High rate of persistent symptoms up to 4 months after community and hospital-managed SARS-CoV-2 infection

The spectrum of recovery following community-managed and hospitalised severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains uncertain (1-5). A prospective cohort (the ADAPT study) was established of all adult patients, with confirmed positive SARS-CoV-2 RNA PCR at St Vincent’s Hospital Sydney, to characterise the long-term effects and explore their association with initial COVID-19 disease severity. Study participants are prospectively observed under a pre-defined schedule of assessments, with follow-up planned through 12 months post-COVID-19. The specific aims of this study are to determine the prevalence and nature of persistent symptoms after SARS-CoV-2 infection, to evaluate lung function, health-related quality of life, neurocognitive and olfactory abnormalities in the recovery period and to characterise the longitudinal immune response. In this letter, we report interim results from the initial study assessments which were performed up to 4 months after first detection of SARS-CoV-2. All individuals with confirmed SARS-CoV-2 RNA positive at St Vincent’s Hospital testing clinics and able to be contacted were offered enrolment into the study (Supplementary Figure 1 - available in PDF). The study was approved by the St Vincent’s Hospital Research Ethics Committee (2020/ETH00964) and the timing of the baseline visit was dependent on this. Between April and June 2020, 78 individuals were enrolled, of whom 69 were managed in the community (30 mild, 39 moderate, see Supplementary Table 1 for definitions - available in PDF) and 9 hospitalised (2 admitted into intensive care for acute respiratory distress syndrome). The mean patient age is 47 (16), with 27 females, 65 Caucasian and 39 infections acquired overseas (see Supplementary Table 2 for demographics - available in PDF). The most commonly self-reported medical co-morbidities were hypertension and asthma, while 37 patients had no co-morbidities. The most common reported initial COVID-19 symptoms were fatigue in 62, cough in 50, and headache in 44 individuals. At median 69 days after diagnosis (IQR 64-83), 31 patients had persistent symptoms including fatigue in 17, shortness of breath in 15 and chest tightness in 4 (Figure 1 - available in PDF), including 7 hospitalised and 24 community-managed individuals. Complex lung function testing at median 113 (IQR 105-131) days post-infection was performed in 65 individuals (Table 1 - available in PDF). Abnormal total lung capacity (TLC) < lower limit of normal (LLN) was seen in a small proportion of patients (12%), but median TLC %-predicted was significantly lower in the hospitalised 91 (IQR 78-99) compared with the community population 102 (IQR 92-107), p=0.02 (Mann-Whitney U Test). Abnormal diffusion capacity for carbon monoxide (DLCO_cor) %-predicted, less than LLN values, was observed in 11 individuals with a trend to higher proportions in the hospitalised population. When considering the largely maintained ventilatory capacity, this may indicate an association with pulmonary vascular disease. Neurocognitive impairment, performed under supervision by trained examiners using the CogState computerised battery, was low (8 individuals) but associated with abnormal olfaction (4 individuals) (6). Concerningly, a considerable proportion of patients experience persistent symptoms after SARS-CoV-2 infection including fatigue, chest pain and breathlessness. Although more common following severe illness, 35% community-managed patients within ADAPT have persistent symptoms several months post infection. Ongoing follow-up of this cohort will generate data on the longer-term trajectory of recovery post COVID-19 illness and provide insights into the mechanisms of systemic inflammation after SARS-CoV-2 infection, and its immunologic correlates.

References:

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