Category: COVID

Categories : COVIDTags :

Cytokine Storms Were Not the Real COVID Killer After All?

On By ModernMedia

Secondary bacterial pneumonia was extremely common in patients with COVID-19, affecting almost half the patients who required support from mechanical ventilation. In a study published in the Journal of Clinical Investigation, researchers applied machine learning to medical record data and found that secondary bacterial pneumonia that does not resolve was a key driver of death in COVID patients.

Bacterial infections may even exceed death rates from the viral infection itself, according to the findings. The study’s researchers at Northwestern University Feinberg School of Medicine also found evidence that COVID does not cause a “cytokine storm,” so often believed to cause death.

“Our study highlights the importance of preventing, looking for and aggressively treating secondary bacterial pneumonia in critically ill patients with severe pneumonia, including those with COVID-19,” said senior author Benjamin Singer, MD, professor at Northwestern.

The investigators found nearly half of COVID patients develop a secondary ventilator-associated bacterial pneumonia.

“Those who were cured of their secondary pneumonia were likely to live, while those whose pneumonia did not resolve were more likely to die,” Singer said. “Our data suggested that the mortality related to the virus itself is relatively low, but other things that happen during the ICU stay, like secondary bacterial pneumonia, offset that.”

The study findings also negate the cytokine storm theory, said Singer, also a professor of Biochemistry and Molecular Genetics.

“The term ‘cytokine storm’ means an overwhelming inflammation that drives organ failure in your lungs, your kidneys, your brain and other organs,” Singer said. “If that were true, if cytokine storm were underlying the long length of stay we see in patients with COVID-19, we would expect to see frequent transitions to states that are characterised by multi-organ failure. That’s not what we saw.”

The study analysed 585 patients in the intensive care unit (ICU) at Northwestern Memorial Hospital with severe pneumonia and respiratory failure, 190 of whom had COVID. The scientists developed a new machine learning approach called CarpeDiem, which groups similar ICU patient-days into clinical states based on electronic health record data. This novel approach, which is based on the concept of daily rounds by the ICU team, allowed them to ask how complications like bacterial pneumonia impacted the course of the illness.

These patients or their surrogates consented to enrol in the Successful Clinical Response to Pneumonia Therapy (SCRIPT) study, an observational trial to identify new biomarkers and therapies for patients with severe pneumonia. As part of SCRIPT, an expert panel of ICU physicians used state-of-the-art analysis of lung samples collected as part of clinical care to diagnose and adjudicate the outcomes of secondary pneumonia events.

“The application of machine learning and artificial intelligence to clinical data can be used to develop better ways to treat diseases like COVID and to assist ICU physicians managing these patients,” said study co-first author Catherine Gao, MD.

“The importance of bacterial superinfection of the lung as a contributor to death in patients with COVID-19 has been underappreciated, because most centres have not looked for it or only look at outcomes in terms of presence or absence of bacterial superinfection, not whether treatment is successful or not,” said study co-author Richard Wunderink, MD.

The next step in the research will be to use molecular data from the study samples and integrate it with machine learning approaches to understand why some patients go on to be cured of pneumonia and some don’t. Investigators also want to expand the technique to larger datasets and use the model to make predictions that can be brought back to the bedside to improve the care of critically ill patients.

Source: Northwestern University

Categories : COVIDTags :

After COVID, Experts Advise Against Universal Masking in Healthcare

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While masking was a critical preventative measure to protect healthcare workers, patients and visitors during the COVID pandemic, infectious disease researchers argue against masking, saying that that as the pandemic dies down, the routine use of masking should be reconsidered. Previous policies over healthcare masking use against SARS-CoV-2 transmission were formulated against a background which assumed no population immunity and no countermeasures.

In editorial published in Annals of Internal Medicine, the authors argue for the discontinuation of universal COVID masking in healthcare settings as infection rates and mortality have fallen and access to testing and therapeutics is widespread, as is immunity. Universal masking is therefore no longer of benefit and its own drawbacks, such as facial irritation and hindering communication, are more of a hinderance.

In addition to difficulties faced by speakers of different languages as well as the hard of hearing, masks have a number of detrimental effects for communication. “The increase in listening effort required when masks are used in clinical encounters is associated with increased cognitive load for patients and clinicians,” the authors wrote. In addition to making clinicians’ jobs harder, they also impact the all-important clinician–patient relationship, as face masks “obscure facial expression; contribute to feelings of isolation; and negatively impact human connection, trust, and perception of empathy.”

