We present 13 our patients with generalized autoimmune MG and COVID-19.
Patient`s myasthenic distribution and severity is categorized according to the Myasthenia Gravis Foundation of America (MGFA) classification. Exacerbation of myasthenic weakness was defined as a MGFA score worsening from the baseline when baseline scor is defined on recent neurological control or clinical descriptions one month prior to the hospitalization .
Depending on severity of clinical condition, patients were divided into two groups: more severe- those who required hospitalization and group with milder condition, treated at home.
Almost equal number of presented patients were in hospitalized group (7 patients) and treated at home (6 patients). Only men were in more severe group, while milder group consisted of both sexes equally. Slightly older patients were in more severe group (58±13,81) compared to the group with a milder clinical picture (40,16±11,71) .
According to their antibody status, MG patients are grouped in seropositive group (AChR-antibody positive), muscle specific tyrosine kinase (MuSK) antibody positive and sero-negative group .
A 43 year old male with a history of Morbus Sjogren, hypertensia and obesitas, has been diagnosed with seronegative generalized MG (MGFA 3A) three years ago. Thymectomy performed year and half after the diagnose made and thymic hyperplasia seen on biopsy. His last exacerbation was prior thymectomy, with remission after plasma exchange (PE).
The patient was stable at the time of the pandemic with prednisolone, pyridostigmine and azathioprine in therapy (Table 1).
He had fever (39°C) followed by malaise, myalgia and pain in his chest on February this year. His test was positive for SARS-CoV-2 (PCR). Chest MSCT demonstrated patchy ground glass opacities in both lungs. CRP was increased (maximal 291 mg/L); but D dimer was normal in laboratory.
He treated with antibiotics and antiaggregation therapy during hospital (Table 1). Saturation was 90-92% and oxygen applied during nights.
Regression of inflammation seen on control chest radiography after 10 days of hospitalization.
Myasthenic deterioration (MGFA 2B) developed two weeks after discharge from hospital when increase dose of prednisolone (60/20mg) and pyridostigmine (300mg daily) was sufficient for stabilization his condition.
Male, 78 years old with 10 years history of seropositive, generalised MG (MGFA 2A). His clinical remission maintained with pyridostigmine only, for years (MGFA 1). Thymectomy was not done (Table 1).
He has history of hypertension and insulin dependent diabetes mellitus.
He report a fever (38°C), cough, and reduction of smell sensations in February this year when PCR for SARS-CoV-2 was positive. Chest MSCT at the beginning of his hospitalization, showed billateral pneumonia. He was treated with antibiotics and low molecular heparin with moderated flow oxygen support. Prednisolone returned to the therapy due to exacerbation of the MG (MGFA 2).
Control chest radiography showed regression of inflammation.
His condition recovered at the end of hospitalisation, with recommendation for tappering oral corticosteroid therapy.
Male, 70 years old, with seropositive generalized MG diagnosed 2012. (MGFA 3A). Thymectomy was not done. The patient was in remission two and half years ago (MGFA 1) with azathioprine and pyridostigmine in therapy (Table 1.).
The patient report cough and diarrhea on April 2021. PCR test was positive on Covid-19. On chest radiography incipient pneumonia was present; in laboratory normal D-dimer and slighty inceased CRP value. The patient had normal saturation, treated with antibiotic and anticoagulant therapy. Decline in saturation (89%) required high flow of 10% oxygen on 11th day of the infection. Creatine levels elevated as much as CRP and IL-6 in his laboratory (Table 1). Tocilizumab was administered (800 mg i.v.) on 13th day of beginning of the infection with clinical recovery after that. The patient was discharged home in stable condition after one week.
No deterioration of myasthenic symptoms all the time, and the therapy for MG did not changed.
A 58-year-old male with a history of hypertension and seropositive generalized MG (MGFA 3B) diagnosed 2016. His clinical remission (MGFA 1) achived immediately after introduction anticholinergic and immunosuppressive therapy (Table 1). He denided thymectomy.
On January 2021. he reported fever, fatigue, non-productive cough when PCR for SARS-CoV-2 was positive. Billateral pneumonia seen on his chest MSCT, treated with antibiotics.
He hospitalized because of shortness of breath when oxygen applied.
Progression of infiltrations in lungs developed in next few days accompanied by development of renal insufficiency, increasing inflamator factors, as well as IL6 (Table 1.) tried to solve by tocilizumab ordination (800 mg iv). After initial partial recovery, new deterioration required mechanical ventilation, and he died after 5 days.
A 56 year old man with seropositive generalised MG diagnosed 3 years prior COVID-19 pandemia (MGFA 4B), when he required hospitalization for a course of plasma exchanges (PE) and corticosteroid therapy given parenterally. Prednisolone continuited orally with tappering during months, afterward he remained stable (MGFA1) with only pyridostigmine and azathioprine in his therapy (Table 1).
Thymus was unvisible on his chest MSCT, and thymectomy did not performed.
There was no other medical history in his past.
He becomes febrile (39°C) on December last year, when PCR for SARS-CoV-2 was positive. Because of tachypnea and shortness of breath he connected to oxygen next day, immediately upon his admission to the hospital.
Due to deterioration of respiratory status, he was intubated five days after admission. Control MSCT chest demonstrated expansion of inflammation. Just before it, he reported deterioration of myasthenic weakness (MGFA 2B) when parenteral corticosteroid therapy and humane immunoglobulins given intravenously (IVIG) without benefit- he died soon after due to cardio- respiratoria insuffitiention (Table 1).
