Mild COVID-19 Infection Research Articles

Inclusion of Long Covid patients in the care trajectory post-Covid-19: evidence from Belgium

Abstract Background Evidence suggests that 10-30% of COVID-19 infected people develop persistent symptoms that can be diagnosed as Long Covid. Most Long Covid cases are in patients with a mild acute COVID-19 infection and are mainly treated in primary health care. In July 2022, a care trajectory (CT) post-Covid-19 was launched in Belgium, in which Long Covid patients can benefit from reimbursement of treatment costs when consulting health professionals in primary health care for their rehabilitation. Patients are included in this CT mainly through their general practitioner (GP) and depending on patients’ care needs, treatment is organized in a monodisciplinary or multidisciplinary way. Methods A population-based study on data collected by the Belgian network of Sentinel General Practitioners (SGP) on all Long Covid patients consulting their GP during March-December 2023. Information on inclusion in the CT post-Covid-19 was also registered. Descriptive statistics were performed. Results End of 2023 in Belgium, GPs initiated the CT post-Covid-19 for more than 1000 patients, this mainly for monodisciplinary treatment, less than 10% of included patients received multidisciplinary follow-up. By the SGP, among the registered Long Covid sufferers (N = 14), a total of six cases were included in the CT post-Covid-19. Of these cases, the majority were female, of older age, higher educated and had one or two chronic conditions. Most had a mild or moderate prior COVID-19 infection and all were vaccinated multiple times against COVID-19. Symptoms lasted one year or more for 83.3% of included patients. Treatment focused mainly on self-management, energy management and physical exercise programs, mainly in collaboration with physiotherapists. Conclusions This study yields recent data on patients included in the CT post-COVID-19 in primary care in Belgium. It is important to focus on guidance, follow-up and rehabilitation of Long Covid sufferers by healthcare professionals in Belgium. Key messages • Long Covid patients included in the care trajectory post-Covid-19 in Belgium experience years of debilitating symptoms after their prior COVID-19 infection. • The establishment of the care trajectory post-Covid-19 for Long Covid patients in primary care since July 2022 stimulated collaboration between care givers in Belgian primary health care.

Mild COVID-19 Infection Does Not Affect CKD Indices

Mild COVID-19 Infection Does Not Affect CKD Indices

Evaluation of Immuno-Hematological Parameters of Severe and Mild COVID-19 Cases in Babylon Province, Iraq

The hematopoietic system plays a very important role in contracting the corona virus infection. Hematology indicators are among the factors related to the clinical results of patients with covid-19 due to their cost-effectiveness, availability, speed and convenience of testing. The aim of this study was comparing hematological parameters including the number of Red Blood Cells (RBC), hemoglobin, hematocrit, and platelet count among mild and severe COVID-19 patients. Methods: The study was conducted on 100 Iraqi patients COVID-19 patients. Subjects were classified into two groups with mild (n= 50) and severe (n=50) COVID-19 infection symptoms based on the clinical criteria. The hematological parameters measurement included Red Blood Cell (RBC) count, Hemoglobin (Hb) levels, White Blood Cell (WBC) count, Platelet count (PLT), Hematocrit (HCT) levels, Platelet Distribution Width (PDW), and Mean Platelet Volume (MPV). An independent sample T-test was used to compare the means of hematological parameters between two groups. Results: The RBC count was significantly lower in severe group compared to mild group (P ≤ 0.05). HCT levels were significantly reduced in the severe group compared to mild group (P ≤ 0.05). The severe patients had a significantly lower PLT than mild patients (P ≤ 0.05). No significant difference in Hb levels was observed between severe and mild patients. The severe patients had a significantly higher PDW than mild patients (P ≤ 0.05). Additionally, the severe patients had a significantly higher MPV than mild patients (P ≤ 0.05). Conclusion: The findings of this study indicate that complete blood count measurements can be used as useful biomarkers to assess the severity of Covid-19. Early identification of severe COVID-19 patients using these markers can help to better manage and accelerate the treatment process for COVID-19 patients.

