At Last, A Great News About Covid-19 In-Hospital Mortality
It’s dropping but younger age or fewer comorbidities are not the only reasons.
At the start of the pandemic, Covid-19 is feared for its high mortality, especially among the seniors and people with comorbidities whose immune systems are less apt to deal with the novel coronavirus. What about now; how lethal is Covid-19?
Covid-19 mortality has indeed been decreasing in the general population and hospitalized patients. The former is largely due to increased testing that identifies a higher proportion of milder cases, particularly in younger people. However, the latter concerns those who present symptoms bad enough to get hospitalized, and now fare better than they would a few months back. Why?
Evidence for falling in-hospital death rates
Leora I. Horwitz, MD, associate professor, and research center director at the New York University Grossman School of Medicine, and co-workers just had their new study, “Trends in Covid-19 risk-adjusted mortality rates in a single health system,” published in the Journal of Hospital Medicine a few days ago. This study analyzed health records of over 5000 Covid-19 hospitalizations in New York City from March to August, and calculated the monthly in-hospital mortality rate.
“Adjusted mortality dropped each month, from 25.6% in March to 7.6% in August,” the authors presented their results. Adjusted means it’s controlled for potential confounders, which in this study were age, sex, race and ethnicity, body mass index, smoking history, and comorbidities (i.e., hypertension, hyperlipidemia, diabetes, cancer, and diseases of the heart, kidney, and lung). Thus, we can say that results are independent and not explained by these confounding factors.
In the unadjusted model, the mortality rates decreased even more. This indicates that the confounding factors were partly, but not fully, responsible for the declining in-hospital death rates to some extent (see figure).
One notably limitation of this study is a geographical restriction based on New York only. Another caveat, the authors pointed out, is that overlooked confounding variables may be present. For instance, seniors hospitalized early in the pandemic might have been frailer compared to recent months. But this is unlikely given that mortality rates dropped across all age groups.
While the declining Covid-19 mortality is great news, the death rate “is still higher than many infectious diseases, including the flu,” Prof. Horwitz said. “It still has the potential to be very harmful in terms of long-term consequences for many people.” The Covid-19 long-haulers that affect one in ten patients are a stark warning of this. “I do think this is good news, but it does not make the coronavirus a benign illness,” she added.
While the declining Covid-19 mortality is great news, the death rate “is still higher than many infectious diseases, including the flu.”
Another positive report is from a pre-print (not peer-reviewed yet) study that examined hospital data of 14,958 Covid-19 patients from March to June in England. Results, adjusted for confounders, also revealed a gradual decline in Covid-19 mortality. “As a linear trend from the first week of April, adjusted mortality risk decreased by 11.2% per week in HDU [high intensive unit], and 9.0% in ICU [intensive care unit],” the authors stated.
All in all, we have data showing the dropping in-hospital Covid-19 mortality in New York and England. And studies showed that this not explained by confounders like younger age or fewer comorbidities. So what are the actual reasons?
Reasons for the falling in-hospital death rates
1. Improved clinical practices
We have increased our understanding of Covid-19 unprecedentedly, with over 60,000 published research papers to date. One breakthrough is the cheap and widely available corticosteroid called dexamethasone that has been shown, in the RECOVERY trial, to reduce death rates of Covid-19 patients on ventilators and supplemental oxygen.
Dexamethasone works well because it stops two phases of inflammation — i.e., the vasodilation and migration of immune cells. In contrast, nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or aspirin only inhibit the vasodilation phase. More details can be found here:
Biology of Dexamethasone: The First Lifesaving Drug for Covid-19
How does it work; how does it fare against other drugs and diseases; its side effects, immunosuppression concerns, and…
Science communications and protocols to manage breathing difficulties have also improved. Doctors now better understand and share information about when and how ventilators should be used and when proning is suitable. Hospitals are also less overwhelmed now, so each patient is better cared for.
“None of our hospitals were flooded,” said Monica Gandhi, MD, professor of medicine, and director of the Gladstone Center for AIDS Research at the University of California. “You have enough nurses. You’re only doing your job, not other people’s jobs. You’re not running around. Rooms are ready. You have PPE [personal protective equipment]. It is the chaos that can occur when hospitals are not ready that absolutely contributes to mortality.”
“As a linear trend from the first week of April, adjusted mortality risk decreased by 11.2% per week in HDU [high intensive unit], and 9.0% in ICU [intensive care unit].”
2. Lower viral inoculum
Another reason, Prof. Horwitz and her team speculated, is the “lower viral load exposure from increased mask-wearing and social distancing.” While social distancing is the top means to counter the novel SARS-CoV-2, mask-wearing brings massive advantages too. Masks attenuate the dose of viruses inhaled, studies show, which has led to a higher prevalence of symptomless and less severe cases than a few months ago.
Besides, masks keep the nose warm, which helps the nasal immune system to function more optimally. Also, winter viruses like rhinovirus (that cause the common cold) and coronaviruses prefer to replicate in cold noses.
If Coronavirus Thrive in Cold Noses, Then Keeping It Warm May Help
An unconventional view of facemasks.
3. Less virulent coronavirus strain?
“It is also possible that earlier periods had a more virulent circulating strain,” Prof. Horwitz and others initially wrote in their pre-print. But this theory is no longer mentioned in her new peer-reviewed published paper.
While many strains are out there, only the G614 strain (that arose from the D614G mutation, where the amino acid D at position 614 mutated to G) dominates. This strain is infamous for its increased infectivity in cultured human cells in the lab, which may or may not translate to human settings. But studies comparing Covid-19 patients infected with the G614 strain vs. the previous strain did not find any mortality differences. This means that the current circulating SARS-CoV-2 strain retains its virulence.
The only evidence on a less lethal SARS-CoV-2 is the Δ382 strain with 382 nucleotides deletion in its genome. This deletion includes the gene that codes for the viral ORF8 protein responsible for evading the host immune system. But as a result of decreased virulence without any increase in transmissibility or infectivity, the Δ382 strain has gone extinct:
Why A Milder Variant of Coronavirus (Δ382) Just Disappeared
Decreased virulence but no boost in transmissibility might have led to its demise.
Covid-19 mortality in the general population and in-hospital patients have been decreasing over time. While the former is mostly due to increased testing that diagnosed more cases of mild diseases and from the younger age groups, the latter is not fully explained by age or comorbidities alone.
Rather, improved clinical care and public health practices such as social distancing and mask-wearing — but not a less fatal virus strain — have most likely helped reduce the high in-hospital Covid-19 mortality to a great extent. Patients are now less likely to die than in previous months, which is wonderful news, although it’s also vital to note that Covid-19 is still not a benign disease.