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.