Shadows of infection: Post-coronavirus disease condition and outcome patterns in patients receiving dialysis and kidney transplant recipients

Abstract

Post-coronavirus disease 2019 (COVID-19) condition describes a constellation of persistent or fluctuating symptoms and organ dysfunction following severe acute respiratory syndrome coronavirus 2 infection. Patients with end-stage kidney disease (ESKD) on dialysis and kidney transplant recipients (KTR) inhabit a landscape of immune dysfunction, multimorbidity, and high healthcare interaction, which may amplify both the risk and consequences of post-COVID condition (PCC). In this article, we aimed to review current evidence on PCC and related post-acute sequelae in dialysis patients and KTR-focusing on symptom burden, risk factors, functional outcomes, health-related quality of life (HRQoL), kidney and graft outcomes, and recovery trajectories. It was found that dialysis patients and KTR experience a substantial burden of PCC superimposed on already complex symptoms and risk profiles. Long COVID in these groups encompasses not only fatigue, dyspnea and a “brain fog” phenomenon but also impaired HRQoL, reduced functional recovery, and potential acceleration of kidney and graft decline. Harmonized PCC definitions, kidney-specific outcome measures, and prospective multicentre studies in ESKD and kidney transplant populations are urgently required to inform prevention and management strategies embedded within the dialysis and kidney transplantation pathways.

Key Words: Post-COVID-19 condition; SARS-CoV-2; Dialysis; Kidney transplantation; Health-related quality of life

Core Tip: Post-coronavirus disease condition (PCC) is increasingly recognized amongst patients receiving dialysis and kidney transplant recipients following severe acute respiratory syndrome coronavirus 2 infection. In these populations, persistent symptoms such as fatigue, dyspnea and cognitive impairment may coexist with reduced functional recovery, impaired quality of life and potential graft or kidney decline. Interpretation is complicated by high baseline symptom burden and heterogeneous PCC definitions. This review summarizes current evidence on epidemiology, risk factors and outcomes of PCC in kidney failure populations and highlights priorities for future research and clinical management.

INTRODUCTION

For many individuals receiving dialysis or living with a kidney transplant, coronavirus disease 2019 (COVID-19) has consequences extending beyond the acute infectious phase. Persistent symptoms including fatigue, dyspnea, cognitive difficulties and reduced functional capacity have been increasingly recognized months after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These prolonged manifestations are now collectively described as post-COVID condition (PCC).

The World Health Organization (WHO) describes PCC as symptoms occurring in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually three months from onset, lasting at least two months and not explained by an alternative diagnosis[1]. In this review, the term PCC is used as the primary descriptor for persistent post-COVID manifestations, while other terminology such as “long COVID” or “post-acute sequelae of COVID-19” is referenced only when reflecting terminology used in specific studies[1]. In parallel, prospective cohorts and meta-analyses have established PCC as a common, heterogeneous outcome in the general population, with pooled prevalence estimates in the 10%-20% range and higher in hospitalized cohorts[2,3].

From a nephrology perspective, COVID-19 casts two major shadows. Firstly, large non-renal cohorts show that infection is associated with increased risks of acute kidney injury (AKI), accelerated estimated glomerular filtration rate (eGFR) decline, incident chronic kidney disease (CKD) and major adverse kidney events, with risk graded by acute disease severity and persisting beyond the infectious episode[4,5]. Secondly, patients with advanced CKD, on dialysis or with a kidney transplant start from a position of reduced physiological reserve and immune competence. Reviews and registry data early in the pandemic highlighted markedly higher acute mortality in these groups compared to the general population[6-8].

As the pandemic has evolved into an endemic virus, attention has shifted towards longer-term consequences. Yet, dialysis patients and kidney transplant recipients (KTR) have often been underrepresented in general PCC cohorts, and their symptoms can easily be misattributed to “background” uremic or transplant-related issues. Understanding the epidemiology, manifestations, risk factors and outcomes of PCC in these populations is therefore both clinically and ethically important.

In this review, we focus on outcome patterns of PCC in end-stage kidney disease (ESKD) and post kidney transplantation-symptom burden, functional status, health-related quality of life (HRQoL), healthcare utilization, mortality, and graft and kidney outcomes-rather than attempting an exhaustive catalogue of every post-COVID abnormality. We also examine definitional and methodological issues that complicate interpretation in these scenarios and outline the priority areas for future research.

LITERATURE SEARCH STRATEGY

This review was conducted as a structured narrative synthesis of available literature relating to PCC in patients with advanced CKD, dialysis, and kidney transplantation. A literature search was performed using PubMed, Scopus, Cochrane and Google Scholar to identify relevant studies published between January 2020 and October 2025. Search terms included combinations of “COVID-19”, “post-COVID condition”, “long COVID”, “post-acute sequelae of COVID-19”, “dialysis”, “hemodialysis”, “peritoneal dialysis”, and “kidney transplant”.

Eligible studies included observational cohorts, registry analyses, and clinical studies reporting persistent symptoms, functional outcomes, HRQoL, or kidney-related outcomes following SARS-CoV-2 infection in patients receiving dialysis or living with a kidney transplant. Studies focusing exclusively on acute infection without post-acute follow-up were excluded. Given the heterogeneity in literature, signs and definitions used in the literature, findings were synthesized narratively rather than through formal meta-analysis.

