Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial.

Background: Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering 'booster' doses of COVID-19 vaccines beyond the standard two-dose series, for this group of patients. Therefore, studying the efficacy of these additional vaccine doses against SARS-CoV-2 and variants of concern is of utmost importance in this immunocompromised patient population. Methods: We conducted a prospective single arm clinical trial enrolling patients with cancer that had received two doses of mRNA or one dose of AD26.CoV2.S vaccine and administered a third dose of mRNA vaccine. We further enrolled patients that had no or low responses to three mRNA COVID vaccines and assessed the efficacy of a fourth dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity, and neutralization activity, which were again assessed at baseline and 4 weeks. Results: We demonstrate that a third dose of COVID-19 vaccine leads to seroconversion in 57% of patients that were seronegative after primary vaccination series. The immune response is durable as assessed by anti-SARS-CoV-2 (anti-S) antibody titers, T-cell activity, and neutralization activity against wild-type (WT) SARS-CoV2 and BA1.1.529 at 6 months of follow-up. A subset of severely immunocompromised hematologic malignancy patients that were unable to mount an adequate immune response (titer <1000 AU/mL) after the third dose and were treated with a fourth dose in a prospective clinical trial which led to adequate immune boost in 67% of patients. Low baseline IgM levels and CD19 counts were associated with inadequate seroconversion. Booster doses induced limited neutralization activity against the Omicron variant. Conclusions: These results indicate that third dose of COVID vaccine induces durable immunity in cancer patients and an additional dose can further stimulate immunity in a subset of patients with inadequate response. Funding: Leukemia Lymphoma Society, National Cancer Institute. Clinical trial number: NCT05016622.

People with cancer have a higher risk of death or severe complications from COVID-19. As a result, vaccinating cancer patients against COVID-19 is critical. But patients with cancer, particularly blood or lymphatic system cancers, are less likely to develop protective immunity after COVID-19 vaccination. Immune suppression caused by cancer or cancer therapies may explain the poor vaccine response. Booster doses of the vaccine may improve the vaccine response in patients with cancer. But limited information is available about how well booster doses protect patients with cancer against COVID-19. Thakkar et al. show that a third dose of a COVID-19 vaccine can induce a protective immune response in half of the patients with cancer with no immunity after the first two doses. In the experiments, Thakkar et al. tracked the immune reaction to COVID-19 booster shots in 106 cancer patients. A third booster dose protected patients for up to four to six months and reduced breakthrough infection rates to low levels. Eighteen patients with blood cancers and severe immune suppression had an inadequate immune response after three doses of the vaccine; a fourth dose boosted the immune response for two-thirds of them, which for some included neutralization of variants such as Omicron. The experiments show that booster doses can increase COVID-19 vaccine protection for patients with cancer, even those who do not respond to the initial vaccine series. Thakkar et al. also show that pre-vaccine levels of two molecules linked to the immune system, (immunoglobin M and the CD19 antigen) predicted the patients' vaccine response, which might help physicians identify which individuals would benefit from booster doses.

Comparison of Patients Discharged to Skilled Nursing and Inpatient Rehabilitation Facilities After Hospitalization for COVID-19: A Retrospective Study.

OBJECTIVE: The aim of the study is to identify differences in demographics, severity of disease, and rates of hospital readmission among adults discharged to skilled nursing facilities and inpatient rehabilitation facilities after hospitalization for coronavirus 2019. DESIGN: This is a retrospective cohort study of adults hospitalized with coronavirus 2019 infection at academic medical centers participating in the Vizient Clinical Data Base between April 1, 2020, and June 30, 2021, who were discharged to skilled nursing facilities or inpatient rehabilitation facilities ( N = 39,882). Data from the Clinical Data Base are used with permission of Vizient, Inc. All rights reserved. RESULTS: Among adults hospitalized with coronavirus 2019 infection, those discharged to skilled nursing facilities were 1.4 times more likely to require hospital readmission than those discharged to inpatient rehabilitation facilities. They were, on average, older (73 vs. 61 yrs, P < 0.001) and had shorter hospital lengths of stay (15 vs. 26 days, P < 0.0001) than the patients discharged to inpatient rehabilitation facilities. Persons discharged to inpatient rehabilitation facilities were more likely to have received intensive care and mechanical ventilation while hospitalized ( P < 0.001). CONCLUSIONS: Individuals discharged to inpatient rehabilitation facilities after hospitalization for coronavirus 2019 differ from those discharged to skilled nursing facilities on a number of key variables, including age, hospital length of stay, having received intensive care, and odds of hospital readmission.

Booster doses of COVID-19 vaccines for patients with haematological and solid cancer: a systematic review and individual patient data meta-analysis.

IMPORTANCE: Patients with cancer have an increased risk of severe disease and mortality from COVID-19, as the disease and antineoplastic therapy cause reduced vaccine immunogenicity. Booster doses have been proposed to enhance protection, and efficacy data are emerging from several studies. OBJECTIVE: To evaluate the proportion of COVID-19 primary vaccination non-responders with cancer who seroconvert after a booster dose. METHODS: PubMed, EMBASE, CENTRAL and medRxiv were searched from 1st January 2021 to 10th March 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal checklist. RESULTS: After the eligibility assessment, 22 studies were included in this systematic review and 17 for meta-analysis of seroconversion in non-responders, pooling a total of 849 patients with haematological cancer and 82 patients with solid cancer. Haematological cancer non-responders exhibited lower seroconversion at 44% (95% CI 36-53%) than solid cancer at 80% (95% CI 69-87%). Individual patient data meta-analysis found the odds of having a meaningful rise in antibody titres to be significantly associated with increased duration between the second and third dose (OR 1.02, 95% CI 1.00-1.03, P ≤ 0.05), age of patient (OR 0.960, 95% CI 0.934-0.987, P ≤ 0.05) and cancer type. With patients with haematological cancer as a reference, patients with lung cancer had 16.8 times the odds of achieving a meaningful increase in antibody titres (OR 16.8, 95% CI 2.95-318, P ≤ 0.05) and gastrointestinal cancer patients had 25.4 times the odds of achieving a meaningful increase in antibody titres (OR 25.4, 95% CI 5.26-492.21, P ≤ 0.05). CONCLUSIONS: administration of a COVID-19 vaccine booster dose is effective in improving seroconversion and antibody levels. Patients with haematological cancer consistently demonstrate poorer response to booster vaccines than patients with solid cancer.

