Introduction
Methods
Inclusion and exclusion criteria
Literature search
Data collection and analysis
Quality assessment
Results
Selection of articles for review
Assessment of study validity (quality assessment and risk of bias)
No. | First author, country | Selection | Comparability | Outcome | Total | |||||
---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 1 | 2 | 3 | ||||
1 | Jakubíková M, Czech [35] | * | * | * | * | * | * | 6 | ||
2 | Kalita J, India | * | * | * | * | * | * | 6 | ||
3 | Sole G, French [15] | * | * | * | * | * | * | 6 |
No. | First author, country | Selection | Comparability | Outcome | Total | ||||
---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 1 | 2 | ||||
1 | Businaro P, Italy [36] | * | * | * | ** | ** | * | * | 9 |
2 | Camelo-Filho AE, Brazil [10] | * | * | * | ** | * | 6 | ||
3 | Stojanov A, Serbia [37] | * | * | * | ** | * | * | 7 |
No. | Major components | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | Were patient’s demographic characteristics clearly described? | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
2 | Was the patient’s history clearly described and presented as a timeline? | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
3 | Was the current clinical condition of the patient on presentation clearly described? | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
4 | Were diagnostic tests or assessment methods and the results clearly described? | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
5 | Was the intervention(s) or treatment procedure(s) clearly described? | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
6 | Was the post-intervention clinical condition clearly described? | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
7 | Were adverse events (harms) or unanticipated events identified and described? | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
8 | Does the case report provide takeaway lessons? | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Overall appraisal | I | I | I | I | I | I | I | I | I | I |
No. | Major components | 1 | 2 | 3 | 4 | 5 | 6 |
---|---|---|---|---|---|---|---|
1 | Were there clear criteria for inclusion in the case series? | Y | Y | Y | Y | Y | Y |
2 | Was the condition measured in a standard, reliable way for all participants included in the case series? | Y | Y | Y | Y | Y | Y |
3 | Were valid methods used for identification of the condition for all participants included in the case series? | Y | Y | Y | Y | Y | Y |
4 | Did the case series have consecutive inclusion of participants? | Y | Y | Y | Y | Y | Y |
5 | Did the case series have complete inclusion of participants? | Y | Y | Y | Y | Y | Y |
6 | Was there clear reporting of the demographics of the participants in the study? | Y | Y | Y | Y | Y | Y |
7 | Was there clear reporting of clinical information of the participants? | Y | Y | Y | Y | Y | Y |
8 | Were the outcomes or follow-up results of cases clearly reported? | Y | Y | Y | Y | Y | Y |