DEFINITIONS, DIAGNOSTIC CRITERIA AND MEASUREMENT CHALLENGES

The WHO anchor and real-world variation

The WHO PCC definition provides a conceptual anchor but was not designed as a rigid research case definition[1]. In practice, studies of dialysis patients and KTR exhibit considerable heterogeneity: Time windows vary from 4 weeks to 12 months after acute infection[6,9-17]. Terms such as “long-lasting clinical symptoms” (LLCS), “post-COVID syndrome”, “post-acute sequelae of COVID-19” (PASC) and “post-COVID complications” are used interchangeably, often without explicit reference to WHO criteria[6,7,9-11,14-16,18]. Some studies define PCC purely symptomatically, others prioritize objective complications (e.g., radiological changes, thromboembolic events, graft dysfunction)[3,7,15,16]. These definition differences partly explain why PCC prevalence in similar populations can range from < 20% to > 60%.

The wide range of reported PCC prevalence across dialysis and transplant cohorts likely reflects methodological differences between studies rather than true biological variability alone. Studies vary substantially in the definitions applied (WHO criteria vs symptom-based definitions), follow-up intervals ranging from several weeks to twelve months, the severity of the initial infection, vaccination status, and the inclusion or exclusion of patients who died during the acute phase. Survivor bias may therefore underestimate PCC prevalence, while symptom-focused surveys may inflate estimates in populations with high baseline symptom burden. These methodological differences must be considered when interpreting prevalence estimates across studies in patients with kidney failure.

Baseline symptom burden and signal-to-noise

Many dialysis patients and KTR already live with high baseline symptom loads: Fatigue, sleep disturbance, cognitive slowing, musculoskeletal pain, mood disorders and reduced physical capacity are all common prior to contracting COVID-19[6,8,9,14]. Without pre-COVID baseline measurements or non-infected controls, there is a real risk of both over-attribution (labelling chronic symptoms as “long COVID”) and under-attribution (dismissing new or worsened symptoms as “just dialysis” or “just transplant life”).

Some cohorts mitigate this by using pre-existing HRQoL data [e.g., EuroQoL-5-dimension (EQ-5D) or Kidney Disease Quality of Life Instrument (KDQOL)] or including matched non-infected comparators. In hemodialysis (HD), longitudinal studies from Poland and Morocco display a clear drop in EQ-5D index and visual analogue scale post-COVID infection, with partial but incomplete recovery of over 3-6 months[9-11]. In KTR, Malinowska et al[14] demonstrated significant reductions in HRQoL at 6 months in those meeting the post-COVID syndrome criteria compared to those who did not, suggesting PCC is more than just a renaming of background complaints.

Survivor bias and selection effects

ESKD and KTR populations suffered high acute COVID-19 mortality, especially in earlier waves of the pandemic[6-8]. Many PCC cohorts therefore included only survivors who were well enough-and willing-to attend follow-up or to answer surveys. Non-participation among those who are frail, cognitively impaired, or socially marginalized may lead to underestimation of the true burden. Conversely, those most troubled by persistent symptoms may be more motivated to respond, pushing estimates upwards.

The French REIN registry study of LLCS at 6 months among chronic dialysis patients is a relative exception, drawing from a large national cohort with systematic attempts at follow-up[6]. Even there, missing data and early deaths complicate precise inference.

Instruments and outcomes: Beyond symptom lists

Renal PCC studies employ a mix of tools: Symptom checklists (bespoke or adapted from general PCC clinics)[6-11,14-16]. Generic HRQoL instruments, such as EuroQol-5-dimension 5-level (EQ-5D-5 L) and EQ-visual analog scale (EQ-VAS)[9,11,14]. Phenotyping approaches: A recent Czech KTR cohort used WHO-aligned PCC criteria plus latent-class analysis to identify distinct long COVID phenotypes (fatigue-dominant, cardiorespiratory, neurocognitive, mixed)[18]. Kidney- and graft-centered outcomes: EGFR trajectories, proteinuria, rejection episodes, and graft loss[7,15,16,19].

Despite this variety, there is a notable absence of renal-specific PCC endpoints such as dialysis tolerance (i.e. intradialytic hypotension, recovery time), vascular access complications, frailty indices, or donor-specific antibody dynamics. Developing such an outcome set would greatly improve the relevance of PCC research to nephrology practice.

BIOLOGICAL AND CLINICAL RATIONALE FOR INCREASED RISKS IN ESKD AND TRANSPLANTATION

Several intersecting mechanisms make PCC not only plausible but more likely to occur in dialysis patients and KTR.

Immune dysregulation and chronic inflammation

ESKD is associated with immune senescence, impaired antigen presentation, T-cell exhaustion, chronic low-grade inflammation, and an altered microbiome[5,6]. KTR add pharmacological immunosuppression, particularly calcineurin inhibitors, antimetabolites, corticosteroids and, in some, lymphocyte-depleting agents.

Leading mechanistic hypotheses for PCC center on: Persistent viral reservoirs or antigen maintaining immune activation. Immune dysregulation with skewed T- and B-cell responses and autoantibody formation. Endothelial dysfunction and microvascular injury, promoting tissue hypoxia.

These processes are amplified against a background of uremia, vascular stiffness, oxidative stress and immunosuppressive therapy, making prolonged recovery and symptom persistence more likely[4-6,20].

