Day: July 4, 2024

Certain types of infection have previously been linked to cognitive impairment, including SARS-CoV-2, especially among patients experiencing long COVID-19; however, it is unclear whether these cognitive deficits can improve over time. To analyze whether these symptoms improve more than a year post infection, a study published in eClinicalMedicine performed 2 rounds of cognitive testing to conduct longitudinal tracking of cognitive performance and deficits up to 2 years after being infected with the virus. Image credit: bizoo_n – stock.adobe.com Past studies have analyzed small, hospitalized cohorts during the first year of the pandemic (prior to vaccination) with somewhat short follow-up (approximately 6-12 months since infection). Further, few studies have used a longitudinal approach to assess the individuals’ cognitive trajectories and whether recovery can influence cognitive performance, according to the authors of the current study. The United Kingdom COVID Symptom Study Biobank (CSSB) held 2 rounds of testing. Round 1 was conducted between July 12, 2021, and August 27, 2021, and round 2 between April 28, 2022, and June 21, 2022), to assess the effects of COVID-19 exposures on cognitive accuracy and reaction times. The virus’s presences, correlations, magnitude, and persistence of effects are relatively unexplored within community-based cases, according to the investigators. There was a total of 3335 individuals who completed round 1, of whom 1768 had also completed round 2. Study participants were divided into 5 groups depending on their infection status and the associated symptom durations at the time of study invitation. Case group 1 included individuals with positive SARS-CoV-2 test but no associated symptoms (asymptomatic COVID); case group 2 included individuals with positive SARS-CoV-2 test with between 1 and 13 days of associated symptoms; case group 3 included individuals with positive SARS-CoV-2 test and at least 28 days of associated symptoms (long COVID); control group 1 included individuals with negative SARS-CoV-2 test with at least 28 days of symptoms at the time of test (long non-COVID); and control group 2 (“healthy controls”) included individuals with negative SARS-CoV-2 test associated with 1-3 consecutive days of symptoms at the time of test with a low symptom burden (healthy non-COVID). In both rounds 1 and 2 of assessment, participants completed 12 different cognitive tasks that assessed different cognitive domains, including working memory, attention, reasoning, and motor control, with a longitudinal analysis assessing change in performance between the 2 rounds. Effects of COVID-19 impairment on cognitive accuracy and reaction times were evaluated, as well as how ongoing symptoms after COVID-19 infection influenced self-perceived recovery. The study results indicate that individuals with community-based SARS-CoV-2 infection present cognitive deficits in performance accuracy compared to their non-infected counterparts when among groups with a ≥12-week symptom duration following infection. Additionally, they presented no evidence that SARS-CoV-2 infection had impacted their reaction time when completing the cognitive tasks. These individuals had self-reported as not being fully recovered. For those who had discernable deficits at initial testing, longitudinal follow-up indicated that the deficits persisted for nearly 2 years since infection. Alternatively, the individuals who reported feeling recovered presented no impairment, including those who experienced long-term illness or symptoms. The findings are similar to a previous study that had reported higher cognitive performance for the 42 participants who self-reported being recovered compared to 117 who experienced ongoing symptoms. The recovery rate was highly correlated with the duration of symptoms, which showed a recovery rate of only 17% for those with ≥12-week symptom duration at 38 weeks since infection. Limitations of the current study include potential selection and participation biases, findings were limited by the CSSB cohort composition, and data that would further contribute to the study were lacking (i.e., prior neurovascular and neurodegenerative comorbidities, cognitive assessment data prior to infection). Further, the study relied on participants voluntarily logging their symptoms and COVID-19 test results for the researchers to derive their infection status and duration of symptoms. Reference Cheetham N J, Penfold R, Giunchiglia V, et al. The effects of COVID-19 on cognitive performance in a community-based cohort: a COVID symptom study biobank prospective cohort study.eClinicalMedicine. Volume 0, Issue 0, 102086 https://doi.org/10.1016/j.eclinm.2023.102086

