ABSTRACT
Background and aimsImmunocompromised patients have a reduced ability to generate antibodies after COVID-19 vaccination and are at higher risk of SARS-CoV-2 infection, complications and mortality. Tixagevimab/Cilgavimab (Evusheld) is a monoclonal antibody combination which bind to the SARS-CoV-2 spike protein, preventing the virus entering human cells. The phase III PROVENT trial reported that immunocompromised patients given Tixagevimab/Cilgavimab had a significantly reduced risk of COVID-19 infection. However, PROVENT was conducted before the SARS-CoV-2 Omicron became prevalent. This systematic review provides an updated summary of real-world clinical evidence of Tixagevimab/Cilgavimab effectiveness in immunocompromised patients. MethodsTwo independent reviewers conducted PubMed and medRxiv searches for the period of 01/01/2021 to 01/10/2022. Clinical studies which reported the primary outcome of breakthrough COVID-19 infections after Tixagevimab/Cilgavimab administration were included in the review. COVID-19-related hospitalisations, ITU admissions and mortality were assessed as secondary outcomes. Clinical effectiveness was determined using the case-control clinical effectiveness methodology. The GRADE tool was used to ascertain the level of certainty for the primary outcome in each study. Results17 clinical studies were included, comprising 24,773 immunocompromised participants of whom 10,775 received Tixagevimab/Cilgavimab. Most studies reported clinical outcomes during the SARS-CoV-2 Omicron wave. Six studies compared a Tixagevimab/Cilgavimab intervention group to a control group. Overall, the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab against COVID-19 breakthrough infection, hospitalisation and ITU admission were 40.47%, 69.23% and 87.89%, respectively. For prevention of all-cause and COVID-19-specifc mortality, overall clinical effectiveness was 81.29% and 86.36%, respectively. ConclusionsThere is a growing body of real-world evidence validating the original PROVENT phase III study regarding the clinical effectiveness of Tixagevimab/Cilgavimab as prophylaxis for immunocompromised patients, notably demonstrating effectiveness during the Omicron wave. This review demonstrates the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab at reducing COVID-19 infection, hospitalisation, ITU admission and mortality for immunosuppressed individuals. It is important that ongoing larger-scale and better-controlled real world studies are initiated and evaluated to provide ongoing certainty of the clinical benefit of prophylactic antibody treatment for immunocompromised patients in the face of new variants.
ABSTRACT
BackgroundHow SARS-CoV-2 infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect sensitivity is unknown. MethodsWe combined SARS-CoV-2 testing and contact tracing data from England between 01-September-2020 and 28-February-2021. We used multivariable logistic regression to investigate relationships between PCR-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using one of four LFDs. Results231,498/2,474,066 (9%) contacts of 1,064,004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower Ct values) e.g., 11.7%(95%CI 11.5-12.0%) at Ct=15 and 4.5%(4.4-4.6%) at Ct=30. B.1.1.7 infection increased PCR-positive results by [~]50%, (e.g. 1.55-fold, 95%CI 1.49-1.61, at Ct=20). PCR-positive results were most common in household contacts (at Ct=20.1, 8.7%[95%CI 8.6-8.9%]), followed by household visitors (7.1%[6.8-7.3%]), contacts at events/activities (5.2%[4.9-5.4%]), work/education (4.6%[4.4-4.8%]), and least common after outdoor contact (2.9%[2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5%(89.4-89.6%) and 83.0%(82.8-83.1%) of cases with PCR-positive contacts respectively. ConclusionsSARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by [~]50%. The best performing LFDs detect most infectious cases. Key pointsIn 2,474,066 contacts of 1,064,004 SARS-CoV-2 cases, PCR-positive tests in contacts increased with higher index case viral loads, the B.1.1.7 variant and household contact. Children were less infectious. Lateral flow devices can detect 83.0-89.5% of infections leading to onward transmission.
ABSTRACT
BackgroundThe COVID-19 pandemic started a healthcare crisis and heavily impacted cancer services. MethodsData from cohort studies of COVID-19 cancer patients published up until October 23rd 2020 from PubMed, PubMed Central, medRxiv and Google Scholar were reviewed. Meta-analyses using the random effects model was performed to assess the risk of death in cancer patients with COVID-19. ResultsOur meta-analyses including up to 5,678 patients from 13 studies showed that the following were all statistically significant risk factors for death following SARS-CoV-2 infection in cancer patients: age of 65 and above, presence of co-morbidities, cardiovascular disease, chronic lung disease, diabetes and hypertension. There was no evidence that patients who had received cancer treatment within 60 days of their COVID-19 diagnosis were at a higher risk of death, including patients who had recent chemotherapy. ConclusionsCancer patients are susceptible to severe COVID-19, especially older patients and patients with co-morbidities who will require close monitoring. Our findings support the continued administration of anti-cancer therapy during the pandemic. The analysis of chemotherapy was powered at 70% to detect an effect size of 1.2 but all other anti-cancer treatments had lower power. Further studies are required to better estimate their impact on the outcome of cancer patients.
ABSTRACT
ObjectivesTo identify putative COVID-19 treatments and identify the roles of immunomodulators and antivirals in disease management. DesignSystematic review. Data sourcesPubMed, bioRxiv.org and medRxiv.org were searched for studies suggestive of effective treatments for COVID-19. Additional studies were identified via a snowballing method applied to the references of retrieved papers as well as a subsequent targeted search for drug names. Review methodsInclusion criteria included any case series or randomised control trials in any language that were published from 18th December 2019 to 18th April 2020 and described COVID-19 treatment. Of an initial 2140 studies identified from the initial search, 29 studies were found to meet the inclusion criteria and included in this comprehensive systematic review. Results19 studies of antiviral treatments for COVID-19 have been reported and seven studies for immunomodulatory treatments. Six randomised controlled trials have been published with one positive trial for Hydroxychloroquine. This small study consisted of 31 patients though subsequent studies showed contradictory findings. All the remaining studies were observational studies, retrospective case reviews or non-randomised trials and these results are difficult to interpret due to methodological issues. ConclusionsTo date, an impressive number of studies have been performed in a short space of time, indicative of a resilient clinical trials infrastructure. However, there is a lack of high quality evidence to support any novel treatments for COVID-19 to be incorporated into the current standard of care. The majority of the studies of treatments for COVID-19 could only be found in pre-print servers. Future clinical reviews should therefore be Comprehensive Systematic Reviews involving pre-print studies to prevent potential unnecessary replications of clinical studies.
