ABSTRACT
A man in his 20s with a history of acute disseminated encephalomyelitis (ADEM) was brought into the emergency department (ED) after his family found him at home collapsed on the floor unresponsive with a blood glucose of 28 mg/dL at the field. In the ED, the patient was tachycardic, tachypnoeic and hypotensive, requiring pressors and intubation at 9 hours and 12 hours after arrival, respectively. Laboratory results revealed a positive COVID-19 test, serum sodium of 125 mmol/L and persistent hypoglycaemia. The patient was given a high dose of dexamethasone for COVID-19 treatment 1 hour before pressors were started. He was then continued on a stress dose of intravenous hydrocortisone with rapid clinical improvement leading to his extubation, and discontinuation of vasopressors and glucose on day 2 of admission. The patient received his last dose of intravenous hydrocortisone on day 4 in the early afternoon with the plan to order adrenal testing the following morning prior to discharge. On day 5, the aldosterone <3.0 ng/dL, adrenocorticotropic hormone (ACTH) level >1250 pg/mL, and ACTH stimulation test showed cortisol levels of 3 and 3 µg/dL at 30 and 60 min, respectively. The anti-21-hydroxylase antibody was positive. The patient was discharged on hydrocortisone and fludrocortisone. The patient's symptoms, elevated ACTH, low cortisol and presence of 21-hydroxylase antibodies are consistent with autoimmune Addison's disease. This is the first case reporting autoimmune Addison's disease in a patient with COVID-19 with a history of ADEM. The case highlights the importance of considering adrenal insufficiency as a diagnostic differential in haemodynamically unstable patients with COVID-19.
Subject(s)
Addison Disease , COVID-19 , Encephalomyelitis , Male , Humans , Addison Disease/complications , Addison Disease/diagnosis , Addison Disease/drug therapy , Hydrocortisone/therapeutic use , COVID-19 Drug Treatment , COVID-19/complications , Adrenocorticotropic Hormone , Mixed Function Oxygenases/therapeutic useABSTRACT
OBJECTIVE: Autoimmune Addison's disease (AAD) entails a chronic adrenal insufficiency and is associated with an increased risk of severe infections. It is, however, unknown how patients with AAD were affected by the coronavirus disease 2019 (COVID-19) pandemic of 2020-2021. This study was aimed at investigating the incidence of COVID-19 in patients with AAD in Sweden, the self-adjustment of medications during the disease, impact on social aspects, and treatment during hospitalization. Additionally, we investigated if there were any possible risk factors for infection and hospitalization. DESIGN AND METHODS: Questionnaires were sent out from April to October 2021 to 813 adult patients with AAD in the Swedish Addison Registry. The questionnaires included 55 questions inquiring about COVID-19 sickness, hospital care, medications, and comorbidities, focusing on the pre-vaccine phase. RESULTS: Among the 615 included patients with AAD, COVID-19 was reported in 17% of which 8.5% required hospital care. Glucocorticoid treatment in hospitalized patients varied. For outpatients, 85% increased their glucocorticoid dosage during sickness. Older age (P = .002) and hypertension (P = .014) were associated with an increased risk of hospital care, while younger age (P < .001) and less worry about infection (P = .030) were correlated with a higher risk of COVID-19. CONCLUSIONS: In the largest study to date examining AAD during the COVID-19 pandemic, we observed that although one-fifth of the cohort contracted COVID-19, few patients required hospital care. A majority of the patients applied general recommended sick rules despite reporting limited communication with healthcare during the pandemic.
