Vaccination leads to smaller reduction in transmission of delta compared to alpha COVID-19 variants

13th January 2022

Vaccination against COVID-19 leads to a higher level of transmission for the delta compared to the alpha variant

Vaccination has been found to result in a smaller reduction in the transmission of the Delta compared to the alpha variant according to a study by researchers from Oxford University, UK.

Vaccination against COVID-19 has been shown to reduce symptomatic infection and even onward transmission of the virus among household contacts. Furthermore, some data indicates that this reduced risk of onward transmission is because of a lower viral load among vaccinated individuals although other evidence points to a similar viral load among those who are vaccinated but infected with the Delta variant.

For the present study, the Oxford team used national contact testing data in England for adults (> 18 yeas of age) with both symptomatic and asymptomatic infections. Their analysis included vaccination with either BNT162b2 or ChAdOx1 to investigate differences in transmission from index patients infected with either variant. The analysis included regression models to determine any associations between onward transmission and the vaccination status of the index patient.

Findings

Among 146,243 tested contacts from a total of 108,498 index patients, with a median age of 34 years (51% female), 37% had a positive PCR test.

Using regression modelling, among index patients doubly vaccinated with BNT162b2 and who became infected, there was a significantly reduced risk of onward transmission of the Alpha variant (adjusted rate ratio, aRR = 0.32, 95% CI 0.21 – 0.48) compared unvaccinated individuals. Similarly, those with two vaccinations of ChAdOx1, also had a reduced risk of onward transmission (aRR = 0.48, 95% CI 0.30 – 0.78) compared to the unvaccinated.

In contrast, the extent of onward transmission of the Delta variant was reduced compared to Alpha by both vaccines but was greater among those doubly vaccinated with BNT162b2 (aRR = 0.50, 95% CI 0.39 – 0.65) compared to ChAdOx1 (aRR = 0.76, 95% 0.70 – 0.82). In other words, index patients vaccinated with BNT162b2 were less likely to have contacts with a positive PCR test for Delta compared to those given the ChAdOx1 vaccine.

The Delta variant was also associated with more onward transmission from both symptomatic index patients (aRR = 1.24, 95% CI 1.12 – 1.38) and from asymptomatic individuals (aRR = 1.40, 95% CI 1.22 – 1.59) and this was independent of both index and contact vaccination status.

Interestingly, the risk of infection with the Alpha variant among fully vaccinated contacts, was much lower among those given BNT162b2 (aRR = 0.15, 95% CI 0.11 – 021) compared to those fully vaccinated with ChAdOx1 (aRR = 0.40, 95% CI 0.27 – 0.59) and the magnitude of these reductions were similar for infections with the Delta variant.

Both symptomatic and asymptomatic index patients infected with the Delta variant had lower Ct values (i.e., higher viral loads) compared to those infected with the Alpha variant. When including Ct values in their regression models, the authors reported that lower Ct values were independently associated with increased transmission of either variant.

The authors concluded that vaccination was associated with a smaller reduction in transmission of the Delta compared to the Alpha variant.

Citation

Eyre DW wt al. Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants. N Eng J Med 2022.

Study shows efficacy of face masks in reducing COVID-19 transmission among infected individuals

30th June 2021

The wearing of face masks in those infected with COVID-19 significantly reduced transmission of the virus.

Mitigation strategies designed to reduce the transmission of COVID-19 have included social distancing and the need to wear face masks. The use of a face mask has been shown to reduce the spread of influenza and there is tentative evidence that face mask wearing might reduce transmission of the virus. Nevertheless, no studies have examined the presence of retained virus on the surface of face masks and whether a mask can reduce transmission of COVID-19. With this level of uncertainty, a team from the Viral Hepatitis Laboratory, Oswaldo Cruz Institute, Brazil, sought to evaluate the efficacy of masks, worn by those known to be infected with COVID-19, at preventing transmission of the virus. The team examined samples taken from infected individuals and compared the amount of COVID-19 obtained from nasal and pharyngeal swabs and from the face mask worn by the individual. The mask itself was cut and different areas of the mask tested separately. The team used the cycle threshold (CT) value during PCR, as a measure of viral load. For instance, during a PCR test, the CT represents the number of amplifying cycles necessary to produce a detectable amount of viral RNA. If a sample requires up to 40 cycles for example, the test is deemed to be negative. Hence the lower the CT value, the higher the concentration of viral genetic material and the CT value can be used as a semi-quantitative measure of viral load. For the present study, the team set the CT value at 38, so any values below this number were indicative of a positive result. In addition, since face masks can be both woven and non-woven, a further consideration for the researchers was to try and establish if there were noticeable differences in potential transmission with different types of face masks.