These mechanisms may be particularly amplified in kidney disease populations. Uremic toxins, chronic microinflammation, and oxidative stress characteristic of advanced kidney disease may intensify immune dysregulation and endothelial injury following SARS-CoV-2 infection. Repeated HD-associated hemodynamic stress may further exacerbate microvascular dysfunction and autonomic instability. In KTR, chronic immunosuppression may alter viral clearance and immune recovery, potentially prolonging antigen persistence and sustaining inflammatory signalling pathways implicated in PCC.

Hemodynamic stress and limited reserve

HD exposes patients to repeated intravascular volume shifts and episodes of intradialytic hypotension, which may “unmask” or exacerbate autonomic dysfunction and microvascular injury triggered by COVID-19[9-11,20]. KTR and dialysis patients also have a high prevalence of heart failure, pulmonary hypertension, anaemia and sarcopenia, lowering the threshold at which modest residual lung or vascular injury translates into disabling fatigue and dyspnea[6,9-11].

Kidney-specific injury and graft vulnerability

COVID-19 is associated with AKI, collapsing glomerulopathy, thrombotic microangiopathy, and other kidney pathologies. In non-kidney disease populations, infection confers an increased risk of sustained eGFR loss and incident CKD[4,5]. In KTR, observational cohorts report: Transient or persistent eGFR decline after COVID-19, sometimes linked to graft rejection, calcineurin inhibitor toxicity, or recurrent infection[15,16,19]. Occasional biopsy-proven graft rejection episodes following immunosuppression reduction during acute illness[7,15,19].

These graft-centric consequences may unfold alongside, or independently of, symptom-defined PCC. It remains uncertain whether persistent graft dysfunction observed after COVID-19 represents a direct manifestation of PCC pathophysiology or instead reflects downstream structural consequences of severe acute infection, immunosuppression modification, or other post-acute complications.

Vaccine response and variant context

Dialysis patients and KTR exhibit blunted humoral and cellular responses to COVID-19 vaccination, with lower antibody titers and faster waning than the general population[21,22]. The RECOVAC program and others have shown that higher post-vaccine antibody levels correlate with lower PCC risk in advanced CKD, dialysis and KTR[13]. Later pandemic waves dominated by Omicron variants and high vaccine coverage appear to be associated with somewhat lower PCC risks in KTR, although residual burden remains substantial[17,21].

EPIDEMIOLOGY OF PCC IN KIDNEY FAILURE

HD and peritoneal dialysis populations

Evidence in dialysis populations comes from registry-based studies, single-center cohorts and, more recently, studies with mixed advanced CKD/dialysis/KTR populations.

In terms of prevalence and symptom clusters: In the French REIN national cohort, Belkacemi et al[6] assessed survivors receiving chronic dialysis 6 months after COVID-19. They reported LLCS-including fatigue, dyspnoea, chest pain, neurological and psychological symptoms-in a substantial minority, with higher risk in those who had been hospitalized or admitted to intensive care. Och et al[9] followed HD patients in northern Poland and found that the majority of survivors reported persistent symptoms at 3 months, and over 80% remained symptomatic at 6 months; fatigue, dyspnoea, palpitations and sleep disturbance were dominant, with HRQoL remaining significantly lower than pre-COVID. A Moroccan multicentre cohort of chronic HD patients described long COVID symptoms in more than half of survivors 2-3 months post-infection, again with fatigue, dyspnoea, anxiety and musculoskeletal pain most frequently reported; diabetes and greater acute severity predicted persistent symptoms[10,11]. A recent Chinese study of maintenance HD patients found a high prevalence of long COVID at 12 months, with sleep disturbance, fatigue and mental-health symptoms being particularly prominent; female sex, comorbidity burden and severe acute disease were associated with PCC[12]. In the RECOVAC nested case-control study, long COVID defined according to the WHO criteria affected 21% of dialysis patients with prior COVID-19, and high symptom burden was common[13].

Peritoneal dialysis (PD) patients are either absent or present in very small numbers in most series, and data specific to home dialysis modalities are almost non-existent.

When we consider methodological caveats, the main caveats include: Survivor and non-response bias-those who died or declined follow-up are not captured, and participation may correlate with symptom burden[6,9-11]. Lack of non-infected controls-only a subset of studies compare infected to non-infected dialysis patients, limiting causal inference for non-specific symptoms[10,13]. Heterogeneous PCC definitions-differences in time thresholds, symptom lists and requirement (or not) for functional impact complicate comparisons[1,6,9-12].

Despite this, a consistent signal emerges: A sizeable fraction of dialysis patients experience persistent multi-system symptoms and reduced HRQoL for months after SARS-CoV-2 infection.

