS: Of 124 enrolled patients, only two (1.6%) had detectable SARS-CoV-2 antibodies on initial blood draw, and no initially seronegative patients developed newly detectable antibodies on subsequent blood draw(s), corresponding to a seroconversion rate of 0% (95% CI, 0.0 TO 4.1%) over 14.8 person-years of follow up, with a median of 13 health care visits per patient. CONCLUSION: These results suggest that patients with cancer receiving in-person care at a facility with aggressive mitigation efforts have an extremely low likelihood of COVID-19 infection.

CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer.

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.

Rates of COVID-19-Related Outcomes in Cancer Compared With Noncancer Patients.

Cancer patients are a vulnerable population postulated to be at higher risk for severe coronavirus disease 2019 (COVID-19) infection. Increased COVID-19 morbidity and mortality in cancer patients may be attributable to age, comorbidities, smoking, health care exposure, and cancer treatments, and partially to the cancer itself. Most studies to date have focused on hospitalized patients with severe COVID-19, thereby limiting the generalizability and interpretability of the association between cancer and COVID-19 severity. We compared outcomes of SARS-CoV-2 infection in 323 patients enrolled in a population-based study before the pandemic (n = 67 cancer patients; n = 256 noncancer patients). After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer was independently associated with higher odds of hospitalization (odds ratio = 2.16, 95% confidence interval = 1.12 to 4.18) and 30-day mortality (odds ratio = 5.67, 95% confidence interval = 1.49 to 21.59). These associations were primarily driven by patients with active cancer. These results emphasize the critical importance of preventing SARS-CoV-2 exposure and mitigating infection in cancer patients.

Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial.

Importance: Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. Objective: To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants. Interventions: Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks. Main Outcomes and Measures: The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants. Results: Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, -9 to 17; vs placebo: 3 milliseconds; 95% CI, -5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered. Conclusions and Relevance: In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04329923.

SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation.

The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms-mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant-looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses.