COVID-19 Is Airborne AIDS: Provocative Oversimplification, Emerging Science, or Something in Between?

HIGHLIGHTS

• •HIV/AIDS and COVID-19 are preventable infectious diseases with chronic systemic impacts, including immune system dysfunction.
• •Chronic inflammation, immune exhaustion, and accelerated biological aging are shared hallmarks of HIV-1/AIDS and Long COVID/postacute sequelae of COVID-19.
• •Tissue reservoir persistence drives long-term damage in both HIV-1 and SARS-CoV-2. SARS-CoV-2 mirrors HIV-1 in its ability to evade immune defenses and cause chronic infection.
• •SARS-CoV-2–associated neurologic disorders parallel HIV-associated neurologic disorders.
• •Both pandemics exhibit failures in global solidarity and reveal inequities in healthcare access.

Abstract

Immune dysfunction and systemic effects in HIV and SARS-CoV-2 infections are distinct but share relevant similarities and downstream consequences. The authors compare and contrast observations of the immunological impacts of COVID-19 and HIV infections. By examining shared and distinct mechanisms, such as immune dysfunction, vulnerability to opportunistic infections, accelerated aging, and neurocognitive disorders, the authors highlight critical parallels and their implications. The authors review the extensive scientific evidence showing that SARS-CoV-2 infections result in immune cell depletion, dysfunction, and exhaustion, with impacts on several immune system cell types. Higher rates of individual susceptibility to infections lead to population-wide increases in diverse infectious diseases, including those that are signatures of immunodeficiency. Finally, the authors characterize societal responses to both pandemics, providing insights into public health strategies and lessons for improving current and future research, treatment, preparedness, and mitigation efforts.

Graphical abstract

INTRODUCTION: WHY COMPARE HIV WITH SARS-COV-2?

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often compared with other pandemics for its societal and global health impact, with some commentators drawing parallels to HIV/AIDS owing to the immune dysfunction caused by both viruses.1, 2, 3, 4

HIV and SARS-CoV-2 infections typically present with cold-like symptoms days after infection—sore throat; malaise and fatigue; and, sometimes, fever or cough—or remain asymptomatic in the acute phase,⁵ complicating differentiation from common self-limiting respiratory infections without testing.⁶ Notably, similarities in the surface glycoproteins of both viruses have led to a higher occurrence of HIV false-positive results in individuals with antibodies against SARS-CoV-2 spike protein.⁷

SARS-CoV-2, a respiratory transmitted disease, spreads over airborne aerosols and respiratory droplets far more easily than HIV, a primarily sexually transmitted disease that can also spread through blood transfusion, organ transplantations, and contaminated needles. A small number of airborne virions suffice for SARS-CoV-2 infection, making containment more challenging.⁸ In 2023, HIV infections dropped to 1.3 million, the lowest since the 1980s,⁹ whereas global SARS-CoV-2 infections number in hundreds of millions to billions annually owing to waning immunity, viral evolution, and limited surveillance.

Especially since the emergence of Omicron sublineages, reinfections are likely to occur at least yearly if not several times per year without protective measures.^10,11 Especially in older individuals, previous Omicron infection can increase the risk of reinfection with the newer variants.¹² Omicron subvariants exhibit enhanced evasion from T-cell recognition.^13,14 In addition, BA.4 and BA.5 subvariants and their descendants have evolved improved suppression of innate immunity compared with earlier subvariants BA.1 and BA.2. Even more recent subvariants BA.2.75 and XBB lineages also exhibit enhanced suppression of innate immune activation.¹⁵

Both infections can cause chronic, multisystemic conditions characterized by immune dysfunction. HIV/AIDS typically leads to permanent, life-threatening immune system damage that develops after several years.⁵ SARS-CoV-2, by contrast, exhibits a wide range of effects that develop in weeks to months and sometimes persist,16, 17, 18, 19, 20, 21 with reinfections compounding organ damage and functional decline.22, 23, 24

Population-wide increases in many infections are being witnessed, including typical opportunistic infections,²⁵ after the widespread infections by SARS-CoV-2—consistent with what would be expected from long-term or cumulative immunodeficiency after COVID-19 infections.^26,27 At the population level, these increases in infections are driven by both reductions in individual immune system competence and the compounding effect of greater exposure to circulating pathogens, linked to weakened immune function. The evidence that this may largely be due to the immunological effects of COVID-19 infections is accumulating.^18,28, 29, 30, 31

Both pandemics persist despite effective prevention measures—such as condoms for HIV and respirator masks for SARS-CoV-2. Societal responses reveal shared themes of limited international solidarity and material inequalitites.^4,32 Patients with AIDS and long COVID have faced stigma, medical gaslighting, and inadequate clinical recognition of symptoms.³³ Early responses to both pandemics were marked by misinformation, governmental failures, and insufficient research.^34,35 Although antiretroviral therapies have reduced AIDS mortality, and effective prophylaxis is available, no comparable treatment exists for long COVID or persistent SARS-CoV-2 infection, and curative, reservoir clearing antiviral therapies or sterilizing vaccines remain unavailable for either disease.

METHODS

This narrative review examines immune dysfunction and systemic impacts of HIV and SARS-CoV-2, focusing on long-term effects such as immune dysregulation, systemic damage, neurocognitive impairment, and population-level consequences. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify relevant studies published between 2019 and 2024 for SARS-CoV-2 and since 2000 for HIV, with earlier foundational studies included where necessary. Search terms combined HIV and SARS-CoV-2 with keywords related to immune dysfunction, immune exhaustion, CD4/CD8 ratio, viral reservoirs, chronic inflammation, neurocognitive impairment, mitochondrial dysfunction, opportunistic infections, endothelial dysfunction, clotting abnormalities, and epigenetic changes.

This review prioritizes these areas owing to their central role in disease progression, long-term health outcomes, and immune system impairment. Given emerging evidence that SARS-CoV-2 may induce chronic immune dysfunction, comparisons with HIV provide insights into shared mechanisms and cumulative effects over time. Studies were selected on the basis of scientific rigor, relevance, and contribution to understanding shared and distinct mechanisms in both diseases, prioritizing peer-reviewed research, systematic reviews, and meta-analyses. This review synthesizes findings narratively rather than conducting a systematic review with meta-analysis to provide a comparative perspective on immune dysfunction, systemic damage, neurocognitive disorders, vulnerability to infections, and long-term sequelae in both diseases instead of directly examining effects, associations, or causality.

Immune System Dysfunction in HIV and SARS-CoV-2: Parallels and Divergences

Comparing CD4+ T-cell lymphopenia induced by SARS-CoV-2 and HIV shows that a single HIV infection exclusively and progressively depletes CD4+ T cells, leading to a progressive deterioration of the immune system and fatal immunodeficiency over years—a process that is well documented and intrinsic to the virus’s pathogenesis (Figure 1).³⁶ Conversely, the long-term impact of SARS-CoV-2 infections on immune function remains uncertain. A single SARS-CoV-2 infection can induce a broader spectrum of immune system dysregulation in days to weeks (Figure 2), including but not limited to T-cell depletion and functional exhaustion of T cells (Table 1^{5,16,17,19,20,}36, 37, 38, 39, 40, 41, 42, 43 provides more details).¹⁶ Namely, T cells expressing coinhibitory receptors are highly activated in acute COVID-19 disease⁴⁴ but become exhausted in patients with long COVID with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)–like chronic illness.⁴⁵ Long-term effects of SARS-CoV-2 infection on immune function sometimes gradually resolve46, 47, 48 but can persist for months or years^18,19,48, 49, 50 and might accumulate through multiple infections. According to a flow cytometry study, in patients with AIDS, the CD8+ cells are slightly elevated, whereas in patients with severe COVID-19, they are markedly reduced. However, the CD4+ cell counts are comparable. Therefore, the CD4+/CD8+ ratios are very low in AIDS and often above normal in COVID-19. The natural killer cells are reduced in both but more markedly in severe SARS-CoV-2 than in HIV infection.¹⁹ Another relevant immunologic observation, common to both diseases, is compromised gut mucosal integrity and microbial translocation as a potential mechanism associated with chronic inflammation. In particular, I-FABP, sCD14, and LPS-BP are considered supporting markers associated with the compromised gut microbial communities.^51,52 A further important similarity between HIV and long COVID is the persistent decline of mucosal-associated invariant T cells in chronic HIV infection and long COVID.^45,53

Figure 1.

A diagram illustrating the immunopathological mechanisms in HIV infection.

Note: This image was created with BioRender.

Figure 2.

A diagram illustrating the immunopathological mechanisms in SARS-CoV-2 infection.

Note: This image was created with BioRender.

Table 1.

