Credit CDC
# 7853
Since H7N9’s emergence last spring in China, researchers have been frantically trying to determine just how much of a threat this virus poses, and how best to treat patients who have been infected. Last May in EID Journal: Clinical Course & Treatment Of Four Early H7N9 Cases we began to see details on the severity of hospitalized H7N9 cases, and since that time roughly 1/3rd of all hospitalized cases have died.
While this fatality rate is less than what we’ve seen with the H5N1 virus, it remains an extraordinarily high for any influenza virus. Unknown, of course, are how many `mild’ cases that never sought hospital care and recovered on their own.
Researchers writing in The Lancet last June (see Clinical Severity Of Human H7N9 Infection) estimated that between 1500 and 27,000 symptomatic infections with avian influenza A H7N9 virus might have occurred as of the end of May, 2013. But unless and until comprehensive seroprevalence studies can be conducted, this remains unproven.
All we really know is that among the 136 cases that were identified and hospitalized, 44 died and many of those that recovered did so only after many weeks of intensive care. Those who were ill enough to be hospitalized were very ill, indeed.
Which brings us to a new study, published yesterday in the Journal of Medical Virology, that describes the laboratory findings of 39 H7N9 patients hospitalized at the First Affiliated Hospital, Zhejiang University between March and April of this year.
The full report is behind a pay wall, but their basic findings are available in their abstract.
Laboratory findings in patients with avian-origin influenza A (H7N9) virus infections
Juanwen Zhang, Ying Zhao, Yu Chen*
Briefly, these researchers found:
Hematological abnormalities
- leukopenia
- lymphopenia
- thrombocytopenia with prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT)
- elevation of D-dimer levels.
Biochemical abnormalities
- elevated serum lactate dehydrogenase (LDH)
- elevated aspartate aminotransferase (AST)
- elevated creatine kinase (CK)
- elevated alanine aminotransferase (ALT) activities,
- increased C-reactive protein (CRP) concentration,
- as well as hyponatremia, hypokalemia, hypocalcemia, hypoproteinemia, and hypoalbuminemia.
Arterial blood gas analysis
- reduced arterial oxygen (PaO2)
- reduced carbon dioxide pressures (PaCO2).
While these laboratory findings were commonly observed in the early stages of H7N9 infection, they are not pathognomonic – that is, diagnostically specific – to H7N9 infection.
Given that some of my readers may be unfamiliar with all of these lab tests, I’ve provided a few general descriptions of these tests below:
The reduced arterial blood gases (PaO2 & PaCO2) are consistent with hypoxia that would be associated with any pneumonia.
In the biochemical analysis, elevated ALT & AST are usually associated with liver damage, while LDH is an enzyme released when certain cells (typically liver, kidney, heart, or muscle) die. An elevated CPK level usually means there has been damage or stress to muscle tissue, the heart, or the brain.
Increased PT, APPT, and elevated D-dimer levels are often associated with DIC (Disseminated intravascular coagulation),a clotting disorder that can lead to serious internal and external bleeding. While sepsis is the primary cause of DIC, it can also be triggered by systemic fungal, bacterial, parasitic (malarial) or viral infections (including influenza).
Hyponatremia, hypokalemia and hypocalcemia refer to low levels of sodium, potassium, and calcium in the blood serum. Hypoproteinemia and hypoalbuminemia refer to low levels of protein and albumin in the blood.
Although a good deal depends upon the degree of deviation from the norm in these blood tests, the picture painted by this study is that these patients experienced profound systemic challenges due to their H7N9 infection, which probably helps to explain the high mortality rate.
In 2008, we looked at an analysis (see Clinical Case Review Of 26 Chinese H5N1 Patients) published in PLoS One that revealed remarkably similar laboratory findings. Of the 26 cases studied, 17 (65%) died.
Some excerpts from that study:
The prevalence of patients with abnormal haematological findings at admission [leukopenia (46%), lymphopenia (62%), and moderate thrombocytopenia (50%)] increased to 92%, 89% and 73%, respectively, during hospitalization.
<snip>
Elevated ALT, AST, creatine kinase (CK), creatine phosphokinase isoenzymes (CPK), lactic dehydrogenase (LDH), and plasma glucose concentration, and decreased albumin levels were observed in more than half of cases at admission, and developed in nearly all cases during hospitalization. Elevated creatine level was observed in 25% of cases during hospitalization. Seventeen (77%) cases developed proteinuria at a median of 9.0 days (IQR 7.0–11) after illness onset.
<snip>
All 17 fatal cases had multi-organ failure, including respiratory failure (94%), cardiac failure (71%), renal failure (27%) and 24% had disseminated intravenous coagulation.
It should be noted that late hospital treatment was the norm among these Chinese H5N1 patients, with some never receiving antivirals, even once hospitalized. The abstract of today’s H7N9 study does not provide comparable details on admissions, treatment, or outcomes.
While the recovery rate with H7N9 last spring was double that which we’ve seen over the years with H5N1, today’s study suggests that both viruses are capable of producing similar pathogenesis in humans. At least among those experiencing the most severe presentation of the illness.
We don’t currently have a vaccine against the H7N9 virus, but early treatment with antiviral medications has been associated with fewer symptoms, more rapid recovery, and a lower mortality rate. The CDC recently released antiviral guidance documentation in the event that the H7N9 manages to spread beyond China.
