Category: Infection

Biological agents threaten people’s life through different ways, one of which lies in the impairment of cognition. It is believed cognitive decline may result from biological agents mediated neuron damage directly, or from the activation of the host immune response to eradicate the pathogen. However, there is limited evidence for direct linkage between infections and cognitive decline. The authors of this article focus on the mechanisms of how different biological viruses, or their induced systemic and local inflammation, link to the cognitive impairment, focusing on the roles of activated microglia and several molecular pathways mediated neurotoxicity. Highlights Infection induced cognitive decline are persistent threat to people’s health. Infection induces neurotoxicity and neuroinflammation which contributes to cognitive decline. Targeting CDK5 or other critical pathway may provide new solutions to alleviate infection induced cognitive decline. Compuscript Ltd Journal reference: Du, C., et al. (2023). Biosafety and mental health: Virus induced cognitive decline. Biosafety and Health. doi.org/10.1016/j.bsheal.2023.04.002.

SINGAPORE – The number of conjunctivitis reports in Singapore has risen significantly in 2023, with a 75 per cent increase in the cases recorded daily between January and July, compared with the same period in 2022. According to the Ministry of Health’s weekly infectious disease bulletin for the week ended July 8, polyclinics logged an average of 63 cases of acute conjunctivitis daily, up from 36 a day in the same period in 2022. The Straits Times reported in March that daily cases had gone up amid the lifting of Covid-19 restrictions. The easing of rules could have facilitated the spread of viruses and bacteria that cause the condition. Commonly referred to as pink eye, conjunctivitis is an inflammation of the conjunctiva, a clear membrane that protects the sclera, which is the white, outer layer of the eye. The most common forms of conjunctivitis infections include viral or bacterial infections, and allergic conjunctivitis. Patients often experience mild to severe itchiness in the eye, sensitivity to light, swollen sclera, watery eyes, eye discharge, blurred vision and, in some cases, pain in the infected eye. Some sufferers may even notice a jelly-like texture on the surface of their eye. Dr Jayant V. Iyer and Dr Jason Lee from The Straits Eye Centre said they have observed a “notable increase” in the number of patients with infective conjunctivitis symptoms. “(This could) be attributed to heightened interpersonal interactions among individuals this year, in contrast to the reduced interactions experienced during the preceding pandemic years,” they said. They added that it is essential for individuals already infected with a viral upper respiratory tract infection or infective conjunctivitis to obtain a medical certificate and practise adequate social distancing at home until recovery. “(Infective conjunctivitis) is highly contagious and spreads through hand-to-eye contact following contact with infected individuals or objects. It can also be transmitted through exposure to coughing or sneezing from individuals with viral upper respiratory tract infections,” they said. The doctors added that infective conjunctivitis can be “debilitating”, with the recovery period ranging from three days to two weeks. Dr Ding Si Yan, a family physician at National Healthcare Group Polyclinics, said the symptoms of conjunctivitis may greatly affect the patient’s ability to concentrate at work or in school. But there are ways to curb the spread of conjunctivitis, he said. He recommends personal hygiene practices such as washing hands with soap and water before and after touching the eyes, and cautions people against rubbing their eyes unnecessarily, as that could cause conjunctivitis to spread to the other healthy eye, or to other individuals.

The novel triazole antifungal agent, isavuconazole, was found to be comparable to other antifungals for the treatment and prevention of invasive fungal infections (IFIs), and is associated with fewer drug-related adverse events and discontinuations, according to a study published in Mycoses. Researchers conducted a systematic review and meta-analysis of studies that included patients who received isavuconazole and other antifungal agents to assess the efficacy and safety of the drug for the treatment of IFIs. Following PRISMA guidelines, the authors searched Scopus, EMBASE, PubMed, CINAHL, and Ichushi for articles in English and Japanese published up to February 7, 2023. Eligible studies were randomized controlled trials and retrospective and cohort studies that reported mortality, IFI rate, discontinuation rate due to adverse events, or incidence of abnormal hepatic function in patients with IFIs treated with and without isavuconazole. The primary outcomes were overall mortality for treatment and IFI rate for prophylaxis. A control group included patients treated with antifungal agents other than isavuconazole. Our findings suggest that ISAV is a useful first-line antifungal agent for the treatment and prophylaxis of IFIs. The analysis included 10 studies, 2 of which were randomized control trials. Control group patients received amphotericin B, voriconazole, and posaconazole for IFIs. Related Content In 6 studies with 870 participants that evaluated mortality for treatment of IFIs, pooled analysis showed no significant decrease in mortality in the isavuconazole group vs the control group in a fixed-effects model (treatment, odds ratio [OR] 1.11; 95% CI, 0.82-1.51; I2=0%). The mortality rate was lower among patients in the isavuconazole group (28.3%) compared with those in the control group (33.6%). In a pooled analysis of 2 studies with 577 patients, the effects of isavuconazole for prophylaxis were found to be comparable to those of with the control groups in terms of the IFI rate (OR, 1.02; 95% CI, 0.49-2.12; I2=0%). Regarding discontinuation rates, 5 studies with 387 participants receiving isavuconazole and 390 patients in the control group receiving other antifungal agents showed discontinuation rates of 9.8% and 16.9%, respectively, in the 2 groups. Patients in the control group had a significant decrease in the continued treatment rate compared with those of the isavuconazole group (OR 1.96; 95% CI, 1.26-3.07; I2=0%). For prophylaxis, the discontinuation rate was not significantly different in the 2 groups (isavuconazole vs control, 9.4% vs 17.9%; OR, 2.01; 95% CI, 0.60-6.78). A pooled analysis of 3 studies that evaluated the incidence of hepatic function abnormalities in treatment showed a significantly increased incidence in the control group vs the isavuconazole group (8.0% vs 16.3%; OR, 2.31; 95% CI, 1.41-3.78). Among several limitations, most patients had a variety of comorbidities, were treated at different drug dosages, and underwent different durations of therapy. Also, randomized control trials and high-quality observational studies were lacking for various IFI subtypes. “Our findings suggest that ISAV is a useful first-line antifungal agent for the treatment and prophylaxis of IFIs,” the authors concluded. This article originally appeared on Dermatology Advisor References: Kato H, Hagihara M, Asai N, et al. A systematic review and meta-analysis of efficacy and safety of isavuconazole for the treatment and prophylaxis of invasive fungal infections. Mycoses. Published online June 10, 2023. doi:10.1111/myc.13622

FDA (Adobe Stock, unknown) Today the FDA announced its approval of AstraZeneca’s monoclonal antibody, Beyfortus (nirsevimab-alip), for preventing respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants entering or during their first RSV season and children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. “RSV can cause serious disease in infants and some children and results in a large number of emergency department and physician office visits each year,” said John Farley, MD, MPH, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research. “Today’s approval addresses the great need for products to help reduce the impact of RSV disease on children, families, and the health care system.” According to the press release, RSV is an often severe virus that causes respiratory infection in individuals of all ages. Infants and young children can develop severe lower respiratory tract diseases like pneumonia and bronchiolitis. Other patients are at higher risk, especially premature infants, those with chronic lung disease of prematurity or congenital heart disease, and older patients. According to the American Academy of Pediatrics, RSV hospitalizes approximately 1% to 3% of children under 12 months of age in the United States annually. As a monoclonal antibody with activity against RSV, it is a “laboratory-made protein that mimics the immune system’s ability to fight off harmful pathogens such as viruses. One dose of Beyfortus, administered as a single intramuscular injection before or during RSV season, may protect during the RSV season,” according to the press release. “RSV can cause serious disease in infants and some children and results in a large number of emergency department and physician office visits each year,” said John Farley, MD, MPH, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research. “Today’s approval addresses the great need for products to help reduce the impact of RSV disease on children, families, and the health care system.” Three clinical trials (Trials 03, 04, and 05) supported the efficacy and safety of Beyfortus. Trial 03 enrolled 1,453 preterm infants born between 29 and 35 weeks of gestational age during their first RSV season. Beyfortus reduced medically attended RSV lower respiratory tract infection (MA RSV LRTI) risk by approximately 70% compared to the placebo. Trial 04 included 1,490 babies born at 35+ weeks. Of those included, 994 infants received Beyfortus, and 496 received a placebo. Beyfortus reduced the risk of MA RSV LRTI by approximately 75% compared to the placebo. Trial 05 tested Beyfortus on 925 at-risk infants up to 24 months old. The results showed it can prevent MA RSV LRTI in this population. The trial was a “randomized, double-blind, active (palivizumab)-controlled, multicenter trial, [that] supported the use of Beyfortus in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season,” according to the press release. Beyfortus may cause rash and reactions at the injection site. It is important to note that infants and children who have experienced severe hypersensitivity reactions to the active ingredients or excipients in Beyfortus should avoid taking this medication. The press release noted that the Beyfortus received a Fast Track designation for this indication.