Efficacy of booster doses in augmenting waning immune responses to COVID-19 vaccine in patients with cancer.

Anti-COVID-19 immunity dynamics were assessed in patients with cancer in a prospective clinical trial. Waning of immunity was detected 4-6 months post-vaccination with significant increases in anti-spike IgG titers after booster dosing, and 56% of seronegative patients seroconverted post-booster vaccination. Prior anti-CD20/BTK inhibitor therapy was associated with reduced vaccine efficacy.

Seroconversion rates following COVID-19 vaccination among patients with cancer.

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.

Teamwork and Leadership Under Fire at the Epicenter of the COVID-19 Epidemic in the Bronx.

The first Covid-19 patient was admitted to Montefiore Medical Center (MMC) on March 10, 2020. Soon thereafter there was a rapid and exponential surge of Covid-19 admissions to MMC that could have resulted in catastrophic consequences if MMC had been overwhelmed, as happened in Europe. To adjust to this crisis our institution, under the inspiring leadership of Dr. Philip Ozuah, President and CEO of Montefiore Medicine, adopted an "all hands on deck" approach, mobilizing our entire workforce to expand our units to accommodate the growing number of patients being admitted. Given that the internal medicine (IM) and ICU units are part of the department of medicine (DOM), the DOM was at the center of this mobilization. The DOM is the largest department at MMC and mobilizing it required careful planning, seamless teamwork, and strong leadership. To achieve that goal, we applied a framework that we designate the "3C framework," denoting Coordination, Communication, and Collaboration. In this report we describe the many initiatives the Montefiore Einstein DOM implemented during the Covid-19 pandemic using the 3C framework. These included establishing the Medicine Covid-19 Taskforce to lead our efforts, starting a daily newsletter for up-to-date communications, rapidly expanding the ICU and IM units, converting most specialty inpatient consults to eConsults, coordinating research studies, and more. The goal of this report is to serve as a guide on how the 3C framework helped us organize, mobilize, and energize the department of medicine effectively and efficiently during this unprecedented crisis.

Internal Medicine Resident Work Absence During the COVID-19 Pandemic at a Large Academic Medical Center in New York City.

BACKGROUND: Montefiore Medical Center (MMC) is a large tertiary care center in the Bronx, New York City, with 245 internal medicine residents. Beginning on February 29, 2020, residents became ill with COVID-19-like illness (CLI), which required absence from work. There was initially a shortage of personal protective equipment and delays in SARS-CoV-2 testing, which gradually improved during March and April 2020. OBJECTIVE: We evaluated the relationship between CLI-related work absence rates of internal medicine residents and MMC's COVID-19 hospital census over time. METHODS: Data on resident work absence between February 29 and May 22 were reviewed along with MMC's COVID-19 hospital census data. To determine the effect of patient exposure on resident CLI incidence, we compared the mean incidence of CLI per patient exposure days (PED = daily hospital census × days pre- or post-peak) before and after peak COVID-19 hospital census. RESULTS: Forty-two percent (103 of 245) of internal medicine residents were absent from work, resulting in 875 missed workdays. At the peak of resident work absence, 16% (38 of 245) were out sick. Residents were absent for a median of 7 days (IQR 6-9.5 days). Mean resident CLI incidence per PED (CLI/PED) was 13.9-fold lower post-peak compared to pre-peak (P = .003). CONCLUSIONS: At the beginning of the COVID-19 pandemic in New York City, a large portion of internal medicine residents at this single center became ill. However, the incidence of CLI decreased over time, despite ongoing exposure to patients with COVID-19.

The Down Side of Prone Positioning: The Case of a Coronavirus 2019 Survivor.

The coronavirus 2019 pandemic has resulted in a surge of patients with acute respiratory distress syndrome. Prone positioning may be used in such patients to optimize oxygenation. Severe infections may leave survivors with significant functional impairment necessitating rehabilitation. Those who have experienced prolonged prone positioning are at increased risk for complications not typically associated with critical illness. This case report describes the course and clinical findings of a survivor of acute respiratory distress syndrome due to coronavirus 2019 who was prone positioned while in intensive care and subsequently admitted to an inpatient rehabilitation facility. Her related complications, as well as those described in the literature, are reviewed. Critical elements of a comprehensive rehabilitation treatment plan for those who have been prone positioned, including implementation of preventive strategies, as well as early recognition and treatment of related injuries, will be described.

Toward better preparedness for the next pandemic.

New York City has been described as the epicenter of the COVID-19 pandemic in the United States. While health care workers are notably at increased risk for COVID-19 infection, the impact on resident physicians remains unclear. In this issue of the JCI, Breazzano et al. surveyed resident physicians for their exposure to COVID-19 during the exponential phase of the COVID-19 pandemic. The researchers also assessed how personal protective equipment and COVID-19 testing protected health care workers from infection. This study highlights resident physician experiences of the first COVID-19 wave that can inform and improve preparedness for upcoming COVID-19 surges and other future epidemics.