Post-acute phase of COVID and Non-communicable diseases

Following the emergence of SARS-CoV-2, more than 660 million cases of COVID-19 have been
reported worldwide, with 183 million cases in the EU alone. These numbers will continue
to grow even after the disease becomes endemic. In some people, after recovery, the
effects of the first waves of COVID-19 persisted beyond the acute phase and increased the
risk of chronic multiorgan symptoms and disease. Up to 70% of people affected by COVID-19
showed reduced organ function even four months or more after COVID-19 diagnosis. Such a
functional decline is associated with an increased risk of the development of
non-communicable diseases (NCDs). This is especially true for individuals aged 65 and
older as the risk of NCDs increases with age.

Diseases of the pulmonary, cardiovascular, and renal systems are the three major NCDs
carrying the most significant burden for the individual as well as society. Studies have
documented compromised function of these 3 organ systems in the PAP of COVID-19 in
30%-70% of patients, regardless of the severity of the acute-phase. As homeostasis of
these three organs depends on interorgan communication with each other, the impact of PAP
of COVID-19 on one will impact the others. The added stress of the PAP of COVID-19
increases the risk of a higher incidence and/or the risk of an accelerated progression of
disease.

The prevalence and socioeconomic cost of the three NCDs is already extremely high.
Without a strong focus on minimmising the increased risk of incidence and accelerated
progression of the NCDs as a result of the PAP of COVID-19, up to 9 million Europeans may
be affected and result in an added direct attributable cost of between 19.564 € - 31.064
€ per year for each person who develop an NCD.

Beyond state of the art: pulmonary, cardiovascular and renal complications after the PAP
of COVID-19

Post-acute COVID-19 and pulmonary complications - Respiratory conditions have been
reported as occurring twice as often after severe COVID-19 as in the general population.
In a study of 135 individuals, the incidence of impaired lung diffusing capacity (DLCO)
and persistent lung damage was demonstrated in 30% of patients 12 months after acute
COVID-19. In another study of 142 individuals, pulmonary abnormalities were observed by
CT scans in 54% of individuals a year after acute COVID-19.

Post-acute COVID-19 and cardiovascular complications - The PAP of COVID-19 is associated
with an increased risk of deep vein thrombosis up to three months after COVID-19
infection, pulmonary embolism up to six months, and a bleeding event up to two months. In
a registry study of 153,760 individuals with COVID-19, the 12 month period following the
acute phase was characterized by an increased risk and an excess disease burden of
cardiovascular diseases, including heart failure, dysrhythmias and stroke. The risks were
evident regardless of age, race, sex, and other cardiovascular risk factors. MRI revealed
cardiac impairment in 78% of 100 individuals in the PAP of COVID-19.

Post-acute COVID-19 and renal complications - A study of 1733 individuals documented
reduced renal function in 35% 6 months after the acute phase of COVID-19 and 13% of
patients who did not have acute kidney injury (AKI) during the acute phase showed a
disproportionate reduction in renal function during follow-up. A study including
>89,000 individuals revealed an increased risk of adverse renal outcomes in
the PAP of COVID-19.

The main unmet needs requiring action at the European level There is an urgent need to
enable a better understanding of the causality between PAP of COVID-19 and the increased
risk of pulmonary, cardiovascular, and renal complications and thereby an increased risk
of onset of disease or aggravation of existing disease. Even though recent studies
suggest such a link, there is a need for a more nuanced study of the correlation on much
larger cohorts to determine the incidence and risk ratio more accurately. Furthermore,
there is a need to compare the outcomes between the early, present, and potential future
strains of SARS-CoV-2 variants responsible for the disease. An increased cohort size will
also allow a better understanding of the impact of socioeconomic status, difference
between sexes, the compounding effects of genotype, pre-existing comorbidities, and use
of prescription drugs and of differences between the PAP of early strains of SARS-CoV-2
in mostly unvaccinated individuals compared with current strains in mostly vaccinated
people. As this knowledge is currently incomplete, there is an immediate risk that a
large part of the European population will not receive optimal and timely care.

Thus far, investigators have concluded that the functional decline of organs caused by
COVID-19 cannot be explained by known risk factors. A review of the recent literature
suggests that the PAP of COVID-19 is associated with immune dysregulation, elevated
levels of autoantibodies, microbiota disruption and clotting and endothelial
abnormalities. However, the same review also concludes that the current understanding is
not sufficient to improve outcomes and calls for additional research. This underscores
the involvement of unidentified molecular mechanisms responsible for the aetiology. A
lack of understanding of these inhibits the development of effective biomarkers and drug
candidates that allow optimal prediction of the prognosis and treatment of patients
following resolution of the initial symptoms of COVID-19.

There is an urgent need for updated clinical practice guidelines and new tools to
diagnose and prevent the development and aggravation of NCDs caused by the PAP of
COVID-19. Currently, there are very few clinical guidelines and recommendations related
to the PAP of COVID-19 and NCDs in general, and there are even fewer clinical guidelines
and recommendations that focus on the effects of the PAP of COVID-19 on pulmonary,
cardiovascular, and renal health. Modern clinical practice guidelines and recommendations
that efficiently bridge the gap between research and current practice are invaluable for
securing best quality of care, patient outcomes and cost effectiveness. Unfortunately,
the development of a guideline or a recommendation does not necessarily lead to changes
in clinical practice. Clinical guidelines and recommendations are not always followed,
and it is estimated that approximately 30%-40% of patients receive treatment that is not
based on scientific evidence and 20%-25% receive treatments that are not needed or
potentially harmful.