on immunity

“People do become very worried if you compare COVID-19 to HIV, but actually HIV has good treatment and life expectancy now.”

Dr. Noor Bari, Emergency Medicine (2023)

❦ on three scenarios

“COVID-19 is fighting back by generally depressing the whole adaptive immune system.

We are showing narrow resilience to COVID reinfections due to adapting – but we are becoming more vulnerable in general to infections of all kinds.

➲ Worst case scenario

A single infection causes on-going and progressive immunodeficiency.

➲ Best case scenario

A single infection causes temporary immunosuppression, and we suppress COVID transmission enough to allow recovery.

➲ Most likely scenario, medium-term

Immunosuppression that becomes continuous and possibly progressive due to reinfections.

Reduced immune function after a viral infection is not unusual.

Many viruses do this.

The concerning issue is the length and breadth of the immune system dysfunction, coupled with emerging evidence of other pathogens taking advantage.”

Dr. Noor Bari, Emergency Medicine (2023)

❦ Immunosuppression ~ Suppression of the immune system and its ability to fight infection.

❦ Immunodeficiency ~ A state in which the immune system’s ability to fight infectious diseases and cancer is compromised, or entirely absent.

❦ on repeated exposure

‘Repeated exposure to a virus such as SARS-CoV-2 will fast-track more people into immunosenescence at ever-earlier ages, with potentially serious repercussions for their health and longevity.’

The John Snow Project (2023)

❦ Immunosenescence ~ The gradual deterioration of the immune system, normally brought on by natural age advancement.

Immunosenescence is closely related to the development of infections, autoimmune diseases, and malignant tumors.

❦ on lymphocytopenia

The most common causes of acquired lymphocytopenia include:

➲ Protein-energy undernutrition.

➲ HIV infection.

➲ COVID-19.

➲ Certain other viral infections.

Patients with HIV infection routinely have lymphocytopenia, which arises from destruction of CD4+ T cells infected with the HIV virus.

➲ Patients with COVID-19 also frequently have lymphocytopenia (35% to 83% of patients).

➲ Patients have recurrent viral, bacterial, fungal, or parasitic infections.

Merck Manual ➲ (2023)

❦ on the hygiene hypothesis, and pathogenic viruses

‘The hygiene hypothesis is the idea that the immune system needs to be “trained” during childhood to properly develop immune tolerance to microbes, but it specifically refers to bacteria, protozoans and helminths, most of which are normally beneficial, neutral or not significantly harmful to humans.

It does not advocate repeated exposure to viruses, especially highly pathogenic ones.’

The John Snow Project (2023)

Archives: Immunity & the Immune System

📖 SARS-CoV-2 spike-driven reactivation of latent herpesviruses as a mechanistic link to post-viral diseases

by Jana et al / Trends Open: Cell Press • 13 July 2026

‘One plausible mechanism is the reactivation of latent human herpesviruses such as HHV-6, HHV-7, and Epstein–Barr virus (EBV), which have increasingly been linked to long COVID [PASC] and ME/CFS-like phenotypes. These viruses persist lifelong in immune and neural cell populations and can reactivate under conditions of cytokine surges, oxidative stress, immune exhaustion, and mitochondrial dysfunction – the very milieu fostered by persistent [SARS-CoV-2] spike signalling.’

A WHO’s Who of VOCs, VOIs and VUMs: Alphabet Stew and Numeric Ragout for Dummies

by C19.Life • 1 November 2025

“We’re going to need a bigger Greek alphabet.”

📖 Long COVID [PASC] associated with SARS-CoV-2 reinfection among children and adolescents in the Omicron era (RECOVER-EHR): a retrospective cohort study

by Zhang et al / The Lancet: Infectious Diseases • 30 September 2025

‘Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. Our paediatric findings also align with adult studies. Research in adults shows that long COVID [PASC] symptoms often worsen with repeated infections, suggesting potential shared mechanisms across age groups.’

☰ 15 studies & articles on... SARS-CoV-2 (COVID-19) reinfections, cumulative damage, and increased risk of all-cause mortality

by C19.Life... et al • 29 September 2025

‘The arrival of the Omicron variant marked a major shift, introducing numerous extra mutations in the spike gene compared with earlier variants. Before Omicron, natural infection provided strong and durable protection against reinfection, with minimal waning over time. However, during the Omicron era, protection was robust only for those recently infected, declining rapidly over time and diminishing within a year.’

