PHOTO: RITZAU SCANPIX DENMARK/REUTERS1180 3 DECEMBER 2021 • VOL 374 ISSUE 6572 science.org SCIENCENEWS | IN DEPTH
I
n November 2020, researchers in Den-
mark published inconclusive results of a
randomized trial to probe whether mask
requirements protect against COVID-19.
Although nearly 5000 people took part
in the DANMASK study, it was too small,
and its time frame too short, to answer the
question. News reports, however, described
the study results as questioning the efficacy
of masks, and a June analysis noted that it fed
into antimasking misinformation campaigns.
Now, another group argues such small,
weak trials of public health measures can do
more harm than good. Writing in Trials last
month, the group argues such studies waste
funding and time, and can give a danger-
ous appearance of certainty. Much research
“does not lead anywhere that is useful,” says
co-author Noah Haber, an independent study
design specialist. “It’s noise at best, and it’s
misinformation at worst, because it looks like
information.” Other researchers, however,
think any evidence is better than none.
Henning Bundgaard, the lead DANMASK
author, could not be reached for comment.
However, in August in the Annals of Inter-
nal Medicine, Bundgaard and co-authors
defended their sample size and methods,
and said the study has been misinterpreted.There’s little doubt that small, weak stud-
ies have proliferated during the pandemic,
which raised pressure to test interventions
fast. A February Nature Communications
analysis of 686 clinical COVID-19 studies
found they had poorer quality methods than
a matched group of trials with similar study
designs. A BMJ review last month of 72 stud-
ies found hand washing and wearing masks
reduced risk of SARS-CoV-2 infection, but it
also said most of the studies had moderate
to serious weaknesses. And a study led by
Haber, posted as a preprint in January, found
that only one of 36 studies of COVID-19 poli-
cies met four criteria that would make results
useful for policymakers, such as tracking out-
comes for long enough that policy measures
had time to influence local infection rates.
Atle Fretheim, a health services researcher
at the Norwegian Institute of Public Health,
thinks Haber and his team are wrong to dis-
miss small studies completely. Because rela-
tively few people in a country or region are
infected at any one time, impractically large
sample sizes would be needed to study pub-
lic health measures with certainty, he says.
In March, Fretheim argued in Trials that
studies like DANMASK can contribute to ev-
idence when taken together. “If face masks
work, more or less, in all the 20 small,
stupid trials that have been done, then wePoor trials of health steps are
worse than none, scientists say
Others say small COVID-19 studies accumulate into
a clear picture over time
COVID-By Cathleen O’GradyPassengers ride a subway in Denmark, where an inconclusive trial on mask wearing took place.recovered from COVID-19 or were vaccinated
are unlikely to completely lose their ability
to neutralize the virus. “But I would expect,
based on this particular combination of mu-
tations, that the drop in neutralization is
larger than for all the other major variants.”
Experiments in the laboratory will have to
show whether he is right. Alex Sigal, an infec-
tious disease researcher at the Africa Health
Research Institute, says he received swabs
with Omicron on 24 November and has
started to grow the virus. Producing enough
of it to test against sera from vaccinated and
recovered individuals will take a week or two,
he says. Other researchers will test viruses
genetically engineered to carry just the spike
protein of Omicron, a process that is faster
than growing the variant itself, but a bit fur-
ther removed from what happens in real life.
As such studies take place, it’s crucial to
closely monitor the pandemic, Farrar says.
“Do you see cases increasing not just in
South Africa, but the broader South African
region?” The same applies to the rest of the
world. The virus has already been picked
up in more than a dozen countries, many
of which are not high on the list of the most
connected places to Johannesburg. “My feel-
ing is that Omicron has likely spread to many
more places where it will soon be detected,”
says Oxford epidemiologist Moritz Kraemer.
Epidemiologists will also watch for changes
in disease severity—how many people are
hospitalized and die. All that will take time.
In the meantime, the European Union, the
United States, and many other countries have
restricted travel to and from southern Africa
in a bid to protect themselves. Travel restric-
tions are unlikely to stop the variant, Farrar
says, but they can buy some time. “The ques-
tion is what you then do with the time.”
But the restrictions could, ironically,
hamper science. “It is really difficult to get
the needed reagents in a plane as the last
10 planes that I tried to get our reagents on
got canceled,” de Oliveira says. And the eco-
nomic and social cost could be a disincentive
to report new variants: “I’ve heard through
the grapevine that countries didn’t push
sequences out very quickly [in the past] be-
cause they were worried about travel bans,”
says Emma Hodcroft, a virologist at the Uni-
versity of Bern. “This is the opposite of what
we want.”
Such considerations did not stop the
South African researchers, de Oliveira says.
“We do risk a massive backlash in case
[Omicron] does not cause a massive wave
of infection and can be controlled,” he wrote
in a message. “But this is a risk that I am
comfortable to live with as the pandemic
has caused so many deaths and suffering.
[Our] hope is that our early identification
will help the world.” j