ByHT Correspondent Jul 18, 2023 01:31 AM IST Share Via Copy Link Health minister Saurabh Bharadwaj said that the government is taking all precautions to ensure that vector-borne diseases are not spread in these camps Delhi health minister Saurabh Bharadwaj on Monday said that cases of conjunctivitis, skin allergies and fever are the most reported medical conditions in government flood relief camps. He added that the Delhi government is taking all precautions to ensure that vector-borne diseases are not spread in these camps. Many low-lying areas around the river were inundated and several families living in slum clusters along the Yamuna had to be shifted to relief camps after water entered their houses. (Vipin Kumar/HT) Also read: Yamuna water level see-saws, people in camps told to stay for now “Currently no cases of vector-borne diseases have been seen in the camps,” Bharadwaj said on Monday after visiting the flood relief camps in east Delhi. “Patients in the relief camps having symptoms of any disease will be admitted and monitored in the disaster management wards of hospitals,” he said, adding that it will also be known whether any new epidemic is spreading in the relief camps. Last week, water levels in the Yamuna started rising and hit a record-high of 208.66mm last Thursday. Many low-lying areas around the river were inundated and several families living in slum clusters along the Yamuna had to be shifted to relief camps after water entered their houses. Parts of east and northeast Delhi were the worst affected by the flooding. On Monday, Bhardwaj visited Swami Dayanand Hospital in east Delhi’s Shahdara and Lal Bahadur Shastri Hospital in Khichripur to take stock of the preparations in the hospitals. Topics Fever Delhi Health Minister

CONNECTICUT — The number of people who have been sickened by a parasite linked to different kinds of fresh produce has grown to 581 people in 31 states, including Connecticut, the Centers for Disease Control and Prevention said in a recent update of its investigation of the intestinal infection cyclosporiasis. The CDC and Connecticut health officials are monitoring intestinal infections caused by the parasite Cyclospora cayetanensis, which is typically spread by eating food or drinking water contaminated with feces. Cyclosporiasis cases are monitored by federal health officials to detect outbreaks that may be linked to a common food source. The illness can cause frequent and, at times, explosive bowel movements, stomach cramps, increased gas, nausea and fatigue. Flu-like symptoms, including vomiting, headache, body aches and fever, often accompany the infection. The CDC said in an update last week that the 581 illnesses have resulted in 55 hospitalizations. That’s an increase from 371 cases since the last update on June 22. Between 1-10 of those cases have been reported in Connecticut. See also: Teen, 16, and 20-Year-Old Killed In Crash The federal health agency said it has not yet identified the specific source of the outbreak, but said state and local health officials are interviewing people who have had illnesses to find out what foods they ate before they got sick. Illnesses are reported all year, but health officials often note increased cases during the spring and summer. Reports tend to increase starting in May, but this year, cases began to spike in April. “It is too soon to tell if this timing indicates a change in the seasonality of cyclosporiasis in the United States,” the investigation notice says. While the illness’ cause can vary, previous outbreaks have been linked to fresh produce, including basil, cilantro, mesclun lettuce, raspberries, and snow peas. Earlier this year, federal health officials investigated a spike of cyclosporiasis cases in Georgia and Alabama linked to raw broccoli that sickened 20 people. Officials determined the broccoli was imported. A cause for the remaining U.S. cases has not been identified and broccoli doesn’t appear to be the source, according to officials. To determine the cause, officials ask sick people what they ate in the 14 days before getting sick. If a common food is found, health officials will issue an advisory if the contaminated food is still available in stores or found in homes. Anyone infected with cyclosporiasis can experience symptoms for several weeks to a month or more. If untreated, symptoms may get better for a while and then return, and this pattern may repeat, health officials said. The illness is treated with antibiotics and the CDC advises health care providers to report any cases to the local health department.