Healthcare workers should instead adopt an approach for SARS-CoV-2 similar to that of any other endemic respiratory disease. Drawing on the experience of the COVID pandemic, they suggest a more flexible, responsive approach to masking policies. In response to future epidemics or localised outbreaks “may justify more widespread or targeted masking policies, respectively, as part of a bundled response. High-quality epidemiologic data with frequent updates and regular reevaluation are needed to inform scale-up or scale-down decisions.”

Categories : COVID VaccinesTags :

SAHPRA Reports 3rd Fatal Case of Guillain-Barré Syndrome Following Janssen Vaccination

On By ModernMedia
Gloved hand holding vial of Janssen COVID vaccine
Photo by Spencer Davis on Unsplash

The South African Health Products Regulatory Authority (SAHPRA) issued media statements on 4 August 2022 and 12 September 2022, relating to two fatal cases of Guillain-Barré syndrome (GBS) following vaccination with COVID-19 Vaccine Janssen. SAHPRA has been informed of a third fatal case of GBS following vaccination with the same vaccine.

A causality assessment of the reported case was conducted by the National Immunisation Safety Expert Committee (NISEC) using the World Health Organization’s (WHO) methodology. Following investigations, the case was classified as a vaccine product-related event. The events reported in the vaccine recipient were consistent with the case definition of GBS and no other likely cause of GBS was identified at the time of illness.

As previously communicated, GBS is a very rare but potentially severe neurological adverse event that is associated with the administration of various vaccines and other medicines and can also be triggered by some bacterial or viral infections, including SARS-CoV-2. Symptoms of GBS range from mild to severe, and may include muscle weakness, muscle pain, numbness, and tingling. In many cases, GBS resolves with no serious after-effects, but in some cases GBS can cause serious or life-threatening problems.

Regulatory authorities have previously investigated reports of GBS associated with COVID-19 vaccines. They concluded that COVID-19 Vaccine Janssen may increase the risk of GBS. GBS is therefore listed as a rare adverse event in the professional information (PI) for COVID-19 Vaccine Janssen.

Investigations and causality assessment of all reported severe adverse events following immunisation (AEFI) with all COVID-19 vaccines are ongoing. The outcomes of these investigations and causality assessments will be shared with the public as soon as they are completed.

Important points to note

  • COVID-19 vaccines have consistently been shown to prevent severe forms of disease, hospitalisation and death. Based on the currently available evidence, SAHPRA has determined that the benefits of COVID- 19 vaccination far outweigh the very low risk of severe adverse events, including GBS. The public are strongly advised not to delay COVID-19 vaccination if eligible in terms of the national vaccination programme.
  • SAHPRA urges the public to report any suspected adverse events following the use of all medicines and vaccines. Reporting can be done at a health facility or by downloading the Med Safety App (https://medsafety.sahpra.org.za/), which is available for Android and iOS phones, or by calling the COVID-19 hotline at 0800 029 999. More information regarding AEFIs reported for the COVID-19 vaccines and how to report an AEFI is available from the SAHPRA website: https://aefi-reporting.sahpra.org.za/.
  • More information regarding AEFIs reported for the COVID-19 vaccines and how to report an AEFI is available from the SAHPRA website: https://aefi-reporting.sahpra.org.za/.

Source: SAHPRA

Categories : COVIDTags :

WHO Updates SARS-CoV-2 Definitions to Reflect Omicron Dominance

On By ModernMedia
Source: Pixabay CC0

The World Health Organization (WHO) announced that it has updated its tracking system and working definitions for variants of SARS-CoV-2, to better reflect the current global variant landscape, to independently evaluate Omicron sublineages in circulation, and classify new variants more clearly when required.

Omicron variants now accounts for 98% of circulating SARS-CoV-2, and new variants will likely emerge from this genetic background. Based on its latest risk assessment [PDF], South Africa has reported a strong increase in XBB.1.5 from 1% in December 2022, to 10% in January 2023, and 76% as of the latest report from February 2023.

