Impact of covid infection on the human body (focus on brain and immune system)— a short review

Why you should prevent being (re)infected.

Reinfections

• Those who had 2 COVID infections were 2.14 times more likely, and those who had 3 or more COVID infections were 3.75 times more likely, to report #LongCOVID than those with one infection. (preprint) https://www.researchsquare.com/article/rs-4909082/v1
• Compared to noninfected controls, cumulative risks and burdens of repeat infection increased according to the number of infections. Limitations included a cohort of mostly white males. The evidence shows that reinfection further increases risks of death, hospitalization and sequelae in multiple organ systems in the acute and postacute phase. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention. https://www.nature.com/articles/s41591-022-02051-3
• Institut national de santé publique du Québec: “Le risque cumulatif d’APC augmente avec le nombre d’infections passant de 13 % avec une infection, à 23 % avec deux infections et atteignant 37 % pour trois infections.” https://www.inspq.qc.ca/en/node/664766
• Participants who experienced multiple infections were more likely to experience various Long Covid symptoms with greater severity. Having two infections is risk factor for many long-term Covid symptoms, and the risk increased exponentially when the number of infections exceeded two. These new data on Long Covid risk after reinfection are remarkably consistent with prior studies.
  Reinfection was associated with milder symptoms but led to a higher incidence and severity of long COVID (OR > 1, FDR < 0.05). Vaccination, particularly multiple boosters, significantly reduced long-term symptoms by 30%–70% (OR < 1, FDR < 0.05). COVID-19 participants also self-reported more bacterial, influenza and mycoplasma infections, and 8%–10% of patients felt SARS-CoV-2-induced chronic diseases. https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(24)00212-8/fulltext

Brain damage/neurological & psychiatric consequences

• Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17–34·07), with 12·84% (12·36–13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78–48·09) and for a first diagnosis was 25·79% (23·50–28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50–0·63) for intracranial haemorrhage, 2·10% (1·97–2·23) for ischaemic stroke, 0·11% (0·08–0·14) for parkinsonism, 0·67% (0·59–0·75) for dementia, 17·39% (17·04–17·74) for anxiety disorder, and 1·40% (1·30–1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24–3·16) for intracranial haemorrhage, 6·92% (6·17–7·76) for ischaemic stroke, 0·26% (0·15–0·45) for parkinsonism, 1·74% (1·31–2·30) for dementia, 19·15% (17·90–20·48) for anxiety disorder, and 2·77% (2·31–3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40–1·47, for any diagnosis; 1·78, 1·68–1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14–1·17, for any diagnosis; 1·32, 1·27–1·36, for any first diagnosis). https://www.thelancet.com/journals/lanpsy/article/PIIS2215–0366(21)00084–5/fulltext
• Mild COVID-19 disrupts brain connectivity and reduces memory function in adolescents and young adults.
  In a case-control study published in the journal Translational Psychiatry, researchers used magnetic resonance imaging (MRI) and cognitive tests to examine brain structure, function, and cognition in adolescents and young adults with mild coronavirus disease 2019 (COVID-19) compared to healthy controls in a pandemic hotspot in Italy. They identified significant changes in brain regions related to olfaction and cognition, with decreased brain volume and reduced functional connectivity in areas like the left hippocampus and amygdala, which were linked to impaired spatial working memory. https://www.news-medical.net/news/20241003/Mild-COVID-19-disrupts-brain-connectivity-and-reduces-memory-function-in-adolescents-and-young-adults.aspx
• There is strong evidence of brain-related abnormalities in COVID-19 1,2,3,4,5,6,7,8,9,10,11,12,13. However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51–81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans — with 141 days on average separating their diagnosis and the second scan — as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up. https://www.nature.com/articles/s41586–022–04569–5

Listen to prof. Altmann from 3:30 until 5:15 commenting on this study based on UK Biobank https://www.youtube.com/watch?v=cnnbS22A5qc
In a nutshell : “If you have SARS-COV-2, even mild SARS-COV-2, it changes your brain, changes the way your brain MRI looks, and makes you more stupid!”

• SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer’s-like neuropathology https://www.biorxiv.org/content/10.1101/2022.01.31.478476v2
• Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30228-5/fulltext
• People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection (N = 326) https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00324-2/fulltext
• The brain deficits found in COVID-19 patients were equivalent to 20 years of brain aging and provided proof of what doctors have feared: that this virus can damage the brain and result in ongoing mental health issues. https://www.medscape.com/viewarticle/new-evidence-suggests-long-covid-could-be-brain-injury-2024a10002v0?form=fpf
• Interesting article by dr. Ziyad Al-Aly https://theconversation.com/mounting-research-shows-that-covid-19-leaves-its-mark-on-the-brain-including-significant-drops-in-iq-scores-224216
• This analysis of 2-year retrospective cohort studies of individuals diagnosed with COVID-19 showed that the increased incidence of mood and anxiety disorders was transient, with no overall excess of these diagnoses compared with other respiratory infections. In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes. Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern. The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects. Our findings are relevant to understanding individual-level and population-level risks of neurological and psychiatric disorders after SARS-CoV-2 infection and can help inform our responses to them. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(22)00260-7/fulltext#supplementaryMaterial
• those who had mild and resolved COVID-19 showed cognitive decline equivalent to a three-point loss of IQ. In comparison, those with unresolved persistent symptoms, such as people with persistent shortness of breath or fatigue, had a six-point loss in IQ. Those who had been admitted to the intensive care unit for COVID-19 had a nine-point loss in IQ. Reinfection with the virus contributed an additional two-point loss in IQ, as compared with no reinfection. https://www.scientificamerican.com/article/covid-19-leaves-its-mark-on-the-brain-significant-drops-in-iq-scores-are/
• Strokes caused by COVID-19 appear to be more disabling and deadly than those not associated with the infectious disease, a new study finds. About one-third of COVID-19 patients develop neurological complications, and many arrive at hospitals with ischemic strokes (blocked blood flow to the brain), according to the researchers who studied cases in North America. https://www.upi.com/Health_News/2022/02/09/stroke-COVID-19/2561644417866/
• COVID-19-related long-term olfactory dysfunction and early damage to olfactory and limbic brain regions suggest a pattern of degeneration similar to that seen in early stages of Alzheimer’s disease, Parkinson’s disease, and Lewy body dementia. Thus, long-term olfactory dysfunction coupled with cognitive and emotional disturbance from COVID-19 may be the first signs of delayed onset dementia from neurodegeneration. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377782/
• GnRH neurons in fetuses and infants could be particularly susceptible to SARS-CoV-2 infection: In sections of the nose and brain of human fetuses, we identified viral susceptibility factors in newborn GnRH neurons, and also showed that the virus could infect cultured embryonic GnRH neurons. Since the normal maturation and activation of GnRH neurons is necessary not only for later reproductive function but also the development of cognitive and sensory functions by the brain, this last finding suggests an increased risk of neurodevelopmental impairments in children born to infected mothers or infected in infancy themselves. To summarize, our work raises the spectre of a second and delayed ‘non-infectious pandemic’ of cognitive, metabolic and reproductive disorders in COVID-19 survivors https://www.openaccessgovernment.org/article/brain-infection-by-sars-cov-2-lifelong-consequences/171391/
• Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00013-0/fulltext
• Neurocognitive Impairment in Long COVID: A Systematic Review https://academic.oup.com/acn/advance-article/doi/10.1093/arclin/acae042/7689909?login=false :
• Neuroimaging studies performed in humans 10 months after they ‘recovered’ from mild-to-moderate SARS-CoV-2 infection showed significant alterations (commensurate with 7 ‘years of healthy aging’) of cerebral white matter https://www.nature.com/articles/s41591-024-03173-6
• COVID-19 can fuse brain cells together according to a new study and could explain symptoms associated with those suffering long COVID such as brain fog, headaches, loss of taste and smell. Prof Yazi Ke: https://www.abc.net.au/news/2023-06-08/covid-19-can-cause-brain-fog-research-shows/102457290
• COVID-19 can accelerate progression of dementia and induce BBB disruption and inflammatory blood clots causally linked with neuroinflammation and neuronal loss. https://www.cell.com/cell/fulltext/S0092-8674(24)01037-7
• Neuroimaging studies performed in humans 10 months after they ‘recovered’ from mild-to-moderate SARS-CoV-2 infection showed significant alterations (commensurate with 7 ‘years of healthy aging’) of cerebral white matter https://www.nature.com/articles/s41591-024-03173-6
• Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer’s disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14089