Targeted MRM-analysis of plasma proteins in frozen whole blood samples from patients with COVID-19: a retrospective study.

The COVID-19 pandemic has exposed a number of key challenges that need to be urgently addressed. Mass spectrometric studies of blood plasma proteomics provide a deep understanding of the relationship between the severe course of infection and activation of specific pathophysiological pathways. Analysis of plasma proteins in whole blood may also be relevant for the pandemic as it requires minimal sample preparation. The frozen whole blood samples were used to analyze 203 plasma proteins using multiple reaction monitoring (MRM) mass spectrometry and stable isotope-labeled peptide standards (SIS). A total of 131 samples (FRCC, Russia) from patients with mild (n=41), moderate (n=39) and severe (n=19) COVID-19 infection and healthy controls (n=32) were analyzed. Levels of 94 proteins were quantified and compared. Significant differences between all of the groups were revealed for 44 proteins. Changes in the levels of 61 reproducible COVID-19 markers (SERPINA3, SERPING1, ORM1, HRG, LBP, APOA1, AHSG, AFM, ITIH2, etc.) were consistent with studies performed with serum/plasma samples. The best-performing classifier built with 10 proteins achieved the best combination of ROC-AUC (0.97-0.98) and accuracy (0.90-0.93) metrics and distinguished patients from controls, as well as patients by severity. Here, for the first time, frozen whole blood samples were used for proteomic analysis and assessment of the status of patients with COVID-19. The results obtained with frozen whole blood samples are consistent with those from plasma and serum.

Complications After Covid-19 Infection In Singapore Military Divers: A Retrospective Cohort Study

ABSTRACT Wei NC, Ming KW. Complications After Covid-19 Infection In Singapore Military Divers: A Retrospective Cohort Study. Undersea Hyperb Med. 2024 Third Quarter; 51(3):221-229. Studies suggest that COVID-19 infections may have longer-term and more significant complications, even with mild or absent symptoms. This may predispose divers to pulmonary barotrauma, arterial gas embolisms, and reduced exercise tolerance, and impact physical and cognitive performance during diving. Military diving is physically, physiologically, and psychologically taxing on the individual. This study aims to assess the incidence of complications after COVID-19 infections in a cohort of active military divers and the incidence of diving-related injuries such as decompression sickness and barotrauma following recovery from acute COVID-19 infections. A single-center, retrospective cohort study of complications after COVID-19 infections was done in a cohort of the Republic of Singapore Navy (RSN) Naval Diving Unit (NDU) Divers and involved the collection of retrospective data for 329 military divers who were diagnosed with COVID-19 infection from 25 Mar 2020 and 13 Feb 2023. We found no clinical or subclinical complications after COVID-19 infection in our fully vaccinated, low-risk population of NDU divers after asymptomatic or mild COVID-19 infection. There were also no incidences of diving-related injuries related to COVID-19 after recovery from the acute illness. Based on the study results, it is recommended that all military divers with asymptomatic or mild COVID-19 infections return to military diving activities immediately after recovery from acute COVID-19 infection with resolution of symptoms. As existing guidelines recommend, divers with moderate to critical COVID-19 infection should be reviewed by a diving physician and undergo necessary investigations before returning to military diving. Keywords: barotrauma; COVID-19; decompression sickness; diving medicine; military diving

Sildenafil-inducing allergic angina in elderly with intertwining sinus arrhythmia, wavy triple sign, wavy double sign (Yasser’s signs), and mild covid-infection; interpretation and management