☰ 9 studies & articles on... SARS-CoV-2 (COVID-19) vaccines, ‘Omicron’, and waning protection

by C19.Life... et al • 7 September 2025

‘Vaccine effectiveness against SARS-CoV-2 [COVID-19] infection declines markedly with time and Omicron variants.’ from ‘Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection and severe outcomes in adults’ by Zhou et al / European Respiratory Review (2024).

📖 SARS-CoV-2 infection heightens the risk of developing HPV-related carcinoma in situ and cancer

by Shih et al / Springer Nature ~ Discover Oncology • 14 August 2025

‘Over a 3-year follow-up period, individuals with SARS-CoV-2 infection had significantly higher risks of developing HPV-related cancers compared to those without infection: a 67% increase in cervical cancer, 131% in vaginal cancer, 98% in vulvar cancer, 92% in anal cancer, and 78% in oropharyngeal cancer. Similar trends were observed for carcinoma in situ, with increased risks of 34% for cervical, 61% for vaginal, 74% for vulvar, 96% for anal, and 78% for oropharyngeal carcinoma in situ.’

☣ Variant Watch: 📖 Antigenic and virological characteristics of SARS-CoV-2 variants BA.3.2, XFG, and NB.1.8.1

by Guo et al / The Lancet ~ Infectious Diseases • 5 June 2025

‘Importantly, NB.1.8.1 shows a balanced profile of ACE2 binding and immune evasion, supporting its potential for future prevalence.’

☣ Variant Watch: 📖 Host cell entry and neutralisation sensitivity of SARS-CoV-2 BA.3.2

by Zhang et al / The Lancet ~ Microbe • 3 June 2025

‘Since late 2024, a potential third major evolutionary shift in SARS-CoV-2 evolution might be unfolding. In November 2024 and January 2025, a highly mutated descendant of the Omicron subvariant BA.3 was detected in South Africa.’

📖 Rates of infection with other pathogens after a positive COVID-19 test versus a negative test in US veterans (November 2021 to December 2023): a retrospective cohort study

by Cai et al / The Lancet: Infectious Diseases • 1 April 2025

‘In the 12 months of follow-up, people with COVID-19 who did not require admission to hospital during the acute phase of infection had increased test-positivity rates for bacterial infections (in blood, urine, and respiratory cultures) and viral diseases (including Epstein–Barr virus, herpes simplex virus reactivation, and respiratory viral infections). Compared with people admitted to hospital for seasonal influenza, those admitted for COVID-19 had higher rates of admission to hospital for infectious illnesses (increased risk of 24%), admission to hospital for sepsis (increased risk of 35%), and in-hospital use of antimicrobials (increased risk of 23%).’

Beyond Long COVID – How reinfections could be causing silent long-term organ damage

by David Putrino ❂ Sonya Buyting ~ Radio-Canada / Canadian Broadcasting Corporation • 20 March 2025

CBC Radio-Canada interview with long COVID [PASC] researcher David Putrino from the Icahn School of Medicine at Mount Sinai in New York.

On the ill-fated ‘natural immunity via infection’ pipe-dream: 📖 Effectiveness of previous infection against reinfection (Omicron)

by Chemaitelly et al / Nature • 5 February 2025

‘Before Omicron, natural infection provided strong and durable protection against reinfection, with minimal waning over time. However, during the Omicron era, protection was robust only for those recently infected, declining rapidly over time and diminishing within a year.’

📖 Human herpesvirus reactivation and its potential role in the pathogenesis of post-acute sequelae of SARS-CoV-2 infection

by Gáspár et al / Springer Nature: GeroScience • 29 August 2024

‘The reactivation of latent herpesviruses, such as EBV [Epstein–Barr virus / human herpesvirus 4], CMV [cytomegalovirus], and HHV-6 [human herpesvirus 6], is a significant concern in patients with COVID-19. Several factors associated with COVID-19, including immune dysregulation, systemic inflammation, and direct viral interactions, can trigger the reactivation of these latent viruses.’

