Differences in Immune Response Among HIV-1-infected Individuals With Previous or Current COVID-19 (CoVIHDis).

Since March 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
pandemic has affected almost five million people in 168 countries on five continents,
with more than 300.000 deaths (1-4). The scientific evidence so far does not suggest that
people with HIV-1 have an increased risk of serious complications if they develop
COVID-19 disease (5-7). In our recent work, we have shown in a few patients that people
with HIV-1 under antiretroviral treatment, with undetectable viral load and a CD4 count
greater than 200 cells/mm3, do not have a higher risk of developing serious complications
than people without HIV-1, but also HIV-1 infected patients does not seem to be protected
of the so-called cytokine storm (8-11). Like in the general population, they would be
more likely to develop serious complications if they are older and with previous
pathologies (comorbidity), such as high blood pressure, diabetes, cardiovascular disease,
chronic lung disease, cancer or immunosuppression (congenital, acquired or due to
treatment with immunosuppressive drugs). Thus, people with HIV-1 who are
immunocompromised with a CD4 count less than 200 cells/mm3, regardless of whether or not
they take antiretroviral treatment should be considered among the vulnerable groups and
therefore at an increased risk of developing serious clinical complications associated to
COVID-19 (12-14). It should be noted, however, that, so far, there is no enough
scientific evidence that can confirm this possibility (10,15-17).

Since March 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
pandemic has affected almost five million people in 168 countries on five continents,
with more than 300.000 deaths (1-4). The scientific evidence so far does not suggest that
people with HIV-1 have an increased risk of serious complications if they develop
COVID-19 disease (5-7). In our recent work, we have shown in a few patients that people
with HIV-1 under antiretroviral treatment, with undetectable viral load and a CD4 count
greater than 200 cells/mm3, do not have a higher risk of developing serious complications
than people without HIV-1, but also HIV-1 infected patients does not seem to be protected
of the so-called cytokine storm (8-11). Like in the general population, they would be
more likely to develop serious complications if they are older and with previous
pathologies (comorbidity), such as high blood pressure, diabetes, cardiovascular disease,
chronic lung disease, cancer or immunosuppression (congenital, acquired or due to
treatment with immunosuppressive drugs). Thus, people with HIV-1 who are
immunocompromised with a CD4 count less than 200 cells/mm3, regardless of whether or not
they take antiretroviral treatment should be considered among the vulnerable groups and
therefore at an increased risk of developing serious clinical complications associated to
COVID-19 (12-14). It should be noted, however, that, so far, there is no enough
scientific evidence that can confirm this possibility (10,15-17).

Indeed, there are two main questions for the management of this disease in this
population, the real incidence of COVID 19 (susceptibility) and if the immune response
could be different in those who were already coinfected.

1. The differences in susceptibility to infection could be related to host factors.
Thus, it is important to characterize and genotyping the main receptor for
SARS-CoV-2, ACE2, and other related receptor, such as CD26, to explore the genetic
background affecting the real incidence of this disease, along CD4 count and
antiretroviral therapy.

2. People with HIV-1 have an impaired immune system, especially in those with less than
200 CD4 cells/mm3. Hence, the immune response in these individuals could be weaker
than in general population, including the cytokine response reported after
SARS-CoV-2 infection (18-20). In addition, the specific CD4/CD8 T cell response
could be altered due to the HIV-1 infection and the level of immunosuppression. This
specific T cell response could be a good marker for the presence or persistence of
immunity against SARS-CoV-2 infections.

In addition, the first line of immune defense is the interaction of the virus with innate
immunity cell members. The toll like receptors (TLRs) family is a group of pattern
recognition receptors that include many different molecules (21-23). These bindings can
activate dendritic cells, monocytes, macrophages. There is an important RNA and DNA
connection, activation of TLRs, the production of type I interferons, and the development
of some autoimmune diseases. TLR7 and TLR8 specifically recognize simple-chain RNA of
viruses and are expressed in endosomal membranes. TLR8 is expressed in regulatory cells
(Treg) and its activation results in inhibition of its regulatory functions. Natural
killer cells (NK) respond to alterations of class I HLA molecules present in infected
cells (24-26). An increase in class I HLA expression could lead to an increase in NK
activation by increasing its ability to produce IFN-gamma. Therefore, the reasons for KIR
binding are often variable between individuals and between populations. However, there
are no data about TLRs activation and KIRs binding in HIV infected patients with SARS
CoV-2 infection.

This project is designed to improve scientific knowledge and give answers to the actual
clinical questions regarding SARS-CoV-2 infection in people living with HIV-1. It could
be of importance to determine the risk of infection not related to HIV-related factors,
and to ascertain the adequation of the immune response of HIV infected patients after a
SARS-CoV-2, identifying therefore those at risk of severe disease.