9 | Was there clear reporting of the presenting site(s)/clinic(s) demographic information? | Y | Y | Y | Y | Y | Y |
10 | Was statistical analysis appropriate? | NA | NA | NA | NA | NA | NA |
Overall appraisal | I | I | I | I | I | I |
Study characteristics
No. | First author, country | Study design | Subject characteristic | Management | Outcome |
---|---|---|---|---|---|
1 | Adhikari R, USA [38] | Case report | 33 y/o, M, AChR Ab, MG diagnosed before COVID-19 | MV, steroid, symptomatic treatment | Deceased |
2 | Aksoy E, Turkey [39] | Case report | 46 y/o, F, AChR Ab, MG diagnosed before COVID-19 | Pyridostigmine (4 × 60 mg), favipiravir, meropenem, oseltamivir, HCQ (2 × 400 mg x 1d, 2 × 200 mg x 4d), MV, linezolid, MP iv (1 × 40 mg), and plasma therapy | Recovery |
3 | Anand P, USA [46] | Case series | MG diagnosed before COVID-19 1: 57 y/o, M, AChR Ab 2: 64 y/o, M, AChR Ab 3: 90 y/o, F, AChR Ab 4: 42 y/o, F, MuSK Ab 5: 64 y/o, F, AChR Ab | 1: HCQ (2 × 400 mg x 1d, 1 × 200 mg × 2d), AZM (1 × 500 mg x 1d, 1 × 250 mg x 2d), TOZ (300 mg × 1 dose), AZA (1 × 50 mg), MV 2: HCQ (2 × 400 mg x 1d, 1 × 400 mg x 4d), AZM (1 × 500 mg x 1d, 1 × 250 mg x 4d), CTX (1 × 2 g x 2d, 1 × 1 g x 3d), prednisone (1 × 10 mg x 9d, 1 × 5 mg), MV 3: HCQ (2 × 400 mg x 1d, 1 × 400 mg x 4d), AZM (1 × 500 mg x 5d), CTX (1 × 1 g x 5 d), IVIG, prednisone (1 × 25 mg x 6d, 1 × 20 mg) 4: Prednisone (1 × 20 mg), IVIG (2 g/kg/d) 5: AZA, prednisone (1 × 60 mg) | 1: Discharged home on day 9 2: Continued MV 3: Discharged to skilled nursing facility on day 19 4: Discharged home on day 5 5: Discharged home on day 9 |
4 | Assini A, Italy [9] | Case report | 77 y/o, M, MuSK Ab, newly diagnosed ocular MG triggered by COVID-19 | Pyridostigmine (4 × 60 mg), AZA (1.5 mg/kg/d) | Recovery |
5 | Essajee F, South Africa [40] | Case report | 7 y/o, F, AChR Ab, newly diagnosed ocular MG triggered by COVID-19 | IV MP (30 mg/kg/d x 3d) → prednisone 2 mg/kg/d gradually weaned over 4 w, IVIG (2 g/kg/d x 2d), pyridostigmine, methotrexate | Discharge on day 30 |
6 | Huber M, Germany [41] | Case report | 21 y/o, F, AChR Ab, newly diagnosed ocular MG triggered by COVID-19 | IVIG (0.4 g/kg/d x 5d), pyridostigmine (3 × 60 mg, increase to 3 × 120 mg next week) | Recovery |
7 | Karimi N, Iran [47] | Case series | Newly diagnosed ocular MG triggered by COVID-19 1: 61 y/o, F, AChR Ab 2: 57 y/o, M, AChR Ab 3: 38 y/o, F, AChR Ab | 1: PE, pyridostigmine (4 × 60 mg), prednisone (1 mg/kg/d), thymoma surgery 2: pyridostigmine (3 × 60 mg), prednisolone (25 mg/d) 3: pyridostigmine (240 mg), prednisone (25 mg/d) | 1: Recovery 2: Recovery 3: Recovery |
8 | Moschella P, USA [42] | Case report | 70 y/o, M, AChR Ab, MG diagnosed before COVID-19 | MV, hydrocortisone iv (100 mg), PE (5x), pyridostigmine (4 × 60 mg), methotrexate | Recovery |
9 | Octaviana F, Indonesia [13] | Case series | MG diagnosed before COVID-19 1: 25 y/o, F 2: 49 y/o, M 3: 42 y/o, F | 1: Vit C (500 mg/d), NAC (600 mg/d), CTX (2 g/d), pyridostigmine (240 mg/d) → 6 d, AZM (500 mg/d x 1d) 2: AZM (500 mg/d), vit C (3000 mg/d), PCT (1500 mg/d), pyridostigmine (180 mg/d), AZA (100 mg/d)→ 5d 3: HCQ (200 mg/d), NAC (600 mg/d)→ 7 days, MP (16 mg/d), pyridostigmine (240 mg/d), mycophenolate (720 mg/d) | 1: Discharge on day 14 2: Discharge on day 14 3: Discharge on day 14 |