This article summarizes an opinion piece in the Proceedings of the National Academy of Science. It explores the history and language of the “standard model” of infectious disease, SIR – Susceptible, Infectious, Recovered. Infectious – the Germ Theory In 1890 Robert Koch published his criteria for the causal relationship between microbes and disease, setting the stage for the germ theory of disease. The influence of this theory cannot be overestimated – it has explained our global life expectancy remaining stubbornly stuck at two to three decades. It allows us to act upon that information with “the advent of hygiene, vaccines, aseptic surgery, and antibiotics….” His first postulate states that a given pathogen is found in all patients with the corresponding disease and not in healthy individuals. But as herpes zoster and COVID clearly demonstrate, that is not true – many patients are host to the microorganism, but far fewer have clinical manifestations, “the corresponding disease.” Tuberculosis is another example of an “infection enigma.” Mycobacterium tuberculosis, the infectious agent of the continuing global problem of tuberculosis, is estimated to reside in 25% of the global population. Yet 90% of those individuals have a latent form, where the mycobacterium is present, it is not contagious, and the patient has no clinical manifestations. René Dubos, more than 70 years ago, recognized these “silent” infections must be due to “a recent causal “weakening” of the sick host, after infection, but before the development of disease.” Those weakenings, or as he described, “changing circumstances,” were attributable to external environmental stressors, “ecological” in the sense that the stress originated in the environment, which could also, in turn, be modified by the host. Vaccines, social distancing, and masks are all environmental modifications. Susceptibility Moving toward genetics Sickle cell anemia or sickle cell disease (SCD) is an inherited disorder, an abnormality in the hemoglobin molecule that reduces oxygen transport ability and causes clumping and clotting. The resultant clumps and clots obstruct blood flow in the smaller vessels and provoke extremely painful sickle cell crises damaging organs like the kidneys. In 1949 a South African geneticist, Anthony C. Allison, was faced with a puzzle. When the hemoglobin abnormality of SCD is found in both genes contributed by the parents, the disease is fatal. But he discovered that upwards to 20% of the Kenyans he assessed had the far less lethal trait, one, not two, abnormal genes. He reported in 1954 that the underlying reason for such a high percentage was that “sickle cell trait provides large African populations with 10-­fold greater protection against the risk of cerebral malaria…[a] population level has never been surpassed by candidate gene or genome-­wide approaches.” Several other notable examples of susceptibility to infections and our underlying genetics exist. Bacterial appendicitis is infectious but not contagious. There are familial clusters of appendicitis. Studies of tuberculosis in twins from the 30s and 40s show a more significant “sharing” of TB with genetically identical (monozygotic) twins at 90% than dizygotic twins, born with differing genetics, at 20% The 1980 HIV epidemic demonstrated how an acquired immunodeficiency could result in specific rare infections, like pneumocystis pneumonia (PCP), caused by the fungus Pneumocystis jirovecii. Similarly, the immunosuppression from drugs used to suppress rejection in transplantation resulted in infections labeled “opportunistic.” All of these instances, from recognizable, overt immunologic compromise, strongly suggest a role for genetics in increasing or decreasing the susceptibility of a host to an infectious organism. Immunity is a spectrum Not all genetic errors affect every individual with the error – a genetic finding termed incomplete penetrance (complete penetrance affects all individuals with the error). The presence of a BRCA (BReast CAncer) gene mutation reduces tumor suppression elevating the risk of breast and ovarian cancer in those with the mutation. Women with a BRCA1 mutation have a penetrance, a clinical manifestation, of 55 to 72%; those with BRCA2 have a penetrance of 45 to 69%. Some inborn errors occur in cytokines; the small protein foot soldiers invoked in immunity’s inflammatory response. Job’s Syndrome, a rare syndrome involving an error in the interleukin cytokine, results in recurrent skin staph infections. [1] Our immunologic responses are not always correct, and we may develop antibodies to ourselves, termed autoantibodies. The presence of autoantibodies may mimic inborn errors in cytokines by reducing the numbers and effectiveness of the normal cytokines, creating an “autoimmune phenocopy” of a disease. Antibodies to one of the interferons (IFN-­α), another of the cytokines involved in our immune defense against viruses, is present in about 1% of adults under age 65 but increase to 4 to 7% in older populations. In a study of 3,595 hospitalized patients with “severe” COVID, autoantibodies