The gut microbiome has been shown to influence the response of tumors to anti–PD-1 (programmed cell death–1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti–PD-1 immunotherapy in 10 patients with anti–PD-1–refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.

Objectives mRNA COVID-19 vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease, and death. Nevertheless, a minority of vaccinated individuals might get infected and suffer significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination. Methods A retrospective multicenter cohort study of 17 hospitals included Pfizer/BioNTech's BNT162b2 fully-vaccinated patients who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed. Results 152 patients were included, accounting for half of hospitalized fully-vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notable, the cohort was characterized by a high rate of comorbidities predisposing to severe COVID-19, including hypertension (108, 71%), diabetes (73, 48%), CHF (41, 27%), chronic kidney and lung diseases (37, 24% each), dementia (29, 19%), and cancer (36, 24%), and only 6 (%) had no comorbidities. Sixty (40%) of the patients were immunocompromised. Higher SARS-CoV-2 viral-load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titers of anti-spike IgG, but these differences did not reach statistical significance. Conclusions We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully-vaccinated individuals with multiple comorbidities. Our patients had a higher rate of comorbidities and immunosuppression compared to previously reported non-vaccinated hospitalized COVID-19 patients. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social-distancing, or by additional active or passive vaccinations.

Objectives: Environmental surfaces have been suggested as likely contributors in the transmission of COVID-19. This study assessed the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contaminating surfaces and objects in two hospital isolation units and a quarantine hotel. Methods: SARS-CoV-2 virus stability and infectivity on non-porous surfaces was tested under controlled laboratory conditions. Surface and air sampling were conducted at two COVID-19 isolation units and in a quarantine hotel. Viral RNA was detected by RT-PCR and infectivity was assessed by VERO E6 CPE test. Results: In laboratory-controlled conditions, SARS-CoV-2 gradually lost its infectivity completely by day 4 at ambient temperature, and the decay rate of viral viability on surfaces directly correlated with increase in temperature. Viral RNA was detected in 29/55 surface samples (52.7%) and 16/42 surface samples (38%) from the surroundings of symptomatic COVID-19 patients in isolation units of two hospitals and in a quarantine hotel for asymptomatic and very mild COVID-19 patients. None of the surface and air samples from the three sites (0/97) were found to contain infectious titres of SARS-Cov-2 on tissue culture assay. Conclusions: Despite prolonged viability of SARS-CoV-2 under laboratory-controlled conditions, uncultivable viral contamination of inanimate surfaces might suggest low feasibility for indirect fomite transmission.

Following low incidence of respiratory syncytial virus (RSV) infections in 2020 during the COVID-19 pandemic, we noted a resurgence in hospitalised children in spring/summer 2021 following relaxation of public health measures. We compared this outbreak to previous autumn/winter seasons. We found higher weekly case numbers and incidence rates, more cases from urban neighbourhoods with lower socioeconomic status, and similar clinical presentation and severity. Public health implications include the re-evaluation of palivizumab administration and the need for surge capacity planning.

Background: We assessed outcome of patients with moderate and severe COVID-19 following treatment with convalescent plasma (CP) and the association with IgG levels in transfused CP. Methods: A prospective cohort study. Primary outcome was improvement at day 14 defined as alive, not on mechanical ventilation, and moderate, mild, or recovered from COVID-19. Antibody levels in CP units were unknown at the time of treatment. IgG against the spike protein S1 was subsequently measured by ELISA. Neutralizing antibodies titers were determined in a subset. Outcome was assessed in relation to the mean antibody level transfused to the patients (4.0 versus >4.0). Findings: Of 49 patients, 11 (22.4%) had moderate, 38 (77.6%) had severe disease, 28 were ventilated. At day 14, 24 (49.0%) patients improved, 9 (18.4%) died, and 13 (26.5%) were ventilated. In 14/98 (14.3%) CP units

The coronavirus disease 2019 global pandemic is reshaping our understanding of medicine, including the diagnostic approach to common medical presentations. We describe a novel case of a 3-year-old male with a clinical diagnosis of Henoch–Schonlein Purpura vasculitis with concurrent SARS-CoV-2 infection. This case highlights a potentially newly described presentation of coronavirus disease 2019 infection.

Background Humoral responses to COVID-19 vaccines in hemodialysis patients can direct vaccination policy. Methods We compared 409 COVID-19 naïve hemodialysis patients from 13 hemodialysis units in Israel to 148 non-dialysis dependent COVID-19 naïve controls. Twenty-four previously infected (anti-nucleocapsid positive) hemodialysis patients were analyzed separately. Blood samples were obtained ≥ 14 days post vaccination (BNT162b2) to assess seroconversion-rates and titers of anti-S and neutralizing antibodies. Results Median time from vaccination to blood sample collection was 82 (IQR 64–87) and 89 (IQR 68–96) days, for hemodialysis patients and controls, respectively. Seroconversion rates were lower in hemodialysis patients compared to controls for both anti-S and neutralizing antibodies (89% and 77% vs. 99.3%, respectively, P < 0.0001). Antibody titers were also significantly lower in hemodialysis patients compared to controls: median 69.6 (IQR 33.2–120) vs. 196.5 (IQR 118.5–246), P < 0.0001; geometric mean titer 23.3 (95% CI 18.7–29.1) vs. 222.7 (95% CI 174–284), P < 0.0001, for anti-S and neutralizing antibodies, respectively. Multivariate analysis demonstrated dialysis dependence to be strongly associated with lower antibody responses and antibody titers waning with time. Age, low serum albumin and low lymphocyte count were also associated with lower seroconversion rates and antibody titers. Hemodialysis patients previously infected with SARS-COV-2 had no difference in their seroconversion rates or antibody titers compared to COVID-19 naïve patients. Conclusion This study demonstrates diminished and waning humoral responses following COVID-19 vaccination in a large and diverse cohort of hemodialysis patients, including those previously infected with SARS-CoV-2. Considering these results and reduced vaccine effectiveness against variants of concern, in addition to continued social-distancing precautions, a third booster dose should be considered in this population.

A patient transferred from South Africa to Israel acquired a Candida auris infection. Phylogenetic analysis showed resemblance of C. auris to isolates from South Africa but not Israel, suggesting travel-associated infection. C. auris infection occurred weeks later in another patient at the same hospital, suggesting prolonged environmental persistence.