With the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world entered a phase of social restrictions which limited routine social and economic activities covering a wide spectrum, accompanied by a soaring and often overwhelming disease and death toll.
A new study, released on the medRxiv* preprint server, examines the effect of a new variant of this virus on the epidemic course within the UK.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Lockdown, weather and viral spread
As vaccines are being rolled out in many countries around the world, the emergence of new variants with increased transmissibility and virulence, and partial resistance, at least, to antibody-mediated immunity, has caused great concern among public health authorities and investigators alike.
Non-pharmaceutical interventions (NPIs) – such as the wearing of face masks, social distancing and lockdowns – were the only methods available for most of the pandemic, since intense research failed to turn up novel or repurposed antivirals that were targeted, safe and effective against the virus. In fact, NPIs h have reduced the spread of the virus, though several successive waves still occurred.
The status of lockdown stringency, and the economic policies put in place, have been carefully monitored by the Oxford University Government Response tracker, for almost all countries, helping understand how effective these strategies were.
Many studies show the transmission of the virus to be higher in cold weather, while humidity appears to reduce it. The researchers in the current study followed an earlier paper, using both lockdown data and weather records to make predictions of viral transmission in the form of the reproductive rate.
The UK variant and pandemic course
Many papers have also reported on viral sequencing. Indeed, this pandemic marks the first occasion on which rapid genomic sequencing has been used at such an enormous scale. The UK leads in this effort, through the COG-UK consortium.
As a result, the UK first recognized the B.1.1.7, or 20I/501Y.V1 or ‘UK’ or ‘Kent’ variant in the latter half of September, 2020. Following the publication of its sequence in October, it was then found to spread, albeit slowly, throughout the population.
At present, this has become the dominant variant in the UK, after being declared a variant of concern by Public Health England in mid-December.
This variant is characterized by multiple spike mutations, raising the fear of vaccine resistance. However, preliminary real-world data indicates vaccine efficacy against symptomatic infection with this variant to be about 74% with the Oxford/AstraZeneca vaccine. This is lower than the 85% protection against the previously dominant variants.
A few cases have shown the presence of an additional E484K mutation, which may increase the resistance of this variant to natural and vaccine-elicited antibodies. Mortality rates with B.1.1.7 are higher by 35% compared to the wildtype virus, says the Scientific Advisory Group for Emergencies (SAGE) in the UK. Meanwhile, it is 70% more transmissible than the original.
The current study aimed to understand how the Kent variant shaped the subsequent course of the UK pandemic.
What were the results?
The researchers observed that of the three factors, the lockdown was most closely associated with the reproduction number of the virus. The closest association was at 12 days, agreeing with the incubation period of 6 days, and a median period of 7 days from the earliest symptom to death.
Humidity was associated with increased viral spread, peaking at 20 days. This could be the result of somewhat delayed transmission by fomites. Interestingly, a positive correlation has not been found in many other studies, with other reported patterns, perhaps because of dissolved salts within the respiratory droplets.
Hotter weather reduces viral transmission, agreeing with the known inactivation of the virus at higher temperatures, as well as the shortened lifespan of respiratory droplets under such conditions.
Predictions remain accurate absent the new variant
The current modeling approach resulted in a predicted cumulative mortality very close to the actual reported mortality on that date. It also closely predicted the peak daily mortality, the date being off by only five days.
The researchers estimated final population immunity was about 32%, though only 25% of people were estimated to be seropositive in the 28 days preceding February 11, 2021. Of course, this does not account for cellular immune responses to the virus.
Immunity predictions are important in this model and is estimated from the cumulative mortality, associated with an infection fatality rate of 0.5%. If natural immunity is not implemented in this model, the predicted number of deaths would have been 7,00, 000, with 140 million infections –double the UK population!
Instead, the predictions follow an older model that used only temperature and humidity, along with the stringency of lockdown and the projected immunity. The predicted viral rate remains unchanged despite the emergence of the UK variant.
Shift in dominant lineage
In the real world, this VOC has become dominant, with higher transmissibility (and potentially higher virulence), indicating a robust selection advantage. This could be due to the known tendency of the virus to adapt during chronic infection. Patients with more severe illnesses and a higher chance of death may likely have had less robust immune systems and a higher viral load.
These patients would then be more likely to provide conditions within which the virus could adapt and develop into the new strain. Thus, such individuals would end up being infected with the UK variant despite having been originally infected with an older one.
The current interest in new and novel mutations may not account for the constant adaptation and mutation that has been occurring since the virus first infected humans. This is interrelated with the immune response and with the ability of the virus to adapt. Immunity cannot be considered in a binary fashion, as ‘Present’ or ‘Absent’, but rather as one point in a range of immunity to the older and the newer variants.
Mutations associated with immune evasion could also reduce viral infectivity, but this could be counteracted by the emergence of more mutations in this scenario. Newer variants may therefore appear to be more infective as individuals become more immune to an older variant.
Again, the tracker of the lockdown strategies used here may not have included unofficial strategies, such as the personal lockdown implemented by many people as they get to know that a more infectious and possibly more virulent variant is on the loose.
This could also contribute to the difference between the actual and predicted results in this study.
Actual vs required lockdown stringency
The study also brings out the delay in lockdown effects, which means that “It is easier to prevent the peak from developing by early modest tightening than flattening it by delayed more stringent measures.”
The researchers estimate that three weeks of lockdown at an effective reproduction number of 0.86 would be necessary to undo the growth caused by one week at an R0 of 1.65, at the low levels of immunity prevalent at the times of the first and second lockdowns.
As the virus infects more and more of the population, its endemicity can be prevented only by vaccination, which could provide large-scale immunity within a short time frame to cut short the pandemic.
What is the conclusion?
The overall course of the Covid-19 pandemic in the United Kingdom does not seem to have been significantly altered by the emergence of the Kent variant of the disease, despite its selective advantage over previous dominant strains.”
Instead, it seems to be predicted accurately by lockdown stringency and climatic conditions, as before.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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