Findings
For the present study, a total of 45 patients of various ages ranging from 20 to 69, were recruited and provided nasal/pharyngeal and mask samples for analysis. The majority of the masks were classed as woven (66.7%) although there was no statistically significant difference in median CT values between woven and non-woven mask fabrics (p = 0.11). Furthermore, COVID-19 viral RNA was only detected on the inner parts of the mask, i.e., the part in contact with the face. The median CT values for the swab samples was 28.41 (range 21.55 – 31.74) and 37.95 for the mask (range 33.50 – 40). With an approximate 10-point lower CT value for swabs compared to masks, the data suggested that there was little, if any viral RNA on the mask. Interestingly, there was a significant difference in CT values for the mask samples between those who presented with and without symptoms (p = 0.004).

Based on these findings, the authors suggested that face mask wearing among those infected with COVID-19 appear to significantly reduce viral transmission and concluded that their data highlighted the importance of mask wearing to limit the spread of COVID-19.

Citation
Mello VM et al. Effectiveness of Face Masks in Blocking the Transmission of SARS- CoV-2: a Preliminary Evaluation of Masks Used by SARS-CoV-2- Infected Individuals. MedRxiv 2021

Research suggests limited risk of COVID-19 transmission from mass gatherings

29th June 2021

Data suggests limited rates of COVID-19 transmission from mass-gathering events involving thousands of people.

A research programme established to determine the extent of COVID-19 transmission with both indoor and outdoor events without social distancing has been published by the UK government. Many mass gathering events such as music festivals, theatres and both indoor and outdoor sporting events were cancelled because of the risk of COVID-19 transmission. As a result, a primary aim of the research, which was conducted on behalf of the UK government, was to obtain an evidence base of the risks associated with COVID-19 transmission at large public events and to hopefully reassure members of the public that it was safe to return to such large-scale events. The first phase of the research consisted of nine pilot events running across multiple days in April and May 2021 and in a variety of outdoor and indoor venues. Each of the pilot sites examined variations in the seating, standing and the structure of the audience and participant numbers. The data captured by researchers was not restricted to transmission of COVID-19 but included monitoring of ventilation, analysis of carbon dioxide and crowd density as a proxy for airborne transmission, observing and analysing crowd behaviour, interviews and surveys with participants. Events included the World Snooker Championship, with 10,147 individuals seated indoors at which social distancing was required for the first five days but dropped for the final although face coverings were mandated at all times. Several football matches were also included and whilst the crowds were outdoors, as with the indoor events, face coverings were required. However, for some events such as one held at a nightclub over two consecutive evenings, with over 3000 people, no social distancing or face coverings were required. Similarly, an outdoor music festival with just over 6000 people there was no requirement for either social distancing or face covering. In addition, all participants were required to have a negative lateral flow test result within 36 hours of the event to be permitted to enter the venue. In addition, PCR testing prior to the event was a voluntary rather than mandatory requirement though it could also be undertaken on the day of the event. Moreover, participants were posted a home PCR test to be used five days later were also used to identify subsequent cases.

Findings
The results showed that there was limited evidence of COVID-19 transmission across all events with only 28 PCR-positive test results recorded, with 11 considered potentially infected before the event. Nevertheless, there were some important caveats with the data. Firstly, the return rate of PCR tests was low, ranging from 8% to 74% before the event to 13% to 66% post-event, hence limiting the estimate of infectivity rates. A further limitation of the data was the during the period of the pilot study estimates of infection rates in the community were low and prior to the emergence of the Delta COVID-19 variant of concern. An operational learning from the pilot was that the current contact tracing infrastructure is not designed for testing at events with large numbers of people.

Although the early results from the pilot are encouraging and inline with other studies and suggest that during mass gathering events there appears to be limited COVID-19 transmission, it should be emphasised that the data are limited because it was based on only a small number who returned their PCR test results.

Events research programme 2021

Preliminary results suggest COVID-19 vaccines effective against Indian variants of concern

18th May 2021

With the belief that recently identified COVID-19 variants are more transmissible, a more important concern is whether these are resistant to current vaccines.