Based on comparisons of antigenic cross reactivity using animal sera, replication studies in experimental models of the human respiratory tract, and evidence from clinical and epidemiological studies in humans, WHO experts conclude that, compared to previous variants, Omicron represents the most divergent variant of concern (VOC) seen so far. Since its emergence, Omicron viruses have continued to evolve genetically and antigenically with an expanding range of sublineages, which so far have had all been characterised by evasion of existing population immunity and a preference to infect the upper respiratory tract (versus lower respiratory tract), as compared to pre-Omicron VOCs.

The previous system classified all Omicron sublineages as part of the Omicron VOC and was not detailed enough to compare new descendent lineages with altered phenotypes to the Omicron parent lineages (BA.1, BA.2, BA.4/BA.5). So, WHO variant tracking system will consider the classification of Omicron sublineages independently as variants under monitoring (VUMs), variants of interest (VOIs), or VOCs.

WHO is also updating the working definitions for VOCs and VOIs. The main update consists in making the VOC definition more specific, to include major SARS-CoV-2 evolutionary steps that require major public health interventions.

In addition, going forward, WHO will assign Greek labels for VOCs, and will no longer do so for VOIs.

With these changes factored in, Alpha, Beta, Gamma, Delta as well as the Omicron parent lineage (B.1.1.529) are considered previously circulating VOCs. WHO has now classified XBB.1.5 as a VOI. 

WHO emphasizes that these changes do not imply that the circulation of Omicron viruses no longer pose a threat to public health. Rather, the changes have been made in order to better identify additional or new threats over and above those posed by the current Omicron viruses in circulation.

Categories : COVID PaediatricsTags :

Common Cold may Have Conferred COVID Immunity to Children

On By ModernMedia
Young girl sneezing
Photo by Andrea Piacquadio on Unsplash

Early in the COVID pandemic, it became clear that children infected with the coronavirus rarely developed serious disease. One hypothesis has been that children already have some immunity provided by memory T cells generated by common colds. Researchers at Karolinska Institutet are now able to show that OC43, one of the coronaviruses that cause common colds, boosts the immune response to COVID. The study, which is published in PNAS, could give rise to more tailored vaccine programmes for children and adults.

After studying unique blood samples from children taken before the pandemic, Karolinska Institutet researchers have now identified memory T cells that react to cells infected with SARS-CoV-2.

This new study reinforces this hypothesis and shows that T cells previously activated by the OC43 virus can cross-react against SARS-CoV-2.

Four coronaviruses cause common colds

One of the four coronaviruses causing seasonal common cold symptoms could stimulate an immune response with T cells able to also react to cells infected with SARS-CoV-2.

“These reactions are especially strong early in life and grow much weaker as we get older,” says the study’s corresponding author Annika Karlsson, research group leader at the Department of Laboratory Medicine, Karolinska Institutet. “Our findings show how the T-cell response develops and changes over time and can guide the future monitoring and development of vaccines.”

Strong immunity at the age of two

The results indicate that the memory T-cell response to coronaviruses develops as early as the age of two. The study was based on 48 blood samples from two- and six-year-old children, and 94 samples from adults between the ages of 26 and 83. The analysis also included blood samples from 58 people who had recently recovered from COVID-19.

“Next, we’d like to do analogous studies of younger and older children, teenagers and young adults to better track how the immune response to coronaviruses develops from childhood to adulthood,” says Marion Humbert, postdoctoral researcher currently at the Department of Medicine Huddinge, Karolinska Institutet, joint first author with Anna Olofsson, doctoral student at the Department of Laboratory Medicine.

Source: Karolinska Institutet

Categories : COVID Diseases, Syndromes and ConditionsTags :

Macrophage Discovery Could Lead to Treatments for Diseases Such as Lupus and COVID

On By ModernMedia
A macrophage engulfing a yeast cell. Source: CC0

Scientistshave made an important breakthrough in understanding failures during the progression of inflammatory diseases and in doing so unearthed a potential new therapeutic target. The scientists report in Nature that an enzyme called Fumarate Hydratase is repressed in macrophages. These immune cells are already implicated in a range of diseases including Lupus, arthritis, sepsis and COVID.

Lead author Luke O’Neill, Professor of Biochemistry at Trinity said: “No-one has made a link from Fumarate Hydratase to inflammatory macrophages before and we feel that this process might be targetable to treat debilitating diseases like Lupus, which is a nasty autoimmune disease that damages several parts of the body including the skin, kidneys and joints.”

