The COVID-19 pandemic, caused by SARS-CoV-2, has had a significant impact on the global economy and public health [8]. Apart from the expected pulmonary involvement in SARS-CoV-2, other organ impacts have also been reported, including kidney involvement in patients with COVID-19 [9, 10]. SARS-CoV-2 infection may lead to various types of kidney damage [11, 12]. Although IgAN has been reported in association with SARS-CoV-2, these reports are limited to individual cases [13, 14]. To the best of our knowledge, this is the first study to compare clinical and pathological characteristics of IgAN between post-SARS-CoV-2 infection group and pre-SARS-CoV-2 infection group.

Starting from December 7, 2022, the relaxation of control measures in China, including the lifting of regional mass testing restrictions and the implementation of home isolation or quarantine, contributed to an unprecedented surge of the Omicron variant. As a result, there was a significant increase in the prevalence rate of COVID-19 [15]. A total of 48 patients were diagnosed IgAN from December 8, 2022 to April 6, 2023 in our hospital. These patients constituted approximately 22.5% of the total patients who underwent renal biopsy during that time. We analyzed the incidence rate of IgAN during the same time period before the COVID-19 outbreak and it ranged between 21.2 and 38.0% in recent three years in our center. Ten patients were excluded from the study due to their ineligibility for inclusion. Among the 38 patients who contracted SARS-CoV-2, 24 had a documented history of nephropathy, 8 had an uncertain nephropathy history, and 6 did not have any prior history of nephropathy before being infected with COVID-19. After SARS-CoV-2 infection, 13.2% of the patients (5/38) presented with gross hematuria. It is well known that many viral and bacterial pathogens have the ability to trigger gross-hematuria and increased proteinuria. Therefore, we can conclude that, as expected, COVID-19 share with other pathogens the ability to exacerbate the clinical features of IgAN. In recent years, there have been several reports of patients with preexisting or newly diagnosed IgAN who are susceptible to gross hematuria after receiving the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine [16]. We also observed that 13.2% of the patients (5/38) experienced an increase in proteinuria after contracting SARS-CoV-2. These findings suggest that SARS-CoV-2 infection may lead to gross hematuria or an exacerbation of proteinuria in a subset of patients with IgAN. It is important to monitor and assess proteinuria levels in individuals with IgAN who have been infected with SARS-CoV-2 to ensure appropriate management and treatment of kidney-related complications.

It is not yet clear whether the occurrence of COVID-19 affects the presentation of the IgAN. One case reports have described five cases of IgAN with gross hematuria that were confirmed by biopsy after SARS-CoV-2 infection [14]. In one case among the reported cases, the individual experienced gross hematuria within two days after the onset of fever. The hematuria lasted for a duration ranging from 1 to 6 days. Additionally, it is worth noting that during the episode of gross hematuria, one patient developed acute kidney injury (AKI). In our study, we found that the cohort of patients infected with SARS-CoV-2 exhibited advanced age, a higher prevalence of hypertension and lower levels of eGFR compared to those in the pre-SARS-CoV-2 infection group. Although there was no statistically significant difference in diabetes incidence between the two groups, the post-COVID-19 infection group had a higher prevalence of diabetes. As for pathological characters, the post-COVID-19 infection group exhibited a higher proportion of sclerotic glomeruli and glomerular ischemic sclerosis compared to the pre-COVID-19 infection group. Even though there was no statistically significant difference in the tubular atrophy/interstitial fibrosis (T1/2), the post-COVID-19 infection group had a higher proportion of T1/2 lesions. This finding suggested the older age in patients with SARS-Cov-2 is consistent with the evidence in the literature and alone can explain the clinical and histological characteristics found in the cohort of patients with covid-19 infection. Indeed, multiple studies have consistently reported the elderly population is known to be more vulnerable to severe illness and complications associated with COVID-19 [13]. Advanced age is recognized as a significant risk factor for developing severe symptoms, experiencing higher rates of hospitalization, requiring intensive care, and facing an increased risk of mortality from COVID-19. Regular monitoring of renal function and appropriate medical care are crucial for identifying and managing any declines in eGFR or related renal complications in elderly individuals who contract COVID-19. As for treatment decision, we found the treatment approach remained consistent regardless of the presence of COVID-19.

So far, the pathogenic mechanism underlying COVID-19-associated kidney damage remains incompletely understood. It has been suggested that elevated levels of a circulating form of abnormal glycosylation (Gd-IgA1) may contribute to the pathogenesis of IgAN [17, 18]. COVID-19 virus primarily affects the respiratory tract, leading to the stimulation of excessive production of IgA1, including Gd-IgA1 [16]. Gd-IgA1 has the potential to recognize specific structures on certain microorganisms and form circulating complexes with them, thereby facilitating antigenic recognition. Previous studies have demonstrated that potential underlying mechanisms of kidney involvement in COVID-19 may include direct kidney infection through ACE-2 receptors expressed in tubular cells and podocytes [19]. Additionally, an indirect mechanism may involve cytokine release syndrome observed in COVID-19 patients [20]. The cytokines released during COVID-19 infection, including IL-1, IL-6, and TNF, have the potential to stimulate the proliferation and maturation of IgA1-producing B cells, thereby contributing to the development and severity of IgAN [21, 22]. In this study, we found no evidence of an increased incidence rate of IgAN during COVID-19 infection. However, we did observe that SARS-CoV-2 infection might be associated with severe kidney damage in these patients. The high prevalence of glomerular sclerosis among our post-COVID-19 infection group suggests a chronic disease trajectory in this population. While a higher proportion of T1/2 lesions suggests that COVID-19 infection may induce tubulointerstitial lesions in the kidney in IgAN, further research is needed to establish a clear causal relationship between COVID-19 and tubulointerstitial damage in this context. In this study, we observed that while Covid-19 infection can exacerbate IgAN, it does not contribute to an increased incidence of IgAN. This suggests that the virus is not a causal factor in the development of the disease.

The present study has several limitations that should be acknowledged. Firstly, it was a retrospective cohort study, which may introduce inherent biases and limit the generalizability of the findings. The small sample sizes in the post-COVID-19 infection group further impact the statistical power and reliability of the results. Secondly, the underlying mechanisms linking COVID-19 infection and the onset as well as clinical manifestations of IgAN remain unclear, and further research is warranted to elucidate these mechanisms.