Langdurige klachten na COVID-19 (2024)

Welke diagnostiek wordt aanbevolen bij patiënten met aanhoudende klachten na COVID-19 in de huisartsenpraktijk?

Achtergrond

Het herstel na COVID-19 is voor iedereen anders. Mensen met milde klachten in de acute fase kunnen binnen een week al beter zijn, maar kunnen ook weken- tot maandenlang last houden en regelmatig een terugval ervaren. Bij mensen die ernstigere klachten hebben gehad, en al dan niet opgenomen zijn geweest in het ziekenhuis, duurt het herstel veelal enkele weken, maar dit kan ook langer zijn. Het is van belang om goed in kaart te hebben welke klachten of schade er kunnen persisteren na een doorgemaakte SARS-CoV-2-infectie, wat er voor nodig is om deze restklachten te herstellen en hoelang het herstel kan duren. In dit detail beschrijven we wat bekend is over resultaten van aanvullende diagnostiek verricht na SARS-CoV-2-infectie.

Methoden/zoeken en selecteren

Voor de uiteenzetting van het bewijs is gebruik gemaakt van de NICE-richtlijn ‘COVID-19 rapid guideline: managing the long-term effects of COVID-19. Evidence review 4: investigations' (laatste update: december 2020).9Op 14 april 2021 is een aanvullende literatuurzoekactie naar systematische reviews (SR’s), randomized controlled trials (RCT’s) en observationeel onderzoek uitgevoerd in PubMed en Embase.

NICE included 18 references in their review, concerning 15 studies that reported on the results of supplementary examinations and/ or diagnostics during the period between 4 and 12 weeks after COVID-19: 11 cohort studies, 2 cross-sectional studies, 1 case-control study and one case-report. Additionally, there was one cohort study reporting on this covering the period >12 weeks after COVID-19. Lastly, they included 1 narrative review and 1 expert opinion.

The supplementary literature search yielded four additional cohort studies.

Hospitalized patients

Psychological health

Four studies reviewed psychological health, using screening instruments, All found abnormal / raised values in post-COVID-19 patients. One study reported that this was significantly more compared to a non-infected group of matched controls (2-3 months post-COVID-19, PHQ-9 score).10

Functional assessment

Three studies reported on functional assessment. Raman et al. (again the only one using a control group) concluded that 2-3 months post-COVID-19 functional status (including physical and social functioning) was significantly worse compared to those that did not suffer from COVID-19.10

Imaging studies

Many studies used imaging when following up patients after COVID-19. This was mostly X-thorax, CT and MRI; one study (only hospitalized patients) reported COVID-19 related lung disease (as found on X-thorax) in 15/119 patients (13%).11However, the same study also concluded X-thorax to be an unreliable marker for recovery, considering that any abnormalities on CT were not related to the presence of abnormalities on X-thorax. A Chinese study investigated 41 post-COVID-19 patients who had been hospitalized and undergone CT imaging during hospitalization by performing a follow-up CT scan at 3 months and 7 months after discharge,12follow-up. They concluded that the majority of patients did not have any abnormalities on CT scan anymore at the last moment of follow-up (66% for the complete group, 86% if only including those without signs of pulmonary fibrosis). In an English study (n=125, hospitalized patients, median follow-up 113 days) 77% of the post-COVID-19 patients had a normal X-ray, 8% had a decrease of >50% of the abnormalities, and the remainder had persisting non-COVID-19 related deviations.13A Chinese study (n=107 post-hospitalized patients, 100 days after discharge), on the other hand reported complete resolution of pulmonary abnormalities (CT thorax) in only 28%.14

Pulmonary function tests

Spirometry and or Medical Research Council Breathlessness Scale were used frequently in the included studies. One study used a COVID-negative control group, and found that hospitalized post-COVID-19 patients more frequently had increased scores for dyspnoea 2-3 months after infection (MRC dyspnoea score ≥2) compared to patients not having suffered from COVID-19 (36/53 [64%] vs. 3/29 [10.3%], p<0.0001).10The same study found a minimal difference in FEV1/FVC (0.77 vs 0.75, p=0.027) between post-COVID-19 patients and controls; FVC and FEV1 individually were not significantly different. Other studies (not using a control group) showed varying results on spirometry (mild abnormalities in ~25-55%), in general not related to the severity of disease during the acute phase.

Additionally, exercise tests were performed, during which exercise tolerance and desaturation (during physical exercise) were measured in patients post-COVID-19. One Italian study (n=238, average age 68, 60% male, all hospitalized patients), performed a pulmonary function test in 224 post-COVID-19 patients 3-4 months after hospital discharge, finding a decreased diffusion capacity in 52% (DLCO <80% of expected). In 16% this was as bad as <60% of expected.15

Laboratory investigations

Investigated laboratory values mostly concerned inflammatory parameters, markers for iron deficiency and anaemia or lipid profile. Dennis et al. found (in unadjusted analysis) abnormal triglycerides (p=0.002), cholesterol (p=0.021), LDL-cholesterol (p=0.005) and transferrin saturation (p=0.005) in hospitalized patients after COVID-19.16Li et al. (China n=107, 100 days after discharge), had a similar conclusion; they found raised LDL-c and HCL values in patients that survived severe tot critical COVID-19.14

Non-hospitalized patients

None of the included studies only included non-hospitalized patients. There were a few studies that had a combined population of hospitalized and non-hospitalized post-COVID-19 patients.

Pulmonary function tests

Two studies described spirometry in post-COVID-19 patients, also including non-hospitalized patients. Frija et al. (18% non-hospitalized patients) found no association between the result of the spirometry and the severity of abnormalities on CT-thorax.17Valiente et al. (preprint, included in NICE review) performed spirometry in 32/108 patients 12 weeks after the acute phase, which was abnormal in 28% of the patients (mostly showing an obstructive.

Functional status

One study (Aliae et al., preprint, included in NICE review) included 98 (24%) non-hospitalized patients and described basic daily functioning using the new post-COVID-19 functional status assessment (PCFS). In this study 11 patients (2.5%) reported moderate to severe limitations in functioning.

Imaging

None of the included studies described imaging in non-hospitalized patients post-COVID-19.

Laboratory investigations

Dennis et al. reported on differences between hospitalized and non-hospitalized post-COVID-19 patients (see in section ‘hospitalized patients’).16Sonnweber et al. (20% non-hospitalized patients) reported that iron homeostasis was more frequently abnormal post-COVID-19.18Additionally they reported an association between the level of ferritin and the severity of acute illness.

Kwaliteit van bewijs

De beschreven onderzoeken zijn van zeer lage kwaliteit en hebben relatief lage patiënten aantallen (grotendeels < 500 patiënten). Geen van de onderzoeken was specifiek ontworpen om de onderzoeksvraag te beantwoorden en deze dienen dus enkel als indirect bewijs. Het risico op bias wordt op 1 onderzoek (matig) na bij alle onderzoeken hoog ingeschat. Redenen hiervoor zijn onder andere het ontbreken van een controlegroep (of een vergelijking met pre-COVID-19-status) en risico op selectiebias.
Daarnaast wordt de generaliseerbaarheid zeer laag geacht, gezien het feit dat de onderzoeken voornamelijk 1) in de tweede lijn werden gedaan (in totaal < 10% niet-gehospitaliseerde patiënten), 2) met een beperkte follow-up (meestal 4-6 weken) en 3) geen kinderen/ouderen beschreven.

Conclusie

• Er is nog zeer weinig bekend over de waarde van aanvullend onderzoek in de post-acute fase van COVID-19.
• We zijn onzeker, maar X-thorax is mogelijk geen goede marker van herstel (kwaliteit van bewijs: zeer laag).