Joint first-author Christian Peace added: “We have made an important link between Fumarate Hydratase and immune proteins called cytokines that mediate inflammatory diseases. We found that when Fumarate Hydratase is repressed, RNA is released from mitochondria which can bind to key proteins ‘MDA5’ and ‘TLR7’ and trigger the release of cytokines, thereby worsening inflammation. This process could potentially be targeted therapeutically.”

Fumarate Hydratase was shown to be repressed in a model of sepsis, an often-fatal systemic inflammatory condition that can happen during bacterial and viral infections. Similarly, in blood samples from patients with Lupus, Fumarate Hydratase was dramatically decreased.

“Restoring Fumarate Hydratase in these diseases or targeting MDA5 or TLR7 therefore presents an exciting prospect for badly needed new anti-inflammatory therapies,” said Prof O’Neill.

Excitingly, this newly published work is accompanied by another publication by a group led by Professor Christian Frezza, now at the University of Cologne, and Dr Julien Prudent at the MRC Mitochondrial Biology Unit (MBU), who have made similar findings in the context of kidney cancer.

“Because the system can go wrong in certain types of cancer, the scope of any potential therapeutic target could be widened beyond inflammation,” added Prof O’Neill.

Source: Trinity College Dublin

Categories : COVIDTags :

New US Report Rekindles ‘Lab Leak’ Debate over COVID Origins

On By ModernMedia

Once again, the ‘lab leak’ theory of COVID’s origin has returned to the headlines. On Sunday, the Wall Street Journal revealed that a US Department of Energy report had determined that the origin of COVID was ” most likely” an accidental release from a laboratory, according to those who had read the report, though the assessment was with “low confidence”.

Ambassador Nicholas Burns told a US Chamber of Commerce event on Monday that China needs to “be more honest about what happened three years ago in Wuhan with the origin of the Covid-19 crisis”.

China’s foreign ministry countered that COVID’s origin “was about science and should not be politicised”.

The FBI assigned “moderate confidence” to a laboratory origin for the virus, while four other US agencies assigned a “low confidence” to a natural origin. Two others, including the CIA, remained undecided. An update on their views has been provided, apparently due to new information, but has not been made public.

To many scientists, the origin of SARS-CoV-2 has been settled as it has been traced to outbreaks in the Wuhan meat market two weeks before its first detection. A literature analysis published in PNAS concluded that the evidence overwhelmingly favoured a natural origin.

Many other scientists are not convinced by the zoonotic hypothesis. Virologist Jesse Bloom, at the Fred Hutchinson Cancer Center, said the PNAS review’s literature analysis was a good idea – but the zoonosis proponents haven’t provided much new data. “What we’ve seen is mostly reanalysis and reinterpretation of existing evidence.”

The PNAS review started out as a Lancet commission led by Jeffrey Sachs, who disbanded the task force due to a number of members with vested interests against the lab leak hypothesis. Their aim was to gather lessons learnt from the pandemic. The Lancet eventually published its own review, which concluded that there was equal probability for a laboratory or natural origin.

Even so, a continued lack of cooperation from China with international investigators has made it virtually impossible to definitively pinpoint the virus’s emergence. Ultimately, the lesson of past pandemics is that outbreaks can result from either zoonotic origins or from laboratory accidents, both of which are factors which need to be safeguarded against by humans.

Categories : Ageing COVIDTags :

COVID Deadlier than Bacterial or Viral Pneumonia for Older ICU Patients

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Source: National Cancer Institute on Unsplash

For older patients in intensive care units (ICUs), COVID is more severe than bacterial or viral pneumonia, suggests new research published in the Journal of the American Geriatrics Society.

Among 11 525 patients aged 70 years and older who were admitted to Dutch ICUs, ICU-mortality and hospital-mortality rates of patients admitted with COVID were 39.7% and 47.6%, respectively. These rates were higher than the mortality of patients admitted because of pneumonia from causes other than COVID. (ICU- and hospital-mortality rates of patients admitted with bacterial pneumonia were 19.1% and 28.8%, respectively, and with viral pneumonia were 22.7% and 31.8%, respectively). Differences persisted after adjusting for several clinical characteristics and intensive care unit occupancy rate.

