Study with deliberate infections uncovers new Covid clues

How long does the Sars-CoV-2 truly take to incubate? When does the viral load peak? How long does someone stay contagious?

The answers to these questions have till now been estimations, based largely on statistical analyses of outbreaks and contact-tracing.

But a controlled clinical study in the UK, the findings of which were made public on Wednesday, now offers more concrete insights, some of which are new. To determine these, 36 men and women in the 18-30 age group were infected with the Sars-CoV-2 through an equal amount of viral load via nasal drops and had swabs taken twice a day while they were at the Royal Free London hospital.

“Our study reveals some very interesting clinical insights, particularly around the short incubation period of the virus, extremely high viral shedding from the nose, as well as the utility of lateral flow tests, with potential implications for public health,” said professor Christopher Chiu from the Imperial College London and the chief investigator of the trial.

While the virus that was used during the study was the D614G variant that caused most infections around the world in 2020, Chiu added that the crucial aspects of the study will hold true for all variants. “While there are differences in transmissibility due to the emergence of variants, such as Delta and Omicron, fundamentally, this is the same disease and the same factors will be responsible for protection against it.

“With a newer strain, there might be differences in terms of size of response, but ultimately we expect our study to be fundamentally representative of this kind of infection,” the professor said in a release shared by the Imperial College.

The new insights

Among the findings that diverged most from estimates gleaned from the real world was of the incubation period. The trial found that symptoms began within two to four days of exposure, contrary to the widespread belief that it takes around five days for the first signs to appear.

Another finding that appeared to go against current assumptions was that there was no difference in how contagious someone was based on symptoms. “Our data clearly show that Sars-CoV-2 viral shedding occurs at high levels irrespective of symptom severity, thus explaining the high transmissibility of this infection and emphasising that symptom severity cannot be considered a surrogate for transmission risk in this disease,” the study, submitted for peer review, added.

Among the other insights, some were new – the virus appeared to first replicate more broadly in the throat – and some were known, like men were significantly more susceptible than women. Among those that got infected, two-thirds were male participants. There were two participants who did not test positive at any time but went on to develop antibodies, and both were women.

Another granular clinical detail was that viral load appeared to rise steeply for five days after infection and viable virus – or virus that could still cause an infection – was detected for up to 10 days on average after an exposure.

Curiously, however, of the 36 who were exposed to the virus through nasal drops, only half – 18 – went on to test positive at all, echoing the mystery of how some people escaped an infection despite having been a close contact.

Unlocking more clues

Why only half were infected despite all of the trial volunteers being exposed is one of the aspects still being studied. “Analysis of local and systemic immune markers… that may explain these differences in susceptibility are therefore ongoing,” the researchers said.

Importantly, the study found that such trials were safe, and they now provide a basis for larger such experiments including different variants, people infected in the past and those who have had a vaccine dose.

“Together, these studies will thus optimise the platform for rapid evaluation of vaccines, antivirals and diagnostics by generating efficacy data early during clinical development and avoiding the uncertainties of studies that require ongoing community transmission,” the researchers said.

“The trial has already provided some fascinating new insights into Sars-CoV-2 infection, but perhaps its greatest contribution is to open up a new way to study the infection and the immune responses to it in great detail and help test new vaccines and treatments,” said Dr Sir Michael Jacobs, consultant in infectious diseases at the Royal Free London hospital.