Rationale: Sildenafil is a phosphodiesterase-5 inhibitor (PDE5-I) drug used to treat erectile dysfunction (ED) and pulmonary arterial hypertension. Allergic angina and infarction are broad-spectrum mast cell activation disorders accompanied by acute coronary syndromes (ACS) and are known as Kounis-Zafras (KZ) syndrome. Sinus arrhythmia is a variation of normal sinus rhythm (NSR) that is associated with an irregular rate in which the change in the R-R interval is greater than 0.12 seconds. Wavy triple and Wavy double ECG signs (Yasser’s sign) are new specific diagnostic and therapeutic signs seen in the cases of hypocalcemia. Mild COVID-19 infection means you have symptoms like cough, sore throat, and fatigue, but no dyspnea. Patient concerns: An elderly married male farmer patient was admitted to the intensive care unit with angina, hypotension, generalized hives, Wavy triple, and Wavy double ECG signs after ingestion of sildenafil tablet with mild COVID-19 infection in a previous chronic obstructive pulmonary disease (COPD). Diagnosis: Sildenafil-inducing Kounis syndrome in the elderly with intertwining sinus arrhythmia, Wavy triple sign, Wavy double sign (Yasser’s signs), and mild COVID-19 infection. Interventions: Electrocardiography, oxygenation, IV fluids, and echocardiography. Outcomes: A dramatic clinical and electrocardiographic improvement had happened. Lessons: Sildenafil-inducing Allergic angina and anaphylaxis may be innovative cardiovascular findings. Mild COVID-19 infection, sometimes, can be insignificant. An associated sinus arrhythmia may be a good cardiovascular sign. The dramatic improvement in both clinical and electrocardiographic ST-segment depressions and elevations supports the efficacy of both anti-ischemic and anti-allergic measures.

Back to Basics: The Diagnostic Value of a Complete Blood Count in the Clinical Management of COVID-19.

Since the beginning of the COVID-19 pandemic, scientists have struggled significantly to understand the complexity of COVID-19 pathophysiology. COVID-19 has demonstrated a notoriously unpredictable clinical course. This unpredictability constituted a significant obstacle to clinicians in predicting the disease course among COVID-19 patients, more specifically, in predicting who would develop severe cases and possibly die from the infection. This brief report aims to assess the diagnostic value of using a complete blood count (CBC) and applying high-dimensional analysis, i.e., principal component analysis (PCA), on it to differentiate between patients with mild and severe COVID-19 infection. The data of 855 patients were retrieved from multiple centres in Saudi Arabia. Descriptive statistics, such as counts, percentages, and medians (interquartile ranges) were used to describe patients' characteristics and CBC parameters. Analytical statistics, such as the Mann-Whitney U test, were used to compare between survivors and non-survivors. PCA was applied using the CBC parameters, and the results were compared between survivors and non-survivors. Patients in this study had a median age of 41, with an almost equal ratio of men to women. Most participants were Saudis, and non-survivors were 13.22% of the total cohort. The median values of all CBC indices were within reference ranges; however, some statistically significant differences were observed between survivors and non-survivors. Non-survivors had lower hemoglobin levels and lower hematocrit, lymphocyte, and eosinophil counts but higher WBC and neutrophil counts compared to survivors. PCA on the CBC results of survivors yielded a significantly different profile than non-survivors, indicating the possibility of its use in the context of COVID-19. The diagnostic value of CBC in the clinical management of COVID-19 should be utilized in clinical guidelines for managing COVID-19 cases.

Dissociable effects of mild COVID-19 on short- and long-term memories.

Recent studies have highlighted the presence of cognitive deficits following COVID-19 that persist beyond acute infection, regardless of the initial disease severity. Impairments in short- and long-term memory are among the core deficits reported by patients and observed in objective tests of memory performance. We aimed to extend previous studies by examining performance in a task that allows us to directly compare and contrast memories at different timescales. More specifically, we assessed both short- and long-term memories for contextual-spatial associations encoded during a common session and probed at different durations using an equivalent task in non-hospitalized individuals recovering from mild COVID-19 compared to healthy controls. The approach equated all aspects of memory materials and response demands, isolating performance changes resulting only from memory timescales and thus allowing us to quantify the impact of COVID-19 on cognition. In addition to providing measures of accuracy and response times, the task also provided a sensitive continuous readout of the precision of memory representations, specifically by examining the resolution with which spatial locations were retained in memory. The results demonstrated selective impairment of long-term memory performance in individuals recovering from mild COVID-19 infection. Short-term memory performance remained comparable to healthy controls. Specifically, poor precision of long-term memory representations was demonstrated, which improved with days since diagnosis. No such relationship was observed for short-term memory performance. Our findings reveal a specific impairment to the precision of spatial-contextual long-term memory representations in individuals recovering from mild COVID-19 and demonstrate evidence of recovery in long-term memory over time. Further, the experimental design provides a carefully controlled and sensitive framework to assess memory across different durations with the potential to provide more detailed phenotyping of memory deficits associated with COVID-19 in general.