“In ICU-patients aged 70 years and older, COVID is more severe – with approximately double mortality rates – compared with bacterial or viral pneumonia. Nevertheless, more than half of these older patients admitted to Dutch ICUs with COVID survived the hospital,” said corresponding author Lenneke E. M. Haas, MD, PhD, of Diakonessenhuis, in the Netherlands. “Our findings provide important additional data to include in informed goals-of-care discussions.”

Source: Wiley

Categories : COVID HospitalsTags :

Ceiling Vents Above COVID Patient Beds Provide Optimal Protection for HCWs

On By ModernMedia
Source: Martha Dominguez de Gouveia on Unsplash

Researchers have modelled the transmission of SARS-CoV-2-containing aerosol particles within an isolation room, and found the optimal layout to reduce the exposure risk for health care workers. In Physics of Fluids, Wu et al. share their findings and guidance for isolation rooms. Their work focuses on the location of the room’s air extractor (air outlet) and filtration rates, the location of the patient’s bed, and the health and safety of the health care workers (HCWs) within the area.

The researchers modelled an isolation room at the Royal Brompton Hospital in London, with the aim of finding out the optimal room layout to reduce the risk of infection for health care staff.

“We modelled the virus transport and spreading processes and considered the effect of the temperature and humidity on the virus decay,” said Fangxin Fang, of Imperial College London. “We also modelled fluid and turbulence dynamics in our study, and explored the spatial distribution of virus, velocity field, and humidity under different air exchange rates and extractor locations.”

They discovered that the area of highest risk of infection is above a patient’s bed at a height of 0.7 to 2 metres, where the highest concentration of SARS-CoV-2 virus is found. After the virus is expelled from a patient’s mouth, it gets driven vertically by buoyancy and wind forces within the room.

Based on the group’s findings, the optimal layout for an isolation room to minimise infection risk is to use a ceiling extractor with an air exchange rate of 10 air changes per hour. The study focused on an isolation room within a hospital and its numerical results are limited due to the omission of droplet evaporation and particle matters, the researchers point out.

Now, the group plans to include evaporation and particle processes in models of a standard hospital patient room, intensive care unit, and waiting room.

“Further work will also focus on artificial intelligence-based surrogate modelling for rapid simulations, uncertainty analysis, and optimal control of ventilation systems as well as efficient energy use,” said Fang.

Source: American Institute of Physics

Categories : COVID Diseases, Syndromes and ConditionsTags :

Prior COVID Infection Linked to New Autoimmune Conditions

On By ModernMedia
Photo by Mufid Majnun on Unsplash

In a new entry to the growing list of lasting complications from COVID infection, a large German cohort study of over 600 000 COVID patients indicates that new autoimmune conditions may result from previous COVID infection. The findings, which are awaiting peer review on the MedRxiv preprint server, show that the odds of new autoimmune conditions appear to increase in line with the severity of COVID infection.

After the acute phase of infection, some people may develop long-lasting symptoms, known as post-COVID, which are consistent with COVID infection and last more than 12 weeks. Most studies to date have focused on symptoms that partly wane over time. Many studies examined a small selective sample of patients, and only a few studies included a control group or information on chronic health conditions, such as SARS-CoV-2 infection.

Compared to post-COVID emergence of cardiovascular and other diseases, autoimmune diseases are less discussed in the literature, although autoantibodies could be found in patients after SARS-CoV-2 infection. So far there is limited evidence on newly manifested autoimmune diseases after an infection based on several case reports and one recent cohort study using UK health record data. In addition, COVID itself has some similarities with systemic autoimmune rheumatic diseases, which could make diagnosis difficult.

The researchers selected a cohort from German routine health care data, identifying individuals with polymerase chain reaction (PCR)-confirmed COVID through December 31, 2020. Patients were matched 1:3 to control patients without COVID. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyse the onset of autoimmune diseases during the post-acute period. The researchers calculated the incidence rates (IR) per 1000 person-years for each outcome and patient group, and estimated incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding COVID.

In total, 641 704 patients with COVID were included. When comparing the incidence rates in the COVID and matched control groups, the researchers found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID were at a greater risk for incident autoimmune diseases. These risk increases were as follows:

  • 41% higher risk of Grave’s disease
  • 42–45% higher risk of rheumatoid arthritis
  • 25% higher risk of type 1 diabetes
  • 27-29% higher risk of Crohn’s disease

The researchers concluded that SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.