KTR

Considering the prevalence and patterns amongst KTR: In Croatia, Basic-Jukic et al[15] followed 104 KTR with COVID-19 and found that only a minority were completely asymptomatic at a median of 64 days; 45% had persisting symptoms and over 70% had at least one laboratory abnormality (e.g., elevated inflammatory markers). Malinowska et al[14] reported post-COVID syndrome in about 70% of 67 KTR at 6 months, with fatigue, hair loss, myalgia, cognitive complaints and sleep disturbance frequent, and significant declines in HRQoL compared with pre-infection measurements. Amorim et al[17] performed a large longitudinal cohort study of 780 KTR in Brazil and found long COVID, defined as persistent organic symptoms at 3 months, in 27%; fatigue, myalgia and neurological symptoms predominated and 17% of employed patients had not returned to work. The same Brazilian group reported that during the Omicron-dominant period in a highly vaccinated KTR population, long COVID remained common (about 50%) but was associated with milder symptoms and better return-to-work rates than in earlier waves[17]. A transplant center abstract by Amorim et al[17] described “high incidence” (28%) of long COVID among > 1700 KTR three months post-infection, with fatigue and dyspnoea the most common complaints. Zahradka et al[18] applied WHO-aligned criteria in a nationwide Czech cohort of 596 KTR and found PCC in 34%; latent class analysis identified eight symptom phenotypes (fatigue-dominant, cardiorespiratory, neurocognitive, musculoskeletal and mixed), highlighting the heterogeneity of long COVID in KTR. A solid-organ transplant cohort from Spain (Morená et al[21]) reported post-acute sequelae after predominantly Omicron infections, with fatigue, dyspnoea and neurocognitive symptoms common and KTR showing patterns similar to other organs.

Overall, KTR appears to have long COVID prevalence estimates broadly similar to other high-risk groups, but with added complexity from graft function and immunosuppression.

CLINICAL MANIFESTATIONS AND SYMPTOM TRAJECTORIES

Fatigue, neurocognitive impairment and mental health

Fatigue is the leitmotif of PCC across almost all cohorts[2,3,14-18]. Dialysis patients describe a deeper exhaustion than their pre-COVID baseline, slower recovery after sessions, and reduced tolerance for routine physical tasks; nurses often notice increased intradialytic somnolence or reduced engagement[9-11].

Neurocognitive complaints (“brain fog”, poor concentration, slowed thinking, forgetfulness) and sleep disturbance are also frequent. In HD cohorts, EQ-5D domains for anxiety and depression and usual activities remain impaired at 3-6 months[9-11]. In KTR, Malinowska et al[14] and Amorim et al[17] both report significant decrements in HRQoL and emotional well-being among those with post-COVID syndrome or long COVID compared with other transplant recipients.

Anxiety, depression and post-traumatic stress disorder symptoms may be amplified by fear of graft loss, disruption to transplant services, and prolonged isolation. It is likely that long COVID neuropsychiatric symptoms and pre-existing mental health burdens in ESKD interact bidirectionally.

Cardiopulmonary sequelae

Dyspnoea is another dominant symptom in dialysis and KTR cohorts. HD patients report persistent breathlessness on exertion and, in some cases, at rest; 6-minute walk test distances are reduced compared with pre-COVID values when measured[9-11]. In KTR, dyspnoea, chest pain and palpitations often co-occur with radiological abnormalities, though routine imaging beyond the acute phase is uncommon[15,16].

Cardiovascular events (heart failure exacerbations, arrhythmias, thromboembolism) and respiratory complications (organizing pneumonia, fibrosis) are described in post-COVID KTR and dialysis patients, but attribution to PCC vs independent sequelae of severe acute illness is not straightforward[4,6,7,15,16].

Autonomic dysfunction and dysregulated physiology

Orthostatic intolerance, tachycardia, temperature dysregulation and sleep fragmentation are increasingly recognized features of long COVID in clinical settings[3,20]. In ESKD, dialysis-related hemodynamic instability and underlying autonomic neuropathy may exacerbate these phenomena, but systematic autonomic testing is rarely reported in renal PCC cohorts.

Renal-specific considerations

In terms of graft function in KTR, KTR cohorts show: Transient declines in eGFR after COVID-19, with partial recovery in many but persistent impairment in a subset, particularly those with severe acute disease or biopsy-proven rejection[15,16,19]. New-onset or worsened proteinuria in some patients, occasionally associated with histological evidence of rejection or recurrent glomerular disease[19]. These patterns represent a “structural” layer of post-COVID sequelae that may be independent of, or synergistic with, symptom-defined PCC.

Considering dialysis tolerance and frailty, HD patients with PCC report: Increased intradialytic hypotension, cramps and post-dialysis malaise. Weight loss and altered dry-weight targets, often with overt or occult volume overload. Reduced physical activity and worsening frailty indices, though formal frailty assessment has not been performed frequently[9-11]. These changes may contribute to a vicious cycle of deconditioning, symptom persistence and greater healthcare resource utilization.

RISK FACTORS FOR DEVELOPING PCC

Across the advanced CKD, dialysis and KTR cohorts, several risk factors recur: Severity of acute COVID-19: Intensive care unit admission, need for oxygen or mechanical ventilation, and AKI are associated with higher PCC risk and worsened kidney outcomes[4,6,12,13,15,16]. Baseline kidney status: Advanced CKD, dialysis dependence and transplant status are associated with higher odds of PCC compared with non-CKD controls in mixed cohorts[4,5,13]. Comorbidity burden and frailty: Diabetes, cardiovascular disease, obesity, chronic lung disease and higher comorbidity indices consistently predict PCC and worse long-term outcomes[5,6,9-11,13-15,17,18]. Immunosuppression and vaccine response: In KTR, high-dose steroids and antimetabolites are associated with reduced vaccine responses and more breakthrough infections; however, specific maintenance regimens have not shown clear independent associations with PCC after controlling for disease severity[17,18,21-23]. Low post vaccination antibody levels: In RECOVAC, each 10-fold increase in anti-S antibody level after vaccination was associated with lower PCC odds, while COVID-19-related hospitalization increased PCC risk[13]. Socioeconomic and ethnic factors: General population and CKD studies suggest increased PCC risk and worse kidney outcomes among socioeconomically deprived and minoritized groups; similar gradients likely exist in ESKD and KTR but remain underexplored[2,4,5].