Male, 65 years old with seropositive, generalised MG diagnosed 4 years ago (MGFA 4B), treating during hospitalization with pyridostigmine, parentheral corticosteroid and PE, with remission achieved. Prednisolone tappered over the time and he remained stable all the time with pyridostigmine and azathioprine in therapy. Thymectomy was not performed.
His mild hypertension was regulated by medicament.
Prednisolone reinstatement at the end of last year due to myasthenic deterioration (MGFA 2). As the patient become febrile in the following days, he was tested and was positive for SARS COV-2 (PCR).
He hospitalized at emergency department after few days, and immediatelly intubated due to saturation of 60%. Billateral ground glass opacities are seen in his MSCT chest. He was treated with parenteral atibiotics, IVIG, and parentheral corticosteroid (Table 1), but control chest MSCT showed extended inflammation.
Letal outcome occurred 15 days after admission to hospital.
Male, 32 years old, with history of seronegative generalized MG diagnosed on 2013. (MGFA 3A). Thymectomy performed next year. Stable postoperative course (MGFA 1) maintained with pyridostigmine and azathioprine all the time (Table 1.).
Due to cough and loss of sense of smell et the end of last year, he was tested on Covid-19, when PCR was negative. Symptoms lasted for a month with spontaneous recovery and without deterioration symptoms of MG.
Moreover, contact with the virus has been confirmed when anti SARS-CoV-2 antibodies were detected in his sera three months later.
Male, 57 years old, with seropositive generalized MG (MGFA 3B.) diagnosed last year.
Due to the pandemic planned thymectomy suspected thymoma was postponed, but symptoms were reduced (2B) with pyridostigmine, prednisolone and cyclosporine A (Table 1).
The patient developed cough, ageusia, anosmia, myalgia, headache and become febrile (38°C) at the beginning of this year. His PCR test was positive for SARS-CoV-2 and chest radiology showed pronounced broncho-vascular pattrn .
The patient was treated at home with an oral antibiotic and multivitamin therapy (Table 1.), without deterioration MG symptoms. Infective symptoms resolved over 2-weeks period.
Female 42 years old, with 12 years old history of seropositive MG (MGFA 4A). Thymectomy was performed immediately after the diagnosis made (PH thymoma).
She was on permanent therapy with pyridostigmine, prednisolone and azathioprine (Table 1.) for a long time, with partial reduction of myasthenic symptoms (MGFA 2A).
Sniffle and exhaustion were reason for PCR test when Covid-19 confirmed. Laboratory, CRP and D-dimer were normal (Table 1.).
The infection treated at home with polyvitamine therapy and acetylsalicylic acid when her condition did not change significantly- she had occasional and mild fluctuations in muscle weakness within grade 2A.
A 48-year-old female without preceding illnesses, has been diagnosed with seropositive generalized MG (MGFA 3A) at 2015. She was in clinical remission for years (MGFA 1) with pyridostigmine, prednisolone and azathioprine after thymectomy (Table 1).
Due to fatigue, dry cough and diarrhea, she performed PCR on SARS-CoV-2 and it was positive in the middle of last year. She stayed at home and used only vitamins and probiotics.
There was no clinical deterioration all the time- neither myasthenic weakness nor symptoms of the infection.
Female, 20 years old, with seropositive generalized MG (MGFA 2A) diagnosed at the beginning of last year, and thymectomised shortly after the diagnosis performed. She was in a stable condition all the time with pyridostigmine and prednisolone with tappering regiment (Table 1.).
Although she had no infective symptoms, anti SARS-CoV-2 antibodies in sera was done on personal request and were positive. It was interpreted as a consequence of asymptomatic Covid-19.
Male, 40 years old, with seropositive MG since 2012. (MGFA 3A). Although thymectomy performed at the same year, he is unstable in the postoperative course (MGFA 2B) with pyridostigmine, prednisolone and cyclosporine A continuously for the last 3 years (Table 1.).
He became febrile (38,5°C), coughed, lost his sense of smell on March this year when PCR for SARS-CoV-2 was positive. He was hospitalized because of billateral interstitial pneumonia on his MSCT chest, and flavipiravir is prescribed immediately upon his receipt while cyclosporine A was excluded from his therapy. As decreased saturation was accompanied by an increase in IL-6 in next 3 days, the patient received tocilizumab and transferred to the intensive care unit for non-invasive ventilation (NIV) after that. He recovered in the comming days, and discharded to home after one month of hospital treatment.
The patient was in clinical remission 6 months after tocilizumab therapy out of need for cyclosporine A in his therapy again.
Male, 43 years old with seropositive generalised MG diagnosed 2004. (MGFA IIIB). He thymectomised immediatelly thereafter (PH thymoma) and re-thymectomised because of rest thymoma in the same year. He was in clinical remission after irradiation and chemotherapy for 12 years and without therapy for MG (MGFA I).
Milder form of Covid-19 infection he developed on November last year, when he treated at home with antibiotic, vitamines, alpha lipoic acid and anti-aggregation therapy (Table 1). The fever withdrewed after 2 days, and respiratory disturbances after 4 days, without myasthenic egzarcerbation.
Burning sensation in his hands and feets evolved 5 months after the infection, when chronic inflammatory demyelinating polyneuropathy (CIDP) verified by electroneurography. The new symptoms treated with prednisolone and pregabalin. Control radiology and puncture biopsy confirmed thymoma in his chest again, and VATS thymectomy planed.