All 54 COVID-19 patients who underwent cardiopulmonary resuscitation (CPR) in a Michigan hospital died, leading to questions about the risks and benefits of performing a procedure that exposes healthcare personnel to the coronavirus amid limited supplies of personal protective equipment (PPE), according to a news report from the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota.
The findings, published in a research letter in JAMA Internal Medicine, found that 52 of 54 patients who experienced cardiac arrest from March 15 to April 3 (96.3 percent) had non-shockable rhythms, 44 (81.5 percent) with pulseless cardiac electrical activity, and 8 (14.8 percent) with asystole (flatlining). Non-shockable rhythms are those in which the use of defibrillation is highly unlikely to restore a normal heartbeat.
Two patients (3.7 percent) had pulseless ventricular tachycardia (an abnormally fast heart rhythm). CPR achieved a return of spontaneous circulation (ROSC) in 29 patients (53.7 percent) after a median of 8 minutes. Of the 29 patients, 15 (51.7 percent) had their code status changed to do not resuscitate, and 14 patients (48.3 percent) were recoded and underwent additional CPR; all died.
Median time from hospital admission to cardiac arrest was 8 days, and median duration of CPR was 10 minutes. At cardiac arrest, 43 patients (79.6 percent) were receiving mechanical ventilation, 18 (33.3 percent) were on dialysis, and 25 (46.3 percent) required vasopressor drugs to treat low blood pressure.
Median patient age was 61.5 years, 33 of 54 patients (61.1 percent) were men, 36 (66.7 percent) were black, and many had obesity (median body mass index was 33 kg/m2), high blood pressure (42 patients, 77.8 percent), diabetes (50 [55.6 percent]), and high cholesterol (27 [50.0 percent]).
Model shows how COVID-19 could lead to runaway inflammation
A study from the University of Pittsburgh School of Medicine and Cedars-Sinai addresses a mystery first raised in March: Why do some people with COVID-19 develop severe inflammation? The research shows how the molecular structure and sequence of the SARS-CoV-2 spike protein – part of the virus that causes COVID-19 – could be behind the inflammatory syndrome cropping up in infected patients, according to a press release.
The study, published in the Proceedings of the National Academy of Sciences, uses computational modeling to zero in on a part of the SARS-CoV-2 spike protein that may act as a “superantigen,” kicking the immune system into overdrive as in toxic shock syndrome – a rare, life-threatening complication of bacterial infections.
Symptoms of a newly identified condition in pediatric COVID-19 patients, known as Multisystem Inflammatory Syndrome in Children (MIS-C), include persistent fever and severe inflammation that can affect a host of bodily systems. While rare, the syndrome can be serious or even fatal.
The research team created a computer model of the interaction between the SARS-CoV-2 viral spike protein and the receptors on human T cells, the foot soldiers of the immune system. Under normal circumstances, T cells help the body fight off infection, but when these cells are activated in abnormally large quantities, as is the case with superantigens, they produce massive amounts of inflammatory cytokines – small proteins involved in immune system signaling – in what’s known as a cytokine storm.
Using this computer model, the team was able to see that a specific region on the spike protein with superantigenic features interacts with T cells. Then they compared this region to a bacterial protein that causes toxic shock syndrome and found striking similarities in both sequence and structure. Importantly, the proposed SARS-CoV-2 superantigen showed a high affinity for binding T cell receptors – the first step toward touching off a runaway immune response. By finding protein-level similarities between SARS-CoV-2 and the bacterial structure that causes toxic shock syndrome, the researchers said they may have opened up new avenues for treating not only MIS-C patients, but also adults with COVID-19 infection experiencing cytokine storm.
Scientists discover genetic and immunologic underpinnings of some cases of severe COVID-19
New findings by scientists at the National Institutes of Health (NIH) and their collaborators help explain why some people with COVID-19 develop severe disease, according to a press release from the NIH. The findings also may provide the first molecular explanation for why more men than women die from COVID-19.
The researchers found that more than 10 percent of people who develop severe COVID-19 have misguided antibodies – autoantibodies – that attack the immune system rather than the virus that causes the disease. Another 3.5 percent or more of people who develop severe COVID-19 carry a specific kind of genetic mutation that impacts immunity. Consequently, both groups lack effective immune responses that depend on type I interferon, a set of 17 proteins crucial for protecting cells and the body from viruses. Whether these proteins have been neutralized by autoantibodies or – because of a faulty gene – were produced in insufficient amounts or induced an inadequate antiviral response, their absence appears to be a commonality among a subgroup of people who suffer from life-threatening COVID-19 pneumonia.
These findings are the first published results from the COVID Human Genetic Effort, an international project spanning more than 50 genetic sequencing hubs and hundreds of hospitals. The effort is co-led by Helen Su, MD, PhD, a senior investigator at the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH; and Jean-Laurent Casanova, MD, PhD, head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University in New York.
