HIV and SARS Awareness

I. DEFITION OF TERMS:
1. HIV stands for human immunodeficiency virus, a virus that attacks the body’s immune system.

What it does:
HIV destroys CD4 cells, a type of white blood cell, which weakens the immune system. This makes it harder for the body to fight infections
and diseases.

Stages of HIV: HIV has three stages:

• Acute HIV: Some people experience flu-like symptoms a month or two after infection, which usually go away within a week to a
month.
• Chronic stage/clinical latency: People can have HIV for many years without feeling sick, but they can still spread it to others.
• AIDS: The most serious stage of HIV, when the immune system is severely weakened. People with AIDS are more likely to get
opportunistic infections and certain cancers.

Treatment:
There is no cure for HIV, but people with HIV can live long, healthy lives with proper medical care. Antiretroviral drugs (ARVs) are used to
treat HIV.

Prevention:
Using condoms, getting tested for HIV and other sexually transmitted infections, and taking PrEP or PEP can help prevent HIV.

Risk factors for HIV include:

Unprotected anal or vaginal sex, Having another sexually transmitted infection, Needle sharing, Medical procedures involving unsterile cutting
or piercing, and Needlestick injury.

2. Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-associated coronavirus.

What it does:
A virus known as SARS-associated coronavirus (SARS-CoV) causes the illness. Coronaviruses commonly cause mild to moderate upper-
respiratory illness in humans, but can cause respiratory, gastrointestinal, liver, and neurologic diseases in animals.

Stages of SARS-CoV-2 (www.health.com):

Incubation, acute symptoms, and recovery

Treatment:
Despite a concerted global effort, scientists have yet to find an effective treatment for SARS. Antibiotic drugs don’t work against viruses, and
antiviral drugs haven’t shown much benefit.

Prevention:
In general, you can reduce the risk of spreading viruses (like SARS) and other infectious diseases by:
 • Washing your hands frequently.
• Not being around people when you’re sick.
• Wearing a mask if you need to be around people when you’re sick.
• Covering your mouth and nose with your elbow when you cough or sneeze.

Risk factors for SARS-CoV-2 include:

In general, people at greatest risk of SARS are those who have had direct, close contact with someone who’s infected, such as family members
and health care workers.

II. ABSTRACT:

Both HIV and SARS-CoV-2 pandemics are caused by RNA viruses and have reached us from animals. These two viruses are different in the
transmission mode and in the symptoms they generate. However, they have important similarities: the fear in the population, increase in
proinflammatory cytokines that generate intestinal microbiota modifications or NETosis production by polymorphonuclear neutrophils, among
others. They have been implicated in the clinical, prognostic and therapeutic attitudes.

I. HIV
• was discovered in the 80’s (1981), when the first cases were known in young adults in California.
• It is believed that HIV spread to humans through direct contact with the infected blood of chimpanzees and were affected by severe
pneumonia caused by Pneumocystis jiroveci or with Kaposi’s sarcoma.
• The transmission mechanism was sexual contact, drugs injection, blood transfusions and mother-to-child. A social stigma was
generated.

The first isolation of HIV infection was achieved in 1983 by Barré-Sinoussi and collaborators at the Pasteur Institute in Paris.

1.a. RESULTS AND DISCUSSION:

The HIV virion is a spherical particle, with around 100 nm of diameter, that contains two copies of single-stranded RNA together with the
enzymatic machinery (reverse transcriptase and integrase) implicated in its transformation from RNA to DNA in the cytoplasm of the host cell
and the subsequent integration of this material into the cell genome (proviral DNA) 11. The HIV-1 envelope is formed by viral gp41 and gp120
envelope glycoproteins, with ability to bind to the CD4 surface protein, present in certain cells, including T lymphocytes and mononuclear
phagocytic cells. This union produces a conformational change in the viral glycoprotein that allows its subsequent interactio n with one of the
chemokine receptors (CCR5 and CXCR4), which act as co-receptors for the virus, allowing its entry into the cell. Once inside, it will use the
enzyme reverse transcriptase to convert its RNA into DNA, which will be later transported to the nucleus and integrated into the cellular DNA.
As mentioned above, HIV-1 infects immune system key cells, mainly CD4+ T helper lymphocytes. Consequently, there is a depression of the
immune system. If this depression becomes chronic, the patient progresses to AIDS 12.

