A growing field of research has suggested possible mechanisms for tumor resolution, including an acute infection leading to remission by inducing an immunological mechanism, which may have occurred in our patient, who developed COVID-19 [
7]. A metalloproteinase, angiotensin-converting enzyme 2 (ACE2) acts as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19 [
8]. ACE2 is highly expressed in the lungs, heart, gastrointestinal tract, kidneys, and bladder, with the lungs being the primary target of SARS-CoV-2. Once SARS-CoV-2 is bound, the spike protein undergoes protease cleavage [
9]. As the virus attaches to ACE2 in the lung epithelium, macrophages, epithelial cells, and dendritic cells serve as the innate immune response until adaptive immunity is triggered. T-cell immunity has been studied in COVID-19 response [
10]. At the site of infection, T cells produce cytokines, chemokines, and cytotoxic molecules. Cytokines directly inhibit viral replication, chemokines recruit additional cells to the site, and cytotoxic molecules directly kill the infected cells to eliminate the pathogen [
11]. Memory T cells play a protective role after the infection resolves. Previous studies have demonstrated the role of virus-specific memory T cells in patients with respiratory diseases, including their correlation with protection during the recent epidemic caused by the H1N1 strain of the influenza A virus [
11]. Many virus-specific CD4 and CD8 T cells remain in the body long after acute infection. For example, memory CD4 T cells specific for the HLA-DR08- and HLA-DR15-restricted epitopes within the S protein of SARS-CoV have been identified in recovered individuals, and respond to the similar SARS-CoV-2 [
12]. Patients with COVID-19 show activation of the innate immune defense, leading to increased levels of circulating monocytes and activation of macrophages and antigen-presenting (dendritic) cells. These cells trigger the adaptive immune system (antibodies) along with natural killer cells (CRP elevation) to attack SARS-CoV-2. T lymphocytes are activated during the first phase of the disease and produce interferon gamma (IFN-γ). This response leads to an exaggerated immune response, damaging the lung tissue, and possibly selectively targets microadenomas. We hypothesized that two or more acute inflammatory responses occur simultaneously in patients with both tumors and inflammation caused by viral infection, ultimately negating the inhibitory effect of systemic inflammation on innate immunity. Thus, the activation of cells of the innate immune system, such as natural killer and dendritic cells, in patients with tumors results in spontaneous remission [
8]. This case report presented the disease course of a man who presented with symptoms of COVID-19 and had a medical history of pituitary microadenoma that had been confirmed using MRI. The tumor went into remission after the patient contracted COVID-19, a change that was hypothesized to have occurred because of the induction of the innate and adaptive immune systems by viral infection. Remission progressed gradually, starting with improvement of the baseline symptoms of pituitary microadenoma, and remission of the pituitary microadenoma was confirmed using MRI (Fig.
3,
4). In the absence of specific treatment, remission may have been induced by COVID-19. Pituitary microadenomas rarely undergo spontaneous remission, as they are typically fixed in size and difficult to treat. PA, a reported cause of remission of a pituitary adenoma, was unlikely in the present case as it generally occurs in patients with macroadenomas and would have led to an empty sella along with symptoms of hypopituitarism, such as hypothyroidism or decreased libido, which were not observed in the present case. Other studies reported cases similar to ours and observed features similar to lymphocytic hypophysitis, an autoimmune disease in which the pituitary gland is infiltrated by lymphocytes, plasma cells, and macrophages, thereby impairing its function. However, the pathogenesis of lymphocytic hypophysitis remains unclear. Both autoimmune pathogenesis and viral origin have been suggested [
1]; however, lymphocytic hypophysitis has characteristic features including symmetrical swelling, thickened pituitary stalk, and autoimmune disease. These features (except autoimmune disease and viral origin) were not present in our case with COVID-19-induced remission by immunity induction, which led to improvement in function [
1]. A similar case report described remission of Hodgkin’s lymphoma after COVID-19. The authors hypothesized that SARS-CoV-2 infection triggered an antitumor immune response, which resulted in the cross-reactivity of pathogen-specific T cells with tumor antigens and natural killer cell activation by inflammatory cytokines produced in response to viral infection [
2].