The Truth About COVID, HIV, and Cytokine 'Storms'

The difference between a mild, sometimes unnoticeable, case of COVID-19 and a deadly one may be an overactive immune system. Earlier this year, The Lancet published an editorial calling on frontline workers to consider that cytokine storm syndromes and immunosuppression could be at play in the more severe COVID-19 cases.

A cytokine storm occurs when the immune system releases too many cytokines into the blood too quickly. According to the National Cancer Institute, cytokines play an important role in normal immune responses, but too many can create inflammation that becomes harmful or even deadly.   

Charles Dela Cruz, a pulmonologist at Yale School of Medicine who is researching COVID-19, explained to The Scientist that the immune system mounts an inflammatory response against an invading virus. However, in some people the response is “too much and hyper-inflames, causing a lot of side effects in terms of tissue damage and organ failure.” 

Potential treatments, which may attempt to suppress the immune system response to avoid its overreaction, also run the risk of opening someone up to opportunistic infections, which could be just as deadly, so TheLancet urges caution in this approach.

Cytokine storms can also occur in those with untreated HIV. A 2020 study in the journal BMC Medicine noted a connection between cytokines, immune cell dynamics, and the capacity for the HIV virus to replicate in those with hyper-acute HIV. Those who had the cytokine storms also had the more intense HIV, so researchers concluded “viral virulence” had a role in driving the out-of-control inflammatory response.

Echoing previous studies indicating early treatment has long-term benefits, the researchers also learned that while starting antiretroviral treatment did calm the cytokine storm, it did not reverse HIV-induced immune changes. In other words, getting on treatment early and staying on it can help prevent you from facing long-term medical issues.

The investigational HIV medication leronlimab (PRO 140) is still a year way from approval to treat HIV. But since it blocks cytokines it has been granted rushed approval for clinical trials (and use in New York hospitals) to see if it can fight COVID-19’s deadly symptoms.

That both COVID-19 and HIV can cause similar runaway immune systems that turn on one’s own body, obviously raises the question of whether people living with HIV are at higher risk for contracting COVID-19 or are more likely to experience severe illnesses from the novel coronavirus. After all, a drug to treat HIV has been most useful in treating COVID-19.

Although there has not been a great deal of research on those with both HIV and COVID-19, the data available has been completely straightforward.

In March, a pathologist at Wuhan University, an institution in the Chinese city where the novel coronavirus was first detected, reported that there had been no cases of COVID-19 among 199 HIV-positive people who were taking ritonavir-boosted lopinavir or integrase inhibitors, and eight COVID-19 cases in a group of 947 individuals taking nucleoside reverse transcriptase inhibitors plus non-nucleoside reverse transcriptase inhibitors.

That finding drove some speculation that people with HIV who were on treatment might be resistant to COVID-19. Scientists are currently running trials on using the antiretroviral medication tenofovir as a potential pre-exposure prophylaxis for the novel coronavirus (essentially PrEP for COVID-19). Still, many of those who serve people living with HIV have suggested that poz folks are at higher risk of contracting COVID-19 as well as having poor health outcomes once they do.

In May, a Spanish study in TheLancet concluded that those living with HIV “seemed to be similarly affected by SARS-CoV-2 compared with the general population in terms of clinical presentation, but we can only speculate about the incidence. Notably, comorbidities were risk factors for COVID-19 diagnosis in this population. By contrast, there was no evidence that any specific antiretroviral drug affected COVID-19 severity.”

In other words, this study found that there was no difference in the severity of COVID-19 for HIV-positive people regardless of what HIV treatment they were on before contracting the disease. But the researchers did find that 63 percent of HIV-positive people who acquired COVID-19 had at least one comorbidity — mostly high blood pressure or diabetes — compared to only 38 percent of people with HIV who did not get COVID-19.

The study also found that low CD4 counts didn’t seem to impact one’s risk of contracting COVID-19, but “immunosuppression did seem to affect disease severity” so those with low CD4 counts could have worse symptoms, longer recoveries, and more significant side effects (including death).

Although the research on COVID-19 and people living with HIV is still in its infancy, there is some indication that those at highest risk of contracting the coronavirus are those who are not on treatment and have a second factor (ill, immune suppressed, or with a comorbidity). Poz folks who are also over 65 or those of any age have other chronic or acute illnesses — particularly those impacting their lungs and heart health — should be extra cautious, wear masks, social distance, and avoid contact with someone who might be ill, even if they are asymptomatic.