Subject(s)
Addison Disease , COVID-19 , Self-Management , Adult , Humans , Addison Disease/epidemiology , Addison Disease/complications , Retrospective Studies , Sweden/epidemiology , Pandemics , Glucocorticoids/therapeutic use , COVID-19/epidemiology , COVID-19/complicationsABSTRACT
Background At the initial stage of COVID-19 outbreak, most medical education institutions in China had to accept the sudden shift from classroom teaching to nearly 100% online instruction for different curricula. However, little has been known about medical students’ learning efficiency when learning has been completely conducted online. This study aimed at investigating medical students’ perspectives on online learning efficiency during the early phase of the COVID-19 outbreak and finding possible factors that could damage online learning efficiency.Methods Between May and July, 2020, the authors electronically distributed a self-designed questionnaire to all the 780 medical students who attended the Rural-oriented Free Tuition Medical Education program in Guangxi Medical University that locates in the southwestern China. Data on participant demographics, learning phases, academic performance, and perceptions regarding learning efficiency of online and classroom learning were collected. Wilcoxon rank sum test, Kruskal Wallis test, and polynomial Logistic regression were employed to detect differences of learning efficiency between online and classroom learning, and associations among learning phases, academic performance and online learning efficiency.Results A total of 612 medical students validly responded to this survey (valid response rate 78.46%), and they reported more positive perceptions of efficiency in the circumstance of face-to-face learning than of online learning despite of gender (P<0.001), learning phases (P<0.01), and academic performance (P<0.01). Learning phases and academic performance positively corelated with online learning efficiency (P<0.01). In responders’ opinion, the five top factors that most damaged online learning efficiency were low academic motivation, poor course design, inferiority in online teaching ability, limited interactions between faculty and students or among students, and insufficient learner engagement.Conclusion This study indicates obviously negative impact brought by pure online learning on perceived learning efficiency of medical students, and positive associations amid learning phases, academic performance, and online learning efficiency. We advise that instead of pure online instruction, more effort should be put into developing new online course design to improve learning efficiency when online instruction is conducted in large scale, and learning phase and academic performance should be taken into account for effective implementation of online learning.
Subject(s)
Addison Disease , Learning Disabilities , COVID-19ABSTRACT
Background Healthcare workers (HCWs) face a high risk of infection during pandemics or public health emergencies as demonstrated in the ongoing COVID-19 pandemic. Understanding how governments respond can inform public health control measures and support health system functioning. An economic impact analysis examining HCW COVID-19 infections in Kenya and three other countries estimated that the total economic costs related to HCW COVID-19 infections costs and deaths in Kenya were US$113.2 million (range US$35.8-US$246.1). We examined the governance arrangements for and implementation of HCW protection during the COVID-19 pandemic in Kenya between March 2020 and March 2021.Methods We conducted a scoping review of 44 policy and legislative documents and reports on HCW protection and 22 media articles. We adopted the transparency, accountability, participation, integrity and capacity (TAPIC) governance framework to analyse and summarize our findings into policy gaps and implementation challenges. We followed the guidance of the Preferred Reporting Items for Systematic reviews and Meta-analysis extension for Scoping Reviews (PRSIMA-ScR).Results Policy design gaps included inadequate provisions for emerging threats, inconsistencies with the devolved context and inadequate structures to monitor, inform and respond to HCW COVID-19 infections. Implementation challenges were attributed to inadequate quantity and quality of PPE, difficulty in accessing medical care for HCWs, delays in HCW remuneration, insufficient infection prevention and control measures, the top-down application of plans, difficulties in working in a decentralized context, and pre-existing public finance management (PFM) bottlenecks.Conclusion Implementation of HCW protection during the COVID-19 pandemic and beyond could leverage the revamping of current legislation on labour relations to reflect devolved governance and develop a broader and long-term approach to occupational health and safety implementation that considers all HCWs. Improvements in PFM arrangements coupled with increased investment in the health sector and attention to efficient use of resources will also impact positively on HCW protection.
Subject(s)
Addison Disease , Death , COVID-19ABSTRACT
Healthcare workers (HCWs) face a high risk of infection during pandemics or public health emergencies as demonstrated in the ongoing COVID-19 pandemic. Understanding how governments respond can inform public health control measures and support health system functioning. An economic impact analysis examining HCW COVID-19 infections in Kenya and three other countries estimated that the total economic costs related to HCW COVID-19 infections costs and deaths in Kenya were US$113.2 million (range US$35.8-US$246.1). We examined the governance arrangements for and implementation of HCW protection during the COVID-19 pandemic in Kenya between March 2020 and March 2021. We conducted a scoping review of 44 policy and legislative documents and reports on HCW protection and 22 media articles. We adopted the transparency, accountability, participation, integrity and capacity (TAPIC) governance framework to analyse and summarize our findings into policy gaps and implementation challenges. Policy design gaps included inadequate provisions for emerging threats, inconsistencies with the devolved context and inadequate structures to monitor, inform and respond to HCW COVID-19 infections. Implementation challenges were attributed to inadequate quantity and quality of PPE, difficulty in accessing medical care for HCWs, delays in HCW remuneration, insufficient infection prevention and control measures, the top-down application of plans, difficulties in working in a decentralized context, and pre-existing public finance management (PFM) bottlenecks. Implementation of HCW protection during the COVID-19 pandemic and beyond could leverage the revamping of current legislation on labour relations to reflect devolved governance and develop a broader and long-term approach to occupational health and safety implementation that considers all HCWs. Improvements in PFM arrangements coupled with increased investment in the health sector and attention to efficient use of resources will also impact positively on HCW protection.
Subject(s)
Addison Disease , Death , COVID-19ABSTRACT
Background The COVID-19 pandemic has presented new opportunities for corruption to infiltrate health and pharmaceutical sectors globally, increasing health inequities within and between countries. COVID-19 vaccine procurement and distribution are specific areas that are vulnerable to corruption due to their attraction of large amounts of public and private funding, involvement of a high number of stakeholders, and lack of centralized oversight. We conducted a descriptive, qualitative study of corruption risks and the use of anti-corruption, transparency, and accountability (ACTA) mechanisms in the international COVID-19 vaccine and distribution process.Results We identified 34 academic articles and policy documents and triangulated documentary data with 16 key informant interviews. A review of the literature identified four distinct corruption risks in the international COVID-19 vaccine procurement and distribution process: (1) a lack of transparency and accountability in the operation of the COVAX Facility; (2) a lack of transparency in the vaccine procurement process; (3) a risk of bribery; and (4) a risk of vaccine theft or the introduction of substandard and falsified vaccines at the point of distribution. Key informants further articulated concerns about a lack of transparency in vaccine pricing and vaccine contracts and the exclusion of civil society organizations from the vaccine deployment process. Reported ACTA mechanisms implemented across various levels of the international vaccine procurement and distribution chain focused primarily on transparency mechanisms, including institutional oversight processes, blockchain-based supply-chain solutions, and civil society engagements.Conclusion Emergency responses to public health crises expose institutions, such as governments and international organizations, to high risks of corruption without adequate ACTA mechanisms. Experiences during the COVID-19 vaccine deployment process demonstrate that efforts to improve transparency will be insufficient without commensurate sanctions programs in place.
Subject(s)
Addison Disease , COVID-19ABSTRACT
Background: Vitamin D can stall hyper-inflammatory responses, and there are mechanistic reasons for the positive effects of vitamin D in COVID-19 patients. Objectives: Therefore, this study aimed to evaluate the effect of a single high dose of vitamin D on inflammatory markers in critical patients with COVID-19. Design and patients: A single center, double-blind, randomized clinical trial was conducted on 61 patients with COVID-19 admitted to the intensive care units. The intervention and placebo groups received a dose of 300,000 IU vitamin D intramuscularly and identical placebo respectively. Patients were followed up for one week. Lactate Dehydrogenase (LDH) (IU/ml), C-reactive protein (CRP) (mg/L), interleukin-6 (IL-6) (Pg/L), lymphocyte, neutrophil, and neutrophil/lymphocyte (N/L) ratios were checked at the beginning and 7 th day of the study. Key results: A total of 44 patients with COVID-19 have completed this trial with vitamin D insufficiency in the baseline. The lymphocyte level increased while LDH (IU/ml), neutrophil level, and N/L ratio decreased after intervention with a high vitamin D dose, which was insignificant. The CRP (mg/L) and IL-6 (Pg/L) were significantly reduced after high-dose vitamin D intervention. Conclusions: Based on the results, the effect of high doses of vitamin D on inflammatory indices was significant in patients with COVID-19 hospitalized in the ICU.