📖 Solving the puzzle of Long Covid

by Al-Aly & Topol / Science • 22 February 2024

‘Reinfection, which is now the dominant type of SARS-CoV-2 infection, is not inconsequential; it can trigger de novo Long Covid or exacerbate its severity. Each reinfection contributes additional risk of Long Covid: cumulatively, two infections yield a higher risk of Long Covid than one infection, and three infections yield a higher risk than two infections.’

📖 Long-term risks of respiratory diseases in patients infected with SARS-CoV-2: a longitudinal, population-based cohort study

by Meng et al / The Lancet: eClinical Medicine • 17 February 2024

❦ ‘The occurrences of respiratory disorders among patients who survived for 30 days after the COVID-19 diagnosis continued to rise consistently, including asthma, bronchiectasis, COPD, ILD, PVD*, and lung cancer. * COPD = Chronic obstructive pulmonary disease . ILD = Interstitial lung disease . PVD = Peripheral vascular disease . With the severity of the acute phase of COVID-19, the risk of all respiratory diseases increases progressively. Besides, during the 24-months follow-up, we observed an increasing trend in the risks of asthma and bronchiectasis over time, which indicates that long-term monitoring and meticulous follow-up of these patients is essential. These findings contribute to a more complete understanding of the impact of COVID-19 on the respiratory system and highlight the importance of prevention and early intervention of these respiratory sequelae of COVID-19. In this study, several key findings have been further identified. Firstly, our research demonstrates a significant association between COVID-19 and an increased long-term risk of developing various respiratory diseases. Secondly, we found that the risk of respiratory disease increases with severity in patients with COVID-19, indicating that it is necessary to pay attention to respiratory COVID-19 sequelae in patients, especially those hospitalized during the acute stage of infection. This is consistent with the findings of Lam et al., who found that the risk of some respiratory diseases (including chronic pulmonary disease, acute respiratory distress syndrome and ILD) increased with the severity of COVID-19. Notably, however, our study found that asthma and COPD remained evident even in the non-hospitalized population. This emphasizes that even in cases of mild COVID-19, the healthcare system should remain vigilant. Thirdly, we investigated differences in risk across time periods, as well as the long-term effects of COVID-19 on respiratory disease. During the 2-years follow-up period, the risks of COPD, ILD, PVD and lung cancer decreased, while risks of asthma and bronchiectasis increased. Fourthly, our study showed a significant increase of the long-term risk of developing asthma, COPD, ILD, and lung cancer diseases among individuals who suffered SARS-CoV-2 reinfection. This finding emphasizes the importance of preventing reinfection of COVID-19 in order to protect public health and reduce the potential burden of SARS-CoV-2 reinfection. Interestingly, vaccination appears to have a potentially worsening effect on asthma morbidity compared with other outcomes. This observation aligns with some previous studies that have suggested a possible induction of asthma onset or exacerbation by COVID-19 vaccination. It suggests that more care may be necessary for patients with asthma on taking the COVID vaccines. The underlying mechanisms associated with COVID and respiratory outcomes are not fully understood, but several hypotheses have been proposed. First, SARS-CoV-2 can persist in tissues (including the respiratory tract), as well as the circulating system for an extended period of time after the initial infection. This prolonged presence of the virus could directly contribute to long-term damage of the respiratory tissues, consequently leading to the development of various respiratory diseases. Second, it has been observed that SARS-CoV-2 infection can lead to prolonged immunological dysfunctions, including highly activated innate immune cells, a deficiency in naive T and B cells, and increased expression of interferons and other pro-inflammatory cytokines. These immune system abnormalities are closely associated with common chronic respiratory diseases – asthma, bronchiectasis, COPD, as well as the development of lung cancer. Next, SARS-CoV-2 itself has been shown to drive cross-reactive antibody responses, and a range of autoantibodies were found in patients with COVID-19. In conclusion, our research adds to the existing knowledge regarding the effects of COVID-19 on the respiratory system. Specifically, it shows that the risk of respiratory illness increases with the severity of infection and reinfection. Our findings emphasize the importance of providing extended care and attention to patients previously infected with SARS-CoV-2.’ ❂ 📖 (17 Feb 2024 ~ The Lancet: eClinical Medicine) Long-term risks of respiratory diseases in patients infected with SARS-CoV-2: a longitudinal, population-based cohort study ➤ © 2024 The Lancet: eClinical Medicine .

Genomic mapping of SARS-CoV-2 / COVID-19 variants and subvariants for 2020, 2021, 2022, 2023, 2024.