to IFN-­α were found in 13.6% and were present in 18% of the patients who died. In a new study reported in Nature, the same research group identified a variant of the HLA gene that confers a more robust immunity to COVID. In their study, 13,000 individuals in a donor registry, whose genes had been characterized were found to be positive for COVID. But 10% of those individuals were symptom-free. Roughly 20% of these symptom-free individuals had a specific mutation of their HLA-B gene that made them “especially potent at clearing SARS-CoV-2.” And when that mutation, which has an incidence of roughly 10% in those with European ancestry, is homozygous (coming from both mother and father), it increases the likelihood of remaining asymptomatic in the presence of a positive COVID test 8-fold. A new paradigm “It is, admittedly, difficult to measure the weights of causal factors, and comparing the respective contributions of the germ and host theories is intellectually challenging.” It is the nature of scientific knowledge to build upon the work already done. The development of the germ theory as the explanation of infection has served us well, but it was developed before we had knowledge of immunity, let alone an immune system. For all its explanatory power, the germ theory could not incorporate what Donald Rumsfeld characterized as the “unknown unknowns.” Our understanding

Naegleria fowleri, the amoeba responsible for the child’s death, enters the body via the nose and travels to the brain where it begins destroying tissue. (Image credit: Shutterstock) A 2-year-old boy in Nevada has died after being infected with a “brain-eating” amoeba after visiting a natural hot spring in the state. In a statement published July 20, the Nevada Division of Public and Behavioral Health (DPBH) announced that the boy — named Woodrow Bundy, according to a Facebook post from his family — was likely exposed to the microbe at Ash Springs in Lincoln County. According to the DPBH, the Centers for Disease Control and Prevention (CDC) confirmed that the child’s condition was caused by Naegleria fowleri, a single-cell organism known to cause such brain infections. Typically found in soil and warm fresh water, such as lakes, rivers, hot springs and sometimes freshwater spouting from splash pads, the amoeba can cause a rare but deadly infection of the brain, known as primary amebic meningoencephalitis (PAM). “If you wind up getting infected with it, chances are you’re going to die,” Brian Labus, an epidemiologist and associate professor at the University of Nevada, told FOX5. “Very few people have actually survived this type of infection.” Related: ‘Brain-eating’ amoeba ruled out in ‘cluster of illnesses’ in Oklahoma. What could the cause be? CDC figures show that, of the 154 people known to have been infected by N. fowleri between 1962 and 2021, only four have survived. People typically become infected when water carrying the amoeba enters their nose, likely during swimming or diving, and travels up to the brain via nerves in the nasal cavity. From there, N. fowleri begins to destroy brain tissue, resulting in its nickname as a “brain-eating amoeba.” “It progresses rather rapidly because it’s actively destroying brain tissue, so it’s very difficult for your body to deal with something like that and fight it off,” Labus told FOX5. Symptoms of PAM usually begin around five days after exposure to the amoeba, the CDC states, and they can include headaches, fever, nausea or vomiting. At later stages of the disease, victims may experience a stiff neck and confusion and show a lack of attention to people and surroundings, and they may also develop seizures or hallucinations. They may even fall into a coma. Usually, a patient will die around five days after symptoms emerge. According to the CDC, young boys like Bundy are at the highest risk of being infected with N. fowleri, compared to other demographics. The reason why is unclear, but the agency suggests this could be because boys more often take part in water activities, such as diving and playing in the sediment at the bottom of lakes and rivers. (The DPBH didn’t note whether Bundy was swimming at the time of his exposure or potentially encountered the amoeba some other way.) N. fowleri can’t be spread from one person to another — it enters the body only through exposure to contaminated water. The DPBH noted that there is “no means to eliminate the ameba from fresh bodies of water,” so people should “always assume there is a risk,” of exposure, even if that risk is extremely low. “The only sure way to prevent an infection is to avoid water-related activities in warm fresh water, especially during summer months,” the CDC notes. People who choose to swim, however, can reduce their risk of infection by stopping water going up their nose. This could involve avoiding diving, using nose clips or not putting your head under water, the CDC suggests.