As of Wednesday, 12 July, no human contacts of A(H5N1) positive cats have reported any symptoms, the UN health agency said, adding that the surveillance period for all contacts has now complete. National first There have been previous “sporadic” cases of what is more commonly referred to as the bird flu virus, but the cases in Poland are the first time high numbers of infected cats have been reported over a wide geographical area within a single country, WHO said. “The risk of human infections following exposure to infected cats at the national level is assessed as low for the general population, and low to moderate for cat owners and those occupationally exposed to H5N1-infected cats, such as veterinarians, without the use of appropriate personal protective equipment”. WHO advised those exposed to animal flu viruses and all contacts of confirmed human cases, to monitor their health for the duration of the known exposure period, plus an additional minimum of seven days. ‘No change’ in WHO advice WHO said that the report of the infections among cats does not change its current recommendations on public health measures and surveillance. “Due to the constantly evolving nature of influenza viruses, WHO continues to stress the importance of global surveillance to detect and monitor virological, epidemiological and clinical changes associated with emerging or circulating influenza viruses that may affect human or animal health and timely virus-sharing for risk assessment,” the agency said. The UN agency called on public health and animal health authorities to collaborate closely, share information, and conduct joint risk assessment and response to outbreaks of zoonotic influenza at the human-animal interface, adhering to the One Health approach. Cat deaths According to WHO, as of 11 July, authorities in Poland tested 47 samples from 46 cats and one captive caracal wild cat. Of these, 29 were found to be positive for influenza A (H5N1). Fourteen cats were reportedly euthanized, and a further 11 died, with the last death reported on 30 June. The positive samples were reported from 13 geographical areas within the country. Source of exposure ‘unknown’ The source of exposure to the virus is currently unknown and epizootic investigations are ongoing. “There are several possibilities for the source of infection, among which the cats could have had direct or indirect contact with infected birds or their environments, ate infected birds, or ate food contaminated with the virus,” WHO said adding that, authorities are investigating “all potential sources and to date have not ruled out any.” Of the 25 cats for which information is available, two were outdoor, 18 were indoor with access to a balcony, terrace, or backyard, and five without access to the outside environment. Seven of the 25 cats reportedly had the opportunity for contact with wild birds. Ongoing monitoring WHO said that together with the UN Food and Agriculture Organization (FAO) and World Organisation for Animal Health (WOAH), it continues to monitor rapidly evolving virus, and updating recommendations for curbing its spread, in addition to working with countries in preparedness and response. The UN health agency is also evaluating the existing candidate vaccine viruses of A(H5N1) through its Global Influenza Surveillance and Response System to ensure valid candidate vaccine viruses are developed.