OUTCOMES AND PROGNOSIS

Functional status and quality of life

Long COVID survivors in dialysis and KTR cohorts exhibit persistent impairments in physical functioning and HRQoL: In HD cohorts, EQ-5D index and EQ-VAS scores remain depressed at 3-6 months compared with pre-infection or historical controls, with slow and incomplete recovery[9-11]. In KTR, Malinowska et al[14] and Amorim et al[17] found meaningful decrements in HRQoL measures in those with PCC; domains most affected include fatigue, pain, usual activities and emotional well-being.

Return to work is particularly affected in KTR. In Amorim’s Brazilian cohort, 17% of previously employed patients with long COVID had not resumed work at 3 months in the pre-Omicron era, whereas over 90% returned to work during Omicron when vaccination rates were higher and the PCC phenotype appeared milder[17,23].

Healthcare utilization

COVID-19 survivors on dialysis and KTR tend to have higher rates of: Rehospitalization for cardiovascular events, infections, fluid overload and graft-related problems[6,7,10,11,15,16]. Outpatient visits, imaging and laboratory monitoring. The extent to which this is driven by PCC vs unmasked comorbidities is still uncertain, but the net effect is clearly an increased health-system burden.

Mortality and morbidity signals

Post-acute mortality in dialysis and KTR cohorts remain elevated: In HD, studies with long follow-up periods report ongoing mortality after discharge, particularly from cardiovascular causes; whether PCC independently predicts death is not yet clear[6,9-11]. Amongst advanced CKD patients with PCC in the RECOVAC study, symptom burden correlated with healthcare utilization and poorer perceived health, but causal links with hard endpoints require longer follow-up[5,13].

Graft outcomes in KTR

Graft outcomes after COVID-19 remain a key concern: Basic-Jukic et al[15] reported eGFR decline and late events (including death and graft loss) after COVID-19 in KTR, particularly in those with severe acute illness. Other case series have described biopsy-proven rejection, chronic allograft dysfunction and opportunistic infections in the months following COVID-19, often in the context of modified immunosuppression[7,16,19]. Whether PCC symptom status adds incremental prognostic information beyond these established risk markers remains unknown.

Recovery patterns in dialysis patients

Recovery trajectories in dialysis patients appear heterogeneous: Some return to pre-COVID levels of functioning and HRQoL within 3-6 months. Others remain symptomatic at 6-12 months, especially those with diabetes, pre-existing cardiovascular disease, or severe acute COVID-19[6,9-13]. Prospective frailty and functional assessments would help distinguish persistent PCC from irreversible “scars” in this population.

IMPACT OF VACCINATION, ANTIVIRALS, AND EVOLVING VARIANTS

Evidence regarding antiviral therapies and their potential role in reducing PCC risk in dialysis and kidney transplant populations remains limited. Agents such as nirmatrelvir-ritonavir have demonstrated benefit in preventing severe COVID-19 in high-risk populations; however, their use in patients with advanced kidney disease requires careful consideration of renal dose adjustment and potential drug-drug interactions with calcineurin inhibitors and other immunosuppressive agents. Further studies are required to determine whether early antiviral treatment modifies the long-term risk of PCC in these patient groups.

COVID-19 vaccination has substantially reduced the incidence of severe disease, but immunogenicity is blunted in dialysis and KTR[21,22]. Longitudinal vaccine studies in CKD demonstrate: Lower antibody titers and faster waning in CKD stage 4-5, dialysis and KTR compared to healthy controls[21,22]. Improved responses after additional vaccine doses, but with persistent gaps in KTR[22].

In RECOVAC, advanced CKD patients with prior COVID-19 had higher odds of PCC than those without infection, but higher antibody levels after vaccination were associated with lower PCC risk, and COVID-19-related hospitalization increased it[13]. These findings mirror general population data suggesting vaccination attenuates, but does not abolish PCC risk[2].

In KTR, Amorim et al[17,23] observed that long COVID during Omicron predominance in a largely vaccinated cohort, had a somewhat milder phenotype and less impact on return to work than in earlier waves, though prevalence remained high. Solid-organ transplant cohorts also suggest that Omicron-era PCC may be less severe but still clinically relevant[21].

Evidence on antivirals (e.g., nirmatrelvir and ritonavir) and PCC prevention in ESKD and KTR is limited; many pivotal trials excluded these groups or provided only small numbers. Drug-drug interactions with calcineurin inhibitors and dosing challenges in low eGFR further complicate routine use.

MANAGEMENT STRATEGIES AND CLINICAL PATHWAYS

In clinical practice, a pragmatic approach may involve integrating PCC screening into routine dialysis and transplant follow-up pathways. Patients recovering from COVID-19 may be reviewed at approximately three months following infection with structured symptom assessment, functional evaluation, and health-related quality-of-life measurement. Individuals reporting persistent symptoms or functional decline may then undergo targeted investigations and multidisciplinary assessment involving cardiology, respiratory medicine, rehabilitation, or mental health services where appropriate.

