Case Report of 78 –year-old man with meningitis, Pulmonary Thromboembolism & SARS-Coronavirus-2 infection

The novel corona virus infection involve both Central & Peripheral Nervous System . Some of the presentations include: acute cerebrovascular disease, impaired consciousness, transverse myelitis, encephalopathy, encephalitis and epilepsy. Our patient was 78 year –old man with dementia and diabetic nephropathy which was admitted two times for possibly COVID19 infection. At the �rst hospitalization, the patient is treated with hydroxychloroquine and kaletra based on clinical symptoms and initial laboratory �ndings due to suspicion of COVID19 . After the negative RT-PCR test of nasopharyngeal sample for covid19 and evidence of aspiration pneumonia in CT scan, the patient was discharged with oral antibiotics. Five weeks later, he was rehospitalized with loss of consciousness, fever and hypoxemia in physical exam he had neck stiffness in all directions, So the CNS infection was suspected, the CSF sample was in favor of aseptic meningitis and second RT-PCR test of nasopharyngeal sample for COVID19 was positive but Brain MRI just showed small vessel disease without evidence of encephalitis. In the second hospitalization, he had acute renal failure, which was treated with supportive care, and also suffered from pulmonary embolism with cavitary lesions in his lungs. Meningitis with pulmonary embolism and acute renal failure have not yet reported. Our patient is the �rst one, so we decided to share it. This case showed different presentation of COVID19 without typical lung involvement. So we must pay attention to any sign & symptoms in a patient suspected of having a COVID19 .

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Version of Record: A version of this preprint was published at ACTA MEDICA IRANICA on December 18th, 2021.See the published version at https://doi.org/10.18502/acta.v59i12.8070.

Introduction
The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2019 and rapidly spread worldwide.(1,2).World Health Organization (WHO) declared it a pandemic on 11 March 2020 (3).By 26 th May 2020 there are more than 5 million con rmed cases and about 350000 death reported.(4)The primary manifestation is respiratory but neurological features are also being reported such as headache, acute cerebrovascular disease, impaired consciousness, transverse myelitis, encephalopathy and encephalitis.(1)Meningoencephalitis just reported in two case reports.(5,6) Meningitis with pulmonary embolism and acute renal failure have not yet reported.Our patient is the rst one, so we decided to share it.

Case Report
A 78-year-old man with a history of type 2 diabetes from 10 years ago and CKD from two years ago due to diabetic nephropathy with creatinine in the range of 1.5-2mg/dl .He was treated with insulin glargine.
One year ago was diagnosed with dementia and has been hospitalized several times in recent year due to high blood sugar and aspiration pneumonia.His last hospitalization was about 35 days ago in the infectious diseases ward, where he was hospitalized due to fever, sweating, vomiting and lung involvement and suspicious for COVID19 infection.Lab test showed leukocytosis which was associated with severe neutrophilia , lymphopenia and thrombocytopenia , creatinine was 1.5mg/dl (Table 1).The patient was initially treated with hydroxychloroquine and Kaletra (lopinavir/ritonavir) for a possible diagnosis of covid19, on the other hand because of suspected bacterial infection he received Imipenem and levo oxacin.After the RT -PCR for COVID19 from the patient's nasopharynx was negative and according to the radiologist's CT scan report, the patient was more likely had aspiration pneumonia than COVID 19 (Figure 1),so the patient was discharged.Five weeks after discharge, again he was brought to emergency ward wih ambulance due to fever, productive cough, hypoxemia (O 2 Saturation 80% without oxygen) and loss of consciousness.At emergency room the patient's vital signs were: T: 38.5 0c , PR: 130 / min , RR: 22 / min, BP: 110/70 mmHg.He was awake on neurological examination, but had no visual or verbal communication and did not obey orders.The pupils are mid-size with response to light and he did not have neurologic focal de cit.He had neck stiffness in all directions.Auscultation the lungs showed crackles in base of both lungs.There were no other signi cant signs.The patient was transferred to the ICU and further tests such as blood and urine cultures as well as Lumbar Puncture are performed.We repeated the sample of nasopharynx for COVID19 test.The lung CT scan revealed the patchy ground glass opacities in left upper lobe ,accompanied by peri-bronchial thickening and mild pleural effusion on the left side (CORADS-4).(gure2) In the CSF sample, the protein and sugar were normal, but white blood cells was 60 with predominance of PMN(90%).RT-PCR COVID19 was requested in the CSF sample which was negative.Procalcitonin was more than 10, and ferritin, D-dimer were also high.Creatinine was also increased compared to the previous hospitalization .(Table1)CTscans of paranasal sinuses showed no evidence of sinusitis, CT scan of the brain showed generalized atrophy, and only small vessel disease was reported in Brain-MRI.(gure3) All patient's cultures were negative.CSF sample for herpes virus and tuberculosis was also negative.Therefore, patient was diagnosed with aseptic meningitis due to covid infection and pneumonia, with acute on chronic renal failure which was treated with meropenem, linezolid and uid therapy.The patient's blood sugar was high at the beginning of admission, which was controlled with basal &short acting insulin.In the course of hospitalization, the patient's fever was stopped after 48 hours and the patient's level of consciousness increased on the fourth day of hospitalization as he made eye and verbal communication.On the 14th day of the patient's hospitalization, suddenly he became tachycard and tachypenic, we suspected to pulmonary thromboembolism so have done pulmonary artery CT angiography and color doppler ultrasound of the veins of both lower limbs which was normal, the CT showed thrombosis in the sub-segmental of right upper lobe branches, in the parenchymal cuttings of the lungs, a consolidation with cavity was evident in the anterior segment of the LUL.Since the thrombosis was sub-segmental so we just continued anticoagulant (heparin) as prophylaxis .After three weeks of treatment with improvement of general condition he was discharged.

Discussion
COVID19 involve both Central & Peripheral Nervous System some of the presentations include: dizziness, headache, acute cerebrovascular disease, impaired consciousness, transverse myelitis, encephalopathy, encephalitis, epilepsy, hyposmia (1).In our patient, he was initially treated as possible covid19 infection for six-day course, but because CT scans of the lungs was not in favor of covid19 and the RT-PCR of covid19 was negative, therefore the treatment of covid19 was stopped and the patient was discharged with oral antibiotics for aspiration pneumonia.At the next visit, ve weeks later, due to clinical signs and physical examinations that raised the possibility of CNS involvement and the pulmonary opacities, (CORADS 4), was hospitalized and evaluated.The second time nasopharyngeal swab sample for RT-PCR COVID 19 was positive.The acute meningitis panel and HSV & TB at the CSF were all negative and the pattern was consistent with aseptic meningitis because sample was taken at the rst 24 hours of infection.Therefore, the predominance of PMN can be explained because in viral meningitis, PMN can predominate rst and then lymphocytes increase.Since the treatment of aseptic meningitis is usually supportive, so the patient just treated for pneumonia.Rate of thromboembolic events in severe cases of covid19 is higher .In this patient presence of thrombosis is another important sign of severe disease, coincidence of these two complications, meningitis and thrombosis is rare and requires more studies.

Declarations
We(authors) declare no con ict of interest.We reported a case and our works as part of standard guidelines and regulations.Our patient has demantia and impaired judgment so we ask permision from his greatest son to participate and publish the case.Brain MRI

Table 1 :
Lab tests at first and second admissions of patient