Let’s all take a moment and show some gratitude to our immune systems—day in and day out, intricate molecular machines are at work protecting our bodies from the microbial milieu that we inhabit. One of the immune system’s most important constituents are T cells (named after a fascinating organ called the Thymus, where they mature), which are present throughout the body and coordinate immune responses against pathogens. T cells exist in a variety of types—from ‘helper’ CD4+ to ‘killer’ CD8+ cells—but many share a general mechanism of activation: they initially lie dormant before being activated by an immunological stimulus, fight off the threat, then return to the dormant state. This cycle of activation-deactivation is critical for our immune systems to remain nimble in response to infections while avoiding prolonged inflammation and damage to healthy tissue. However, decades of research have revealed another side to this coin: a phenomenon termed T cell exhaustion. Although the exact definition is still under debate, T cell exhaustion generally refers to a progressive loss of functionality in T cells which are persistently stimulated over long periods of time. Exhaustion is theorized to represent a fail-safe mechanism to prevent chronic, deleterious immune overactivation, but exhausted T cells are also implicated in the progression of chronic infections and various cancers, making this an important phenomenon to better understand. The Lund Lab in the Vaccine and Infectious Disease Division at Fred Hutch studies immune responses to viruses of public health concern. A recent study from the lab led by former lab members Drs. Veronica Davé, Laura Richert-Spuhler, and Tanvi Arkatkar asks an interesting question about T cell exhaustion after infection with herpes simplex virus 2 (HSV-2), a pernicious virus infecting roughly ten percent of people nationwide which poses significant quality of life and health risks. HSV-2 infection—which causes the disease known commonly as genital herpes—is characterized by long periods of viral latency punctuated by brief episodes of recurrence (‘flare-ups’) of painful sores. As Dr. Davé puts it, “When you read about immune activation and T cell exhaustion, it’s usually grouped into two bins: acute activation (which happens when you get a vaccine or the flu) and chronic activation (which happens with a tumor, for example). We quickly realized that HSV-2 infection, with its brief bouts of acute immune activation and deactivation occurring over years-long time periods, doesn’t fit neatly into either of those bins, and presents an interesting opportunity to study how chronic viral reactivation impacts T cell health in the affected tissues.” To study the effects of chronic HSV-2 reactivation on T cells, the team made two important decisions: first, that they would primarily use samples from HSV-2 positive human patients rather than an animal model, and second, that a longitudinal study design (sampling the same HSV lesions in the same patients over time) would provide the most informative system to relate viral reactivation and subsequent immune involvement. Working with minute quantities of lesion biopsy tissue, Davé and colleagues used cutting-edge multi-parameter flow cytometry to sort and characterize lesion-associated immune cells based on a panel of cell surface markers. Here, she made the first interesting discovery: while viral recurrence leads to a sharp increase in total T cell abundance followed by a gradual return to baseline as lesions healed, the composition of the immune cell compartment (that is, the relative proportions of different T cell and other immune cell types) remained relatively unchanged throughout recurrence and even compared to adjacent, non-lesion tissue.

Even with the extreme scarcity of available data, there is sufficient information from the limited reporting on levels of SARS-CoV-2 in wastewater to conclude a summer surge in COVID infections is well under way in the United States. It began even before mid-May, when President Joe Biden terminated the national COVID emergency response, effectively turning out all the lights on any direct measurement of the state of the pandemic. As shown by the CDC graph below, in April 2023 levels of SARS-CoV-2 in wastewater began to rise steadily, an indirect indicator of community-level spread. Over the month of June, there was a more than 60 percent rise in wastewater levels of the virus, with more than 1,300 sites participating in providing the public health agency with data. It is worrisome however that in the last two weeks of July there has been a precipitous drop in the number of sites reporting these figures (a 22 percent decline) with a corresponding blunting of the SARS-CoV-2 levels reported. Although the CDC explained that this is a normal lag and data would be added retroactively, given the agency’s previous lack of transparency, such assurances cannot be taken as read. Percent of sites in each percent change category over time, United States. [Photo: Centers for Disease Control and Prevention] For instance, a similar