Inflammatory Myocardial Disease Case Report Following COVID-19 Infection: Giant Cell Myocarditis versus Cardiac Sarcoidosis: To Be or Not to Be

Abstract COVID-19 can induce cardiac involvement, which can include myocardial infarction, various types of arrhythmia, atrioventricular block, myocarditis, acute heart failure, and sudden cardiac death, in approximately 30% of infected patients. There are some reports on the triggering of sarcoid-like reactions and inflammatory myocardial processes by various types of infections. However, little is known about the relationship between COVID-19 and inflammatory cardiomyopathies such as cardiac sarcoidosis (CS) and giant cell myocarditis (GCM). Herein, we describe the clinical course, management, and follow-up of an unmasked inflammatory cardiomyopathy in a 57-year-old Iranian woman, who presented with ventricular arrhythmia 4 months after mild COVID-19 infection. The onset of symptomatic inflammatory myocardial disorders such as CS or GCM may be triggered by COVID-19 infection. The best approach to the management of myocardial inflammatory COVID-19 should probably be individualized based on the patient’s clinical presentation and severity of cardiac involvement.

A comparative study on anti-MOG and anti-AQP4 associated optic neuritis following mild COVID-19: insights from a Chinese single-center experience.

Research on the relationship between mild COVID-19 and the subsequent development of isolated optic neuritis (ON) with antibodies specific to myelin oligodendrocyte glycoprotein (MOG-ON) and aquaporin 4 (AQP4-ON) is limited, particularly case-control studies that directly compare these conditions within the same affected population. A retrospective analysis of initial MOG-ON and AQP4-ON cases during the COVID-19 peak and subsequent months. Patients were classified as possible COVID-19 related ON (PCRON) or non-COVID-19 related ON (NCRON). The study compared epidemiology, comorbidities, and clinical features between these groups. Patients with MOG-ON tended to develop ON symptoms closer in time to a mild COVID-19 infection compared to those with AQP4-ON (6.87 ± 6.25 weeks vs. 11.06 ± 5.84 weeks; p = 0.038), a significantly higher proportion of patients with MON-ON developing symptoms within 6 weeks after COVID-19 compared to those with AQP4-ON (15/23 [65.2%] vs. 5/17 [29.4%]; p = 0.025). Comparing MOG-ON and AQP4-ON patients, MOG-ON patients were more likely to have a recent infection before ON onset (73.1% vs. 30%; p = 0.007) and had better peak and post-treatment visual acuity (p = 0.01; p < 0.001). In contrast, AQP4-ON patients frequently showed comorbid connective tissue diseases (30.0% vs. 0%, p = 0.004) and antinuclear antibody abnormalities (40.0% vs. 7.7%, p = 0.012). Among MOG-ON patients, PCRON had increased rates of atherosclerotic vascular diseases (AVDs) (53.3% vs. 9.1%, p = 0.036), phospholipid antibody abnormalities (60.0% vs. 18.2%, p = 0.04), and bilateral visual impairment (66.7% vs. 9.1%, p = 0.005). Multivariate analysis pinpointed AVDs (OR = 15.21, p = 0.043) and bilateral involvement (OR = 25.15, p = 0.015) as independent factors related to COVID-19 associated MOG-ON, with both being good discriminators for PCRON (AUC = 0.879). No differences were found between the PCRON and NCRON groups in AQP4-ON patients. Mild COVID-19 is more likely associated with MOG-ON than AQP4-ON. MOG-ON that develops within 6 weeks following a COVID-19 infection may be associated with the COVID-19 infection. AVDs may have a synergistic effect on MOG-ON in patients with COVID-19, which warrants further investigation. COVID-19 related MOG-ON often affects both eyes, and acute visual function damage can be severe, but generally has a good prognosis.