1.b. HIV EPIDEMIOLOGY:

According to UNAIDS (United Nations on HIV/AIDS) in its most recent update in 2018, there are 37.9 million estimated individuals living
with HIV all over the world. There are estimations that predict 1.8 million of new HIV-1 infections each year. The results show that new
infections (of all ages) decreased from a peak of 3.4 million in 1996 to 1.8 million in 2017 13. From the start of the pandem ic until 2018, 32
million people died from AIDS-related illnesses 13.

1.c. HIV TRANSMISSION AND MECHANISM:

Sexual, Parenteral and Vertical – three transmission and mechanisms of HIV infection.

HIV is found in blood, pre-seminal fluid, semen, vaginal fluids, and breast milk, and is transmitted through direct contact of these fluids with
the mucosa or bloodstream of another person.

According to the data available, in Spain, the most frequent transmission mechanism nowadays is sexual, mainly from men who have sexual
relations with other men (approximately 54.3% of all new cases), followed by heterosexual transmission (28%) and injecting drug use (less
than 3.1%) 12.

1.d. HIV SYMPTOMATOLOGY:

The symptoms generated by HIV infection begin to appear between 2 and 6 weeks after contact with the virus and can be divided into early
infection (within the first two months after infection) or chronic. During the early or acute phase of infection, infected people present fever,
headache, muscle pain, rashes, sore throat and mouth sores, and swollen lymph nodes. These symptoms can be so mild that are almost not
noticed.

In the phase of chronic infection, the virus continues spreading and destroying immune cells, causing immunosuppression. Usually, if it is not
treated, HIV turns into AIDS in an average of 10 years. When AIDS occurs, the immune system is already severely damaged, opportunistic
infections, neurodegenerative diseases and cancers occur in infected individuals.

1.e. TREATMENT AND VACCINE DEVELOPMENT:

After the initial discovery of some drugs that had shown high toxicity and scarce benefit (zidovudine, didanosine, zalcitabine), in 1995 the
discovery of a combination therapy, which initially included antiprotease drugs (indinavir, saquinavir) was such a change that it was possible
to significantly reduce mortality. Antiretroviral therapies (ART) have tranformed HIV infection into a chronic disease. After 2008, the
emergence of new drugs, including integrase inhibitors, has led to significantly less toxicity and excellent tolerance.

However, HIV persists in the body due to the early establishment of reservoirs, which cannot be eliminated with any of the current antiretroviral
regimens. Reservoirs are defined as anatomical sites or cells in which HIV infection is persistent and stable allowing competent viruses to
replicate under permissive conditions.

Studies searching for vaccines have not been successful yet.

2. SARS-CoV-2
• SARS-CoV-2 is a β-coronavirus, from the sub-genus Sarbecovirus, subfamily Orthocoronavirinae.
• The size of the SARS-CoV-2 virion is approximately 50 to 200 nm of diameter, and its genome is single-
stranded positive-sense RNA.
 • Confirmed that SARS-CoV-2 uses the ACE2 receptor to enter into the cells, just as SARS-CoV-1 does. This
receptor is expressed in the lung, heart, blood vessels, intestine and kidneys

2.a SARS-CoV-2 EPIDEMIOLOGY:

The situation of SARS-CoV-2 infection, November 7th 2020, according to the WHO, is as follows: 48,534,508
confirmed cases worldwide with 1,231,017 deaths since the start of the pandemic in December 2019. Currently,
the continent with most cases is America with 21,168,405 confirmed cases and 650,705 deaths. In Europe, the
confirmed cases are 12,490,012 with 303,707 deaths.

The mortality rate of SARS-CoV-2 (3.8%) is lower than that of SARS-CoV-1 or MERS-CoV (Middle East
Respiratory Syndrome Coronavirus), whose rates were 10% and 37.1% respectively, but the number of cases of
infection is 10 times higher. This is due to the fact that SARS-CoV-2 can be transmitted from people with no
symptoms or with mild infections. These characteristics can explain the sudden pandemic spread of the virus 33.
In general the mortality rate is 5% 34, being 49% in critical cases.

2.b. SARS-CoV-2 TRANSMISSION MECHANISM:

The virus is transmitted through the air, mainly due to small drops of saliva from infected people by coughing or
sneezing that can reach two meters. The transmission is also produced by direct contact with these secretions or by
objects contaminated by them.

2.c. SARS-CoV-2 SYMPTOMATOLOGY:

The symptoms generated by SARS-CoV-2 begin to appear between 2 and 14 days after the contact with the virus.
The most common symptoms include fever, cough, and dyspnea. Diarrhea and abdominal pain are also frequent.
Although most cases have mild symptoms, in the most severe cases, the infection can cause pneumonia, severe
difficulty breathing, kidney failure, and even death.