PCC in dialysis and KTR is not a single disease but a collection of overlapping trajectories-symptomatic, functional, and structural. Management therefore needs to be: Structured, to ensure systematic identification and follow-up. Individualized, to account for comorbidities, frailty, and patient goals. Integrated, embedded in existing renal pathways rather than siloed.

Screening and follow-up models

Pragmatic steps include: Incorporating a brief PCC symptom checklist and HRQoL measure (e.g., EQ-5D or KDQOL) at 3-, 6- and 12-months post-COVID infection in dialysis and transplant clinics. Prioritizing patients with severe acute illness, frailty, or low vaccine responses (where measured) for more intensive review[9-13,15-17]. Documenting baseline symptoms and HRQoL where possible, to help interpret future post-infection changes.

Rehabilitation, fatigue management and mental health

Rehabilitation principles from general PCC services can be adapted: Graded and paced physical rehabilitation with physiotherapy and occupational therapy input, tailored to dialysis schedules and recovery following transplantation. Energy-conservation strategies for fatigue, including activity pacing and prioritization. Psychological support, including screening for depression, anxiety and post-traumatic stress disorder, and referral pathways to counselling or psychiatry input where indicated[2,3,9-11,14].

Adjusting immunosuppression: What the evidence does and doesn’t say

Current evidence does not support chronic reduction of maintenance immunosuppression solely to treat PCC in KTR. Principles might include: Avoiding reflex long-term down-titration of calcineurin inhibitors or antimetabolites for non-specific symptoms such as fatigue or myalgia. Considering individualized, time-limited adjustments only when clearly justified (e.g., recurrent infection, suspected drug toxicity), with careful graft monitoring[7,15,16,19]. Prioritizing optimal vaccination and pre-emptive therapy for new infections.

Integration with transplant and dialysis services

Rather than building separate “PCC clinic” services for renal patients, many centers may find it more realistic to: Embed PCC assessment and management into existing transplant and dialysis treatment pathways. Develop shared care agreements with cardiology, respiratory medicine, neurology and rehabilitation services for complex cases. Use multidisciplinary meetings to review patients with persistent, multi-system symptoms, graft dysfunction or frequent hospitalizations.

METHODOLOGICAL LIMITATIONS AND EVIDENCE GAPS

The current evidence base has important limitations for consideration: Inconsistent PCC definitions: Time thresholds, symptom lists, and requirements for functional impact vary widely[1,2,6,9-16]. Survivor and selection bias: High acute mortality and non-response may skew the sample toward healthier or more motivated survivors[6,9-11,15-17]. Small, single-center cohorts: Most studies enroll tens to a few hundred patients only, limiting power and generalizability[9-11,14-18]. Sparse data in PD and underrepresented groups: PD patients, younger individuals, and many ethnic groups are currently understudied[5,6,13]. Limited mechanistic data: There are few studies integrating detailed immunophenotyping, endothelial and autonomic assessment, imaging and histology in renal PCC cohorts[4-6,20]. These gaps constrain our ability to quantify risk, predict trajectories, and design tailored interventions for dialysis and KTR populations.

FUTURE DIRECTIONS

Important knowledge gaps remain in populations underrepresented in current studies, including patients receiving PD, home dialysis therapies, and those living in low- and middle-income countries. Structural barriers to healthcare access, differences in dialysis infrastructure, and socioeconomic determinants of health may influence both the recognition and outcomes of PCC in these groups. Future studies should therefore prioritize inclusive cohort designs that capture diverse patient populations and healthcare settings. Looking ahead, several priorities emerge.

Harmonized definitions and renal-specific core outcome sets

Adoption of WHO-aligned PCC criteria with explicit reporting of time windows, coupled with renal-relevant symptom scales, HRQoL measures, frailty indices, and kidney and graft outcomes[1,6,13,14].

Large registries and multicentre cohorts

Expansion of initiatives like RECOVAC and national dialysis/transplant registries to systematically capture PCC events and link it to administrative outcome data[5,6,13].

Trials tailored to ESKD and KTR

Randomized trials of rehabilitation approaches, pharmacological interventions (e.g., anti-inflammatory or anti-fibrotic agents), and dialysis-prescription modifications specifically targeting PCC symptoms and functional recovery. Future studies should include kidney transplantation trials evaluating immunosuppression strategies and antiviral therapies with both PCC and graft outcomes prespecified.

Mechanistic studies

Integrated virology, immunology, vascular biology and imaging studies in CKD, dialysis and KTR cohorts to dissect pathways from acute infection to long-term symptom and organ trajectories[4-6,20].

Equity-focused research

Studies specifically addressing PD, home dialysis, low- and middle-income settings and structurally disadvantaged populations, where the intersection of PCC and kidney disease may be most acute.

CONCLUSION

Dialysis patients and KTR stand at a crossroads of vulnerability and resilience. The emerging data is clear that PCC is not a rare curiosity in these populations, but a recurrent sequel of infection: A palimpsest of fatigue, dyspnoea, cognitive fog, mood disturbance, functional decline, and, in some, accelerated kidney and graft injury (Tables 1 and 2)[6,9,10,12,13,14-18,21,24].

Table 1 Post-coronavirus disease condition clinical outcomes in dialysis patients.