The association of non-severe COVID-19 infection and progression to frailty among robust older veterans

BackgroundStudies have shown that frailty was increased in hospitalized COVID-19 patients. However, it is not clear whether non-severe COVID-19 increases the risk for pre-frailty and frailty development. Our study aimed to determine the risk of developing frailty and pre-frailty in robust veterans who contracted non-severe COVID-19. MethodsWe conducted a retrospective cohort study to assess the association of SARS-CoV-2 infection with the development of pre-frailty and frailty status among robust U.S. veterans using VA COVID-19 Shared Data Resource. We included patients 55 years and older who had at least one SARS-CoV-2 testing between March 15, 2020, and November 30, 2020, had been active patients in the past 12 months, and had a VA frailty index of zero (robust status) at the time of testing. Cox proportional hazard model was used to assess the association between COVID-19 infection and developing frailty or pre-frailty and frailty. We also assessed the association by patients’ age groups, sex, and race. FindingsWe identified 82070 veterans mean age 68.3 ± 7.8, 74738 (91.1%) male, 53899 (65.7%) white, 7557 (9.2%) with mild COVID-19 infection. Over the follow up period of 36 months, testing positive for COVID-19 was associated with a 66% increase in the hazard of becoming frail (adjusted HR = 1.66, 95%CI: 1.32–2.08), and a 68% increase in the hazard of becoming pre-frail (adjusted HR = 1.68, 95%CI: 1.45–1.94). Among male patients, mild COVID-19 infection was associated with a 54% increase in the hazard of becoming frail (adjusted HR = 1.54, 95% CI: 1.21−1.96), while among female patients there was a 330% increase (adjusted HR = 4.30, 95% CI: 2.13−8.64). Conclusions and relevanceNon-severe COVID-19 infection that occurred in robust older adults increased the risk of developing frailty. Further multi-center prospective cohort studies evaluating the mechanism of action and clinical trials of treatment options for post-COVID frailty are indicated in Veterans to support clinical care.

Titers of IgG and IgA against SARS-CoV-2 proteins and their association with symptoms in mild COVID-19 infection

Humoral immunity in COVID-19 includes antibodies (Abs) targeting spike (S) and nucleocapsid (N) SARS-CoV-2 proteins. Antibody levels are known to correlate with disease severity, but titers are poorly reported in mild or asymptomatic cases. Here, we analyzed the titers of IgA and IgG against SARS-CoV-2 proteins in samples from 200 unvaccinated Hospital Workers (HWs) with mild COVID-19 at two time points after infection. We analyzed the relationship between Ab titers and patient characteristics, clinical features, and evolution over time. Significant differences in IgG and IgA titers against N, S1 and S2 proteins were found when samples were segregated according to time T1 after infection, seroprevalence at T1, sex and age of HWs and symptoms at infection. We found that IgM + samples had higher titers of IgG against N antigen and IgA against S1 and S2 antigens than IgM − samples. There were significant correlations between anti-S1 and S2 Abs. Interestingly, IgM + patients with dyspnea had lower titers of IgG and IgA against N, S1 and S2 than those without dyspnea. Comparing T1 and T2, we found that IgA against N, S1 and S2 but only IgG against certain Ag decreased significantly. In conclusion, an association was established between Ab titers and the development of infection symptoms.