2.d. TREATMENT AND VACCINE DEVELOPMENT:

COVID-19 treatment initially included drugs previously used in HIV treatment, such as lopinavir; subsequent
studies demonstrated its lack of efficacy. Moreover, as in the case of HIV infection, the first antiviral used
(Remdesivir) has shown very limited efficacy. Apart from corticosteroids to decrease cytokine storm, there are no
other useful drugs against SARS-CoV-2 infection.

Many trials are being done to find a vaccine against SARS-CoV-2 44, some of them with encouraging results in
phase II.

III. DIFFERENCES BETWEEN THE TWO VIRUSES:

 IV. SIMILARITIES BETWEEN THE TWO VIRUSES:

(a) Fear in the population HIV can affect anyone, independently of their social status, race, gender, etc. This can affect people psychologically,
making them feel fear, stress or anxiety. Apart from those factors, in COVID-19, there are others that can make people feel this - the virus is
new, there are not known effective antivirals, the disease is more contagious than expected, it can even severely affect young individuals with
no previous pathologies, respiratory failure forces hospitalization for many days. In addition, the panic is even increased by the presence of the
Internet, over-information, spreading of unfounded rumors, and hyper connectivity in our lives nowadays.

(b) Existence of animal reservoirs. The existence of natural animal reservoirs is another point in common, although they are found in different
animals, being non-human primates in the case of HIV, and bats in the case of SARS-CoV-2.

(c) Increased synthesis of proinflammatory cytokines. Both viruses generate an increase in the production of cytokine, and this is linked to the
viral load in the case of SARS-CoV-2. These cytokines are related with secondary complications in infected people.
It is well known that in HIV infection, the cytokine release is a chronic mechanism that generates prolonged inflammation. Sustained
inflammatory status has been related with increased intestinal permeability and bacterial translocation, detected in HIV-infected patients.
Intestinal permeability, bacterial translocation or systemic inflammation cannot be reversed with antiretroviral therapies. Residual viral
replication and other co-infections also contribute to prolonged inflammatory status. Serum levels of the proinflammatory interleukin 6 has
been independently associated to morbidity (cardiovascular disease, cancer, etc.) and mortality in patients with controlled HIV replication.

Regarding COVID-19, the cytokine secretion is an acute response and is implicated in clinical manifestations. Proinflammatory cytokines and
chemokines attract more inflammatory cells to migrate from the blood, inducing an amplification of the deleterious r esponse; in fact, a
substantial part of the therapy is aimed at blocking pro-inflammatory cytokines. Cytokine storm is implicated in the acute respiratory distress
syndrome or multiple-organ dysfunction. Increased markers of systemic inflammation are prognostic variables in COVID-19.

(d) Modifications of the intestinal microbiota. It has been proved that patients infected with SARS-CoV-2 who develop cardiac complications
have higher levels of intestinal permeability and activation of inflammasomes, suggesting a heart-intestine axis in COVID-19. In fact, one of
the vaccines being developed is a genetically modified probiotic with a plasmid that contains the DNA of the SARS-CoV-2 protein.

HIV infection has an unfavorable effect on the interaction between the commensal microbiota and the immune system. Microbiota modifications
(increase in pro-inflammatory bacteria and a reduction in those that promote homeostasis) have been detected in HIV infected people with
pathogenic consequences on bacterial translocation (see above) and immune responses. It is important to mention that elite controllers have
microbiomes more similar to those of healthy individuals than other groups of HIV-infected patients, and they also show lower levels of immune
activation and HIV reservoirs.

(e) Neutrophil extracellular traps (NETs) formation. The two viruses share a mechanism known as NETosis. This is a neutrophil death
mechanism in which neutrophils release nets of chromatin fibers into the extracellular space. Those nets contain histones, microbicidal peptides
or oxidizing enzymes. NETs are very adherent and capture extracellular microbes, such as some bacteria, fungi and virus, stimulating its
removal. Acute NETosis against infectious agents is an efficient defense mechanism that avoids collateral tissue damage, concentrating the
antimicrobial action and reducing the toxicity attributable to the proteases. However, a chronic or acute aberrant NETosis may contribute to the
pathology. In HIV infection, NETosis has been suggested to be involved in the atherosclerosis development. In COVID-19, the virus-induced
NETs can circulate in an uncontrolled way, giving rise to an extreme systemic response of the body, increasing the concentrations of cytokines,
chemokines and increasing inflammation. In addition to promoting the cytokine storm, NETs in COVID-19 patients are also responsible for the
thrombotic complications they present, as is the case in HIV patients.