The emergence of COVID-19 variants with increased viral fitness has created a great deal of concern, in particular, variants, B.1.617 and B.1.618, both identified in India and which appear to be more transmissible. Genomic analysis has revealed that both variants have mutations in the spike protein involved with antibody binding but whether this leads to antibody escape is uncertain. In a preliminary study, a team from the department of microbiology, Grossman School of Medicine, New York, US, sought to address the extent of antibody resistance together with the affinity of the two variants, to the angiotensin converting enzyme 2 (ACE-2) receptor, used by COVID-19 to gain entry to host cells. To understand the mechanism of COVID-19 binding, the team developed recombinant lentiviruses. These viruses, which are similar in structure to a coronavirus, can be used to express the modified spike protein of the variants, enabling researchers to assess both the neutralising capacity of various antibodies and the extent to which the spike protein binds to ACE2. The team tested the resistance to antibody neutralisation using convalescent plasma, vaccine-elicited antibodies and the therapeutic monoclonal antibodies used in Regeneron COV2 therapy.

Findings
Both B.1.617 and B.1.618 demonstrated a 2.3- and 2.5-fold (respectively) resistance to neutralisation by convalescent plasma. Similarly, there was a 4-fold (B.1.617) and 2.7-fold (B.1.618) resistance to antibodies in serum obtained from individuals vaccinated with either BNT162b or mRNA-1273 (Moderna). B.1.617 displayed a 4.7-fold decrease in neutralising titre with the Regeneron COV2 antibody cocktail but there was no change for the B.1.618 variant. Finally, there appeared to be a 6-fold increase in binding to the ACE2 receptor for both variants.

The authors commented on how their preliminary results indicated that despite an increased level of binding with the ACE2 viral receptor and partial resistance to all of the antibodies tested, it was still very likely that vaccination will protect against both variants. Moreover, while the data were derived from only two of the current COVID-19 vaccines, there was no reason to suggest that antibody neutralisation would be different for any of the other vaccines.

Citation
Tada T et al. The Spike Proteins of SARS-CoV-2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine-elicited and Therapeutic Monoclonal Antibodies. MedRxiv 2021

Analysis reveals the duration of viral shedding in COVID-19

23rd October 2020

Understanding the transmission dynamics of COVID-19 has significant implications for hospital infection control and prevention measures as well as public health policies.

This information is also important to inform the requirements for in-patient and outpatient isolation and it is necessary to gain a better insight of the potential significance of positive PCR tests over longer periods of time. Now researchers from the Division of Infectious Diseases, Oregon University, have undertaken a review of published data to determine the duration of viral shedding among those infected with COVID-19 and their findings have implications for the risk of transmission. The team queries public databases including PubMed, LitCoVID, the WHO COVID-19 literature repository and Google scholar for relevant articles. In each case, the articles were reviewed and assessed in terms of the design, population, healthcare setting, diagnostic testing methods and patient symptoms and illness severity.

Findings
A total of 77 studies were eligible for analysis and included prospective case studies, retrospective series, case reports, point prevalence studies and position statements. Only 59 studies were peer-reviewed, 6 were pre-prints and 13 researcher letters or a letter to the editor of a journal and 70 of the studies described hospitalised patients. All of the studies reported PCR-based assessment of viral shedding and 12 studies reported viral culture data. In terms of viral shedding, the data revealed that the duration ranged from a minimum of 1 day to 83 days although the pooled median duration of RNA shedding from respiratory samples based on 28 studies was 18.4 days (95% CI 15.5–21.3 days). When stratifying by disease severity, the median duration of RNA shedding was 17.2 days (95% CI 14–20.5 days) for those with mild to moderate disease and 19.8 days (95% CI 16.2–23.5 days) for those with severe disease. In general terms, the authors found that viral loads were highest within 1–2 weeks of illness onset but declined gradually although this rarely extended past 25 days. In discussing their results, the authors noted that while PCR positive tests can be prolonged, viral culture data suggested that viable virus samples could only be obtained from between 6 days prior to symptom onset but no later than 20 days after.

Reference
Fontana L et al. Understanding viral shedding of SARS-CoV-2: review of current literature. Infect Control Hosp Epidemiol 2020;1-35. doi:10.1017/ice.2020.1273