A rare post-infectious autoimmune manifestation of COVID-19

The incidence of post-infectious autoimmune diseases has been on the rise following the COVID-19 pandemic. Recently, an autistic patient was admitted to the hospital presenting with a mild upper respiratory system COVID-19 infection. Months after recovery and polymerase chain reaction negativity, the patient developed HEp-2 cell positivity and presented with relapsing polychondritis (RP), a rare autoimmune disease. The mechanism of this autoimmune invasion is ultimately caused by activating a myriad of immune reactions. Lymphocytopenia almost always accompanies various clinical forms of COVID-19; however, it may drive the lymphocytopenia-induced proliferation of autoreactive T cells via the activation of interleukin-6 (IL-6). Moreover, high levels of neutrophils during infection promote autoimmune disease by releasing cytokine and chemokine cascades that accompany inflammation, and neutrophil extracellular traps regulating immune responses through cell–cell interactions. Furthermore, autism spectrum disorder patients display an altered immune system that includes an augmented inflammatory cytokine milieu leading to an increased pro-inflammatory Th1/Th2 ratio. In addition, the pathophysiology of RP is majorly associated with a cell-mediated immune reaction; thus, the predisposing exaggerated immune system of such patients must also be considered as a predisposing factor to the development of post-infectious autoimmune diseases.

Venous Thromboembolism in Patients Diagnosed with Coronavirus Disease 2019

Background Coronavirus disease 2019 (Covid-19) infection is associated with an increased risk of venous thromboembolism (VTE). However, it is unclear if mild Covid-19 infection is a significant risk factor for VTE. Our goal was to investigate the overall incidence of VTE in Covid-19 patients at our community hospital and assess its correlates. Methods We retrospectively reviewed the medical records of patients 18 years and older who tested positive for Covid-19 at our hospital between March 2020 and September 2021. Results A total of 5926 patients aged 18 to 99 years had Covid-19. Of these patients, 64 (incidence of 1.08%) had VTE; 63% were male and 58% were African Americans. The highest rate of VTE was seen in patients with cardiovascular risk factors (n=47, 73%) followed by a history of thromboembolism (n=19, 30%); patients (n=6, 9%) with mild Covid-19 also developed VTE. Conclusions In our study of a predominantly African American population, the VTE incidence (1.08%) was ten times higher than the general population’s rate of 0.1%. Covid-19 infection, even mild category, not requiring hospitalization was a risk factor for VTE. The risk was increased in men and those who have cardiovascular risk factors and/or prior history of thromboembolism.

“Ultrastructural changes of platelets in COVID-19 and chronic viral hepatitis patients “

ABSTRACT Platelet-viral interactions are evolving as a new concern. Coagulation disorder is a major consequence of the COVID-19 infection. In chronic hepatitis virus infections, defect in coagulation factors, thrombocytopenia and platelet function abnormalities are common. A SARS-CoV-2 infection on top of chronic viral hepatitis infection can be common in areas where viral hepatitis is endemic. Here, we investigate the platelet ultrastructural changes and estimate the serum platelet factor-4 (PF-4), ferritin, CRP, and D-dimer in COVID-19 patients (n = 60), COVID-19 patients with associated chronic viral hepatitis (n = 20), and healthy subjects (n = 20). Ultrastructural changes were demonstrated in all test groups, denoting platelet activation. In chronic viral hepatitis patients, Platelet ultrastrustural apoptotic changes were also seen. Significantly high levels of PF-4 were confirmed in moderate and severe COVID-19 patients (P.value <0.001), with a cut off value of 17 ng/ml for predicting disease severity. A positive correlation of PF-4 with the level of serum ferritin, CRP, and D-dimer (p value < 0.001) was noted, while negatively correlated with platelet count and platelet granule count (p value < 0.001). In our study, chronic viral hepatitis patients presented mild COVID-19 signs, and their PF-4 level was comparable with the subgroup of mild COVID-19 infection. The platelet’s critical role in COVID-19 coagulopathy and chronic viral hepatitis is evidenced by the ultrastructural changes and the high levels of PF4. Moreover, a dual viral infection poses a substantial burden on the platelets, necessitating close monitoring of the patient’s coagulation profile.