⚒ Resource: Genomic Mapping of SARS-CoV-2 / COVID-19 Variants

by NextStrain.org / GISAID.org • 21 January 2024

⚒ Resource: SARS-CoV-2 / COVID-19 Genomic Sequence Variant Visualiser

by Mike Honey • 19 January 2024

❦ Mike Honey’s Variant Visualiser (COVID-19 Genomic Sequence Analysis). The region of ‘Oceania/Australia’ is set by default, as the visualiser was created by Mike Honey , a Data Visualisation and Data Integration specialist in Melbourne, Australia. ➲ Choose your country by clicking on the ‘ Continent, Country, Location ’ dropdown menu in the top-right-hand corner . The variant visualiser is free to use, and is automatically updated every time you open the link. ❂ © 2024 Mike Honey .

📖 Beyond breathing: How COVID-19 affects your heart, brain and other organs

by Michael Merschel / American Heart Association • 16 January 2024

“I would argue that COVID-19 is not a disease of the lungs at all. It seems most likely that it is what we call a vascular and neurologic infection, affecting both nerve endings and our cardiovascular system.”

On Omicron JN.1: 📖 A letter to Amanda Pritchard, Chief Executive Officer of NHS England, from the British Medical Association (BMA)

by Professor Phil Banfield (BMA) & Dr. Barry Jones (CAPA) • 22 December 2023

‘It is accepted that COVID-19 can be and is spread by the airborne route. The recent evidence given at the UK COVID-19 Inquiry clearly shows that aerosol transmission is a significant, and almost certainly the dominant, route of transmission for COVID-19.’ The British Medical Association (22 Dec 2023)

📖 COVID JN.1 variant: Royal College of Nursing (RCN) seeks assurance on new PPE advice

by Royal College of Nursing (RCN) (UK) • 21 December 2023

‘The RCN is urging healthcare employers to assess the risk posed by COVID-19 and put appropriate safeguards in place for patients and staff. WHO [has] advised healthcare workers and health facilities to implement universal masking in health facilities, as well as appropriate masking, respirators and other personal protective equipment for health workers caring for suspected and confirmed COVID-19 patients; and to improve ventilation in health facilities.’ ✾ ❦ We’ve contacted chief nursing officers in all four UK countries and the UKHSA to find out what action will be taken in response to WHO’s statement on a new COVID-19 variant of interest. The RCN is asking for a revision to current guidelines , to introduce universal implementation of the two measures advised by the World Health Organization (WHO) to help protect healthcare staff against COVID-19. Earlier this week, in light of the new COVID JN.1 variant, WHO advised healthcare workers and health facilities to: implement universal masking in health facilities , as well as appropriate masking , respirators and other personal protective equipmen t for health workers caring for suspected and confirmed COVID-19 patients ; improve ventilation in health facilities . The existing national infection prevention and control manuals don’t require standardised masking for COVID-19, and decisions on respiratory protective equipment are left to local risk assessments. This is now inconsistent with WHO’s latest advice . We also have concerns about the adequacy of ventilation in general ward and outpatient areas within hospital buildings and believe that action must be taken to assess and improve this. Although evidence suggests that the global public health risks from the new variant are low, WHO has warned that onset of winter could increase the burden of respiratory infections in the Northern hemisphere. This comes when there are already unsustainable pressures on the health service. Figures show that there has been a rise in COVID-19 cases and hospitalisations , and the RCN argues that without proper protections , ill health could continue to rise in nursing staff and impact their ability to deliver safe and effective patient care . WHO has advised that it is continuously monitoring the evidence and will update the JN.1 risk evaluation as needed. The RCN is urging healthcare employers to assess the risk posed by COVID-19 and put appropriate safeguards in place for patients and staff . Our COVID-19 workplace risk assessment toolkit aims to help assess and manage the risks associated with respiratory infections such as COVID-19, highlights the duties of nursing staff in specific roles (such as health and safety reps), has advice for employers and leaders, and provides the latest information on risk assessment. ❂ 📖 (21 Dec 2023 ~ Royal College of Nursing / RCN Magazine) COVID JN.1 variant: RCN seeks assurance on new PPE advice ➤ © 2023 Royal College of Nursing (RCN).