phenomenon occurred in late December 2022 when there was a precipitous drop in SARS-CoV-2 wastewater levels with a corresponding drop in the number of sites reporting, amid an ongoing winter surge of infections. The CDC blamed the Christmas holiday season for the aberration, but this was completely irresponsible. Precisely when a massive surge in cases was under way, the necessary data to “inform the public” was conveniently unavailable. There was a huge drop in the virus level, but that is likely due to the sites that contribute most, in metropolitan areas, going dark. It would not be surprising to see this effective blackout repeated, so that in the next few weeks we might hear the CDC claim that the summer break led to a decline in participating facilities, hiding the advance of another surge. If one were to extrapolate the end of June projections into July, they suggest not only has the peak in cases not been reached, but that it will match or exceed the level of COVID in previous winter and summer peaks. Data from Biobot Analytics, which is considered more reliable than the limited CDC reporting, confirms the ongoing surge in wastewater coronavirus right up to the present. Biobot explained that they use statistical techniques that adjust for dilution and population size and, as wastewater-based epidemiology advances, they will adjust to account for the technical factors and introduce “the concept of effective concentration as a transparent and future-proof approach” that will ensure the data reliably reflects trends in the population-wide COVID-19 burden.” As Biobot noted, the current epicenters for the summer 2023 COVID surge are in the Northeast and South, where in conjunction with the rise in wastewater virus levels, the heat wave and the air pollution from the Canadian forest fires have driven people indoors. In California, Los Angeles has recently reported a rise in COVID cases although their figures, as they note, represent only a fraction of actual COVID cases, suggesting the summer COVID wave is just beginning in the second largest US city. The reliance by the CDC on wastewater surveillance underscores the reality that such indicators lack any real-time value, are prone to manipulation and provide little clinical guidance to direct local public health authorities and health systems. The agency uses wastewater tracking to inure the population against the threat posed by COVID or any other pathogen, while maintaining the farce that the national public health edifice is functioning to protect the population, although hardly anyone believes that any more. As data scientist and modeler JWeiland noted on his Twitter social media account, the current wastewater SARS-CoV-2 levels correspond to an estimated daily infection rate of more than 310,000 or a ratio of one in every 1,060 people becoming infected every day and at least one percent of the population currently infected. Irrespective of the current low fatality rate which is still higher than the flu and could skyrocket should viral evolution produce a more deadly variant, as it has in the past, one in 10 people infected with Omicron sub-variants develop Long COVID, regardless of disease severity or age. US COVID Projections July 18, 2023. [Photo by J. Weiland] As Dr. Marc Sala of Northwestern University Medicine recently said, “You will have many patients come to us still in good numbers to fill up our clinic with maybe the third, fourth, fifth infection and now having finally developed post-COVID syndrome … with symptoms that are enough to be disabling to their lives as previously known.” Although these patients are filling up hospitals and ICUs as in the past, the long-term implications are even worse. Long COVID is already the third leading cause of neurological disorders. Mehring Books COVID, Capitalism, and Class War: A Social and Political Chronology of the Pandemic A compilation of the World Socialist Web Site‘s coverage of this global crisis, available in epub and print formats. Buy your copy today In children, the lingering effects after a COVID infection can include various neurocognitive complaints like loss of smell, fatigue, and brain fog. These lead to the inability to think or remember clearly. More serious signs include atrophy of the brain’s grey matter, which can be associated with cognitive dysfunction and symptoms like anxiety and depression. These findings have been repeated internationally and will have long-lasting consequences and harken back to the lie perpetrated during the first years of the pandemic that children are immune to the ravages of the disease. Nonetheless, the current surge has finally provided the first clinical glimpse of its impact on the national arena despite the very limited surveillance capacity. Emergency room visits climbed 7.1 percent compared to the previous week. The test positivity rate,