Immunological Markers in HIV and SARS-CoV-2 Infections and Key Differences

Immunological marker	HIV	SARS-CoV-2	Key differences
CD4+ T-cell count	Progressive and severe depletion over time. In untreated HIV, CD4+ counts can drop below 200 cells/μL (normal range: 500–1,500 cells/μL)37	There is a spectrum of CD4+ depletion with close to 200 cells/μL in severe cases.16 Some patients with long COVID may show long-term reduction.17	HIV directly targets and depletes CD4+ T cells over time, leading to severe immunodeficiency. In COVID-19, depletion is typically limited to up to 8–12 months unless severe disease or potentially multiple infections occur.
CD8+ T-cell count	Initial CD8+ activation and expansion during acute infection. Long-term infection leads to CD8+ exhaustion and dysfunction38,39	CD8+ T cells are activated during acute COVID-19 but may become exhausted in severe cases. Recovery occurs in most mild/moderate cases,20 but exhaustion can persist in severe cases or PASC.40	CD8+ exhaustion is a hallmark in both diseases, but HIV causes chronic CD8+ dysfunction, whereas in COVID-19, CD8+ exhaustion typically relates to severe cases or PASC.
CD4/CD8 ratio	Decreased in AIDS. A CD4/CD8 ratio <1 is common in untreated HIV (normal ratio: 1.5–2.5). It declines progressively as HIV advances.5	May also decrease during severe COVID-19.54 Can be increased owing to CD8 depletion or decreased owing to their proliferation.41 In long COVID, it can remain low but not as dramatically as in HIV.42	In HIV, the CD4/CD8 ratio remains persistently low owing to ongoing immune deterioration. In COVID-19, changes to the ratio are often more reversible, and it can also be increased owing to CD8 depletion.
Immune activation	Chronic immune activation, even under ART, due to the presence of viral reservoirs. Continuous activation contributes to systemic inflammation and disease progression36,43	Acute immune activation during infection, particularly marked by elevated cytokines (IL-6, TNF-α). In long COVID, low-level chronic inflammation may persist.19	Both cause chronic immune activation, in both cases probably largely due to persistent viral reservoirs. In COVID-19, this may also have other causes (increased membrane permeability, endothelialitis, autoimmune processes, dysbiosis)
Unique immunological markers	HIV persistence in latent reservoirs, specifically in CD4+ T cells, and ongoing immune activation despite ART36	SARS-CoV-2 viral persistence in tissues (e.g., brain, lungs, gut) is associated with long COVID symptoms. Elevated markers of inflammation (e.g., IL-6, D-dimer) are common40	HIV directly infects and hides within the immune system, whereas SARS-CoV-2 can also persist in nonimmune tissues and triggers a broader, less specific immune dysfunction

ART, antiretroviral therapy; PASC, postacute sequelae of COVID-19.

Repeated infections with SARS-CoV-2 are associated with a cumulative increase in the risk and severity of long COVID and postacute sequelae of COVID-19 (PASC).55, 56, 57, 58, 59, 60 Immune system dysregulation is associated with other types of damage and symptoms found in long COVID.^45,61, 62, 63, 64, 65, 66, 67 This indicates a potential parallel⁴⁰ in which the immune system may experience gradual deterioration or increased dysregulation with successive infections.

A common outcome in both HIV and SARS-CoV-2 infections is increased vulnerability to infections. Immune function after COVID-19 infections is characterized by increased risk of infections,^57,68, 69, 70, 71 including a greater risk of antibiotic-resistant infections than of influenza⁷² and emerging evidence for opportunistic, AIDS-defining⁷³ infections such as various mycoses,74, 75, 76, 77 pneumocystis jirovecii,⁷⁸ tuberculosis,⁷⁹ cryptococcosis,^80,81 cryptosporidiosis,⁸² methicillin-resistant Staphylococcus aureus,⁷² and others,^83,84 likely also several types of cancer.85, 86, 87, 88, 89, 90, 91 Immunodeficiency and other long-term COVID-19 effects such as mitochondrial⁹² and DNA damage^93,94 provide potential mechanistic explanations for increased risk of cancer onset and/or progression.85, 86, 87, 88, 89, 90, 91

Increases in the incidences of infectious diseases are observed population wide in current sustained widespread SARS-CoV-2 replication and mutation conditions. Comparing vulnerability to infections between COVID-19–infected and –uninfected populations^57,68,70,71 shows increased risks of many infections after SARS-CoV-2 infection. Such comparisons become increasingly difficult as the uninfected population shrinks under the conditions of ongoing uncontrolled spread, and because no reliable biomarkers for SARS-CoV-2 naivety are available.

Some SARS-CoV-2–reinfected patients can experience less severe symptoms in the acute phase; however, meta-analyses point to similar acute severity of reinfections.⁹⁵ The effect sizes of acquired immunity and eventual infection-induced immunodeficiency on the severity of acute symptoms remain unclear because subjective experience of symptoms in acute infections is not attributable only to the effects of the pathogens themselves but also to the immune response against them.⁹⁶ Acute severity of SARS-CoV-2 reinfections can also be enhanced, especially in individuals with increased exposure to reinfections,²⁴ with a relatively high risk of hospitalization among the reinfected cases.⁹⁷ Regardless of the severity of acute disease, the long-term symptoms, organ damage, and health risks increase with each SARS-CoV-2 reinfection.^57,59 SARS-CoV-2 reinfections are increasingly common post-Omicron infection.⁹⁸

Although SARS-CoV-2 can directly infect T lymphocytes,^99,100 this is likely not the primary mechanism of immune dysfunction. Instead, COVID-19 immunopathology is diverse, involving reductions in both CD4 and CD8 T cells, their functional exhaustion and premature senescence,^45,101 dendritic cell deficiencies,⁴⁶ neutrophilic granulocyte dysfunction,¹⁰² impaired B-cell function,¹⁰³ gastrointestinal dysbiosis,⁶⁶ endotheliopathy,^104,105 reprogramming,²¹ autoimmunity,^30,106, 107, 108 and pathological clotting.109, 110, 111 In addition, in Omicron lineages, there is enhanced inhibition of major histocompatibility complex class I expression¹⁴ and suppression of innate immunity.¹⁵ As a highly cytotoxic virus, SARS-CoV-2 can also promote lymphocytopenia by direct damage to secondary lymphoid organs.^112,113

Unlike other acute infections such as influenza, where immune dysregulation is typically brief even after severe acute disease,¹¹⁴ studies suggest that post–COVID-19 immune abnormalities—such as impaired cell function, disrupted microbiota, and other perturbations—can persist for 6–12 months after mild acute disease¹⁸ and may improve by 24 months.⁵⁰ However, the rapid waning of acquired immunity in the post-Omicron era often makes reinfections more frequent without protective measures.¹¹⁵

In summary, whereas HIV is best known for directly targeting CD4+ T cells, SARS-CoV-2 triggers a broader immune system dysfunction. Direct comparisons of immune markers show that whereas HIV depletes CD4 cells to fatal levels if untreated over years, the onset of immune dysfunction caused by SARS-CoV-2 can be within days to weeks, with some effects that can last for months or years, even after mild-to-moderate initial disease.^65,116, 117, 118 In both cases, immune system exhaustion increases vulnerability to infections and impairs the body's ability to control other pathogens.

Tissue Reservoirs and Long-Term Persistence of Viral Effects

Both HIV and SARS-CoV-2 persist in tissue reservoirs, contributing to chronic immune dysregulation and systemic damage. HIV integrates into the host genome,³⁶ making eradication nearly impossible, whereas SARS-CoV-2, although not integrating into DNA, has been detected in tissues such as the brain, heart, lymphoid organs, gastrointestinal tract, and lungs long after infection.^116,119, 120, 121, 122, 123 Whereas people living with HIV (PLWH), both with and without antiretroviral therapy (ART), consistently experience persistent viral reservoirs, this is still under investigation in Long COVID and likely does not affect all patients. Estimates of viral persistence also known as chronic infection in patients with Long COVID vary across studies. Evidence has been found that one fourth of patients with Long COVID in general124, 125, 126, 127 have viral persistence,124, 125, 126, 127 with some subsets up to 40% with gastrointestinal symptoms¹²⁸ and up to 60% with inflammatory bowel diseases.¹²⁹ It may also affect some patients after SARS-CoV-2 infection without obvious long COVID symptoms.¹³⁰ The influence of this on chronic pathology remains undetermined. Although systemic viremia, common in untreated HIV infection, has been detected in 5%–25% of patients with long COVID,¹²¹ it correlates with severe neurologic dysfunction and immune dysregulation. Episodic detection and compartmentalization (e.g., in monocytes or gut) suggest that viremia may be underreported.¹²³ The characteristic of viremia in long COVID remains unknown, including the eventual episodic nature consistent with the episodic nature of the symptoms, which may additionally complicate detection, especially because low-level viremia may be missed by standard polymerase chain reaction (PCR). Standard PCR tests (typically sensitive to ∼100 copies/mL) frequently miss low-level viral presence. Studies using ultrasensitive methods such as digital PCR and SIMOA (single molecule array) have detected viral components in up to 68% of postinfection cases,¹²⁶ suggesting that conventional PCR testing underestimates persistent infection. By contrast, a recent small cohort study failed to detect viremia using digital transcriptomic analysis in patients with long COVID with ME/CFS at 12 months after SARS-CoV-2 infection.¹³¹ HIV infection and, sometimes, SARS-CoV-2 infection are associated with the expansion of erythroid progenitors/precursors, defined as CD71+ erythroid cells, in the periphery. These cells may suppress T-cell effector functions or serve as HIV¹³² and SARS-CoV-2 reservoirs.^133,134 In both diseases, viral reservoirs enable the virus to evade immune clearance, perpetuating long-term organ damage and preventing full recovery.

Systemic Impacts and Organ Damage

HIV (AIDS). AIDS is a syndrome caused by a persistent viral infection with the RNA retrovirus HIV, which utilizes reverse transcriptases to become transcribed into the host's genome. It causes direct infection and progressive depletion of CD4 cells, and under the threshold of 200 cells/mm³ CD4 T cells (normal 500–1,600), there is a high vulnerability to opportunistic infections, and it is at this stage that the HIV-infected persons are considered to have progressed to AIDS. This damage occurs in all infected patients with rare exceptions and is usually permanent and fatal in the absence of treatment.

In addition, HIV/AIDS is characterized by central and peripheral nervous system damage and resulting neurologic symptoms, including a premature dementia complex sharing many pathophysiologic mechanisms with neurodegenerative conditions such Alzheimer’s dementia (see HIV-associated neurocognitive disorder [HAND]).

The initial infection with HIV is often barely noticed and typically resembles the common cold or a flu-like disease until its damage manifests itself years later, leading to death in the absence of treatments.^5,37 During the latent period, there is a standoff between the HIV virus and the immune system. Only when this battle is almost inevitably lost by the immune system does the clinically apparent immune deficiency manifest itself. This insight led to the early treatment of HIV infection by multidrug therapies, which inhibit HIV replication.¹⁰⁶ Although ART is effective at suppressing viral presence in the blood, HIV still remains in tissue reservoirs—the latently infected cells (CD4+ T cells) and the tissues containing them.³⁶ The majority of patients estimate their quality of life (QOL) to be good or very good QOL after about 4 months of ART.¹³⁵

SARS-CoV-2 (postacute sequelae of COVID-19 or long COVID). Originally named after the acute respiratory syndrome caused by blood vessel damage in the lungs, SARS-CoV-2 is a primarily vascular virus that spreads through the airways mainly through aerosols.^8,136 Although the initial infection is often characterized by a mild, flu-like disease, especially in the postvaccine era, it is followed by a complex chronic symptomatic condition often called long COVID in a significant subset of patients,^117,137, 138, 139 which grows cumulatively with subsequent reinfections^23,57,58 and more widely in organ damage and other infection sequelae known as PASC.^60,93,140, 141, 142, 143 This may often be due to persistent infection of tissue reservoirs^{120,122,123,130,144} because the virus remains detectable in tissues even at autopsy of recovered patients months after infection.¹²² A study conducted by Peluso et al.¹¹⁶ demonstrated SARS-CoV-2 antigen positivity in plasma of individuals during the postacute phase of COVID-19 for up to 14 months. This provides evidence of a distant viral reservoir or focus and an ongoing immune response.

A key distinction between the long-term effects of HIV and SARS-CoV-2 is the presence of microclots in the plasma of individuals with long COVID.¹⁴⁵ Pretorius and colleagues¹⁴⁵ (2021) identified microclots or amyloid deposits in the plasma of patients with long COVID, which were resistant to fibrinolysis owing to elevated levels of antiplasmin. Kruger et al.¹⁰⁷ later analyzed these microclots, finding a dysfunctional fibrinolytic system and a range of antibodies within them. A 2024 review highlighted ongoing endothelial inflammation and vascular endothelial damage as central to the pathogenesis of long COVID,¹⁴⁶ potentially explaining its multisystemic effects.¹⁴⁷ Widespread clotting, fibrinolysis-resistant microclots, and endothelialitis likely impair cellular oxygen delivery, causing tissue hypoxia.^146,148,149 Blocked capillaries and associated mitochondrial dysfunction,¹⁵⁰ as emphasized by Molnar and colleagues,¹⁵¹ may further contribute to neurologic and systemic symptoms in patients with long COVID.152, 153, 154

The potential postacute impacts of SARS-CoV-2 infection include symptomatic long COVID, often resembling ME/CFS and dysautonomia with prolonged symptoms and severely reduced QOL, and PASC that may or may not immediately produce symptoms, including new onset and worsening of previous conditions such as heart disease and diabetes.^57,117,155, 156, 157 The reduction in QOL in patients with long COVID is comparable with that in those with Stage 4 cancers¹⁵⁸ (Table 2 presents a head-to head comparison).