Ref.	Setting and design	Population	Definition/timing of PCC	Key outcomes	Risk factors/notable points
Belkacemi et al[6], 2022	National registry-based cohort of all chronic dialysis patients with COVID-19 in 2020; survey at 6 months	1217 dialysis survivors with complete 6-month symptom data	LLCS at 6 months = any of: Extreme fatigue, weight loss > 5%, respiratory symptoms, tachycardia, chest/joint/muscle pain, anosmia/ageusia, neuro-cognitive issues, PTSD, depression, anxiety	17.7% had ≥ 1 LLCS at 6 months. Symptoms mainly fatigue, psychological and cardiorespiratory complaints	Higher odds of LLCS with hospitalisation (OR = 1.64) and ICU stay (OR = 5.03). Each additional year on dialysis, diabetes, overweight, and obesity are all independently associated with LLCS
Och et al[9], 2021	Single-centre longitudinal cohort of hospitalised maintenance HD patients with COVID-19, follow-up at 3- and 6-months post-discharge	79 HD survivors (out of 206 hospitalised; high in-hospital and early post-discharge mortality)	“Post-COVID-19 syndrome” = persistent/new symptoms beyond 12 weeks, assessed at 3 and 6 months	At 3 months, 93.7% had ≥ 1 persistent symptom; 72% had ≥ 3 symptoms. At 6 months, 81% still had ≥ 1 symptom and 53% had ≥ 3. Fatigue/muscle weakness, palpitations, sleep disturbance and nausea were common. Sustained deterioration in EQ-5D-5 L and EQ-VAS vs pre-COVID; dyspnoea burden remained higher at 6 months than baseline	Very frail, high comorbidity HD population. Persistent multi-symptom burden and impaired QoL out to 6 months despite some improvement. No specific multivariable risk model, but high pneumonia and oxygen requirement in the acute phase
Bouchari et al[10], 2025	Multicentre cohort of chronic HD patients across 9 centres; retrospective + interview-based assessment at about 3 months post-infection	163 chronic HD patients with documented COVID-19 infection	Long COVID ≥ 1 persistent symptom 2-3 months after infection, lasting ≥ 2 months and impacting daily function	68% met long COVID criteria; 29% had ≥ 3 symptoms. Fatigue (62%), anxiety (53%), arthralgia (40%), cough (33%), weight loss, sleep disturbance and anosmia are common	Long COVID is strongly associated with diabetes (adjusted OR = 3.8). Obesity, hospitalisation, oxygen therapy and corticosteroids were tracked with persistent fatigue, anxiety, dyspnoea and weight loss. Highlights heavy psychological symptom load (anxiety in > 50%)
Zhao et al[12], 2024	Prospective cohort of maintenance HD patients with COVID-19; telephone/clinic follow-up at 12 months	About 350-400 maintenance HD patients (exact number varies slightly by analysis)	Long COVID defined as per WHO-aligned criteria at 12 months: At least one persistent or new symptom starting in first 3 months and lasting ≥ 2 months	Long COVID prevalence around two-thirds at 12 months. Fatigue, sleep disturbance, dyspnoea, cognitive complaints and mood symptoms frequent; significant impact on HRQoL scales	Risk factors: Female sex, higher comorbidity burden, severe acute COVID-19, and markers of anxiety/depression associated with persistent symptoms. Vaccination appeared partly protective but did not eliminate long COVID
Bouwmans et al[13], 2024	Multicentre Dutch cohort of CKD stage 4-5, dialysis and KTR patients; PCC and symptom burden in 2022-2023 (largely Omicron, high vaccination)	779 patients with prior COVID-19; includes CKD stage 4-5, dialysis, and KTR strata	PCC as per WHO consensus (symptoms ≥ 3 months, lasting ≥ 2 months, no alternative diagnosis); symptom burden quantified	PCC prevalence: About 21% in dialysis, 24% in KTR, about 29% in non-dialysis CKD stage 4-5. Many had high symptom burden (multiple domains, fatigue prominent)	Dialysis and KTR patients had higher PCC-associated functional limitations than matched controls but broadly similar PCC prevalence between modalities, suggesting shared mechanisms (multimorbidity, inflammation) rather than transplant-specific effects alone

CKD: Chronic kidney disease; COVID-19: Coronavirus disease 2019; HD: Hemodialysis; HRQoL: Health-related quality of life; ICU: Intensive care unit; KTR: Kidney transplant recipients; LLCS: Long-lasting clinical symptoms; PCC: Post-coronavirus disease condition; PTSD: Post-traumatic stress disorder; QoL: Quality of life; WHO: World Health Organization; OR: Odds ratio; EQ-5D-5 L: EuroQol-5-dimension 5-level; EQ-VAS: EQ-visual analog scale.

Table 2 Post-coronavirus disease condition clinical outcomes in kidney transplant recipients.