Subject(s)
Addison Disease , COVID-19ABSTRACT
Background Data from numerous studies demonstrate the high frequency of vitamin D deficiency (VDD) and insufficiency (VDI) in many countries worldwide that depend on age and sex, the seasons, country, and concomitant pathology. This research was aimed to study vitamin D status in the Ukrainian population during 2016–2022 years depending on age, sex, month, and year of the observation and compare the results with the data of previous Ukrainian epidemiologic studies.Methods In a single-center cohort study, we analyzed the serum level of a total 25-hydroxyvitamin D (25(OH)D) in 7,418 subjects aged 20–99 years. The analysis was performed depending on the age, sex, month, season, and year of the observation. Also, we compared the results with the data of previous Ukrainian studies. 25-hydroxyvitamin D (25(OH)D) level was measured using the electrochemiluminescence method.Results The mean serum 25(OH)D level in the total group was 31.0 [22.3–41.1] ng/mL, the lowest level was in the age group 90–99 years old. No gender differences were found in 25(OH)D levels, except the one for the women aged 60–69 years old, who had higher vitamin D levels compared to male parameters. 41.6% of the subjects had an optimal (> 30–50 ng/mL) 25(OH)D level, 27.3% had VDI, and 19.5% had a VDD. The suboptimal and high serum concentration of 25(OH)D (> 50–100 ng/mL) had 11.4% of the subjects. Also, we established the increase of serum 25(OH)D level from 2016 to 2022 with the highest values in 2020–2022. Seasonal variations of 25(OH)D concentration found the highest index in autumn (33.0 [24.0-42.4] ng/mL) and the lowest one in the spring (28.5 [19.7–38.7] ng/mL) with the highest 25(OH)D level in September and the lowest one in March.Conclusion Our results confirmed a decrease in VDD, and VDI in 2020–2022 in the Ukrainian population compared to previous years (2016–2019) and previous Ukrainian studies with similar age and seasonal particularities. It may be the consequence of an improvement in public awareness of global vitamin D deficiency, its positive skeletal and extra-skeletal effects, as well as more intensive vitamin D supplementation due to COVID-19 pandemic in recent years.
Subject(s)
Vitamin D Deficiency , Addison Disease , Seasonal Affective Disorder , COVID-19ABSTRACT
BACKGROUND: COVID-19 has different manifestations from respiratory to GI problems, and some of them are more common, but some are rare. Reporting rare cases can significantly advance our understanding of the disease. CASE PRESENTATION: In this case, we report an 18-year-old teenage boy with chest pain and resistant hypotension following COVID-19 infection, finally diagnosed as primary adrenal insufficiency and COVID-19 myocarditis. CONCLUSION: Adrenal insufficiency can be life-threatening due to its adverse effects on hemodynamic and electrolyte equilibrium. In addition, COVID-19 induced myocarditis can make the situation more complicated.
Subject(s)
Addison Disease , Adrenal Insufficiency , COVID-19 , Myocarditis , Male , Humans , Adolescent , COVID-19/complications , Myocarditis/diagnosis , Myocarditis/etiology , Adrenal Insufficiency/complications , Adrenal Insufficiency/diagnosisABSTRACT
Ethiopia is the second most populous country in Africa and the sixth most affected by COVID-19 on the continent. Despite having experienced five infection waves, >499 000 cases, and ~7 500 COVID-19-related deaths as of January 2023, there is still no detailed genomic epidemiological report on the introduction and spread of SARS-CoV-2 in Ethiopia. In this study, we reconstructed and elucidated the COVID-19 epidemic dynamics. Specifically, we investigated the introduction, local transmission, ongoing evolution, and spread of SARS-CoV-2 during the first four infection waves using 353 high-quality near-whole genomes sampled in Ethiopia. Our results show that whereas viral introductions seeded the first wave, subsequent waves were seeded by local transmission. The B.1.480 lineage emerged in the first wave and notably remained in circulation even after the emergence of the Alpha variant. The B.1.480 was out-competed by the Delta variant. Notably, Ethiopia lack of local sequencing capacity was further limited by sporadic, uneven, and insufficient sampling that limited the incorporation of genomic epidemiology in the epidemic public health response in Ethiopia. These results highlight Ethiopia role in SARS-CoV-2 dissemination and the urgent need for balanced, near-real-time genomic sequencing.
Subject(s)
Severe Acute Respiratory Syndrome , Addison Disease , COVID-19ABSTRACT
Cardiovascular sequelae of severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) disease 2019 (COVID-19) contribute to the complications of the disease. One potential complication is lung vascular remodeling, but the exact cause is still unknown. We hypothesized that endothelial TLR3 insufficiency contributes to lung vascular remodeling induced by SARS-CoV-2. In the lungs of COVID-19 patients and SARS-CoV-2 infected Syrian hamsters, we discovered thickening of the pulmonary artery media and microvascular rarefaction, which were associated with decreased TLR3 expression in lung tissue and pulmonary artery endothelial cells (ECs). In vitro, SARS-CoV-2 infection reduced endothelial TLR3 expression. Following infection with mouse-adapted (MA) SARS-CoV-2, TLR3 knockout mice displayed heightened pulmonary artery remodeling and endothelial apoptosis. Treatment with the TLR3 agonist polyinosinic:polycytidylic acid reduced lung tissue damage, lung vascular remodeling, and endothelial apoptosis associated with MA SARS-CoV-2 infection. In conclusion, repression of endothelial TLR3 is a potential mechanism of SARS-CoV-2 infection associated lung vascular remodeling and enhancing TLR3 signaling is a potential strategy for treatment.
Subject(s)
Severe Acute Respiratory Syndrome , Addison Disease , COVID-19 , Vascular RemodelingABSTRACT
Pneumonia is an acute respiratory disease of varying aetiology, which drew much attention during the COVID-19 pandemic. Among many thoroughly studied aspects of pneumonia, lipid metabolism has been addressed insufficiently. Here, we report on abnormal lipid metabolism of both COVID-19- and non-COVID-19-associated pneumonias in human lungs. Morphometric analysis revealed extracellular and intracellular lipid depositions, most notably within vessels adjacent to inflamed regions, where they apparently interfere with the blood flow. Lipids were visualized on Sudan III- and Oil Red O-stained cryosections and on OsO4-contrasted semi-thin and ultrathin sections. Chromato-mass spectrometry revealed that unsaturated fatty acid content was elevated at inflammation sites compared with the intact sites of the same lung. The genes involved in lipid metabolism were downregulated in pneumonia, as shown by qPCR and in silico RNAseq analysis. Thus, pneumonias are associated with marked lipid abnormalities, and therefore lipid metabolism can be considered a target for new therapeutic strategies.
Subject(s)
Addison Disease , Respiratory Tract Diseases , Pneumonia , Inflammation , COVID-19ABSTRACT
For improved safety, children are vaccinated with a lower dose and extended interval for mRNA COVID-19 vaccines; however, whether there is protection before dose 2 is unknown. We recruited 113 children receiving BNT162b2 primary vaccination during an Omicron wave. After dose 1, 96% had detectable anti-Spike(S) IgG and 100% had S-reactive T cells; those with both had a lower risk of symptomatic infection compared to those with undetectable anti-S IgG [RR 0.19 (95% CI; 0.06, 0.59)]. This suggests that dosing can be extended without risk of insufficient early protection.
Subject(s)
Addison Disease , COVID-19ABSTRACT
COVID-19 aggravates pre-existing diabetes mellitus and contributes to newly discovered hypertension by increasing blood pressure by inhibiting the activity of angiotensin-converting enzymes 2 in the rennin-angiotensin system. Diabetes patients may be more vulnerable to COVID-19 due to chronic comorbidities such as obesity and cardiovascular disease such as hypertension. On March 23, 2022, a retired black African woman in her sixties was taken into the emergency room with the chief complaints of frequent midnight urine, hazy vision, headache, fever, and tingling in her hands and feet. A throat swab polymerase chain reaction test that revealed positive results after 28 hours was used to confirm COVID-19. Her electrocardiogram showed sinus tachycardia with a heart rate of 105 beats per minute. Fluid resuscitation (0.9% normal saline) of 1000 mL and drip insulin administration were commenced as soon as she was brought to an intensive care unit. In this case report, the patient had been previously diagnosed with type 2 diabetes mellitus. COVID-19 affects the beta cells, forcing them to release insulin and increasing the insulin insufficiency, which leads to her blood glucose raising. Type 2 diabetes mellitus is therefore the most frequent comorbidity of COVID-19 in this case report. Poor blood glucose management in the case of COVID-19 may increase the pathogen's susceptibility, the likelihood that patients will be admitted to the hospital, and the likelihood that mortality will be enhanced.
Subject(s)
Diabetes Mellitus , Fever , Addison Disease , Obesity , Diabetes Mellitus, Type 2 , Hypertension , Cardiovascular Diseases , Tachycardia, Sinus , Headache , COVID-19ABSTRACT
Background The use of antigen rapid tests (Ag-RDTs) for self-testing is an important element of the COVID-19 control strategy and has been widely supported. However, scale-up of self-testing for COVID-19 in sub-Saharan Africa is still insufficient and there is limited evidence on the acceptability of self-testing and agreement between Ag-RDT self-testing and Ag-RDT testing by professional users. A joint collaboration (BRCCH-EDCTP COVID-19 Initiative) was established between Lesotho and Zambia to address these gaps in relation to Ag-RDT self-testing and contribute to increasing its use in the region. Methods A cross-sectional study was conducted with qualitative and quantitative data analysis. Firstly, 11 in-depth cognitive interviews (5 in Zambia and 9 in Lesotho) were performed to assess the participants understanding of the instructions for use (IFU) for self-testing. In a second step, evaluation of test agreement between Ag-RDT self-testing and Ag-RDT testing by professional user using SD Biosensor STANDARD Q COVID-19 Ag-RDT was performed. In Zambia, usability and acceptability of self-testing were also assessed. Results Cognitive interviews in Lesotho and Zambia showed overall good understanding of IFU. In Zambia, acceptability of self-testing was high, though some participants had difficulties in conducting certain steps in the IFU correctly. Agreement between Ag-RDT self-test and Ag-RDT by professional users in Lesotho (428 participants) and Zambia (1136 participants) was high, 97.6% (404/414, 95% CI: 95.6-99.8) and 99.8% (1116/1118, 95% CI: 99.4-100) respectively. Conclusion Findings from this study support the use of Ag-RDT self-testing within COVID-19 control strategies in sub-Saharan Africa, contributing to increase the testing capacity and access in hard-to reach settings.