In a recent study published in Nature, researchers describe the findings of the COVID-19 Citizen Science Study, a large-scale study directly examining human leukocyte antigen (HLA) variation(s) in a prospective cohort comprising individuals with mild coronavirus disease 2019 (COVID-19). They invited 29,947 volunteer bone marrow donors with high-resolution HLA genotyping data to develop this prospective cohort and two additional independent cohorts. Study: A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection. Image Credit: sciencepics/Shutterstock.com Background Numerous studies intending to understand the genetic basis of differential outcomes in COVID-19 have examined genetic associations with severe disease course, primarily in hospitalized cohorts, e.g., the multicentre Host Genetics Initiative. However, few studies have examined genetics in non-hospitalized, prospective, community-based cohorts. Studies directly examining HLA associations with infection had relatively small cohorts and fetched mixed and inconclusive results. Hundreds of genes govern human immune responses to diseases, of which HLA variants have the most robust associations with viral infections. It makes them relevant molecular targets for COVID-19 vaccine development. Individuals expressing HLA-B*46:01 might be more vulnerable to COVID-19. Conversely, HLA-B*15:03 protects against COVID-19 by presenting highly conserved SARS-CoV-2 peptides to T cells. More in-depth insights into the impact of HLA variation(s) in infectious diseases could inform vaccine development and potential immunotherapies for COVID-19. About the study The present study had a smartphone-based study design which helped the researchers track COVID-19 symptoms and outcomes, including positive reverse transcription-polymerase chain reaction (RT-PCR) test results of nearly 30,000 individuals previously HLA genotyped for five loci, HLA-A, -B, -C, -DRB1 and -DQB1. Related Stories Notably, they included positive test result data till 30 April 2021 from people who self-identified as belonging to the ‘white’ ethnicity. They retrieved their data from a pre-existing database for medical research named the National Marrow Donor Program (NMDP). Further, they contextualized the study results by examining T cell reactivity, T cell receptor (TCR) repertoire, affinity, and structural implications for the observed HLA associations. Furthermore, the researchers examined the crystal structures of the HLA-B*15:01 molecule in a complex with peptides from other seasonal coronaviruses (CoVs), e.g., HKU1-CoV and OC43-CoV, at concentrations of five μM and ten μM. Results The main study finding was that the HLA-B*15:01 allele was markedly associated with asymptomatic infection in participants reporting a SARS-CoV-2-positive test result. Nearly 10% of individuals with European ancestry carry this common allele and remain asymptomatic post-SARS-CoV-2 infection than those who do not. Another important effect of HLA-B*15:01 homozygosity was that it increased the likelihood of remaining asymptomatic during SARS-CoV-2 infection by >eight times. Asymptomatic patients in two independent cohorts of the study also had highly similar frequency distributions of HLA-B*15:01. Furthermore, the study results showed that the HLA-DRB1*04:01 allele augmented the HLA-B*15:01 effect when paired, like in the United States (US)-origin people who self-identified as white. Upon analyzing immunodominant epitopes in T cells in human peripheral blood mononuclear cells or PBMCs from pre-pandemic healthy donors, the authors observed that the cells from donors carrying HLA-B*15:01 allele unexposed to SARS-CoV-2 were reactive to the SARS-CoV-2 spike (S) peptide NQK-Q8, and most cells displayed a memory phenotype. Thus, this amino acid sequence identity between seasonal CoVs and SARS-CoV-2 S peptides explains the T cell cross-reactivity. The presence of high-affinity, cross-reactive memory T cells in unexposed donors further corroborated the robust association between the allele HLA-B*15:01 and asymptomatic COVID-19. Other recent studies have also shown that SARS-CoV-2-specific memory T cells are enriched at the site of infection and help rapidly clear the overt onset of symptoms by secreting more interferon-gamma (IFN-Ύ). S peptides from SARS-CoV-2 and other CoVs, namely NQK-Q8 and NQK-A8, showed comparably stabilized the HLA-B*15:01 molecule. Also, HLA-B*15:01 presented these peptides in similar structural conformation, which gives a molecular basis to pre-existing immunity and T-cell cross-reactivity. More importantly, despite limited data on HLA-B*15:01 epitopes found in SARS-CoV-2 patients, this study’s results found NQK-Q8 as the prime candidate peptide governing HLA-B*15:01-mediated T cell cross-immunity with seasonal CoVs. Conclusions The study results strongly support the role of the HLA-B*15:01 allele in mediating asymptomatic COVID-19 through pre-existing T-cell immunity due to previous exposure to other CoVs. The understanding that HLA class I alleles play a crucial role in early infection and the mechanisms underlying early viral clearance leading to asymptomatic SARS-CoV-2 infection have important implications. It becomes the framework for future studies refining vaccine development and therapies for early disease. Journal reference: