The Recovery Trial
The Randomized evaluation of COVID-19 therapy, the
RECOVERY trial, has reiterated what many frontline workers had been
experiencing. Steroids work! This was a 176 center, randomized control
pragmatic trial comparing the effect of 6 mg dexamethasone for 10 days
along with usual care to usual care alone in patients with COVID-19
infections.
There were 2104 patients who received dexamethasone
and 4321 got only usual care. Primary outcome measured was mortality at
28 days and secondary outcomes were need for oxygen or ventilation.
Overall, the dexamethasone group had a significantly lower mortality of
21.6% compared to the non-dexamethasone group (24.6%).
What was more striking was the reduction in mortality
in those requiring oxygen or mechanical ventilation. Dexa-methasone
reduced deaths by one-third in patients receiving invasive mechanical
ventilation (29.0% vs. 40.7%; P<0.001) and by one-fifth in
patients receiving oxygen without invasive mechanical ventilation (21.5%
vs. 25.0%; P=0.002). Patients who were not on oxygen did
not benefit from dexamethasone, and, in fact there was a trend for
increased mortality in those who received dexamethasone (not
statistically significant). Patients who received dexa-methasone after 7
days of onset of symptoms showed more benefit than those who received it
early in the course of the disease.
Benefits accrued by patients on oxygen or mechanical
ventilation and after 7 days of illness suggest that dexamethasone makes
a difference at a stage when immune-mediated injury predominates over
the initial viral replication. The low cost and wide availability of the
drug make it an attractive option in serious COVID-19 infections.
(MedRxiv 22 June 2020)
Utility of Antibody Tests in COVID-19 Infections
Two recent meta-analyses have evaluated the utility
of serological tests for SARS-CoV-2 infections. One included 40 studies
and the other 54. Three types of antibody tests were used - Enzyme
linked immunosorbent assays (ELISA), chemiluminescent immunoassays
(CLIA) and lateral flow immunoassays (LFIA). The LFIA is typically used
for point of care testing with either a dipstick format or cassette such
as used in the common pregnancy test.
The sensitivities and specificities depended on the
type of test done, the timing of the test after onset of illness, the
type of antibody looked for (e.g, IgA, IgM or IgG) and the
population characteristics. If the test was done between day 1-7, the
sensitivity for a combination of IgG/IgM was 30.1%. It was 72.2% for day
8 to 14 and 91.4% for day 15 to 21. For day 21-35, the sensitivity was
96% but there was inadequate data for tests done beyond day 35.The
sensitivity of the LFIA (which is the potential point of care test
method) was lowest at 66%. Tests using ELISA had sensitivities of 84.3%
and CLIA fared best at 97.8%. Specificities of all tests range from
92-98%.
The performance of the test also depends on the
population being tested. For example, in healthcare workers with
respiratory symptoms with an expected prevalence of 50%, in 1000 people
tested, 43 would be missed and 7 would be falsely positive. In national
surveys where one would expect a prevalence of 5%, of every 1000 people
tested 4 would be missed and 12 would be falsely positive.
Overall it appears that antibody testing may be
useful clinically after 15 days of onset of illness to complement other
tests.
(Cochrane Database Syst Rev 2020;BMJ 1 July 2020)
Lessons from the Spanish Seroprevalence Study
A nationwide COVID-19 seroprevalence study of more
than 60,000 people conducted in two stages in April and May, 2020 in
Spain (ENE-COVID) has revealed valuable information. A history of
symptoms was collated and point of care testing for antibodies using
LFIA was done, with further testing using a chemiluminescent assay in
those consenting.
The country-wide seroprevalence was 5% by point of
care testing and 4.6% by chemiluminescent assay. Children had lower
levels of seroprevalence with 1.1% in infants and 3.1% between 5-9
years. Seroprevalence in health care workers (10%) was higher than any
other occupational group. About 32.7% of people with a positive serology
were asymptomatic.
The key message from this well-conducted study was
that though Spain incurred a huge burden of mortality in the pandemic,
the overall seroprevalence was inadequate to provide herd immunity. This
means further epidemic control by allowing natural infections will
result in large number of deaths. Social distancing, and identifying and
isolating new cases will continue to be important till an effective
vaccine is available.
(Lancet 6 July 2020)