☣ Variant Watch: 📖 World Health Organization (WHO) Media Advisory for the COVID-19 variant of interest (VOI) JN.1

by The World Health Organization (WHO) • 19 December 2023

❦ ‘Due to its rapidly increasing spread , WHO is classifying the variant JN.1 as a separate variant of interest ( VOI ) from the parent lineage BA.2.86 . It was previously classified as VOI as part of BA.2.86 sublineages. Based on the available evidence, the additional global public health risk posed by JN.1 is currently evaluated as low. Despite this, with the onset of winter in the Northern Hemisphere, JN.1 could increase the burden of respiratory infections in many countries. ➲ Read the risk evaluation: ‘Tracking SARS-CoV-2 variants’ . WHO is continuously monitoring the evidence and will update the JN.1 risk evaluation as needed. Current vaccines continue to protect against severe disease and death from JN.1 and other circulating variants of SARS-CoV-2, the virus that causes COVID-19. COVID-19 is not the only respiratory disease circulating. Influenza, RSV and common childhood pneumonia are on the rise. ➲ WHO advises people to take measures to prevent infections and severe disease using all available tools . These include: • Wear a mask when in crowded, enclosed, or poorly ventilated areas, and keep a safe distance from others, as feasible. • Improve ventilation . • Practise respiratory etiquette – covering coughs and sneezes. • Clean your hands regularly. • Stay up-to-date with vaccinations against COVID-19 and influenza, especially if you are at high risk for severe disease. • Stay home if you are sick . • Get tested if you have symptoms, or if you might have been exposed to someone with COVID-19 or influenza. ✻ ➲ For health workers and health facilities , WHO advises : • Universal masking in health facilities , as well as appropriate masking , respirators and other PPE for health workers caring for suspected and confirmed COVID-19 patients . • Improve ventilation in health facilities. Note : Updated 19 Dec 2023 with additional information for health workers and facilities. ’ ❂ 📖 (19 Jan 2023 ~ WHO / World Health Organization) World Health Organization (WHO) Media Advisory for the COVID-19 variant of interest (VOI) JN.1 ➤ © 2023 WHO / World Health Organization. ❦ Date accessed : 11 Jan 2024 .

Show More Articles

❦ Immunity & the Immune System ~ Scientific papers & media articles

✒ 2023

📖 (Accessed 20 Sep 2023 ~ University of Oxford) Autoimmune disorders found to affect around one in ten people ➤

❂

📖 (13 Sep 2023 ~ 1 News/NZ) Covid may have permanently damaged people's immunity ➤

❂

📖 (18 Aug 2023 ~ Cell) Epigenetic memory of coronavirus infection in innate immune cells and their progenitors ➤

❂

📖 (16 Aug 2023 ~ The Lancet / eClinicalMedicine) Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study ➤

❂

📖 (9 Aug 2023 ~ Science: Translational Medicine) Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts ➤

❂

📖 (4 Aug 2023 ~ Pre-print) Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2 ➤

❂

📖 (19 Jun 2023 ~ Clinical Rheumatology) Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study ➤

❂

📖 (3 Jun 2023 ~ The Lancet) Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK ➤

❂

📖 (3 May 2023 ~ Infectious Diseases) Evaluation of Waning of SARS-CoV-2 Vaccine-Induced Immunity – A Systematic Review and Meta-analysis ➤

❂

📖 (25 Apr 2023 ~ International Journal of Molecular Sciences) Deciphering the Relationship between SARS-CoV-2 and Cancer ➤

➲ 'Some viruses are known to be associated with the onset of specific cancers.

These micro-organisms, oncogenic viruses or oncoviruses, can convert normal cells into cancer cells by modulating the central metabolic pathways or hampering genomic integrity mechanisms, consequently inhibiting the apoptotic machinery and/or enhancing cell proliferation.

Seven oncogenic viruses are known to promote tumorigenesis [the formation of a cancer] in humans: human papillomavirus (HPV) [associated with genital warts], hepatitis B and C viruses (HBV, HCV), Epstein-Barr virus (EBV) [human herpesvirus 4], human T-cell leukemia virus 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCPyV).

Recent research indicates that SARS-CoV-2 infection and COVID-19 progression may predispose recovered patients to cancer onset and accelerate cancer development.'