Subject(s)
Addison Disease , COVID-19ABSTRACT
Background Following the mass influx of Rohingya refugees into Cox’s Bazaar, Bangladesh in 2017, makeshift settlement camps in Ukhiya and Teknaf have been overburdened, leading to livelihood challenges for both Rohingya and host communities. The humanitarian crisis has had adverse effects on vulnerable populations, which include the elderly, persons with disabilities, adolescents, and single female household heads. Using a subset of a larger dataset on households with most vulnerable groups in both communities, we analysed the effect of the pandemic and lockdown on the livelihood of single female household (HH) heads.Methods A cross-sectional household roster survey was designed to collect data from households with most vulnerable groups (MVGs) of host and Rohingya communities from December 2020 to March 2021; 11 host community villages and 10 Rohingya camps purposively selected as per the affiliated intervention of the project. The paper analysed quantitative and qualitative data from the sub-group of single female household heads without no income/low income. Participants were surveyed for their socio-demographic characteristics, COVID-19 experiences and knowledge, and food security situation, social experiences and mental health.Results We surveyed 432 single female HH heads. Support during the pandemic was reported to be low, with less than 50% of HHs reporting relief meeting their needs; only 36% and 15% of these HHs received rations in camps and host communities respectively. Loan facilities were mostly unavailable and there were reported insufficiencies in food consumption. Over 50% of respondents tested positive on the PHQ-2. Further analyses indicates that having a chronic health issue (OR 2.2, 95% CI 1.33–3.66) was positively associated with the PHQ-2 score Rohingya single females. For host single females, having an ill member in the HH (OR 1.46, 95% CI 1.02–2.08) and the inability to save before the pandemic (OR 1.57 95% CI 1.11–2.23) increased the odds of testing positive.Conclusion Our study findings revealed insufficiencies with economic opportunities and food security for single female headed households, as well as a high rate of positive screening for depression amongst this population. These findings call for a more in-depth understanding of the needs of this group.
Subject(s)
Addison Disease , Depressive Disorder , COVID-19ABSTRACT
Background Hyperglycaemia was shown to be among the features of severe acute COVID-19 infection both in the acute and convalescence period. Mechanisms contributing to its development and/or maintenance in a post-COVID phase are still unclear. Materials and Methods Survivors of severe COVID-19 but without a known history of diabetes were examined at baseline (T0) and after 3 (T3) and 6 (T6) months: indirect calorimetry and OGTT. Insulin response and sensitivity (IS) were expressed as insulinogenic (IGI), disposition (DI), and Matsuda insulin sensitivity index (ISI), respectively. Resting energy expenditure (REE) was calculated using the Weir and Harris-Benedict equation and substrate preference using the respiratory quotient (RQ) and nitrogen losses. Results Thirty-two patients (12 women) were available for the analyses at T0 and 26 at T6. Baseline examination was within 21±6.5 days after COVID-19 diagnosis. Patients were hypermetabolic at baseline (30.7 ± 4.3 kcal/kg lean mass/day, ~120% predicted values) but REE declined over the 6 months (ΔT6-T0 mean difference (95% CI): -5.4 (-6.8, -4.1) kcal/kg lean mass/day, p<0.0001). 20 patients at T0 and 13 patients at T6 had hyperglycemia. None of the patients had positive islet autoantibodies. Insulin sensitivity at T0 was comparable between hyperglycaemic (H) vs. normoglycaemic (N) patients (T0 ISIH=3.07 ± 1.18, ISIN=3.23 ± 1.72, p=0.66), whereas insulin response was lower in the H group only (DIH=3.19 ± 2.16 vs DIN=8.78 ± 6.37, p=0.005). Over the 6 months, IS improved in the H group (ΔT6-T0 mean difference for ISI (95% CI): 1.84 (0.45, 3.24), p=0.01)), whereas IGI and DI did not improve in either group. Conclusions Severe COVID-19 infection was associated with hypermetabolism that did not persist over the follow-up. Patients were insulin resistant in the acute phase, but only those with insufficient insulin response developed hyperglycaemia. Insufficient beta cell response was a possible mechanism leading to hyperglycaemia.
