Table 8.
Summary of studies addressing management of long-COVID/postCOVID-19 condition
| Study | Study design | Participants and setting | Timing | Number included | Intervention | Comparison | Outcome | Results | Quality assessment |
|---|---|---|---|---|---|---|---|---|---|
| Rehabilitation | |||||||||
| Reina-Gutierrez et al., 2021 [89] | SR and MA of RCTs | Patients with interstitial lung diseases, including those caused by coronaviruses. One trial post-COVID discharge (see Liu et al. [90]) | Any time | 11 RCTs with 637 patients | Pulmonary rehabilitation | Most noncomparative | Lung function, exercise capacity, health-related quality of life and dyspnoea | Significant improvement in all outcome (see text for details) | AMSTAR grade: Low |
| De sire et al., 2021 and Ceravolo et al., 2020 [91,92] | SR and MA | Patients with COVID-19, both acute and post-acute phases | Any time | 24 studies “post acute” phase, 10 studies “chronic” phase, including case reports and series | Rehabilitation | Most noncomparative (comparative studies included in this SR are presented separately in this table) | “All type of outcome measures" | “Sparse and low quality evidence concerning the efficacy of any rehabilitation intervention to promote functional recovery" | AMSTAR grade: Critically low |
| Liu et al., 2020 [90] | RCT | Elderly (age ≥65 y) recovering “with satisfying results” from COVID-19 | Hospital discharge | 72 (36 vs 36) | Respiratory rehabilitation (once daily 10 min for 6 wk, including (1) respiratory muscle training; (2) cough exercise; (3) diaphragmatic training; (4) stretching exercise; and (5) home exercise | No intervention | 1. PFT (FEV1, FVC, FEV1/FVC, DLCO%) 2. 6MWT 3. Quality of life score (Short Form-36) 4. Anxiety score (SAS) 5. Activity of daily living (FIM) 6. Depression score (SDS) |
Significant improvement in all PFT; 6MWT; quality of life score (SF36); and anxiety score SAS) | Unclear risk of bias for concealment; low risk for generation; open |
| Sinha et al., 2020 [163] | Prospective cohort | Acute COVID-19 in ICU | ICU admission until 1 mo after discharge | 150 | Structured exercise protocol | None (comparison between start and end of intervention) | Functional status by FIM and POMA | Significant improvement in both FIM and POMA | NCOS: 2 |
| Hermann et al., 2020 [164] | Prospective cohort | Patients with postdischarge severe COVID-19 (most ICU), in inpatient rehabilitation clinic setting | ≥10 d of COVID onset, with 2 d asymptomatic | 28 | Cardiopulmonary rehabilitation (2–4 wk program) | None | Functional assessment by 6MWT) and feeling thermometer | Significant improvement in both 6MWT and feeling thermometer | NCOS: 4 |
| Udina et al., 2021 [165] | Prospective cohort | Post-acute COVID-19 care facility, most after ICU | After discharge | 33 | Multicomponent therapeutic exercise protocol | None | Physical performance, including gait performance, exercise capacity (6MWT), ADL (Barthel index) | Significant improvement in all measures | NCOS: 4 |
| Piquet et al., 2021 [166] | Retrospective cohort | Inpatients with acute COVID-19 in specialized rehabilitation unit | Mean 20.4 ± 10.0 d from COVID-19 onset | 100 | Inpatient specialized rehabilitation unit | None | Barthel ADL Index; sit-to-stand frequency; and grip strength | Significant improvement in all measures | NCOS; 4 |
| Hameed et al., 2021 [94] | Prospective cohort | Discharged patients with COVID-19 with persisting symptoms | Outpatients after discharge | 106 | Three groups: 44 patients virtual rehabilitation program; 25 patients home physical therapy; 17 patients independent exercise program | 20 patients: No intervention | Sit-to-stand scores and step test | Significant improvement in both tests with virtual rehabilitation and home physical therapy | NCOS: 6 |
