Table 2.
Summary of investigations leading to ACTD diagnosis
| Title | Time between onset of COVID-19 and autoimmune symptoms (days) | ESR pre-CTD-diagnosis (mm/hr) | CRP pre-CTD diagnosis (mg/L) | ESR post-CTD diagnosis and treatment (mm/hr) | CRP post-CTD diagnosis and treatment (mg/L) | CTD serology and basic biochemistry/haematology markers (where reported) | Imaging and findings (as reported) | Other investigations |
|---|---|---|---|---|---|---|---|---|
| Zhang et al. 2022 [22] | 21 | 94 | 110 | – | – | Positive anti-Ku, anti–SAE 1 IgG, anti–SS‐A | MRI: diffuse muscle oedema and enhancement, with region of myonecrosis | |
| Ramachandran et al. 2022 [30] | – | – | – | – | – |
Positive ANA 1:1280, speckled pattern; dsDNA 150 IU/ml Low C3 and C4 |
Nil described | Renal biopsy: focal segmental glomerulosclerosis, collapsing variant. Light microscopy: mild podocyte hyperplasia, increase in mesangial cellularity and matrix. Severe interstitial fibrosis and tubular atrophy involving 70–80% of the cortical parenchyma with focal dense inflammation. Electron microscopy: glomeruli with global sclerosis and intracapillary deposits. Stage IV lupus nephritis |
| Pereira et al. 2022 [40] | 56 | – | – | – | – |
Raised CPK (3736 IU/L) ANA and anti-smooth muscle antibodies were negative Positive anti-Jo-1 |
PET/CT MIP: abnormal increased FDG uptake in multiple muscle regions, more intense in the upper-limb muscles, suggesting possibility of inflammatory polymyositis (PM) and changes of interstitial lung disease with septal thickening and bronchiectatic changes in the right lower lobe | |
| Okayasu et al. 2022 [23] | 28 | – | 117 | – | – |
ANA < 40 C3 126, C4 31 KL-6 332 MPO-ANCA < 1.0; Positive anti-SSA/Ro < 1.0; Anti-SSB/La autoantibodies < 1.0; CCP Antibodies < 0.6; Cardiolipin antibodies < 4.0; IgG4 111 |
MRI (STIR) thighs: irregular high-intensity areas in both adductor muscle groups, suggesting necrotizing fasciitis. CT chest: no obvious interstitial pneumonia or lymphadenopathy suspicious for lymphoid species | |
| Okada et al. 2022 [24] | 28 | – | – | – | – |
Creatine kinase 1495 U/l D-dimer 6.1 µg/ml. Positive anti-NXP2 |
CT thorax, abdomen, pelvis: no malignancy nor interstitial lung disease MRI (STIR): intramuscular hyperintensity in proximal limbs |
|
| Nunes et al. 2022 [38] | 29 | 51 | 201 | – | – |
C3 0.66 g/L (0.83–1.93 g/L), C4 0.1 (0.15–0.57) Positive ANA 1:1,280, nuclear homogeneous pattern ENA antibodies SSA60 (Ro60)/SSB (La) positive |
Nil described | Urine analysis: 24 h proteinuria: 642 mg/24 h (50–80 mg/24 h) |
| Kazzi et al. 2022 [31] | 42 | – | – | – | – |
Positive ANA, positive double-stranded DNA antibody Hypocomplementemia, leukopenia |
CT thorax, abdomen, pelvis: subtle bilateral infiltrates may be secondary to atypical pneumonia. Mild thoracic, abdominal, and pelvic lymphadenopathy, non-specific. Mild mesenteric stranding may be secondary to mesenteric panniculitis, with possible pancreatitis | Proteinuria |
| Holzer et al. 2022 [19] | 14 | – | < 5 | – | – |
CK 19,647 Positive ANA: 1:640 Positive anti-NXP2 |
MRI muscle: Bilateral myositis of muscles of the pelvic hip girdle and thighs | |
| Giuggioli et al. 2022 [41] | 28 | – | 65 | – | – | Positive ANA, anticentromere pattern | Nailfold capillaroscopy: “early scleroderma pattern” | |
| Chandra and Kahaleh 2022 [42] | – | – | – | – | Positive ANA > 1:1280 | HRCT chest: interstitial lung disease, findings suggestive of non-specific interstitial pneumonia | ||