Table 2.

Systemic Impacts in AIDS and Long COVID (PASC)

Aspect	HIV (AIDS)	SARS-CoV-2 (long COVID)
Nature of the virus	Persistent RNA virus utilizing reverse transcriptase to integrate into the host genome.	Primarily a vascular RNA virus that spreads by aerosols through airways and affects all tissues through endothelial infection
Primary target	CD4+ T cells (progressive depletion)	Endothelial cells, glands, immune cells, and other tissue types
Natural history	Acute infection often mild, long latent period with an immune system standoff; symptoms manifest years after infection.	Acute infection often mild, but chronic symptoms (long COVID) accumulate with reinfections
Primary features of immunopathology	Direct depletion of CD4+ T cells, leading to immune deficiency and vulnerability to opportunistic infections.	Persistent viral reservoirs, immune dysregulation, microclots, endothelial damage, and mitochondrial dysfunction, leading to vulnerability to infections (including opportunistic infections)
Systemic and neurologic damage	High vulnerability to opportunistic infections. Neurologic symptoms resembling Alzheimer’s dementia (HAND).	Multisystemic impacts owing to endothelial inflammation, microclots, mitochondrial dysfunction Neurologic symptoms resembling Alzheimer’s dementia (SAND)
Viral reservoirs	Latently infected CD4+ T cells and tissues containing them	Persistent SARS-CoV-2 antigen positivity in tissues and plasma months after infection
Vascular and clotting abnormalities	Not a primary feature	Presence of fibrinolysis-resistant microclots, endothelialitis, and widespread clotting impairing oxygen delivery
Chronic conditions	Typically progresses to AIDS with immune system collapse; fatal without treatment	Chronic conditions such as heart disease, diabetes, and organ dysfunction; long COVID symptoms
Quality of life	Improves with ART; good or very good after 4 months of treatment	Comparable with Stage 4 cancer in patients with long COVID
Prognosis and treatment	Fatal without ART; manageable with treatment	PASC may lead to life-threatening acute or chronic conditions. No treatment available

ART, antiretroviral therapy; HAND, HIV-associated neurocognitive disorder; PASC, postacute sequelae of COVID-19; SAND, SARS-CoV-2–associated neurocognitive disorder.

Neurologic Impacts and Cognitive Decline: Comparing HIV-Associated Neurocognitive Disorders in HIV/AIDS and SARS-CoV-2–Associated Neurologic Disorders in SARS-CoV-2/Long COVID/Postacute Sequelae of COVID-19

SARS-CoV-2–associated neurocognitive disorders (SANDs) describe the cognitive impairments, such as memory loss, concentration problems, and decision-making difficulties, commonly reported in patients with long COVID, even after mild acute disease.^56,117,142,159, 160, 161, 162 Similar to HAND, SAND is linked to chronic neuroinflammation resulting from the viruses crossing the blood–brain barrier.^104,141 HAND appears in PLWH after many years, whereas cognitive impairment can occur in SARS-CoV-2–infected individuals within months after the infection.^56,163, 164, 165 Both conditions involve overlapping neurodegenerative pathways, including mechanisms seen in Alzheimer's disease,166, 167, 168, 169, 170, 171 raising concerns about long-term cognitive decline. There are both notable similarities and differences between these 2 neurocognitive disorder groups. In particular, galectin-9 is associated with cognitive impairments in both conditions.^{45,52,172,173} The neurologic dysregulation in patients with long COVID with ME/CFS-like symptoms is highly diverse.¹⁷⁴ Artemin, a neurotrophic factor associated with pain and cognitive impairment in patients with long COVID, is highly elevated in the plasma of patients with long COVID and is strongly associated with pain indexes and cognitive impairment scores.⁴⁵ However, its plasma levels are markedly reduced in PLWH, even lower than the levels in healthy individuals.⁵² Its exact role both in HAND and in SAND remains to be determined.

SARS-CoV-2–induced damage to the endothelia affects many organs, including the brain. Infection can reduce gray matter mass,¹⁶³ which is associated with cognitive decline,^142,175, 176, 177, 178 decreases in intelligence quotient scores even after mild resolved infection,¹⁶⁴ increased risk of psychiatric disorders,^161,179, 180, 181 and exacerbation of dementia.¹⁷⁸ Loss of smell and taste is associated with behavioral, functional, and structural brain alterations.¹⁶⁵

In HIV, these impairments are tied to viral reservoirs in the central nervous system and chronic immune activation, whereas in SARS-CoV-2, the role of viral persistence remains unclear, with contributing factors such as hypoxia, clotting disorders, and autoimmune responses also implicated. HAND management includes ART, which significantly reduces viral load but does not fully eliminate cognitive dysfunction. For SAND, there is no specific antiviral treatment targeting long COVID–related cognitive symptoms, and management focuses on supportive therapies.