10 | Peters BJ, USA [48] | Case series | MG diagnosed before COVID-19 1: 71 y/o, M 2: 41 y/o, F 3: 59 y/o, M | 1: Remdesivir (200 mg/d x 1d, 100 mg/d x 4d), dexamethasone iv (6 mg/d x 10d), lenzilumab (3 × 600 mg), mycophenolic acid 2: Remdesivir (200 mg/d x 1d, 100 mg/d x 4d), dexamethasone iv (6 mg/d x 10d), mycophenolate (1000 mg in morning, 1500 mg in evening), pyridostigmine (6 × 60 mg), prednisone after dexamethasone (1 × 5 mg) 3: Prone position, remdesivir (200 mg/d x 1d, 100 mg/d x 4d), dexamethasone iv (6 mg x 1d)→ prednisone 60 mg/d, AZA (100 mg in morning, 50 mg in evening), pyridostigmine (3 × 60 mg), MV | 1: Deceased 2: Transferred out of the ICU 3: Discharged to home |
11 | Ramaswamy SB, USA [43] | Case report | 42 y/o, F, AChR Ab, MG diagnosed before COVID-19 | Prednisone (1 × 30 mg), mycophenolate (2 × 1000 mg) | Recovery |
12 | Reddy YM, India [19] | Case report | 65 y/o, M, AChR Ab, newly diagnosed MG triggered by COVID-19 | Remdesivir, IVIG (0,4 mg/kg/d x 5d), prednisolone (30–40 mg/d), AZT (2 × 50 mg), pyridostigmine (4 × 60 mg) | Discharge on day 23 |
13 | Saied Z, Tunisia [14] | Case series | MG diagnosed before COVID-19 1: 40 y/o, F 2: 60 y/o, F 3: 37 y/o, F, AChR Ab 4: 57 y/o, M, AChR Ab 5: 54 y/o, F, AChR Ab | 1: AZM (500 mg/d × 5 d), vit C (1000 mg/day x 10d), vit D (20,000 IU), LMWH x 10d 2: AZM (500 mg/d × 5 d), Vit C (1000 mg/day x 10d), vit D (20,000 IU x 10d), AZA (150 mg/d), pyridostigmine (8 × 60 mg) 3: AZM 500 mg/d × 5 d), vit C (1000 mg/day x 10d), vit D (20,000 IU/d) 4: MV, levofloxacin (500 mg/d), AZA (150 mg/d), pyridostigmine (8 × 60 mg), prednisone (40 mg/d) 5: AZM (500 mg/d × 5 d), Vit C (1000 mg/d × 10 d), Vit D (20,000 IU), LMWH × 10 d, AZA (150 mg), pyridostigmine (8 × 60 mg), IVIG (0.4 g/kg/d × 5 d) | 1: Recovery 2: Recovery 3: Recovery 4: Deceased 5: Recovery |
14 | Singh S, USA [44] | Case report | 36 y/o, F, negative AChR Ab and MuSK Ab, MG diagnosed before COVID-19 | PE (5x), mycophenolate, MV, stress dose steroid iv | Discharged after 1 month, persistent anosmia |
15 | Sriwastava S, USA [45] | Case report | 65 y/o, F, AChR Ab, newly diagnosed ocular MG triggered by COVID-19 | Pyridostigmine (4 × 60 mg decrease to 3 × 60 mg when admitted to hospital again due to COVID-19 infection), dexamethasone iv (4 doses of 6 mg), azithromycin, 1 unit convalescent plasma | Discharged after 10 days with residual symptoms of COVID-10 and ocular MG |