Ref.	Setting and design	Population	Definition/timing of PCC	Key outcomes	Risk factors/notable points
Malinowska et al[14], 2021	Longitudinal cohort of KTR from north Poland with prior COVID-19; 6-month assessment of symptoms and HRQoL	67 KTR	“Post-COVID-19 syndrome” defined as persistent symptoms ≥ 12 weeks; follow-up at median 6 months	About 70% fulfilled criteria for post-COVID syndrome; fatigue, myalgia, cognitive complaints and sleep disturbance were common. Significant decline in HRQoL (EQ-5D-5 L, EQ-VAS) vs pre-COVID, especially pain/discomfort and anxiety/depression domains	Older age and a higher Charlson Comorbidity Index are associated with post-COVID syndrome. Authors compare burden with haemodialysis cohorts and the general population, suggesting KTR and HD both show disproportionate long-COVID-related QoL loss
Basic-Jukic et al[15], 2021	Single-centre prospective cohort of KTR surviving acute COVID-19; early post-infection follow-up	104 KTR	Prolonged symptoms or clinical complications at a median of 64 days post-diagnosis; not strictly WHO-PCC but early PASC	45% had prolonged symptoms or clinical complications; 71% had lab abnormalities (e.g., elevated D-dimer, inflammatory markers). Decline in eGFR and higher rejection episodes in those with more severe acute disease	Older age, lower baseline eGFR and clinical complications during acute COVID-19 are associated with poorer composite outcomes; calcineurin inhibitor dose reduction is associated with better outcomes in this cohort
Basic-Jukic et al[15], 2021 (“Late Effect in KTR” study)	Longer-term follow-up of KTR after early-wave COVID-19, stratified by severity	About 150 KTR with prior COVID-19, followed up to 24 months	Not symptom-based PCC; focuses on late graft and patient outcomes after COVID-19	Severe acute COVID-19 is associated with higher late mortality, graft loss, and larger eGFR decline compared to mild/moderate disease. Symptom persistence is less central than structural outcome signals	Suggests that in KTR, “long COVID” can be biochemical/structural (eGFR decline, rejection, graft loss) as well as symptomatic, and that acute severity imprints a long-term trajectory
Shafiekhani et al[16], 2023	Prospective cohort of hospitalised COVID-19 patients; KTR vs non-transplant controls, 6-month follow-up	148 KTR, 100 non-KTR	Post-COVID complications (clinical + radiological + functional) at 6 months	KTR had a higher prevalence of post-COVID complications than controls, including dyspnoea, fatigue and radiographic lung changes, plus more rehospitalizations	Risk factors for complications in KTR included CKD, hypertension, prior cerebrovascular disease and diabetes. Emphasises interaction between transplant-related immunosuppression and classic vascular comorbidity
Amorim et al[17], 2022	Large multicentre survey of KTR with confirmed COVID-19 infection; 3-month follow-up	780 KTR	Long COVID is defined as ≥ 1 organic symptom persisting at 3 months	27%-28% met long COVID criteria. Fatigue, dyspnoea, myalgia and cognitive complaints are the most frequent. 17% had not returned to work at 3 months	The main independent predictor of long COVID was the number of symptoms during the acute infection. No clear association with baseline immunosuppression pattern. Provides a large, real-world estimate of long COVID burden in KTR
Zahradka et al[18], 2025	Nationwide survey of KTR with prior COVID-19; latent-class modelling of symptom clusters	596 KTR, median follow-up about 1 year	WHO-aligned PCC criteria; clustering of symptom profiles	33.7% met PCC criteria. Eight distinct phenotypes identified (fatigue-dominant, cardiorespiratory, neurocognitive, musculoskeletal, etc.). Many patients had overlapping clusters	Risk: More severe acute COVID-19, higher BMI, ongoing corticosteroid use. Male sex appeared protective (OR = 0.69). Highlights that long COVID in KTR is heterogeneous, not a single syndrome
Morená et al[21], 2024	Prospective SOTR cohort (kidney, liver, heart, lung) in Spain in an Omicron-dominant, highly vaccinated setting	Mixed SOTR; substantial KTR subset	PASC is defined at > 12 weeks post-infection	PASC is still frequent but somewhat lower than early-wave reports; fatigue and dyspnoea predominate	Vaccination and Omicron seem to shift the severity spectrum, but do not abolish PASC. KTR behave similarly to other SOTR with regard to symptom profiles
Sandoval et al[24], 2025	Multicentre SOT cohort (including KTR) evaluating self-reported long COVID and risk factors	Mixed SOT; KTR an important subgroup	Patient-reported long COVID several months post-infection	Long COVID prevalence in SOT is broadly comparable to high-risk general populations; symptom clusters are similar (fatigue, dyspnoea, cognitive issues)	More severe acute disease, female sex, and psychological comorbidity are associated with PASC; the specific effect of immunosuppression intensity is less clear

BMI: Body mass index; OR: Odds ratio; COVID-19: Coronavirus disease 2019; eGFR: Estimated glomerular filtration rate; HD: Hemodialysis; HRQoL: Health-related quality of life; KTR: Kidney transplant recipients; QoL: Quality of life; SOT: Solid organ transplant; SOTR: Solid organ transplant recipients; PASC: Post-acute sequelae of coronavirus disease-19; PCC: Post-coronavirus disease condition; WHO-PCC: World Health Organization-post-coronavirus disease condition criteria; EQ-5D-5 L: EuroQol-5-dimension 5-level; EQ-VAS: EQ-visual analog scale.

At the same time, the story is unfinished. Many patients recover substantially; others plateau or decline. The task now is not simply to label clinical presentations as “PCC in ESKD” or “PCC in transplantation”, but to address these phenomena rigorously, understand its mechanisms, and weave its management into the fabric of kidney care. With better definitions, more inclusive cohorts and targeted interventions, the shadows of infection need not define the rest of the narrative for these patient populations.