Accelerated Senescence and Immune Exhaustion in HIV and SARS-CoV-2

Both HIV and SARS-CoV-2 accelerate biological aging, although at different rates (Table 3^{38,39,43,92,101,151,}182, 183, 184, 185, 186, 187, 188). HIV induces gradual aging over years through immune cell depletion and systemic inflammation, whereas SARS-CoV-2 can rapidly trigger signs of early senescence in CD4 and CD8 cells as well as epigenetic, mitochondrial, and other aging markers, even after initially mild infections.¹⁰¹ Both viruses ultimately lead to premature exhaustion of immune resources, increasing vulnerability to age-related diseases.^{38,39,182,189} The slow, progressive damage of HIV contrasts with the rapid onset premature aging signs in SARS-CoV-2 survivors and is particularly concerning for those with multiple reinfections.^93,184

Table 3.

Accelerated Senescence Mechanisms in HIV and SARS-CoV-2 Infections

Aspect	HIV	SARS-CoV-2
Time scale	Years to decades; chronic, ongoing aging process38,182	Acute to subacute, especially after severe disease (months to a few years).183 Ongoing effects and effects of multiple reinfections still unknown
Hypothesized driving factors	Chronic immune activation and ART side effects43	Acute infection, chronic immune activation, PASC184
Telomere impact	Persistent, significant telomere shortening38	Evidence of shorter telomeres, not necessarily dependent on acute disease severity, associated with long-term tissue abnormalities185,186
Aging-associated T-cell changes	Long-term loss of naïve T cells, CD4/CD8 imbalance39	Lymphocytopenia, T-cell exhaustion, and senescence101
Epigenetic changes	Methylation clocks show hallmarks of accelerated aging187	Methylation clocks show hallmarks of accelerated aging188
Mitochondrial dysfunction	Chronic mitochondrial damage from sustained inflammation and ART toxicity; elevated ROS drives immune senescence	Acute and postacute mitochondrial dysfunction with fragmentation, reduced ATP production; increased ROS production92,151

ART, antiretroviral therapy; ATP, adenosine triphosphate; PASC, postacute sequelae of COVID-19; ROS, reactive oxygen species.

Sociopolitical and Economic Contexts of 2 Pandemics

In the 1980s, stigma associating HIV/AIDS with male-to-male sexual activity, drug use, and sex work delayed public health responses until heterosexual transmission was recognized, prompting health education campaigns.190, 191, 192, 193 Today, HIV is a manageable chronic condition in wealthy nations owing to therapies such as pre-exposure prophylaxis and antiretrovirals, but AIDS continues to devastate sub-Saharan Africa, where 1 in 30 adults lives with HIV, accounting for two thirds of global cases.⁵ Poverty, lack of public health mitigations, and other diseases exacerbate the burden in the Global South.^194,195

Similarly, COVID-19 disproportionately affects marginalized groups owing to poverty, racism, inequities in healthcare access, and pre-existing burdens of chronic illness and infectious diseases.196, 197, 198, 199, 200, 201 The distribution of COVID-19 vaccines globally has been markedly inequitable, with the populations of low- and middle-income countries far less likely to have received even the initial doses, much less boosters.²⁰²

Unlike HIV, SARS-CoV-2’s airborne transmission poses a universal threat and is harder to control. Social media has spread both information and conspiracy theories.^34,35 Stigma initially targeted infected individuals, those defying public health mandates,^32,203 and healthcare workers, believed to be contaminated owing to their front-line work.²⁰⁴ Racism against Chinese communities also surged owing to the virus’s origins in Wuhan.²⁰⁵

As governments rolled back public health protections, leaving the public to navigate the uncontrolled spread on their own, stigma shifted to patients with long COVID and those advocating for continued precautions. These individuals are frequently dismissed as fearmongers, anxious, or overly cautious despite the objective ongoing and significant harms caused by the pandemic. Medical professionals pushing for mitigation measures face governmental and media backlash.206, 207, 208, 209, 210 Meanwhile, patients with long COVID experience persistent gaslighting and ignorance from healthcare professionals,²¹¹ exacerbating their struggles to access appropriate care.212, 213, 214, 215

The Economist estimates that COVID-19 caused up to 35 million excess deaths worldwide by 2022,²¹⁶ whereas the projected economic toll of long COVID in the U.S. alone exceeds $4 trillion.^217,218 The average total cost of a long COVID case is estimated to be about $5,000–$12,000 per year.²¹⁹

DISCUSSION: AIRBORNE AIDS?

