Within household transmission of SARS-CoV-2 infections, a multicentre prospective cohort-study

SARS-CoV-2 outbreak was first reported in the city of Wuhan, China, on 31
December 2019 and was declared a Public Health Emergency of International
Concern (PHEIC) by WHO on 30 January 2020. Because of the speed and scale of
transmission of this emerging disease, the WHO declared the global COVID-19
outbreak has a pandemic on March 11th. Globally, more than 500.000 cases have
now been reported to WHO from all continents. At the start of the pandemic, the
number of cases reported outside China has increased almost 13-fold, and the
number of affected countries expanded rapidly. On March 13th, the WHO declared
that Europe is now the epicenter of the COVID-19 epidemic, with the largest
number of cases reported from Italy.

In December 2021, the COVID-19 pandemic has again taken a new turn with the
emergence of the Omicron Variant of Concern (VoC). This VoC, first detected in
South Africa in November 2021, is characterized by a high number of mutations
in immunodominant areas of the Spike protein. Preliminary results of in vitro
immunological studies and epidemiological observations suggest that Omicron has
increased transmissibility and/or a higher level of immune evasion from prior
infection or vaccination, compared to Delta and other variants previously
circulating. Further insight into the transmission characteristics emerging
VoCs, and how this compares to the current epidemiology driven by infections
with earlier variants, in populations with variable level of (vaccine)
immunity is urgently needed to inform epidemic projections, mitigation policies
including non-pharmaceutical interventions and vaccine (boosting) strategy.

Substudy:
Reinfections with SARS-CoV-2 occur frequently due to declining immunity after
previous infection and/or vaccination and the emergence of new virus variants
that partially circumvent existing immunity. Therefore, there remains a risk of
new corona waves in the current phase of the Covid-19 pandemic, especially
during the winter season. A better understanding of the longevity of protective
immunity and the risk of reinfections, including their impact on individual
health, allows improved preparedness and can inform optimally targeted measures
to limit the impact on individuals and society.

Estimate key transmission parameters of SARS-CoV-2 in Europe from observing
within household virus spread and seroconversion of household members, and to
characterize the views and experiences of households regarding perceptions,
practices regarding infection control, and impacts of imposed isolation
measures.

: In the RECOVER-VERDI household (CORONAthuis) substudy on SARS-CoV-2
reinfections, the overall aim is to investigate risk factors, including
existing SARS-CoV-2-specific antibody immunity, and health impact of
reinfections, including the nature, severity and duration of symptoms, during
the autumn, winter and spring seasons of 2022-2023. This will allow to identify
populations at increased risk for reinfections, estimate the impact on
individual health and society of reinfections and inform targeted measures to
mitigate this impact.

This is a prospective observational cohort study of households with a confirmed
SARS-Cov-2 infection in one of the household members. Households are enrolled
as soon as possible following identification of the index case and no later
than 2 days after a positive SARS-CoV-2 test. At enrolment, a nose-throat swab
(NTS) and in a subset saliva is collected from each household member
irrespective of symptoms. Follow-up for disease symptoms starts immediately
after enrolment and continues daily for at least 21 days. Symptom follow-up
will be prolonged in case a new suspected or confirmed SARS-CoV-2 emerges in
the household during follow-up. In this case, follow-up is continued until 21
days after the date of onset of symptoms, or date of positive SARS-CoV-2 test
in the last detected household case. At enrolment and at 4-6 weeks
post-enrolment, a capillary blood sample on filter paper (dry-blot-spot) will
be collected from all household members for SARS-CoV-2 serology testing.
In a subset of participants, a qualitative interview by phone will be conducted
to explore participants perceptions, needs and behavioural practices with
respect to the COVID-19 pandemic.
As of January 2022, a more intensive sampling scheme will be used to
comprehensively capture household transmission early after introduction. This
has been decided based on results thus far of the household study that nearly
all transmission occurs in the first week after detection of the index. In
addition, several studies have now confirmed the added value of saliva sampling
in detecting PCR positive individuals. Therefore, three NTS and saliva
sampling time-points are added in the first week after enrollment (day 2, 4 and
7) and on day 14. Stool samples will be no longer requested. This has no added
value to the repeated NTS and saliva samples and has proven cumbersome for
participants.

For the substudy on reinfections, participants consenting to take part in the
sub-study will undergo four additional 3-monthly sampling timepoints from
November 2022 (M0) to July 2023 (M9). Biological specimens, clinical data and
psychosocial data will be collected prospectively. Biological specimens that
are collected include self-collected capillary blood by the participant (M0,
M3, M6 and M9). During the same period, participants who develop new symptoms
suggestive of SARS-CoV-2 reinfection or have a SARS-CoV-2 infection independent
of symptoms, are instructed to self-collect a nose and throat swab and send to
the laboratory. Self-administered questionnaires will also be collected at the
predefined time-points and in case of suspected reinfection. The study will be
conducted completely remote.

We estimate the risks for the participants to be small. Participants are sent
all materials for collecting blood, nose-throat and some stools and saliva.
Collecting the body material can be a little painful for the fingerstick and
the nose-throat a bit annoying, but not painful. The questionnaires have been
kept short and the diaries are quick and easy to complete.