Immune system

• Repeated SARS-CoV-2 infections may be prematurely aging human immune systems, research suggests https://nationalpost.com/health/is-covid-prematurely-aging-our-immune-systems
• We observe a comparable reduction in B cells in both diseases and a more severe reduction in the total amount of T cells in COVID-19 as compared to AIDS patients. The analysis of the T cells subpopulations indicates that there is a comparable reduction in the CD4+ cells count. Conversely, a remarkable difference between them is observed in the CD8+ counts. In AIDS patients the CD8+ cells are slightly higher than normal, while in COVID-19 patients the CD8+ cell count is markedly reduced. As a result, the CD4+/CD8+ ratios, is very low in AIDS and higher than normal in COVID-19 patients. The NK cells are reduced in both diseases, but SARS-CoV-2 infection causes a more severe reduction compared to HIV infection. In conclusion, both HIV and SARS-CoV-2 viruses induce major changes in the lymphocytes count, with remarkable similarities and differences between them. The total absolute numbers of T cells and, in particular of the CD8+ subpopulation, are lower in COVID-19 patients compared to AIDS ones, while the CD4+ are reduced in both at similar levels. These results indicate that the host immune system reacts differently to the two infection, but they are responsible of a comparable dropping effect on the serum levels of CD4+ T cell population https://www.researchgate.net/publication/342997179_AIDS_and_COVID-19_are_two_diseases_separated_by_a_common_lymphocytopenia
• Patients with HIV infection routinely have lymphocytopenia, which arises from destruction of CD4+ T cells infected with the HIV virus (1). Lymphocytopenia may also reflect impaired lymphocyte production arising from destruction of thymic or lymphoid architecture. In acute viremia due to HIV or other viruses, lymphocytes may undergo accelerated destruction from active infection with the virus, may be trapped in the spleen or lymph nodes, or may migrate to the respiratory tract. Patients with COVID-19 also frequently have lymphocytopenia (35 to 83% of patients) (2). Lower lymphocyte counts portend a poor prognosis and an increased likelihood of requiring ICU admission and of dying from the disease. The cause of the lymphocytopenia is not completely understood, but COVID-19 can directly infect lymphocytes, and a cytokine-related apoptosis of the cells is likely. https://www.msdmanuals.com/professional/hematology-and-oncology/leukopenias/lymphocytopenia#Etiology_v970788
• Covid infection leads to substantial higher risk of other consequences, including other infectious diseases https://www.nature.com/articles/s41586-021-03553-9#MOESM4 (see table 2, partial screenshot below; last column = hazard ratio after covid infection).

For instance in Sweden (which never had lockdowns, thus contradicting the false ‘immune debt’ fantasy), the following charts show this unfolding reality in the charts below. https://www.karolinska.se/4a94bd/globalassets/global/2-funktioner/funktion-kul/klinisk-mikrobiologi/epidemiologi/rapport-influensa--och-rs-virus-och-andra-luftvagspatogener.pdf

Only in Sweden? No, below for instance the UK.