| Curci et al., 2021 [167] | Retrospective cohort | Post-ICU patients with COVID-19 in inpatient rehabilitation setting | After ICU | 41 | Patient-tailored rehabilitation plan | None | Disability by Barthel index scale; resistance by 6MWT; and fatigue by Borg Rating of Perceived Exertion | Significant improvement in all measures | NCOS: 5 |
| Al Chikhanie et al., 2021 [93] | Prospective cohort | Post-ICU COVID-19 in a dedicated rehabilitation centre | After ICU | 42 | Pulmonary rehabilitation | Non-COVID-19 respiratory failure after ICU | 6MWT | Significant improvement in 6MWT between start and end of intervention in COVID-19 group and between this group and controls | NCOS: 6 |
| Bowles et al., 2021 [168] | Retrospective cohort | Discharged patients referred to home health care | After discharge | 1409 | Home health care | None | Symptoms and functional dependencies | Significant improvement in symptoms and function, as measured by frequency of pain, dyspnoea, cognitive function, anxiety, and functional status by ADL | NCOS: 4 |
| Pulmonary abnormalities | |||||||||
| Myall et al., 2021 [98] | Prospective cohort | Discharged patients with clinical, radiological and functional interstitial lung disease consistent with organizing pneumonia | 6 wk after discharge | 30 | Corticosteroids (maximum dose 0.5 mg/kg prednisolone) for 3 wk | None | Symptoms, lung function, radiological findings | Significant improvement in all measures | NCOS: 3 |
| Goel et al., 2021 [99] | Retrospective cohort | Abnormal chest computed tomography and desaturation (at rest <90% or decline of >4% during 6MWT) | At least 4 wk after acute COVID-19 | 24 | Equivalent of prednisolone 0.25–0.5 mg/kg and tapering for 6–8 wk | None | Symptoms, saturation, radiological findings | Significant improvement in all measures | NCOS: 2 |
| Anosmia/dysgeusia | |||||||||
| Addison et al., 2021 [108] | SR | Postinfectious olfactory dysfunction (non-COVID) | Not significant | 2352 | Any intervention (including olfactory training and various systemic and topical drugs) | Any control | Improvement in olfaction | No MA performed; authors conclusions supported olfactory training, and consider steroids (nasal or systemic), theophylline, and sodium citrate | AMSTAR grade: Low |
| Abdelalim et al., 2021 [109] | RCT | Patients recovering from COVID-19 (70% mild) | Recovering or discharged with 2 negative PCR tests | 108 randomized, 100 evaluated (50 per group) | Topical corticosteroid nasal spray (mometasone furoate) for 3 wk with olfactory training | Olfactory training alone | Number with recovered smell sense at 3 wk, change in smell score according to patient-reported degree of anosmia/hyposmia (subjectively with visual analogue scale) | Number recovered: 31 (62%) intervention, 26 (52%) control (p = 0.31) | Unclear risk of bias for concealment and generation; open |
| Mohamad et al., 2021 [110] | RCT | “Post COVID-19″ patients with olfactory loss | “Post COVID" | 40 randomized (20 evaluated in intervention group, 16 in control) | Insulin fast-dissolving film for intranasal delivery | Placebo (insulin-free fast-dissolving film) | Smell sensation improvement at 4 wk (using olfactory detection score) | Significantly higher olfactory detection scores with intervention (p = 0.0163) | Unclear risk of bias for concealment and generation; double blind |
6MWT, 6-minute walk test; ADL, activity of daily living; AMSTAR, A MeaSurement Tool to Assess systematic Reviews; DLCO, diffusing lung capacity for carbon monoxide; FEV1, forced expiratory volume at 1 second; FIM, functional independence measure; FVC, forced vital capacity; ICU, intensive care unit; MA, meta-analysis; NCOS, Newcastle–Ottawa score; PFT, pulmonary function test; POMA, performance-oriented mobility assessment; RCT, randomized controlled trial; SDS, self-rating depression score; SR, systematic review.