Brain temperature and free water increases after mild COVID-19 infection

The pathophysiology underlying the post-acute sequelae of COVID-19 remains understudied and poorly understood, particularly in healthy adults with a history of mild infection. Chronic neuroinflammation may underlie these enduring symptoms, but studying neuroinflammatory phenomena in vivo is challenging, especially without a comparable pre-COVID-19 dataset. In this study, we present a unique dataset of 10 otherwise healthy individuals scanned before and after experiencing mild COVID-19. Two emerging MR-based methods were used to map pre- to post-COVID-19 brain temperature and free water changes. Post-COVID-19 brain temperature and free water increases, which are indirect biomarkers of neuroinflammation, were found in structures functionally associated with olfactory, cognitive, and memory processing. The largest pre- to post-COVID brain temperature increase was observed in the left olfactory tubercle (p = 0.007, 95% CI [0.48, 3.01]), with a mean increase of 1.75 °C. Notably, the olfactory tubercle is also the region of the primary olfactory cortex where participants with chronic olfactory dysfunction showed the most pronounced increases as compared to those without lingering olfactory dysfunction (adjusted pFDR = 0.0189, 95% CI [1.42, 5.27]). These preliminary insights suggest a potential link between neuroinflammation and chronic cognitive and olfactory dysfunction following mild COVID-19, although further investigations are needed to improve our understanding of what underlies these phenomena.

Hippocampal neurometabolic and structural changes from pre-to post-COVID-19: A case-series study

BackgroundNeurological complications of the COVID-19 infection may be caused in part by local neurochemical and structural abnormalities that could not be detected during routine medical examinations. We examined within subject neurometabolic and structural brain alterations from pre-to post-COVID-19 in the hippocampal region of three elderly individuals (aged 63–68 years) who had a COVID-19 infection with mild symptoms. Patients were participating in an interventional study in which they were closely monitored at the time they were diagnosed with COVID-19. Patients 1 and 2 just completed 18–20 resistance training sessions prior to their diagnosis. Patient 3 was assigned to a non-training condition in the same study. MethodsWhole brain magnetic resonance imaging (MRI) images and proton magnetic resonance spectroscopy (1H-MRS) of the left hippocampus were collected before and after infection. Structural and spectroscopic imaging measures post-COVID-19 were contrasted to the pre-COVID-19 measures and were compared with values for Minimal Detectable Change at 95% (MDC95) and 90% (MDC90) confidence from a group of six elderly (aged 60–79 years) without COVID-19 that participated in the same study. ResultsAfter SARS-COV-2 infection, we observed a reduction of glutamate-glutamine (Glx) in Patients 1 and 2 (≥ 42.0%) and elevation of myo-inositol (mIns) and N-acetyl-aspartate (NAA) in Patient 3 (≥ 36.4%); all > MDC90. MRI findings showed increased (Patients 1 and 2) or unchanged (Patient 3) hippocampal volume. ConclusionsOverall, findings from this exploratory study suggest that mild COVID-19 infection could be associated with development of local neuroinflammation and reduced glutamate levels in the hippocampus. Our 1H-MRS findings may have clinical value for explaining chronic neurological and psychological complaints in COVID-19 long-haulers.

GrimAge is elevated in older adults with mild COVID-19 an exploratory analysis.

COVID-19 has been contained; however, the side effects associated with its infection continue to be a challenge for public health, particularly for older adults. On the other hand, epigenetic status contributes to the inter-individual health status and is associated with COVID-19 severity. Nevertheless, current studies focus only on severe COVID-19. Considering that most of the worldwide population developed mild COVID-19 infection. In the present exploratory study, we aim to analyze the association of mild COVID-19 with epigenetic ages (HorvathAge, HannumAge, GrimAge, PhenoAge, SkinAge, and DNAmTL) and clinical variables obtained from a Mexican cohort of older adults. We found that all epigenetic ages significantly differ from the chronological age, but only GrimAge is elevated. Additionally, both the intrinsic epigenetic age acceleration (IEAA) and the extrinsic epigenetic age acceleration (EEAA) are accelerated in all patients. Moreover, we found that immunological estimators and DNA damage were associated with PhenoAge, SkinBloodHorvathAge, and HorvathAge, suggesting that the effects of mild COVID-19 on the epigenetic clocks are mainly associated with inflammation and immunology changes. In conclusion, our results show that the effects of mild COVID-19 on the epigenetic clock are mainly associated with the immune system and an increase in GrimAge, IEAA, and EEAA.

