Persistence, prevalence, and polymorphism of sequelae after COVID-19 in unvaccinated, young adults of the Swiss Armed Forces: a longitudinal, cohort study (LoCoMo)

Abstract

Background: Persistent COVID-19 sequelae could have global, public health ramifications. We therefore aimed to describe sequelae presenting more than 180 days after COVID-19-focussing on several organ systems, general health, and laboratory parameters-in non-hospitalised, unvaccinated, young adults.

Methods: We did a longitudinal cohort study of all army bases in Switzerland. Eligible participants were personnel of the Swiss Armed Forces (SAF) who were aged 18-30 years with a positive or negative RT-PCR test for SARS-CoV-2 during their service between March 1, 2020, and Dec 31, 2020. Exclusion criteria were unwillingness to participate in testing. Females or men with a known reproductive anomaly were excluded from the optional component of male fertility testing. COVID-19 was defined as a positive diagnostic RT-PCR test result for SARS-CoV-2 with concurrent symptoms compatible with COVID-19. Participants were subdivided into four groups: control group (ie, serologically negative), asymptomatic infection group (ie, serologically positive but with no symptoms), non-recent COVID-19 group (>180 days since positive PCR test), and recent COVID-19 group (≤180 days since positive PCR test). Outcomes of interest were part of a comprehensive, intensive test battery that was administered during a single day. The test battery quantified the effect of SARS-CoV-2 infection on cardiovascular, pulmonary, neurological, renal, ophthalmological, male reproductive, psychological, general health, and laboratory parameters. This study was registered with ClinicalTrials.gov, number NCT04942249.

Findings: Between May 20, 2021, and Nov 26, 2021, we enrolled 501 participants. 29 (6%) of 501 were female and 464 (93%) were male, and the median age was 21 years (IQR 21-23). Eight (2%) of 501 had incomplete data and were not included into the study groups. 177 participants had previous COVID-19 that was more than 180 days (mean 340 days) since diagnosis (ie, the non-recent COVID-19 group) compared with 251 serologically negative individuals (ie, the control group). We included 19 participants in the recent COVID-19 group and 46 in the asymptomatic infection group. We found a significant trend towards metabolic disorders in participants of the non-recent COVID-19 group compared with those in the control group: higher BMI (median 24·0 kg/m2 [IQR 22·0-25·8] vs 23·2 kg/m2 [27·1-25·0]; p=0·035), lower aerobic threshold (39% [36-43] vs 41% [37-46]; p=0·012), and higher blood cholesterol (4·2 μM [3·7-4·7] vs 3·9 μM [3·5-4·5]; p<0·0001) and LDL concentrations (2·4 μM [1·9-2·9] vs 2·2 μM [1·7-2·7]; p=0·001). The only significant psychosocial difference was found in the results of the Chalder Fatigue scale with the non-recent COVID-19 group reporting higher fatigue scores than the control group (median 12 points [IQR 11-15] vs 11 [9-14]; p=0·027). No significant differences in other psychosocial questionnaire scores, ophthalmological outcomes, and sperm quality or motility were reported between the control group and non-recent COVID-19 group.

Interpretation: Young, previously healthy, individuals largely recover from SARS-CoV-2 infection. However, the constellation of higher BMI, dyslipidaemia, and lower physical endurance 180 days after COVID-19 is suggestive of a higher risk of developing metabolic disorders and possible cardiovascular complications. These findings will guide future investigations and follow-up management.

Funding: Swiss Armed Forces.

Conflict of interest statement

Declaration of interests We declare no competing interests.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Test battery used in the Long COVID in Military Organisations study The test battery was used to evaluate the long-term sequelae of COVID-19 in young adults. A variety of quantitative tests and standardised questionnaires were used to measure the effect on various organ systems and parameters in participants following COVID-19, asymptomatic SARS-CoV-2 infection, or in individuals who were non-exposed to SARS-CoV-2. Anti-N=anti-SARS-CoV-2 nucleocapsid. Anti-S=anti-SARS-CoV-2 spike. BDI-13=Beck Depression Inventory (13 items). CFQ-11=Chalder Fatigue Scale. eGFR=estimated glomerular filtration rate. FeNO=fractional exhaled nitric oxide. FSH=follicle stimulating hormone. HbA1c=glycated haemoglobin. IES-R=Impact of Event Scale-Revised. LH=luteinising hormone. mMRC=modified Medical Research Council. NT-proBNP=N-terminal pro-B-type natriuretic peptide. POMS2=Profile of Mood States 2. PTSD-19=COVID-19 post-traumatic stress disorder questionnaire. STAI-Y= State-Trait Anxiety Inventory form-Y. TSH=thyroid stimulating hormone. ZSDS=Zung Self-Rating Depression Scale.

Figure 2

Flow chart of the LoCoMo study (A) and background epidemiological data for COVID-19 in Switzerland (B) Background epidemiological data in Switzerland show the waves of infection, the dominant variants, and the timing of vaccination programmes for young adults in relation to infection levels and testing of the cohort. LoCoMo=Long COVID in Military Organisations.

Figure 3

Multi-system sequelae after COVID-19 Participants more than 180 days after confirmed COVID-19 (ie, non-recent COVID-19 group) were compared with non-infected individuals (ie, control group). ORs for various parameters were calculated. Error bars are 95% CIs. BDI-13=Beck Depression Inventory (13 items). BF=Breathing frequency. CFQ-11=Chalder Fatigue Scale. CPET=cardiopulmonary exercise test. CRP=C-reactive protein. eGFR=estimated glomerular filtration rate. FSH=follicle stimulating hormone. L1 density=overall superficial capillary plexus density. L1 fovea=superficial capillary plexus density at the fovea. L1 parafovea=superficial capillary plexus density parafoveal. L1 whole ETDRS=superficial capillary plexus Early Treatment Diabetic Retinopathy Study score. L2 density=overall deep capillary plexus density. L2 fovea=deep capillary plexus density at the fovea. L2 parafovea=deep capillary plexus density parafoveal. L2 whole ETDRS=deep capillary plexus Early Treatment Diabetic Retinopathy Study score. LH=luteinising hormone. MCH=mean corpuscular haemoglobin. MCV=mean corpuscular volume. OD visus=visus (with best correction) of the right eye. OR=odds ratio. OS visus=visus (with best correction) of the left eye. POMS2=Profile of Mood States 2. PTSD-19=COVID-19 post-traumatic stress disorder questionnaire. RPC=radial peripapillary capillary. STAI-S=State-Trait Anxiety Inventory State. STAI-T=State-Trait Anxiety Inventory Trait. TDI=Threshold-Discrimination-Identification. TSH=thyroid stimulating hormone. ZSDS=Zung Self-Rating Depression Scale.

Figure 4

Signs of metabolic disorders after COVID-19 Limits of normal values (25 kg/m for BMI, 5 μM for total cholesterol, and 3 μM for LDL) are indicated as horizontal lines.