An illustrated model of the novel coronavirus. Image: CDC/Unsplash
- Many calls to protect immunocompromised patients have missed a crucial public health point: by protecting people with weakened immune systems, we all protect ourselves.
- The creation of variants is driven by the amount of replicating virus in existence. Whether evolutionary branching eventually sets in is a product of viral fitness, selection pressures, and host susceptibility.
- When a severely immunocompromised person is infected with the novel coronavirus, large amounts of virus can replicate for weeks or even months.
As the omicron wave wanes, people across the United States are cheering for a reprieve from a virus that has killed nearly a million Americans and hospitalized millions more. But as recent articles in the New York Times, Atlantic, and other outlets have pointed out, the threat of COVID-19 still looms over millions of Americans with compromised immune systems. As mask mandates expire and social distancing measures are reduced, cancer patients receiving chemotherapy, patients on aggressive immunosuppressive regimens, transplant recipients and many others at high risk of severe COVID-19 continue to live in fear.
And their fear is well founded.
Even after vaccination, severely immunocompromised people are at substantial risk. For example, when researchers measured the mortality of fully vaccinated solid organ recipients, they found that, of those who suffered breakthrough infections, nearly one in 10 died. (Notably, this analysis predates the widespread use of useful boosters.)
But many of the calls to protect immunocompromised patients have missed a crucial public health point: protecting them is not only an important issue of health equity and social justice, it is an essential part of efforts to to prevent the rise of new variants of coronavirus. Simply put, by protecting people with weakened immune systems, we are all protecting ourselves.
The creation of variants is driven by the amount of replicating virus in existence. Whether evolutionary branching eventually sets in is a product of viral fitness, selection pressures, and host susceptibility. This equation explains why the most immunocompromised among us are so critical to preventing the rise of new mutations. When a severely immunocompromised person is infected with the novel coronavirus, large amounts of virus can replicate for weeks or even months. And if natural immune responses and therapeutic treatments fail, this uncontrolled viral replication can lead to the creation of mutant strains. Due to high viral loads, variants can easily spread to other susceptible individuals if enhanced isolation precautions are not strictly followed.
Careful case reports confirm this reality. A case study of a patient with leukemia and acquired immune deficiency who caught COVID-19 found that she shed the virus for 70 days and the virus evolved significantly inside her during this period. Similar reports have found evidence of intra-host viral evolution of the SARS-CoV-2 virus in transplant recipients and in patients with autoimmune diseases requiring aggressive immunosuppression. Patients on treatment regimens designed to suppress B cells, the cells that produce our natural antibodies, appear to be at particularly high risk for long-term infection and accumulation of viral mutations.
If not used with care, antiviral and antibody therapies, which many experts believe are even more essential for curing COVID-19 in immunocompromised hosts, risk compounding the problem by exerting evolutionary pressure that selects resistant strains. Unfortunately, there are few, if any, high-quality studies that physicians can use as a guide to maximizing the benefits of these therapies for immunocompromised patients while minimizing public health risks.
The reality of this concern was demonstrated by British researchers when they sequenced viral samples from a COVID-19 lymphoma patient who had been treated with the antiviral remdesivir and convalescent plasma. Over time, the researchers found evidence that the treatment selected for antibody-resistant mutations in the plasma. This model has since been replicated by researchers at the University of Sydney, who published their findings last week in correspondence in the New England Journal of Medicine. They identified eight patients with sustained SARS-CoV-2 infections who were treated with sotrovimab, the only recommended monoclonal antibody with retained efficacy against the omicron variant. Fifty percent of people treated with the antibody developed mutations that blocked the drug’s effectiveness.
These are not new principles in microbiology. Infectious disease experts have long known that TB patients who stop their treatments before the infection is cleared are at higher risk of developing drug-resistant strains. Similarly, HIV-positive patients who do not consistently adhere to treatment regimens are more likely to develop antiretroviral-resistant strains of the virus. Lawrence Corey, an expert in virology and immunology at the Fred Hutchinson Cancer Research Center, and colleagues summarized the phenomenon in a recent commentary on COVID-19 variants: “Prolonged viral replication in the context of an inadequate immune response facilitates the emergence of immune pressure to escape mutations.
Fortunately, we have ways to protect immunocompromised groups and to fight against the emergence of new variants. In the absence of widespread masking, access to the most effective masks, namely N-95 respirators, will be increasingly important for the “one-way” protection of immunocompromised people. So will other non-pharmacological interventions, such as quality indoor ventilation, rapid antigen testing for close contacts, and maintaining physical distancing options in school and work environments. Fourth doses of vaccines and increased use of long-acting antibody therapy can add additional layers of protection. And for those infected, meeting personalized test-based criteria for ending isolation precautions can help them avoid transmitting potential new variants to others.
However, patients with cancer, transplants and autoimmune diseases are not the only immunocompromised patients. It is estimated that 38 million people worldwide are living with HIV. Although treatment efforts have made huge strides, only three out of four patients were on antiretroviral therapy in 2020, according to UNAIDS, and two-thirds of patients completely cleared the virus.
A case report released by the Centers for Disease Control and Prevention last October demonstrated that patients with uncontrolled HIV/AIDS are also at increased risk of variant generation. In one of these patients, SARS-CoV-2 was able to replicate and mutate for weeks, eventually acquiring mutations associated with resistance to immune knockout.
But the case report also revealed a key to preventing the emergence of new variants in HIV patients: After the patient started antiretroviral therapy, her HIV viral load dropped to almost undetectable levels and, shortly soon after, she also cleared her SARS-CoV-2. infection. The result suggests that the public health strategy of “treat as prevention” – treating HIV to also block transmission via viral load suppression – may be doubly important for HIV patients during the pandemic as it can reduce damage caused by two viruses instead of one.
Strategies to minimize the risk of creating COVID-19 variants in patients with uncontrolled HIV/AIDS are very different from those they use for transplant recipients, cancer patients, and people with autoimmune diseases. immune. Unlike other groups, whose lives depend on maintaining their immunosuppression, patients with uncontrolled HIV/AIDS can reverse their immunosuppression, usually by taking just one pill once a day. The challenge for patients with uncontrolled HIV/AIDS is that many of them are disconnected from the health care system. This means that public health efforts must focus not only on medical innovation, but also on providing social support to combat the multitude of diseases that disproportionately affect people with unchecked HIV/AIDS – a combination of poverty, stigma, substance abuse, housing instability and mental illness.
As a physician who has cared for patients with COVID-19 in the clinic, hospital, and intensive care unit, I understand all too well the acute threat COVID-19 poses to immunocompromised patients. And I also understand that the mounting evidence is clear: if we care to reduce the risk of the next deadly variant of SARS-CoV-2, it is imperative that we do all we can to protect immunocompromised people. By doing what we can to save them, we could also save the world.
Michael Rose is a senior resident physician specializing in internal medicine and pediatrics at Johns Hopkins University School of Medicine and holds a degree in public health policy from the Harvard TH Chan School of Public Health.
This article was originally published on Not dark.