❂

📖 (18 Apr 2023 ~ Journal of Medical Virology) Long-term risk of herpes zoster following COVID-19: A retrospective cohort study of 2 442 686 patients ➤

➲ 'The risk of herpes zoster (HZ) (Shingles) remained significantly [+60%] higher in patients with COVID-19 compared with those without COVID-19.

The higher risk of HZ in the COVID-19 cohort compared with that in the non-COVID-19 cohort remained consistent across subgroup analyses regardless of vaccine status, age, or sex.

The risk of HZ within a 12-month follow-up period was significantly higher in patients who had recovered from COVID-19 compared with that in the control group.'

❂

📖 (18 Apr 2023 ~ BMC Infectious Diseases) Fungal infection profile in critically ill COVID-19 patients: a prospective study at a large teaching hospital in a middle-income country ➤

➲ 'Critically ill COVID-19 patients are highly susceptible to opportunistic fungal infection due to many factors, including virus-induced immune dysregulation, host-related comorbidities, overuse and misuse of antibiotics or corticosteroids, immune modulator drugs, and the emergencies caused by the pandemic.

Fungal coinfection is a common complication of critically ill COVID-19 patients admitted to the ICU. Candidiasis, aspergillosis, and mucormycosis are the most common COVID-19-associated fungal infections and have a great impact on mortality rates.'

❂

📖 (14 Apr 2023 ~ Viruses) SARS-CoV-2 Reinfection and Severity of the Disease: A Systematic Review and Meta-Analysis ➤

➲ 'Reinfection with SARS-CoV-2 does occur, suggesting that natural immunity is not long-lasting in COVID-19 patients. Female patients seem more likely to experience reinfection than male patients.

Thus far, no clear evidence for a difference in severity between the first infection and reinfection has been observed.'

❂

📖 (12 Apr 2023 ~ Nature Reviews: Rheumatology) High risk of autoimmune diseases after COVID-19 ➤

➲ 'Two studies that use large cohorts now highlight that SARS-CoV-2 infection is linked to a substantially increased risk of developing a diverse spectrum of new-onset autoimmune diseases.

The reports by Chang et al and Tesch et al provide a comprehensive overview of diverse new-onset autoimmune conditions after COVID-19.

In addition, an earlier preprint of a retrospective matched cohort analysis using data from the Clinical Practice Research Datalink Aurum database of 458,147 SARS-CoV-2-infected and 1,818,929 uninfected adults across England between 31 January 2020 and 30 June 2021 reported that the incidence of type 1 diabetes mellitus, inflammatory bowel disease and psoriasis are significantly associated with SARS-CoV-2 infection.'

❂

📖 (21 Mar 2023 ~ Infection Control Today) COVID-19: Study Suggests Long-term Damage to Immune System ➤

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📖 (March 2023 ~ Asia Pacific Allergy) Immunological dysfunction and mast cell activation syndrome in long COVID ➤

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📖 (16 Feb 2023 ~ BMC Biology) High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients ➤

❂

📖 (7 Feb 2023 ~ Journal of Allergy and Clinical Immunology) SARS-CoV-2 infection of thymus induces loss of function that correlates with disease severity ➤

➲ 'Lymphopenia, particularly when restricted to the T-cell compartment, has been described as one of the major clinical hallmarks in patients with coronavirus disease 2019 (COVID-19) and proposed as an indicator of disease severity.

Although several mechanisms fostering COVID-19-related lymphopenia have been described, including cell apoptosis and tissue homing, the underlying causes of the decline in T-cell count and function are still not completely understood.

Patients with COVID-19 had reduced thymic function that was inversely associated with the severity of the disease.

Our data demonstrate that the human thymus is a target of SARS-CoV-2 and thymic function is altered following infection.'

Note: Lymphopenia (also called lymphocytopenia) is a disorder in which your blood doesn't have enough white blood cells called lymphocytes. Lymphocytes play a protective role in your immune system.

❂

📖 (18 Jan 2023 ~ Nature) How your first brush with COVID warps your immunity ➤

❂

📖 (13 Jan 2023 ~ Preprint) Structure-based discovery of inhibitors of the SARS-CoV-2 Nsp14 N7-methyltransferase ➤

❂

📖 (12 Jan 2023 ~ News-Medical.Net) New insights into deadly fungal invasion in people with compromised immune systems ➤

➲ 'Fungi such as Aspergillus are so common in our surroundings that we breathe in hundreds to thousands of spores every day.

