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Infectious Disease and “Lluita contra la SIDA Foundation”
Hospital Universitari Germans Trias I Pujol
Josep M. Llibre, MD, PhD, has disclosed that he has served on an advisory board or panel and as a consultant for Gilead Sciences, Janssen, MSD, and ViiV.
COVID-19 at CROI 2020
People living with HIV (PLWH) are scared of COVID-19, the disease caused by the novel coronavirus SARS-CoV-2. Phone calls asking what to do in the middle of this pandemic are pouring into our quarantined hospitals in Spain, with the outpatient HIV clinic offices currently closed. The impact of the pandemic was strongly felt at CROI 2020, where many clinicians from abroad, including myself, were facing the challenge of not being able to attend in person because of at-home healthcare system needs and government-mandated travel restrictions. That situation turned out to be universal when the conference planning committee made the difficult decision to transition the entire conference to a virtual meeting. The topic of COVID-19 also became an important theme of the meeting itself, with a special session added to address the growing crisis. Although the session was timely and informative, the rapidly changing nature of this pandemic renders the information relayed during the session now nearly obsolete. Therefore, in this ClinicalThought commentary, I would like to address the latest COVID-19 situation in Spain, in particular what we have seen related to infection and disease risk, and what it means for people living with HIV (PLWH).
HIV and COVID-19 Risk
There are basically 3 categories of patients with HIV to consider in terms of COVID-19 risk: 1) those with unsuppressed HIV viremia, 2) those with suppressed HIV viremia but immune discordance (generally defined as having a CD4+ cell count < 350 cells/mm3 despite suppressed HIV-1 RNA), and 3) those with suppressed HIV viremia and acceptable immune reconstitution (CD4+ cell count > 350 cells/mm3).
In Spain, we have sadly surpassed 100,000 cases of COVID-19 at the time of this writing (April 1, 2020), with a mortality rate of 8.9% among those diagnosed. Quite unexpectedly, we have seen that PLWH are not at increased risk of acquiring COVID-19 or of progressing to acute respiratory distress syndrome (ARDS) once infected, across the 3 risk classes defined above. For reasons that are as yet unknown, it appears that their risk may even be lower than that of the general population.
It is also not yet known whether HIV PIs could effectively inhibit the 3-chymotrypsin-like and papain-like proteases of SARS-CoV-2. Nevertheless, many PLWH are receiving ART regimens based on INSTIs rather than PIs. Therefore, potential protection from the use of HIV PIs does not seem to be a plausible explanation for the apparent decreased risk.
Viral Pathogenesis of Coronaviruses vs HIV
The absence of an increased risk for COVID-19 among PLWH is surprising because dysregulation of the immune response, particularly by T lymphocytes, seems to be highly involved in the pathologic process of COVID-19, and lymphocytopenia is a well identified risk factor for ARDS and death among individuals with COVID-19. Viral host receptors are important determinants of viral pathogenicity, tissue tropism, and host range. The key functional host receptors used by human pathogenic coronavirus surface structural spike glycoprotein (S) include angiotensin-converting enzyme 2, and the viral machinery used during cleavage and binding at the cell surface seems to be independent of the CD4 receptor and, therefore, distinct from HIV. Another difference between coronaviruses and HIV relates to viral assembly and budding. With HIV, assembly and budding take place at or near the plasma membrane, whereas coronaviruses carry out these processes at the endoplasmic reticulum.
Therefore, currently available data on host cell entry mechanisms and the intracellular pathways harnessed by each virus suggest that HIV and coronavirus do not show cooperative pathogenesis. This information coupled with early observations suggesting that HIV infection is not associated with increased risk for SARS-CoV-2 infection or for more severe COVID-19 manifestations is very reassuring for our PLWH. This is particularly true because previous studies showing that human APOBEC3G, a member of the APOBEC3 cytidine deaminase family, was able to associate with both HIV and SARS-CoV structural proteins through a potentially similar, RNA-mediated mechanism raised concerns for potential shared pathogenesis.
Organ Transplantation and COVID-19 Vulnerability
Among populations with immune suppression in Spain, SARS-CoV-2 has hit solid organ transplant recipients very hard, particularly kidney transplant recipients. Ironically, mycophenolic acid, an antirejection drug commonly used by these patients, exhibits antiviral activity in vitro against several viruses, including hepatitis B virus, hepatitis C virus, and arboviruses, and was identified as a potential anti-MERS-CoV drug. However, renal transplant recipients who were receiving maintenance mycophenolate mofetil therapy also developed severe and sometimes fatal MERS. Therefore, it seems clear that organ transplant recipients are particularly sensitive to coronaviruses.
People actively receiving chemotherapy for neoplasms are also among those at higher COVID-19 risk. By contrast, people receiving antirheumatic drugs, including disease-modifying agents and biologics, do not appear to be at increased risk for COVID-19. Because these immunomodulators are increasingly being used to treat many rheumatologic, skin, gastrointestinal, and respiratory conditions, there was substantial concern for a high rate of COVID-19 among patients receiving those treatments, but so far this has not been the case.
Lessons for the Future
The information we are learning at this time is highly relevant not only for the current COVID-19 pandemic but also for future anticipated coronavirus pandemics.
It is worth highlighting that the infectious disease community was warned in 2007 by Vincent C. C. Cheng that coronaviruses are well known to undergo genetic recombination, creating the potential for emergence of new genotypes and outbreaks, that this potential represented a time bomb for the re-emergence of new SARS epidemics, and that the need for preparedness should not be ignored. A visionary. We would probably be doing better today if we had paid more attention to his premonitory words.
What specific concerns do you have related to the health and safety of your PLWH during the COVID-19 pandemic? What concerns and questions have your patients expressed and how are you counseling them? Please share your thoughts in the comments box and let us know how your PLWH are dealing with the COVID-19 pandemic in your countries and clinics.