COVID-19 Warning! Case Studies Show That HIV Patients Contracting COVID-19 Are Ideal Vivo Laboratories For Creating Worrisome SARS-CoV-2 Mutations!
Numerous case studies are emerging that special attention needs to be paid to HIV patients should they contract the COVID-19 disease as their immunocompromised conditions make them perfect ‘vivo laboratories’ for the SARS-CoV-2 to constantly mutate and develop more potent and worrisome mutations and resultant variants.
In one case study published on a preprint server by researchers from South Africa, a female HV patient in South Africa became a veritable COVID-19 variant laboratory as the virus mutated more than 30 times in 216 days of her infection! https://www.medrxiv.org/content/10.1101/2021.06.03.21258228v1.full
Although most individuals effectively clear SARS-CoV-2, there are several reports of prolonged infection in immunosuppressed individuals.
In this case report cum study, the researchers presented a case of prolonged infection of greater than 6 months with shedding of high titter SARS-CoV-2 in an individual with advanced HIV and antiretroviral treatment failure.
Through whole genome sequencing at multiple time-points, the study team demonstrated the early emergence of the E484K substitution associated with escape from neutralizing antibodies, followed by other escape mutations and the N501Y substitution found in most variants of concern.
Alarmingly this provides support to the hypothesis of intra-host evolution as one mechanism for the emergence of SARS-CoV-2 variants with immune evasion properties.
Importantly the new properties developed by the SARS-CoV-2 virus during its incubation in this HIV patient’s body enabled it to increase in strength, resist certain vaccine compounds and block some COVID-19 therapeutics.
In this case report, altogether there were 13 genetic changes related to the virus’ spike protein and 19 additional genetic changes that further changed its behavior.
Some of these changes became persistent, and then declined as other mutations became more prevalent. Consequently, the variant that emerged was better able to evade the body’s immune system.
The study team from the University of KwaZulu-Natal in South Africa told Thailand Medical News, “Unlike many of the other reported cases, virus evolution was not driven by the receipt of immune-based therapies (convalescent plasma or monoclonal antibodies).”
The team suggests the viral evolution “may have been driven by selective pressure from an impaired neutralizing antibody response.”
For instance, the E484K mutation in the spike receptor binding domain emerged very early in the course of the infection ie 19 days after the first onset of symptoms. Typically, this mutation occurs late in the course of COVID-19. It is associated with resistance to class 2 neutralizing antibodies.
Subsequently at day 34, the Y144 deletion emerged and persisted until day 106. It is in one of the recurrent deletion regions in neutralizing antibodies that are associated with neutralizing antibody escape.
Interestingly as the virus persisted, the E484K mutation was replaced by mutations at site
s in the receptor binding domain that were associated with resistance to class 1, 2 and 3 neutralizing antibodies.
Numerous other research reports document prolonged infections in patients with immunosuppressed patients, such as those with organ transplants. Most, however, were resolved in about one month. None-the-less, many showed intra-host evolution of the SARS-CoV-2 virus that often is characterized by mutations in the spike glycoprotein. https://www.nature.com/articles/s41586-021-03291-y
As a result of the SARS-CoV-2 virus persisting longer in HIV or other immunocompromised patients than in otherwise healthy people, this suggests that immunocompromised populations could be a long-term source of transmission, as well as of viral mutation.
Importantly this could reprioritize the need to vaccinate and treat immunocompromised patients early against COVID-19, as one way to slow the emergence of new variants.
The research was part of a 300-person study documenting the effect of the SARS-CoV-2 virus on HIV patients.
The female patient in her late 30s from the KwaZulu province of South Africa, had an advanced stage of HIV and had failed antiretroviral treatment. She had received neither clinically-induced immunosuppression nor neutralizing antibody-based treatment for COVID-19.
The patient was hospitalized September 2020 after experiencing sore throat, cough, and dyspnoea 12 days earlier. She also had chronic asthma (treated with inhaled budesonide and salbutamol) and in 2006 experienced one episode of tuberculosis. Treatment was a six-day course of dexamethasome and oxygen (via face mask). After nine days, she was discharged.
The study team reported the patient was asymptomatic on day 34, but complained of chest tightness on day 71. A chest X-ray showed non-specific perihilar infiltrates, so she was treated as an outpatient for Pneumocystis jiroveci pneumonia. On day 106 she was tired, and on day 190 she was asymptomatic again. At that point, her antiretroviral medication was changed a fixed-dose combination of tenofovir, lamivudine, and dolutegravir. On day 206, she achieved HIV viral load suppression.
Significantly throughout all this, her PCR tests were always positive for the SARS-CoV-2 virus.
Clinical data indicates she carried mutations seen in both the UK strain (now dubbed Alpha) and South Africa strain (dubbed Beta) of the virus.
It was reported that as of the most recent posting (May 2021), Health Department of the KwaZulu-Natal province of South Africa said the province accounted for 20% of all cases of COVID-19 ie the second-highest incidence rate in the nation, and the fourth highest in terms of COVID-19-related deaths.
The incidence rate is increasing as the cooler autumn months begin in the southern hemisphere.
It should also be noted that South Africa has the largest HIV program in the world. In 2019, approximately 14% of the South African population was living with HIV and nearly 20% of those age 15 to 49 years according to Statistics South Africa. KwaZula-Natal typically is mentioned as the hardest-hit province.
The study team concluded, “If persistent infection does occur more frequently in the context of HIV, it may provide justification for prioritizing people living with HIV for COVID-19 vaccination.”
It was also reported that a presentation at this year's European Congress on Clinical Microbiology & Infectious Diseases (ECCMID), held online this year, will discuss the growing evidence that the beta SARS-CoV-2 variant first identified in South Africa is leading to more severe disease in people living with HIV, and that failure to clear SARS-CoV-2 infection in a patient with advanced HIV creates conditions that can lead to evolution of dangerous mutations in SARS-CoV-2. https://www.eccmid.org/
Accordingly the control of HIV with antiretroviral therapy could be the key to preventing such evolution of SARS-CoV-2 in patients with advanced HIV, since clearance of the virus is compromised if HIV is allowed to replicate for a long time and results in major damage to the immune system.
Dr Alex Sigal from the Africa Health Research Institute, KwaZulu-Natal, South Africa, and Max Planck Institute for Infection Biology, Berlin, Germany explained during the presentation at ECCMID21, "Evolved mutations lead to escape from neutralization, which means antibodies made as a result of previous natural infection or vaccination would work less well to protect you from a new infection. SARS-CoV-2 may mutate extensively within one person if infection persists."
Dr Sigal will also present the case study of a patient with advanced HIV who, despite having only mild COVID-19 illness, tested SARS-CoV-2 positive for 216 days. Genomic sequencing revealed shifts in the patient's SARS-CoV-2 viral population over time, involving multiple mutations at key sites including the spike protein domain which SARS-CoV-2 uses to enter human cells. The evolved virus was tested and shown to have variant-like properties in terms of its ability to escape antibodies.
Dr Sigal explained, "Such findings underline the need to make sure everyone living with HIV has appropriate treatment. If not, it is possible that potentially more potent variants than the ones circulating now could emerge from people whose immune systems are severely damaged.”
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