Subject(s)
Diabetes Mellitus , Hyperglycemia , Insulin Resistance , Addison Disease , COVID-19ABSTRACT
Importance Post COVID-19 condition (PCC) is known to affect a large proportion of COVID-19 survivors. Robust study design and methods are needed to understand post-COVID-19 diagnosis patterns in all COVID-19 survivors, not just the ones clinically diagnosed with PCC. Objective To assess which diagnoses appear more frequently after a COVID-19 infection and how they differ by COVID-19 severity and vaccination status. Design We applied a case-crossover phenome-wide association study (PheWAS) in a retrospective cohort of COVID-19 survivors, comparing the occurrences of 1,649 diagnosis-based phenotype codes (PheCodes) pre- and post-COVID-19 infection periods in the same individual using a conditional logistic regression. Setting Patients tested for or diagnosed with COVID-19 at Michigan Medicine from March 10, 2020 through May 1, 2022. Participants 36,856 SARS-CoV-2-positive patients and 141,615 age- and sex-matched SARS-CoV-2-negative patients as a comparison group for sensitivity analysis. Exposure SARS-CoV-2 virus infection as determined by RT-PCR testing and/or clinical evaluation. Main Outcomes and Measures We compared the rate of occurrence of 1,649 disease classification codes in “pre-” and “post-COVID-19 periods”. We studied how this pattern varied by COVID-19 severity and vaccination status at the time of infection. Results Using a case-crossover PheWAS framework, we found mental, circulatory, and respiratory disorders to be strongly associated with the “post-COVID-19 period” for the overall COVID-19-positive cohort. A total of 325 PheCodes reached phenome-wide significance (p<3e-05), and top hits included cardiac dysrhythmias (OR=1.7 [95%CI: 1.6-1.9]), respiratory failure, insufficiency, arrest (OR=3.1 [95%CI: 2.7-3.5]) and anxiety disorder (OR=1.7 [95%CI: 1.6-1.8]). In the patients with severe disease, we found stronger associations with many respiratory and circulatory disorders, such as pneumonia (p=2.1e-18) and acute pulmonary heart disease (p=2.4e-8), and the “post-COVID-19 period,” compared to those with mild/moderate disease. Test negative patients exhibited a somewhat similar association pattern to those fully vaccinated, with mental health and chronic circulatory diseases rising to the top of the association list in these groups. Conclusions and Relevance Our results confirm that patients experience myriad symptoms more than 28 days after SARS-CoV-2 infection, but especially mental, circulatory, and respiratory disorders. Our case-crossover PheWAS approach controls for within-person confounders that are time-invariant. Comparison to test negatives with a similar design helped identify enrichment specific to COVID-19. As we look into the future, we must be aware of COVID-19 survivors’ healthcare needs in the period after infection. Key Points Question What patterns of clinical diagnosis tend to occur more frequently after a COVID-19 infection and how do they vary by COVID-19 severity and vaccination status? Findings In a cohort of 36,856 COVID-19-positive patients, using a case-crossover phenome-wide association analysis that controls for within-subject confounders, we found symptoms such as anxiety disorder, cardiac dysrhythmias, and respiratory failure to be significantly associated with the “post-COVID-19 period.” Patients with severe COVID-19 were more likely to receive diagnoses related to respiratory conditions in their “post-COVID-19 period” compared to those with mild/moderate COVID-19. The landscape of phenome-wide association signals for the vaccinated group featured common chronic conditions when compared to the signals in the unvaccinated group. Meaning Symptoms across multiple organ systems, especially in the mental, circulatory, and respiratory domains, were associated with the “post-COVID-19 period.” Characterization of post-COVID-19 diagnosis patterns is crucial to understand the long term and future healthcare burden of COVID-19.