| Bouchard Marmen et al. 2022 [43] | 28 | – | 61 | – | – |
CK 7696, Positive ANA and anti-Jo-1 |
CT thorax: missed opacities with sub segmental consolidation MRI: oedema of the gluteal and thigh muscles consistent with myositis |
|
| Blum et al. 2022 [44] | 91 | – | – | – | – |
Positive ANA Positive anti-RNP and ani-SSA antibodies |
CT chest: ground-glass opacities possibility indicating interstitial lung disease | |
| Assar et al. 2022 [32] | 18 | 53 | – | 53 | – |
Positive ANA Positive anti-dsDNA Positive P-ANCA |
CT thorax and abdomen: pericardial and pleural effusion and enlarged liver and abdominal lymph nodes | |
| Anderle et al. 2022 [45] | – | – | 60 | – | – |
CK 246 U/L Positive ANA, fine speckled pattern 1:320 Anti-Ro-60 Ab at 23 U/mL (ULN ≤ 10 U/mL) Aanti-MDA-5 14 U/mL (ULN ≤ 10 U/mL) |
CT chest (week 2): patchy ill-defined consolidations and areas of ground-glass opacifications in the periphery of both lower lobes and subtle thickening of the bronchial walls and hepatic steatosis 3-Tesla, gadolinium contrast enhanced MRI: T2 fat saturated bilateral hyperintense signal alterations of bilateral proximal thigh muscles compatible with myositis |
|
| Amin et al. 2022 [27] | 112 | – | 40.5 | – | 12.2 | Nil described |
CT thorax, abdomen, pelvis: enlarged fatty liver and atrophic left kidney MRI shoulder and hip muscles: inflammatory changes in the muscles of the shoulder and pelvic girdle, chest, and anteromedial and lateral compartments of the thigh |
|
| Ali et al. 2022 [33] | – | 102 | 153 | – | – |
Positive ANA, anti-smith (Sm) and U1 small nuclear ribonucleoprotein (U1-RNP) Positive rheumatoid factor C3 and C4 within range |
Nil described | |
| Zamani et al. 2021 [34] | 56 | 74 | 34 | Normal | Normal |
Total complement activity (CH50), 45 (50–150); C3 133 mg/dL (90–180 mg/dL); C4 14 mg/dL (10–40 mg/dL) Anti-La/SSB, 160 U/ml (< 12 U/mL); anti-SSA/Ro, 200 U/mL (< 25 U/mL) Anti-CCP 48 IU/mL (< 20 IU/mL) Anti-dsDNA 70 IU/mL (< 35 IU/mL) Positive fluorescence ANA 1/160. Anticardiolipin, lupus anticoagulant, anti-beta-2 glycoprotein 1, C-ANCA, P-ANCA were negative |
CT chest: two ground-glass opacity nodules in the lower lobes of both lungs | Renal biopsy: mild mesangial hypercellularity (lupus nephritis class I) |
| Slimani et al. 2021 [35] | – | – | – | – | – |
Elevated PT, APTT Positive ANA, ds-DNA, anti-cardiolipin, beta-2-glycoprotein, lupus anticoagulant |
Nil described | |
| Dadras et al. 2021 [25] | – | 57 | – | – | – |
ANA, anti‐ds‐DNA, anti‐Smith antibody negative Myositis‐specific antibodies including anti‐Mi‐2, ‐Ku, ‐PM/Scl‐100, ‐Scl‐75, ‐SRP, ‐PL‐7, ‐PL‐12, ‐EJ, ‐OJ, ‐Jo‐1, and ‐Ro‐52 were negative |
CT abdomen and pelvis: normal CT chest: bilateral multifocal patchy consolidations with reverse halo view suggestive of the chronic phase of organising COVID‐19 pneumonia |
Three skin biopsies from different skin sites were taken with differential diagnoses of dermatomyositis and lupus erythematosus; the first was sent for examination under direct immune fluorescence, with findings in favour of lupus erythematosus. The second (from a Gottron papule) and third (from a vesicle on the extremities) biopsies were evaluated using hematoxylin‐eosin staining; findings indicated dermatomyositis‐lupus overlap features and were compatible with a collagen vascular disease |
