Under COVID of the night

In this issue of Blood, Vijenthira and colleagues report that patients who have 2 life-threatening conditions, a hematologic malignancy and infection with the virulent microbe COVID-19, face a risk of dying that is ∼1 in 3.¹ 

Severe acute respiratory syndrome coronavirus 2 proved to be the perfect pathogen for a world unprepared. Because it is a novel virus, few people had any immunity, although some may have been spared its nastier consequences from past coronavirus infections. It spread efficiently, with a reproductive number (R0, indicating the contagiousness of the disease) between 2 and 3, meaning 1 infected person transmitted the virus to 2 or 3 others. Compare that to the R0 for the influenza pandemic of 1918, which was 2.0, or of 2009, which was 1.7.²  It proved deadly in higher numbers of people than did influenza, with a case fatality rate of ∼3% in the general populations of the United States. Our global economy and general wanderlust enabled infected hosts to spread the virus to those in immediate filial and social circles, and nearby or far-away states and countries efficiently, whereas geopolitics helped delay recognition of the seriousness of the pandemic and thwart implementation of measures to clamp it down.

Particularly vulnerable populations to COVID-19 proved to be the aged and infirm, who are more likely to have complicated comorbidities and might have an exaggerated inflammatory immune response to the virus³ ; those already at risk for adverse health outcomes based simply, and tragically, on their race⁴ ; and people with immune systems that were functionally compromised. Patients with hematologic malignancies are potentially ideal viral breeding grounds, with immune systems already corrupted and rendered at least somewhat incompetent by cancer, and by both cytotoxic and immunologic therapies which, by design, further suppress immune function. A recent study of >3000 patients hospitalized with COVID-19, of whom 100 had cancer, showed that patients with hematologic malignancies had higher COVID-19 viral loads, and that this was, in fact, associated with higher mortality rates.⁵ 

Vijenthria et al conducted a systematic review of studies published in PubMed and EMBASE databases, and reported on patients with hematologic malignancies and COVID-19 to determine risk of death and serious complications, such as intensive care unit admission and ventilation support. A total of 34 adult and 5 pediatric studies were included, comprising 3377 patients, the majority of which were descriptive cohort studies. Types of hematologic malignancies included lymphoid malignancies (∼66% of included patients), plasma cell dyscrasias (12%), myeloproliferative neoplasms (8%), acute leukemias (8%), and bone marrow failure syndromes (7%).

The pooled risk of death was 34%, higher (39%) for the 2361 inpatients, and lower (4%) for the 102 pediatric patients. Patients had about a 21% chance of requiring intensive care and 17% chance of being placed on mechanical ventilation. As expected, younger patients (<60 years) had a mortality risk almost half that of older patients (≥60 years, 25% vs 47%, P < .00001), and disparate health outcomes based on race were reinforced, with non-White patients more than twice as likely to die compared with White patients (relative rate = 2.2, P = .003). Recent receipt of anticancer therapy did not affect mortality risks, but cancer subtype may have, with risk of death highest for those with acquired bone marrow failure syndromes and acute leukemias. The study may have overestimated COVID-19–related deaths, as it was enriched by hospitalized patients, and as patients with advanced stage cancers may have died anyway from their competing risk.

I came of professional age in an era when practicing evidence-based medicine was held up as the gold standard for competent and trusted physicians. When faced with a new and poorly defined contagion, with conflicting data about its etiology, transmissibility, lethality, and prevention, and few rigorous studies providing insight into this basic information, I feel unmoored.

This systematic review provides us with data we can use in the common conversations we are now holding daily with our hematologic malignancy patients: That yes, they should continue to practice social distancing, wear masks, engage in good hand hygiene, and avoid risky infectious behaviors; that if they catch the virus, their chance of landing in an intensive care unit is 1 in 5, and of requiring mechanical ventilation is 1 in 6. In fact, their chance of dying from COVID-19 is >10 times higher than the general population. However, as we weigh the relative risks and benefits of initiating treatment of their cancers, we can rest easier that chemotherapy does not appear to increase their chances of dying from the virus. We await population-based studies to answer the question of whether our patients are also at higher risk of catching COVID-19.

The song Undercover of the Night by the Rolling Stones⁶  explores political corruption in Central and South America in the 1980s, an area of the world also hit hard by COVID-19. Similar to the virus’ path, the sinister forces of which Mick Jagger sings take people’s lives by dark of night, while the rest of us “curl up tight,” hoping that we also will not get stricken. As we await widespread implementation of an effective vaccine, our best medicine against COVID-19 is to exhort our patients to engage in preventive practices to avoid a substantial risk of dying, so that we can all walk the streets safely again one day.