16 | Zupanic S, Belgian [49] | Case series | MG diagnosed before COVID-19 1: 55 y/o, F, AChR Ab 2: 67 y/o, M, AChR Ab 3: 80 y/o, M 4: 63 y/o, M, AChR Ab 5: 59 y/o, F, negative Ab 6: 58 y/o, M, negative Ab 7: 51 y/o, M, AChR Ab 8: 66 y/o, F | 1: IVIG (0,4 g/kg/d × 5 d), pyridostigmine (240 mg/d), AZA (100 mg), prednisolone (20 mg/d) 2: IVIG (0,4 g/kg/d x 5d), pyridostigmine (300 mg/d), prednisolone (60 mg/d) 3: Pyridostigmine (90 mg/d), remdesivir/5 d, dexamethasone (8 mg × 10 d) 4: IVIG (0,4 g/kg/d x 5d), pyridostigmine (360 mg/d), AZA (100 mg), prednisolone (60 mg/d), MV 5: Pyridostigmine (300 mg/d), dexamethasone (8 mg x 10d) 6: IVIG (0,4 g/kg/d x 5d), pyridostigmine (420 mg/d), prednisolone (30 mg/d), remdesivir/5d, MV 7: IVIG (0,4 g/kg/d x 1d), pyridostigmine (300 mg/d), remdesivir/5d 8: IVIG (0,4 g/kg/d x 5d), prednisolone (20 mg/d), remdesivir/5d, MV | 1: Discharge on day 7 2: Discharge on day 12 3: Discharge on day 10 4: Discharge on day 16 5: Discharge on day 8 6: Discharge on day 15 7: Discharge on day 24 8: Deceased |
No. | First author, country | Study design | Sample characteristic | Outcome measure | Result |
---|---|---|---|---|---|
1 | Businaro P, Italy [36] | Cross-sectional | 162 patients (11 patients had COVID-19 → 65 y/o, 54% M) | Outcome | 3 patients needed MV and 2 patients died. 1 patient experienced worsening MG and improved after increasing steroid dose. COVID-19 patients significantly associated with MGFA ≥ III (p: 0,01) |
2 | Camelo-Filho AE, Brazil [10] | Cross-sectional | 15 patients; 60% F (34.5 y/o), 40% M (61.3 y/o); 10 AChR Ab, 1 MuSK Ab | Outcome | 87% admitted in the ICU, 73% needed MV, and 30% died |
3 | Jakubíková M, Czech [35] | Cohort | 93 patients, 65.33 y/o, 51% M | Risk and protective factor | 11% MG patients were dead due to COVID-19. Older age and long term use of steroid in MG patients were the risk factor of severe COVID-19 (p < 0.001, OR: 1.062, 95%CI: 1.037–1.088; p: 0.002, OR: 14.098, 95% CI: 1.784–111.43), while higher FVC before COVID-19 were protective factor of severe COVID-19 (p < 0.001, OR: 0.957, 95% CI: 0.934–0.98). Immunosuppressive drug (AZA, mycophenolate mofetil, and cyclosporine) were not associated in the worsening of COVID-19 (p: 0.8, OR: 1.147, 95% CI: 0.448–2.935; p: 0.1, OR: 3.375 95% CI: 0.91–12.515; p: 0.3, OR: 0.255, 95% CI: 0.029–2.212) and rituximab in MG patients increased the risk of death by COVID-19 (p: 0.004, OR: 35.143, 95% CI: 3.216–383.971). Remdesivir, favipiravir, and convalescent plasma were not associated with MG exacerbation (p: 0.4, OR: 1.709, 95% CI: 0.885–10.87) |
4 | Kalita J, India | Cohort | 38 patients, 45 y/o, 42.1% F | QoL, daily living, anxiety and depression, and QoS of MG patients in COVID-19 pandemic | QoL, daily living, anxiety and depression, and QoS was impaired significantly in COVID-19 pandemic compared before pandemic (p < 0.05) |
5 | Sole G, French [15] | Cohort | 3558 patients (0.96% had COVID-19 →55 ± 19.9 y/o, F: 55.9%) | Outcome | 28 patients recovered from COVID-19, 1 remain affected, and 5 deceased. MGFA class ≥ IV was related with severe COVID-19 (p: 0.004) |
6 | Stojanov A, Serbia [37] | Cross-sectional | 64 patients, 54.1 ± 16.4 y/o, 61.4% F | Psychological status, QoL, and QoS of MG patients in COVID-19 pandemic | Psychological status and QoL were impaired insignificantly, and QoS was reduced significantly in COVID-19 pandemic compared to 2017 (p < 0.01) |