It is important to distinguish between the general concept of acquired immune deficiency, which refers to a broad range of conditions resulting from compromised immune systems, and AIDS, which is generally associated with HIV but sometimes more specifically termed HIV/AIDS. Although SARS-CoV-2 does not cause HIV/AIDS, its ability to induce immune dysfunction has drawn comparisons with AIDS in a broader sense. Previous reviews have contributed meaningfully to clarifying misinformation and synthesizing evidence.1, 2, 3, 4 This review provides an updated narrative synthesis of current findings that underscore their similarities and divergences. Terms such as airborne AIDS or airborne HIV have been used on social media, in blogs, and in other online forums and referred to in news outlets^220,221 to describe SARS-CoV-2’s impact on the immune system, highlighting both the severity of its effects and provoking a debate over the appropriateness of such terminology.

SARS-CoV-2 and HIV, although distinct, share parallels in their biochemical traits and mechanisms,^1,3,7 long-term impacts, and societal responses.⁴ Both can establish persistent infections in tissue reservoirs^36,127; immune dysfunction^21,48,63,64; vulnerability to other infections, including opportunistic infections^{74,76,77,80,222}; systemic damage, including hallmarks of accelerated biological aging^184,186; and premature neurocognitive disorders.¹¹⁷ HIV integrates into DNA, whereas SARS-CoV-2 and its parts persist in organs such as the blood vessels, brain, heart, tonsils, and lungs.¹²⁷

The statement that SARS-CoV-2 is airborne AIDS may be an oversimplification, but it draws attention to emerging evidence showing that the virus induces a distinct form of acquired immunodeficiency. The phrase emphasizes key similarities and is grounded in evidence of shared outcomes, including immune dysfunction through T-cell depletion and exhaustion,^16,45,101 persistent systemic damage, and neurocognitive decline. These outcomes are further highlighted by the increased vulnerability to infectious diseases,^57,68, 69, 70, 71, 72 including those that are signature indicators of immune deficiency typically associated with HIV/AIDS,^72,74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 as well as likely several types of cancer.85, 86, 87, 88, 89, 90, 91 Combined with its airborne spread and high transmissibility, SARS-CoV-2 is an ongoing threat to immunity and contributes to the population-level spread of many infections, amplifying its impact on public health.

Herd immunity is unattainable for a virus that mutates rapidly and evolves to evade and suppress the immune system.13, 14, 15^,223 Similarly, the rapidly waning hybrid or postinfection immunity²²⁴ offers little long-term utility when achieving it as it requires infection with an immune-dysregulating, organ-damaging virus.^60,123,225 Instead, addressing SARS-CoV-2 as a systemic vascular infection¹⁴⁶ with significant cumulative health impacts^23,24,55,59 necessitates sustained public health measures and innovative strategies to mitigate its ongoing threat to individual and population health. It is essential to prioritize airborne infection prevention, especially while no causal therapies are available for the sequelae of SARS-CoV-2 infection. More research is needed to develop causal treatments for chronic SARS-CoV-2 infection and other biological mechanisms of long COVID: endothelialitis, thrombosis, premature senescence, dysbiosis, and immune dysregulation resulting in increased vulnerability to viral, bacterial, and fungal infections. Five years of the COVID-19 pandemic have provided important insights; however, earlier application of the much older AIDS pandemic's lessons could have and still can significantly strengthen preparedness for the current and future public health threats.

CONCLUSIONS

Although SARS-CoV-2 does not cause HIV/AIDS, its ability to induce immune dysfunction—including T-cell depletion and dysfunction; increased susceptibility to infection, including opportunistic infections; accelerated biological aging; and neurologic and systemic damage—provides parallels in terms of AIDS in the broader immunological context. The virus’s subacute and chronic persistence, vascular pathology, immune evasion, neurologic impacts, systemic damage, and contribution to population-wide immune dysfunction pose a significant long-term public health threat. Addressing these challenges requires sustained infection control measures, research into treatments and biomarkers for persistence, cumulative infection burden, and naivety. Hygienic, informed, evidence-based and compassionate patient care, support for the patients, and updated definitions for chronic SARS-CoV-2 and HIV sequelae are essential. Applying lessons from older pandemics is of vital importance, especially as long as causal and curative treatments remain unavailable. Without decisive action, the long-term consequences of unchecked SARS-CoV-2 infection-similar to those of HIV-may continue to undermine global health for decades.