In healthy people, fungi typically pose no threat, but they can cause deadly infections in those with compromised immune systems.

However, it is increasingly recognized that viral infections such as influenza or SARS-CoV-2 can increase the risk of invasive Aspergillus infections even in healthy people.'

❂

📖 (11 Jan 2023 ~ Nature Reviews: Immunology) Innate immune evasion strategies of SARS-CoV-2 ➤

❂

📖 (January 2023 ~ Clinical Immunology) Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19 ➤

❂

✒ 2022

📖 (26 Dec 2022 ~ Nature) Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19 ➤

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📖 (6 Dec 2022 ~ Best Practice & Research Clinical Haematology) COVID-19 disease and immune dysregulation ➤

➲ 'While COVID-19 was originally characterized as hyperinflammatory in its pathophysiology, emerging evidence demonstrates the possibility of a strongly immunosuppressive phenotype in more critical disease states.

While immune activation from neutrophils and complement may contribute to inflammatory damage in the lungs, decreased antiviral responses, dysregulated macrophages and dendritic cells, and severe lymphopenia contribute to a suppressed state in which viral replication and secondary infections are prone.'

❂

Note: ❊ = Scientific paper illustrating clear immune dysregulation.

❊ 📖 (2 Dec 2022 ~ Frontiers in Immunology) Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals ➤

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❊ 📖 Preprint: (20 Nov 2022 ~ medRxiv) Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 Spike protein ➤

❂

❊ 📖 Preprint: (20 Nov 2022 ~ medRxiv) Elevated circulating monocytes and monocyte activation in pulmonary post-acute sequelae of SARS-CoV-2 infection ➤

❂

📖 (22 Oct 2022 ~ Cleveland.com) In Cleveland and beyond researchers begin to unravel the mystery of long COVID-19 ➤

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📖 (7 Oct 2022 ~ Counter Disinformation Project) "Immunity Debt"? Established 2021 ➤

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📖 (22 Sep 2022 ~ European Respiratory Journal) Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long COVID symptoms ➤

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📖 (12 Sep 2022 ~ Nature: Communications) Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk ➤

❂

📖 (17 Aug 2022 ~ The Conversation) When COVID-19 or flu viruses kill, they often have an accomplice – bacterial infections ➤

➲ 'The 1918 influenza pandemic resulted in the loss of over 3% of the world's population – at least 50 million people.

But it wasn't the flu virus that caused the majority of these deaths.

An analysis of lung samples collected during that flu pandemic indicated that most of the deaths were likely due to bacterial pneumonia, which ran rampant in the absence of antibiotics.

Even in more recent history, like the 1957 H2N2 and 2009 H1N1 flu pandemics, nearly 18% of patients with viral pneumonia had additional bacterial infections that increased their risk of death.

And the COVID-19 pandemic is no different.'

❂

📖 (PDF) (4 Aug 2022 ~ European Respiratory Journal) Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long COVID symptoms ➤

❂

📖 (14 May 2022 ~ Allergy) T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19 ➤

❂

📖 (1 May 2022 ~ Gastroenterology) Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases ➤

❂

📖 (22 Apr 2022 ~ Clinical Infectious Diseases) Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome ➤

❂

📖 (8 Apr 2022 ~ Pre-print) SARS-CoV-2 and its variants, but not Omicron, induces thymic atrophy and impaired T cell development ➤

❂

📖 (23 Mar 2022 ~ Pathogens) Superantigens and SARS-CoV-2 ➤

❂

❊ 📖 (11 Mar 2022 ~ Nature Signal Transduction and Targeted Therapy) ACE2-independent infection of T lymphocytes by SARS-CoV-2 ➤

❂

📖 (10 Mar 2022 ~ Science) The immunology and immunopathology of COVID-19 ➤

❂

📖 (3 Mar 2022 ~ Frontiers) Understanding the Effects of Age and T-Cell Differentiation on COVID-19 Severity: Implicating a Fas/FasL-mediated Feed-Forward Controller of T-Cell Differentiation ➤

❂

❊ 📖 (21 Feb 2022 ~ Frontiers in Immunology) Depletion and Dysfunction of Dendritic Cells: Understanding SARS-CoV-2 Infection ➤