Efficacy and Safety of Andrographolide and Favipiravir Versus Favipiravir Monotherapy in Patients with Mild COVID-19 Infection: A Multicenter Randomized Controlled Trial

Reports indicate that Andrographolide inhibits viral replication and reduces COVID-19 symptoms. This study aimed to determine Andrographolide's additional effect and safety in mild COVID-19 patients treated with favipiravir. A multicenter, open-labeled, randomized controlled trial was conducted from October 2021 to February 2022. The patients were randomized to receive a combination of Andrographolide and favipiravir or favipiravir monotherapy. The primary outcome was the occurrence rate of severe pneumonia. The secondary outcomes were symptom improvement, inflammatory biomarkers, and adverse events on days 7 and 14. 82 mild COVID-19 patients were enrolled; 43 and 39 patients received either combination therapy or favipiravir alone. Baseline characteristics were comparable. None developed severe pneumonia, requiring a mechanical ventilator. The Andrographolide group had a significant reduction of cough compared to the controlled group; 13 (30.2%) vs. 22 (56.4%), p = 0.017 on day 7 and 4 (9.3%) vs. 7 (17.9%), p = 0.025 on day 14. Moreover, the Andrographolide group had significantly lower levels of inflammatory markers on day 7, CRP (5.8 vs. 18.4 mg/L; p = 0.019) and IL-6 (2.0 vs. 21.8 pg/mL; p = 0.001) but not on day 14. Regarding safety outcomes, the Andrographolide group had significantly higher AST levels on day 7 (40.3 vs. 32.2 U/L; p = 0.030) and both AST and ALT levels on day 14 (55.3 vs. 32.0; p = 0.014 and 63.8 vs. 40.0; p = 0.022, respectively). In mild COVID-19 patients, the combination of Andrographolide and favipiravir did not demonstrate additional benefits over favipiravir alone in preventing severe pneumonia. However, Andrographolide significantly reduced cough symptoms, especially during the first week. Furthermore, despite mild transaminitis, patients treated with Andrographolide showed improvements in inflammatory markers.

Biomarkers of coagulation, endothelial, platelet function, and fibrinolysis in patients with COVID-19: a prospective study

Prospective and sequential evaluation of homeostatic changes leading to thrombosis across COVID 19 disease severity spectrum are limited. In this prospective observational study, haemostasis was evaluated in patients with mild, moderate-severe, and critical COVID-19 infection. Markers of endothelial activation [Soluble thrombomodulin (sTM), von Willebrand Factor (VWF)], platelet activation [Soluble P-selectin, beta-thromboglobulin (BTG)] and global haemostasis [Rotational thromboelastometry (ROTEM)] were evaluated on days 1 and 5 after admission. The study cohort comprised of 100 adult patients (mild = 20, moderate-severe = 22, critical = 58). Sixty-five patients received anticoagulation for 10 (7–14) days. Thrombotic events were seen in 9 patients. In-hospital mortality was 21%. Endothelial activation markers were elevated at baseline in all subgroups, with levels in moderate-severe (sTM = 4.92 ng/ml, VWF = 295 U/dl) [reference-ranges: sTM = 2.26–4.55 ng/ml; Soluble P-selectin = 13.5–31.5 ng/ml; BTG = 0.034–1.99 ng/ml] and critical patients (sTM = 6.07 ng/ml, VWF = 294 U/dl) being significantly higher than in the mild group (sTM = 4.18 ng/ml, VWF = 206 U/dl). In contrast, platelet activation markers were elevated only in critically ill patients at baseline (Soluble P-selectin = 37.3 ng/ml, BTG = 2.51 ng/ml). The critical group had significantly lower fibrinolysis on days 1 and 5 when compared with the moderate-severe arm. COVID-19 infection was associated with graded endothelial activation and lower fibrinolysis that correlated with illness severity.