First manic episode during COVID‐19 infection after IVF treatment: A case report

Key Message.

COVID‐19 may cause psychiatric syndromes through multiple mechanisms. The effects of COVID‐19 infection on central nervous system and the social stress it creates can trigger mania symptoms. Antipsychotics are effective in the treatment of a first triggered manic episode during the COVID‐19 infection and cessation of the treatment may be considered according to the patient's condition during the follow‐ups. As with typical manic episodes, long‐term treatment should be considered even after early remission. More comprehensive studies are needed to understand the possible neuropsychiatric effects of COVID‐19 infection in women of reproductive age.

Learning Points

• Manic episodes can occur following a COVID‐19 infection even in a primarily naïve patient.

• Antipsychotics appear to be effective in the treatment.

1. INTRODUCTION

Although COVID‐19 has been mostly causing respiratory system symptoms, some COVID patients have also presented with a various spectrum of neurological and psychiatric symptoms such as dizziness, vertigo, headaches, delirium, agitation, psychotic symptoms, depression, anxiety, and corticospinal system symptoms. ¹ It is suggested that these psychoneurological symptoms are caused by the effects of COVID‐19 on the central nervous system (CNS). ¹ In addition to the CNS effects of COVID‐19 infection, it is indicated that the increase in psychosocial stress due to social isolation and limited stimuli may also cause these symptoms. ²

Although few, cases of mania and psychosis associated with COVID‐19 infection have been reported in the literature. ³ , ⁴ In this case, we present a female patient who experienced their first manic episode during the course of a COVID‐19 infection, with which she was infected after an incidental IVF treatment.

2. CASE REPORT

In this report, we present a 40‐year‐old female patient with no known psychiatric illness or treatment history, who also had no previous medical disorders or regular drug use apart from the infertility treatment they have been receiving. When the family background was assessed, it was found that the patient had no first‐degree relatives with a psychiatric disorder. The patient also showed no sign of apparent childhood trauma or any lifelong hypomania symptoms.

The patient had been receiving infertility treatment and she had undergone an embryo transfer on March 4, 2021. After the embryo transfer, she was started up on estradiol and progesterone. During follow‐ups, it was detected that the patient had developed symptoms of fatigue and coughs after 3–4 days from IVF. COVID‐19 PCR test performed on March 13 came out positive and blood tests analyzed on the same day were detected as the following levels of CRP: 9.66 mg/L; ferritin: 153.9 μg/L; WBC: 4.25·10⁹/L; lymphocytes: 1.26·10⁹/L; AST: 20 U/L; and ALT: 20 U/L. The patient was admitted to the hospital on the same day as the positive PCR test and got isolated for COVID‐19 infection. The levels of B‐HCG were found as 29.72 IU/L on March 19. She showed no respiratory distress or low blood oxygen levels on follow‐ups. After the decision that she did not need further medical treatment for COVID, she was discharged on the 6th day of hospitalization and went under home quarantine. The tenth‐day control COVID‐19 PCR test came out negative on March 22 (Figure 1).

FIGURE 1.

Follow‐up timeline

On March 25, the patient was brought to the emergency department with complaints of sleep impairment, bursts of energy, and symptoms of pressured speech, loose associations, and logorrhea that have been present and progressing for 2 days. Blood levels measured in the ER were CRP of 29.2 mg/L, WBC of 11.6·10⁹/L, ferritin of 323 μg/L, and B‐HCG of 292 IU/L. No organic pathology was detected on the brain MRI. Her neurological examination showed no signs of organic neurological pathologies. There were also no vivid visual hallucinations or smell hallucinations, and the patient's time, place and person orientations were intact. After the first evaluation, the patient was admitted to the psychiatric service considering the diagnosis of a manic episode with concomitant psychotic features.

The patient's first evaluated Young Mania Rating Scale showed a score of 54. The patient was started on haloperidol. Haloperidol treatment had been gradually increased to 20 mg. The patient's current estradiol and progesterone treatments were continued orally. After the patient had experienced minimal vaginal bleeding, intramuscular progesterone was also administered. B‐HCG follow‐ups were done every 2 days. The levels of B‐HCG were found gradually increased as 311‐437‐682‐605‐910 IU/L throughout the hospitalization. On the 14th day of her admission, the patient, whose Young Mania score decreased to 8, was discharged for outpatient follow‐up. During outpatient follow‐ups, haloperidol was decreased gradually and stopped on the second month of outpatient evaluation. There were no symptoms of a recurrent episode of mania, hypomania, or depression after that.

3. DISCUSSION

In this study, we reported a patient who experienced their first manic episode during the course of a SARS‐CoV‐2 infection after an IVF treatment. When the recent psychiatric literature is reviewed, it appears that there have been many COVID‐19 cases associated with neuropsychiatric symptoms. ³ , ⁴

There are a few pathophysiological mechanisms suggested for the virus's effects on the CNS: the virus can induce neuron death through CNS infiltration, there are detected disruptions in the cytokine network, immune cells migrate to CNS, and the post‐infection autoimmunity may also affect the central nervous system. In addition to these mechanisms, it is suggested that the speculated changes in the intestinal flora because of the COVID‐19 infection can have indirect effects on the CNS via the gut–brain axis. ² Aside from the central effects, the COVID‐19 infection has psychosocial effects such as undermining the social protective factors which keep an individual from experiencing a psychosis. Social isolation and restriction of stimuli can trigger psychotic symptoms in patients. ²

Sex hormones have been found to regulate mood and are thought to play an important role in the pathophysiology of schizophrenia and other psychotic disorders, as well as mood disorders. ⁵ There have not been any studies reported in the literature about the psychiatric effects of hormone treatments to treat infertility on patients with bipolar disorder, schizophrenia, or other psychotic disorders. ⁵ Nevertheless, there were no other cases reported about psychiatric complications after an IVF treatment both in post‐COVID and non‐COVID patients.

Hormonal changes and the decrease of estrogen levels may lead to a worse prognosis in patients with schizophrenia and it may also increase predisposition to depression in women. ⁶ For this reason, fertility treatments that trigger hypoestrogenism may have an aggravating effect on depressive or psychotic symptoms. ⁵ On the other hand, current data on the association between progesterone and schizophrenia are inconsistent. Some studies reveal neuroprotective properties for progesterone, while other studies reveal the destructive effects of the hormone. ⁵

Our patient was receiving oral estrogen and progesterone therapy due to bleeding after embryo transfer when they experienced a manic episode. Because the patient had a history of taking oral estrogen and progesterone for infertility beforehand, we did not suspect that the current use of these hormones created a significant effect on the occurrence of this first manic episode. It has been thought that the central effects of COVID‐19 infection and the additional social stress caused by the isolation contributed to the formation of the current picture at hand.

This case caught our attention for its relevance to the relation between COVID‐19 and neuropsychiatric symptoms. While our case report supports the previous literature on this subject, we think that more extensive studies are needed for understanding the neuropsychiatric effects of COVID‐19 infection specifically on female patients of reproductive age.

CONFLICT OF INTEREST

There is no conflict of interest.

DATA AVAILABILITY STATEMENT

Not applicable.