❂

❊ 📖 (22 Jan 2022 ~ Nature Immunology) Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection ➤

❂

❊ 📖 (14 Jan 2022 ~ BMC Medicine) Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection ➤

❂

📖 (13 Jan 2022 ~ Nature) Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection ➤

❂

✒ 2021

📖 (16 Nov 2021 ~ The Journal of Clinical Investigation) PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response ➤

❂

📖 (1 Oct 2021 ~ Pathogens) Uncertainty around the Long-Term Implications of COVID-19 ➤

❂

❊ 📖 (22 Sep 2021 ~ Nature / Signal Transduction and Targeted Therapy) SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism ➤

❂

❊ 📖 (21 July 2021 ~ Nature / Cellular & Molecular Immunology) Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection ➤

❂

📖 (25 May 2021 ~ The Journal of Clinical Investigation) Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier ➤

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📖 (7 May 2021 ~ Frontiers in Immunology) Longitudinal Analysis of COVID-19 Patients Shows Age-Associated T Cell Changes Independent of Ongoing Ill-Health ➤

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📖 (20 Apr 2021 ~ Autoimmunity Reviews) Granulomatous manifestations associated with COVID19 infection: Is there a link between these two diseases? ➤

➲ 'Covid infections are putting people at higher risk of diabetes, strokes, heart disease and other long-term illnesses – but experts warn it may be decades before the full impact is known.'

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📖 (21 Mar 2021 ~ Journal of Cosmetic Dermatology) Oral candidiasis of COVID‐19 patients: Case report and review of evidence ➤

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📖 (11 Mar 2021 ~ The Journal of Clinical Investigation) HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children ➤

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📖 (4 Mar 2021 ~ KFF Health News) Coronavirus Deranges the Immune System in Complex and Deadly Ways ➤

➲ 'While all viruses find ways to evade the body's defenses, a growing field of research suggests that the coronavirus unhinges the immune system more profoundly than previously realized.

Some covid survivors have developed serious autoimmune diseases, which occur when an overactive immune system attacks the patient, rather than the virus.

Doctors in Italy first noticed a pattern in March 2020, when several covid patients developed Guillain-Barré syndrome, in which the immune systems attacks nerves throughout the body, causing muscle weakness or paralysis.

As the pandemic has surged around the world, doctors have diagnosed patients with rare, immune-related bleeding disorders. Other patients have developed the opposite problem, suffering blood clots that can lead to stroke.

All these conditions can be triggered by autoantibodies – rogue antibodies that target the patient's own proteins and cells.'

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✒ 2020

📖 (21 Dec 2020 ~ Frontiers in Immunology) Akt-Fas to Quell Aberrant T Cell Differentiation and Apoptosis in Covid-19 ➤

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📖 (18 Nov 2020 ~ Science / Translational Medicine) Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19 ➤

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📖 (17 Nov 2020 ~ Nature) Immune suppression in the early stage of COVID-19 disease ➤

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❊ 📖 (29 Oct 2020 ~ The Journal of Clinical Investigation) Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection ➤

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❊ 📖 (28 Sept 2020 ~ Nature / Scientific Reports) Immune dysfunction following COVID-19, especially in severe patients ➤

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📖 (24 Sep 2020 ~ Science) Autoantibodies against type I IFNs in patients with life-threatening COVID-19 ➤

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📖 (17 Sep 2020 ~ Cell) Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment ➤

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📖 (16 Sep 2020 ~ The Scientist) The Immune Hallmarks of Severe COVID-19 ➤

➲ 'Researchers are trying to make sense of immune systems gone haywire and develop biomarkers to predict who will become the sickest from a coronavirus infection.'

“Perhaps severe COVID-19 isn't a purely inflammatory disease, but rather a dangerous loop of ineffective human immune responses and continuous tissue inflammation.”

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📖 (16 July 2020 ~ Pre-print) AIDS and COVID-19 are two diseases separated by a common lymphocytopenia ➤

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📖 (29 June 2020 ~ PNAS) Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation ➤

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📖 20 Apr 2021 ~ Nature: Cell Death & Differentiation) SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination ➤

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❊ 📖 (1 May 2020 ~ Frontiers in Immunology) Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) ➤

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Acknowledgement

My sincere thanks to Andrew Ewing of The World Health Network for helping to compile this list.

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