In the table above, the hazard ratio of TB after a covid infection is 1.91.
Now, “up to 13 million people may have latent TB in the U.S, which could be activated by COVID-19. TB has a worrisome connection to the novel coronavirus. For someone with latent TB, contracting COVID-19 could activate the bacterium, potentially leading to an accelerated and more severe form of the disease which could lead to hospitalization and rapid death. Both diseases are airborne. The TB bacterium is an opportunistic pathogen and remains latent, waiting for people’s immune system to become compromised — as in the case of AIDS, or overwhelmed — as in the case of COVID-19.” https://www.sdsu.edu/news/2020/09/covid-19-could-activate-latent-tuberculosis

Children/adolescents impacted

“COVID-19 was associated with a significantly increased risk for RSV infections among children aged 0–5 years in 2022. Similar findings were replicated for a study population of children aged 0–5 years in 2021. Our findings suggest that COVID-19 contributed to the 2022 surge of RSV cases in young children through the large buildup of COVID-19-infected children and the potential long-term adverse effects of COVID-19 on the immune and respiratory system.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582888/.

“The risk of myocarditis for children under 16 years is 37 times higher for those infected with COVID-19 than those who haven’t been infected with the virus, according to a new study.” https://publications.aap.org/aapnews/news/16388?autologincheck=redirected

“Pediatric long COVID is more common than many thought, and we keep letting kids be reinfected with new variants” “Long COVID symptoms appear to occur after about 10 percent to 20 percent of pedriatic infections. https://www.scientificamerican.com/article/long-covid-is-harming-too-many-kids/

“This is the longest follow-up study of children with SARS-CoV-2 infection, showing a significant and long-lasting burden of Long Covid in the pediatric population. Our findings highlight the urgent need of investing in pediatric Long Covid in order to find effective diagnostic and therapeutic approaches, as well can inform preventive strategies in case of future pandemics.” https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00394-8/fulltext

Elevated levels of a biomarker related to blood vessel damage in all children with SARS-CoV-2 infection, even if the children had minimal or no symptoms of COVID-19. A high proportion of children with SARS-CoV-2 infection met clinical and diagnostic criteria for thrombotic microangiopathy (TMA). TMA is a syndrome that involves clotting in the small blood vessels and has been identified as a potential cause for severe manifestations of COVID-19 in adults. https://medicalxpress.com/news/2020-12-elevated-biomarker-blood-vessel-children.html

Mild COVID-19 alters brain structure and connectivity in key areas responsible for memory and cognition, emphasizing the lasting effects on young people’s brain health. https://www.news-medical.net/news/20241003/Mild-COVID-19-disrupts-brain-connectivity-and-reduces-memory-function-in-adolescents-and-young-adults.aspx

Diabetes

Meta-analysis and systematic review:

“At all ages, there was a statistically significant positive association between infection with COVID-19 and the risk of diabetes: <18 years: RR=1.72 (1.19–2.49), ≥18 years: RR=1.63 (1.26–2.11), and >65 years: RR=1.68 (1.22–2.30)” https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02656-y (RR = Relative Risk)

Risk while undergoing surgery

Patients undergoing surgery with COVID-19 elicited a nine-fold increased risk of mortality (relative risk [RR] 8.99, 95% confidence interval [CI] 4.96–16.32) over those without COVID-19. https://www.journalofsurgicalresearch.com/article/S0022-4804(24)00042-8/abstract

Fertility

SARS-CoV-2 significantly reduced ejaculate volume, sperm count, concentration, viability, normal morphology, and total and progressive motility. Furthermore, SARS-CoV-2 led to a reduction in circulating testosterone level, but a rise in oestrogen, prolactin, and luteinizing hormone levels. These findings were associated with a decline in testosterone/luteinizing hormone ratio.
The current study provides compelling evidence that SARS-CoV-2 may lower male fertility by reducing semen quality through a hormone-dependent mechanism; reduction in testosterone level and increase in oestrogen and prolactin levels. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0307396

Arterial thrombotic events

Study with > 15 million people showed the risk (HR) of an arterial thrombotic event, e.g. heart attack or stroke, on day zero of COVID infection was 73x higher for vaccinated people and 255x higher for unvaccinated people. https://www.nature.com/articles/s41467-024-46497-0

Whole body affected

https://www.nature.com/articles/s41586-021-03553-9