The wide variation in the severity of disease caused by SARS-CoV-2, the virus behind COVID-19, has puzzled scientists and clinicians. SARS-CoV-2 can cause anything from a symptom-free infection to death, with many different outcomes in between. Since February 2020, Su and Casanova and their collaborators have enrolled thousands of COVID-19 patients to find out whether a genetic factor drives these disparate clinical outcomes.
The researchers discovered that among nearly 660 people with severe COVID-19, a significant number carried rare genetic variants in 13 genes known to be critical in the body’s defense against influenza virus, and more than 3.5 percent were completely missing a functioning gene. Further experiments showed that immune cells from those 3.5 percent did not produce any detectable type I interferons in response to SARS-CoV-2.
Examining nearly 1,000 patients with life-threatening COVID-19 pneumonia, the researchers also found that more than 10 percent had autoantibodies against interferons at the onset of their infection, and 95 percent of those patients were men. Biochemical experiments confirmed that the autoantibodies block the activity of interferon type I.
Stroke patients with COVID-19 have increased inflammation, stroke severity and death
Stroke patients who also have COVID-19 showed increased systemic inflammation, a more serious stroke severity and a much higher rate of death, compared to stroke patients who did not have COVID-19, according to University of Alabama at Birmingham (UAB) research led by Chen Lin, MD, an assistant professor in the UAB Department of Neurology.
The research, published in Brain, Behavior & Immunity – Health, is a retrospective, observational, cross-sectional study of 60 ischemic stroke patients admitted to UAB Hospital between late March and early May 2020. Ischemic stroke occurs when a blood vessel for the brain is blocked by a clot, depriving some brain tissue of oxygen. All patients were tested for COVID-19 at admission.
The UAB researchers mined electronic medical records of confirmed stroke cases for information on age, gender and race; clinical variables; laboratory data, including complete blood counts, blood chemistry and coagulation tests; and outcomes, including death, length of hospital stay and condition at discharge.
The ratio of the number of neutrophils to the number of lymphocytes, or the NLR, as calculated from blood count data, served as an index of the systemic inflammatory response. While other researchers have associated NLR with COVID-19 disease severity, refractory disease and even as an independent factor for mortality, “our study is the first to associate the NLR in patients with COVID-19 and ischemic stroke and stroke severity,” Lin said. Of the 60 hospitalized patients with acute systemic stroke, nine were positive for a COVID-19 infection.
The UAB research had four major findings. First, patients who were positive for COVID-19 presented with a more severe neurological deficit at admission, as measured by the National Institutes of Health (NIH) Stroke Scale, or NIHSS, score, which averaged 18.4. Second, all patients with an NIHSS score higher than 4 – including uninfected patients – had a significantly higher NLR than those with lower scores. The NIHSS is used to predict lesion size and gauge stroke severity. Third, patients with COVID-19 had an increased inflammatory response, including significantly higher neutrophil counts, lower lymphocyte counts and an increased NLR, compared with uninfected patients. Finally, stroke patients with COVID-19 had a significantly higher mortality rate – 44.4 percent, versus 7.6 percent for uninfected stroke patients.
Measures to prevent spread of SARS-CoV-2 may also mitigate flu
Following widespread adoption of community mitigation measures to reduce transmission of SARS-CoV-2, the percentage of U.S. respiratory specimens that tested positive for influenza decreased from more than 20 percent to 2.3 percent and has remained at historically low inter-seasonal levels, the Centers for Disease Control and Prevention (CDC) reported in its Morbidity and Mortality Weekly Report.
Data from Southern Hemisphere countries also showed little influenza activity, the CDC said.
“These findings suggest that certain community mitigation measures might be useful adjuncts to influenza vaccination during influenza seasons, particularly for populations at highest risk for developing severe disease or complications,” the CDC said.
After recognition of widespread community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by mid- to late-February 2020, indicators of influenza activity began to decline in the Northern Hemisphere, the CDC reported.
Data from clinical laboratories in the United States showed a 61 percent decrease in the number of specimens submitted (from a median of 49,696 per week during September 29, 2019–February 29, 2020, to 19,537 during March 1–May 16, 2020) and a 98 percent decrease in influenza activity as measured by the percentage of submitted specimens testing positive (from a median of 19.34 percent to 0.33 percent). Inter-seasonal circulation of influenza in the United States (May 17–August 8, 2020) is currently at historical lows: a median of 0.20 percent positive tests in 2020, compared with 2.35 percent in 2019, 1.04 percent in 2018 and 2.36 percent in 2017, the CDC said.
During the period of April–July 2020, only 33 influenza positive test results were detected among 60,031 specimens tested in Australia, 12 among 21,178 specimens tested in Chile, and six among 2,098 specimens tested in South Africa, for a total of 51 influenza positive specimens among 83,307 tested in those countries.
“Although causality cannot be inferred from these ecological comparisons, the consistent trends over time and place are compelling and biologically plausible,” the CDC said.