| Lokineni et al. 2021 [29] | 84 | – | – | – | – | Nil described | Unknown | |
| Keshtkarjahromi et al. 2021 [46] | 56 | 20 | 67 | – | – |
Positive ANA, anti-MDA5, SSA-52 (Ro) Low C3 |
1st admission: Diagnostic imaging included MRI of right femur that demonstrated multiple scattered areas of proximal muscle oedema, which while non-specific, was felt to be consistent with an inflammatory myositis CT chest: mild bilateral patchy infiltrates 2nd admission: Repeat CT demonstrated a new, marked consolidative processes within the bilateral lower lobes in a peripheral distribution with pleural sparing |
Skin biopsy of the anterior chest was subsequently performed which demonstrated vacuolar interface dermatitis with an increase in dermal mucin |
| Fineschi S 2021 [47] | 21 | Normal | Normal | – | – |
Strongly positive ANA, nucleolar pattern Positive Anti-PM/Scl 75 and PM/Scl 100 Anti-Scl-70, anti-Jo-1, anti-RNA-polymerase III, and other autoantibodies tested negative |
HCRT: ground-glass opacities with predominantly peripheral and subpleural distribution such as in the early stages of interstitial lung disease | |
| Borges et al. 2021 [20] | 14 | – | – | – | – |
Positive fine speckled pattern ANA (1/640) Positive anti-Mi2, CPK 3518U/l |
Skin biopsy showed lamellar keratosis with foci of vascular changes in the epidermal layer and dilated vessels with a thickened wall and perivascular lymphocytic infiltrate | |
| Assar et al. 2021 [26] | 112 | 87 | – | – | – | Normal ANA, anti-dsDNA, antiphospholipid, anti-Ro, anti-La, ANCA, anti Jo1 antibodies | CT chest: peripheral and multi-lobar fibrotic areas in the lingula, right middle lobe and upper zones which were consistent with fibrotic changes due to previous COVID-19 infection | Electromyography and nerve conduction velocity studies (EMG/NCV) were compatible with inflammatory myopathy. There was no evidence of neuropathy and radiculopathy |
| Ali et al. 2021 [36] | 14 | – | Normal | – | – | Positive anti-dsDNA, anti-Smith, anti-RNP, anti-Ro, anti-La | Echocardiogram: large pericardial effusion | |
| Aldaghlawi et al. 2021 [28] | 21 | – | – | – | – |
CPK 2713 µ/L, lactate dehydrogenase 1348 µ/L, haptoglobin 196 mg/dL, haemoglobin 11.7 gm/dL, platelets 75 k/mm3, aspartate aminotransferase 96 µ/L, alanine aminotransferase 72 µ/L, creatinine 0.6 mg/dL, prothrombin 12.3 s, partial thromboplastin time 32.5 s, fibrinogen 599 mg/dL, IGG 333 mg/dL, immunoglobulin M 26 mg/dL, immunoglobulin A 83 mg/dL Peripheral blood smear revealed marked agglutination of red blood cells and a cold agglutinin with thermal amplitude of 30 °C was identified with complement C3B and C4 identified on red blood cell |
Unknown | Hepatitis B and C viral serologies were negative for acute infection |
| Sacchi et al. 2020 [21] | – | 59.4 | – | – | Positive ANA, cytoplasmic pattern (1:320) granular type, Anti-Ku and anti-MI 2b positivity | Unknown | ||
| Bonometti et al. 2020 [37] | – | – | – | – | – | Positive ANA with cytoplasmic (1: 160), homogeneous (1: 320) and granular (1: 320) pattern, Ku positivity and atypical ANCA | Unknown |
ESR erythrocyte sedimentation rate, CRP C-reactive protein, ANA anti-nuclear antibody, ANCA antineutrophil cytoplasmic antibodies, CT computed tomography, MRI magnetic resonance imaging, CTD Connective tissue diseases, DsDNA double-stranded deoxyribonucleic acid, CPK creatinine phosphokinase, COVID-19 Coronavirus disease 2019, CT computed tomography, RNP ribonucleoprotein