Development of Disseminated Tuberculosis in A Non-Immunocompromised Patient After COVID-19 Infection: A Case Report

Background COVID-19 pandemic has had complications and has changed the pattern of disease incidence. COVID-19 affects the immune system. We present a case of disseminated tuberculosis (TB) in non-immunocompromised person with a history of COVID-19 infection.


Background
Tuberculosis is a contagious disease that is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent. In 2019, about 10 million people developed TB and 1.4 million died [ 1 ].
MTB is transmitted from person to person via the airborne route [ 2 ]. After inhalation, the droplet nucleus is carried down the bronchial tree and implants in a respiratory bronchiole or alveolus. Whether or not inhaled tubercle bacilli establish an infection depends on both host and microbial factors [ 3 ]. Miliary TB is a type of disseminate TB that results from lymphatic and hematologic spread from a TB focus and is very fatal if not treated in time [ 4 ]. In countries with low incidence, delayed diagnosis and treatment, increase mortality [ 5 ].
COVID-19 pandemic has had complications and has changed the pattern of disease incidence. COVID-19 affects the immune system. TB reactivation can be explained by T-cell depletion resulting from COVID-19 infection[ 6 , 7 , 8 ]. Here, we describe a patient who was diagnosed with the disseminated TB and history of COVID-19 infection.

Case Presentation
A 25-year-old Iranian female with complaints of headache and loss of consciousness was hospitalized on 2 Jun 2021. She presented with history of headache last 2 months. The patient's headaches were mostly in the frontal lobes and parietal lobes. She had frequent outpatient visits to the physician for headaches and has taken analgesics during this time.
The patient was non-immunocompromised person. She had a history of COVID-19 infection 3 months ago. Her COVID-19 disease was mild. She had u-like syndrome and lost her sense of smell and taste. She didn't have COVID-19 pulmonary involvement and was not admitted to a hospital. Then the complaint of back pain began. The patient's back pain was on the thoracic vertebrae. The patient back pain has continued until now.
The patient's headache had worsened from 2 weeks before the admission. Finally, she came to the hospital with a severe headache. She had complaints of decreased level of consciousness, nausea, vomiting, diplopia, back pain and bladder incontinency. She had acute onset of lower limb weakness on day prior to the admission that become unable to even stand independently. Patient did not have any medical problem previously. She did not have any cough. There was no family history of TB. She has lost 5 kg in the last month. She had moved from village to city 22 years ago.
On admission, she was lethargic and confused. She had delirium. On physical examination she was afebrile. Signs of meningeal irritation were present. Lower limbs power decreased (4/5). She had nystagmus on eye examination.
Brain magnetic resonance images (MRI) showed diffused leptomeningeal enhancement. Mild hydrocephaly was seen too. There was abnormal signal area with restriction in splenium of corpus callosum without enhancement ( Figure 1).
Spinal MRI showed abnormal signal intensity with enhancement in T8-T9 disc space, adjacent end plates, bodies and posterior elements and small part of body of T10 associated prevertebral soft tissue edema and enhancement ( Figure 2).
On chest computed tomographic scan, poorly spread nodularity was seen throughout the lungs suggesting miliary tuberculosis. Multiple lymphadenopathies were seen in the left axillary and mediastinum that some of them had calci cations ( Figure 3).
Laboratory investigations showed elevated WBC in Cerebral Spinal Fluid (60% lymphocyte), high CSF protein and low glucose (Table 1). Mycobacterium tuberculosis detected with polymerase chain reaction (PCR) of cerebral spinal uid (CSF). Rifampin resistance not detected with the Expert MTB/RIF assay.
Patient started on anti-tuberculosis drugs and steroid. She was started on isoniazid 300mg, rifampin 600mg, pyrazinamide 1200mg and ethambutol 825mg once daily. According to objective neurological ndings, prednisolone 80 mg/day was required, which was gradually tapered and discontinued through 6 weeks. Analysis of Cerebral Spinal Fluid (CSF) on the eighth day of treatment was better. Post treatment showed signi cant neurological improvement. The patient's consciousness gradually improved during the rst week of treatment. Nystagmus and diplopia was improved during the second week. The patient`s headache subsided and was mostly after waking up during the third week. Delirium was completely gone in the third week. From the fourth week, force of her lower limbs improved and she was able to stand independently. Despite T8-T9 spondylodiscitis, the patient had not neurological de cits and cord compression. According to the neurosurgeon consulting, she did not need to surgery and was treated with medical treatment. The patient's liver function tests increased at the beginning of treatment but gradually decreased after 2 weeks of treatment (Table2). The increase in liver function tests was less than 5 fold normal and the patient did not show signs and symptoms of acute hepatitis, so the medication continued. On day 18th of admission, the patient was discharged home in good general condition. The patient was prescribed anti tuberculous treatment for total duration of 12 months with a follow up appointment at the TB clinic. She received prednisolone for rst 6 weeks' duration and her prednisolone decreased weekly.   In endemic areas of tuberculosis, it is important to pay attention to patient's symptoms after COVID-19 infection such as weakness, headache and weight loss. As this case has had weakness, headache, and weight loss for few months. These symptoms may be confused with post COVID-19 syndrome and lead to delays the diagnosis and treatment of tuberculosis.
Given that the COVID-19 infection is a risk factor for TB reactivation. In COVID-19 pandemic, early identi cation of TB patients is important for treatment and infection control.
Due to wide patient involvement, complete and timely treatment of the patient is important. The success of drug treatment, depends upon many factors. Some studies have found an increased risk of relapse among patients with signs of more extensive disease [ 19 ].The patient was prescribed 12 months of antituberculosis treatment. Tuberculosis treatment requires multiple drugs be given for several months. It is di cult for the patient to tolerate the treatment due to the possibility of drug side effects. The patient should be aware of the importance of taking the medication correctly. It is very important that the patient be involved in a making decisions concerning treatment supervision and overall care. International standards also emphasize the importance of using patient centered approaches to the treatment of tuberculosis [ 20 ].

Declarations
Ethical approval and consent to participate This research was approved by the Ethics Committee of our hospital. The patient privacy is respected.
Patient`s name did not be used. Images of patients did not be used.

Consent for publication
Consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Availability of data and materials
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Figure 1 Brain MRI imaging shows diffused leptomeningeal enhancement Spinal MRI imaging shows T8-T9 spondylodiscitis Figure 3