ABSTRACT
This study tested if prior BCG revaccination can further boost immune responses subsequently induced by an otherwise efficacious Oxford/AstraZeneca ChAdOx1nCoV-19 vaccine, referred to as COVISHIELDTM in India. We compared COVISHIELDTM induced longitudinal immune responses in 21 BCG re-vaccinees (BCG-RV) and 13 BCG-non-revaccinees (BCG-NRV), all of whom were BCG vaccinated at birth and latent tuberculosis negative, after COVISHIELDTM prime and boost with baseline samples that were collected pre-pandemic and pre-BCG revaccination. Compared to BCG-NRV, BCG-RV displayed significantly higher magnitude of spike-specific Ab and T cell responses, including a greater proportion of high responders; better quality polyfunctional CD4 and CD8 T cells that persisted and a more robust Ab and T cell response to the Delta mutant of SARS-CoV-2 highlighting greater breadth. Mechanistically, BCG adjuvant effects on COVISHIELDTM induced adaptive responses was associated with more robust innate responses to pathogen-associated-molecular-patterns through TNF-α and IL-1β secretion. This study highlights the potential of using a cheap and globally available vaccine as an adjuvant to enhance heterologous adaptive immune responses induced by COVIDSHIELDTM and other emerging vaccines.
ABSTRACT
Importance: Contracting COVID-19 peri-operatively has been associated with a mortality rate as high as 23%. Using hot and cold sites has led to a low rate of post-operative diagnosis of COVID-19 infection and allowed safe continuation of important emergency and cancer operations in our centre. Objective: The primary objective was to determine the safety of the continuation of surgical admissions and procedures during the height of the COVID-19 pandemic using hot and cold surgical sites. The secondary objective is to determine risk factors of contracting COVID-19 to help guide further prevention. Setting: A single surgical department at a tertiary care referral centre in London, United Kingdom. Participants: All consecutive patients admitted under the care of the urology team over a 3-month period from 1st March to 31st May 2020 over both hot acute admission sites and cold elective sites were included. Exposures: COVID-19 was prevalent in the community over the three months of the study at the height of the pandemic. The majority of elective surgery was carried out in a cold site requiring patients to have a negative COVID-19 swab 72 hours prior to admission and to self-isolate for 14 days pre-operatively, whilst all acute admissions were admitted to the hot site. Main outcomes and measures: COVID-19 was detected in 1.6% of post-operative patients. There was 1 (0.2%) post-operative mortality due to COVID-19. Results: A total of 611 patients, 451 (73.8%) male and 160 (26.2%) female, with a median age of 57 (interquartile range 44-70) were admitted under the surgical team. Of these, 101 (16.5%) were admitted on the cold site and 510 (83.5%) on the hot site. Surgical procedures were performed in 495 patients of which 8 (1.6%) contracted COVID-19 post-operatively with 1 (0.2%) post-operative mortality due to COVID-19. Overall, COVID-19 was detected in 20 (3.3%) patients with 2 (0.3%) deaths. On multivariate analysis, length of stay was associated with contracting COVID-19 in our cohort (OR 1.25, 95% CI 1.13-1.39). Conclusions and Relevance: Continuation of surgical procedures using hot and cold sites throughout the COVID-19 pandemic was safe practice, although the risk of COVID-19 remained and is underlined by a post-operative mortality. Reducing length of stay may be able to reduce contraction of COVID-19.
Subject(s)
COVID-19 , NeoplasmsABSTRACT
Objective: The aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo. Methods: We searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915). Results: From 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (p=0.68). Adverse events with HCQ have a significant difference compared to the control group (p=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (p=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power. Discussion: Due to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events. (1-16)